WorldWideScience

Sample records for denervation

  1. Renal denervation

    DEFF Research Database (Denmark)

    Olsen, Lene Kjær; Kamper, Anne-Lise; Svendsen, Jesper Hastrup

    2015-01-01

    PURPOSE OF REVIEW: Renal denervation (RDN) has, within recent years, been suggested as a novel treatment option for patients with resistant hypertension. This review summarizes the current knowledge on this procedure as well as limitations and questions that remain to be answered. RECENT FINDINGS...... selection, anatomical and physiological effects of RDN as well as possible beneficial effects on other diseases with increased sympathetic activity. The long awaited Symplicity HTN-3 (2014) results illustrated that the RDN group and the sham-group had similar reductions in BP. SUMMARY: Initial studies...

  2. MRI appearance of muscle denervation

    Energy Technology Data Exchange (ETDEWEB)

    Kamath, S. [University Hospital of Wales, Department of Radiology, Cardiff (United Kingdom); Venkatanarasimha, N.; Walsh, M.A.; Hughes, P.M. [Derriford Hospital, Department of Radiology, Plymouth (United Kingdom)

    2008-05-15

    Muscle denervation results from a variety of causes including trauma, neoplasia, neuropathies, infections, autoimmune processes and vasculitis. Traditionally, the diagnosis of muscle denervation was based on clinical examination and electromyography. Magnetic resonance imaging (MRI) offers a distinct advantage over electromyography, not only in diagnosing muscle denervation, but also in determining its aetiology. MRI demonstrates characteristic signal intensity patterns depending on the stage of muscle denervation. The acute and subacutely denervated muscle shows a high signal intensity pattern on fluid sensitive sequences and normal signal intensity on T1-weighted MRI images. In chronic denervation, muscle atrophy and fatty infiltration demonstrate high signal changes on T1-weighted sequences in association with volume loss. The purpose of this review is to summarise the MRI appearance of denervated muscle, with special emphasis on the signal intensity patterns in acute and subacute muscle denervation. (orig.)

  3. Eligibility for renal denervation

    DEFF Research Database (Denmark)

    Persu, Alexandre; Jin, Yu; Baelen, Marie

    2014-01-01

    -resistant hypertension (ENCOReD). The analysis included 731 patients. Age averaged 61.6 years, office blood pressure at screening was 177/96 mm Hg, and the number of blood pressure-lowering drugs taken was 4.1. Specialists referred 75.6% of patients. The proportion of patients eligible for renal denervation according...... undetected secondary causes of hypertension (11.1%). In conclusion, after careful screening and treatment adjustment at hypertension expert centers, only ≈40% of patients referred for renal denervation, mostly by specialists, were eligible for the procedure. The most frequent cause of ineligibility...... (approximately half of cases) was blood pressure normalization after treatment adjustment by a hypertension specialist. Our findings highlight that hypertension centers with a record in clinical experience and research should remain the gatekeepers before renal denervation is considered....

  4. Renal denervation and hypertension.

    Science.gov (United States)

    Schlaich, Markus P; Krum, Henry; Sobotka, Paul A; Esler, Murray D

    2011-06-01

    Essential hypertension remains one of the biggest challenges in medicine with an enormous impact on both individual and society levels. With the exception of relatively rare monogenetic forms of hypertension, there is now general agreement that the condition is multifactorial in nature and hence requires therapeutic approaches targeting several aspects of the underlying pathophysiology. Accordingly, all major guidelines promote a combination of lifestyle interventions and combination pharmacotherapy to reach target blood pressure (BP) levels in order to reduce overall cardiovascular risk in affected patients. Although this approach works for many, it fails in a considerable number of patients for various reasons including drug-intolerance, noncompliance, physician inertia, and others, leaving them at unacceptably high cardiovascular risk. The quest for additional therapeutic approaches to safely and effectively manage hypertension continues and expands to the reappraisal of older concepts such as renal denervation. Based on the robust preclinical and clinical data surrounding the role of renal sympathetic nerves in various aspects of BP control very recent efforts have led to the development of a novel catheter-based approach using radiofrequency (RF) energy to selectively target and disrupt the renal nerves. The available evidence from the limited number of uncontrolled hypertensive patients in whom renal denervation has been performed are auspicious and indicate that the procedure has a favorable safety profile and is associated with a substantial and presumably sustained BP reduction. Although promising, a myriad of questions are far from being conclusively answered and require our concerted research efforts to explore the full potential and possible risks of this approach. Here we briefly review the science surrounding renal denervation, summarize the current data on safety and efficacy of renal nerve ablation, and discuss some of the open questions that need

  5. Pelvic denervation procedures for dysmenorrhea.

    Science.gov (United States)

    Ramirez, Christina; Donnellan, Nicole

    2017-08-01

    Chronic pelvic pain and dysmenorrhea are common conditions affecting reproductive-age women. Surgical pelvic denervation procedures may be a treatment option for women with midline dysmenorrhea, in which medical management is declined by the patient, ineffective at managing symptoms, or medically contraindicated. This review describes the surgical techniques and complications associated with pelvic denervation procedures as well as the current evidence for these procedures in women with primary dysmenorrhea and dysmenorrhea secondary to endometriosis. Presacral neurectomy is the preferred pelvic denervation procedure in patients with primary dysmenorrhea and midline chronic pelvic pain associated with endometriosis. In patients with endometriosis presacral neurectomy is a useful adjunct to excision or ablation of all endometrial lesions to improve postoperative pain relief. There is no additional patient benefit of performing combined presacral neurectomy and uterine nerve ablation procedures. Pelvic denervation procedures can be performed safely and quickly with a low risk of complication if the surgeon is knowledgeable and skilled in operating in the presacral space. Patients should be adequately counseled on expected success rates and potential complications associated with pelvic denervation procedures.

  6. Renal sympathetic denervation in hypertension.

    Science.gov (United States)

    Doumas, Michael; Faselis, Charles; Papademetriou, Vasilios

    2011-11-01

    Despite the abundance of antihypertensive drugs, resistant hypertension remains a major clinical problem. Recent technological advances render interventional management of resistant hypertension one of the hottest topics in the hypertension field. The aim of this review is to present the pathophysiologic background and the mechanisms mediating blood pressure reduction after renal sympathetic denervation, to analyze recent findings with this fascinating approach and to critically suggest future research directions. Catheter-based, ablation-induced renal sympathetic denervation was initially studied in 45 patients with resistant hypertension in a proof-of-concept study. Impressive blood pressure reductions of about 30/15  mmHg were achieved at 6 months, without serious complications. A second, controlled, randomized (but not blinded) study confirmed the results, verifying the efficacy and safety of the procedure. A recent report revealed the 2-year durability of blood pressure reduction. Data published so far indicate that ablation-induced renal denervation is a feasible, effective, and well tolerated interventional approach for the management of resistant hypertension. The groundbreaking studies of renal denervation in drug-resistant hypertension pave the way for further research in other disease conditions in which sympathetic overactivity seems to play a critical role. This initial wave of enthusiasm needs to be followed by rigorous investigation, for the proper identification of the potential and the limitations, indications, and contraindications of this approach.

  7. RENAL DENERVATION IN RESISTANT ARTERIAL HYPERTENSION

    Directory of Open Access Journals (Sweden)

    V. A. Sulimov

    2013-01-01

    Full Text Available A new method of non-drug treatment of resistant hypertension – renal denervation is considered. General information about resistant hypertension, method of renal denervation, the results of clinical studies on efficacy and safety, as well as own clinical case are presented.

  8. RENAL DENERVATION IN RESISTANT ARTERIAL HYPERTENSION

    OpenAIRE

    V. A. Sulimov; A. V. Rodionov; A. A. Svetankova; I. E. Deneka

    2015-01-01

    A new method of non-drug treatment of resistant hypertension – renal denervation is considered. General information about resistant hypertension, method of renal denervation, the results of clinical studies on efficacy and safety, as well as own clinical case are presented.

  9. RENAL DENERVATION IN RESISTANT ARTERIAL HYPERTENSION

    Directory of Open Access Journals (Sweden)

    V. A. Sulimov

    2015-09-01

    Full Text Available A new method of non-drug treatment of resistant hypertension – renal denervation is considered. General information about resistant hypertension, method of renal denervation, the results of clinical studies on efficacy and safety, as well as own clinical case are presented.

  10. Renal denervation: What happened, and why?

    Science.gov (United States)

    Shishehbor, Mehdi H; Hammad, Tarek A; Thomas, George

    2017-09-01

    Despite promising results in initial trials, renal denervation failed to achieve its efficacy end points as a treatment for resistant hypertension in the SYMPLICITY HTN-3 trial, the largest trial of this treatment to date (N Engl J Med 2014; 370:1393-1401). Is renal denervation dead, or will future trials and newer technology revive it? Copyright © 2017 Cleveland Clinic.

  11. [Jejunal myenteric denervation induced by benzalkonium chloride].

    Science.gov (United States)

    Ramalho, F S; Santos, G C; Ramalho, L N; Kajiwara, J K; Zucoloto, S

    1994-01-01

    The effects of benzalkonium chloride (BAC) on the number of myenteric neurons, muscle thickness and external perimeter after acute (until 10 days after BAC application) and chronic (30 and 60 days after BAC application) denervation of the proximal jejunum were determined in rats. There was a significant reduction in the number of myenteric neurons of all segments treated with BAC. The extent of denervation varied along the time, and it was reduced in the denervated segments of the chronic group in comparison with the acute group. This may be due to the neuroplasticity phenomenon appearing during the chronic phase. Myenteric denervation increased the thickness of the propria muscle layer, especially in the longitudinal muscle layer, suggesting a higher sensitivity of this layer to myenteric denervation.

  12. Renal Denervation: a Field in Flux.

    Science.gov (United States)

    Laffin, Luke J; Bakris, George L

    2016-07-01

    SYMPLICITY HTN-3 was a pivotal moment for renal denervation as a treatment option for resistant hypertension. Prior unblinded studies were called into question given the negative results of the first sham-controlled trial of renal denervation. Reevaluation of the renal denervation procedure demonstrated that a more precise approach was needed to adequately denervate the kidney. This new approach has been implemented in two ongoing clinical trials, one on and one off medications to assess the new procedure's efficacy and safety. These and other ongoing trials will be discussed in the context of older studies in this field. We focus on novel findings published following the release of SYMPLICITY HTN-3 data in early 2014 and look to the future of renal denervation in the treatment of primary hypertension.

  13. Insulin action in denervated skeletal muscle

    International Nuclear Information System (INIS)

    Smith, R.L.

    1987-01-01

    The goal of this study was to determine the mechanisms responsible for reduced insulin response in denervated muscle. Denervation for 3 days of rat muscles consisting of very different compositions of fiber types decreased insulin stimulated [U- 14 C]glucose incorporation into glycogen by 80%. Associated with the reduction in glycogen synthesis was a decreased activation of glycogen synthase. Denervation of hemidiaphragms for 1 day decreased both the basal and insulin stimulated activity ratios of glycogen synthase and the rate of insulin stimulated [U- 14 C[glucose incorporation into glycogen by 50%. Insulin stimulation of 2-deoxy[ 3 H]glucose uptake was not decreased until 3 days after denervation. Consistent with the effects on glucose transport,insulin did not increase the intracellular concentration of glucose-6-P in muscles 3 days after denervation. Furthermore, since the Ka for glucose-6-P activation of glycogen synthase was not decreased by insulin in denervated hemidiaphragms, the effects of denervation on glycogen synthase and glucose transport were synergistic resulting in the 80% decrease in glycogen synthesis rates

  14. Renal denervation: unde venis et quo vadis?

    Science.gov (United States)

    Nähle, C P; Düsing, R; Schild, H

    2015-04-01

    Renal denervation is a minimally invasive, catheter-based option for the treatment of refractory hypertension. Indications and contraindications for renal denervation have been defined in an interdisciplinary manner. The efficacy and safety of the procedure were evaluated. Currently, indication for renal denervation is limited to patients with primary hypertension and a systolic blood pressure of ≥ 160 mm Hg (or ≥ 150 mm Hg in diabetes type 2) despite optimal medical therapy with ≥ 3 different antihypertensive drugs. In this specific patient population, an average blood pressure reduction of 32/14 mmHg was observed in non-randomized/-controlled trials after renal denervation. These results were not confirmed in the first randomized controlled trial with a non-significantly superior blood pressure reduction of 14.1 ± 23.9 mm Hg compared to controls (-11.74 ± 25.94 mm Hg, difference -2.39 mm Hg p = 0.26 for superiority with a margin of 5 mm Hg) who underwent a sham procedure. The efficacy and long-term effects of renal denervation need to be re-evaluated in light of the HTN3 study results. To date, renal denervation should not be performed outside of clinical trials. Future trials should also assess if renal denervation can be performed with sufficient safety and efficacy in patients with hypertension-associated diseases. The use of renal denervation as an alternative therapy (e. g. in patients with drug intolerance) can currently not be advocated. The indication for renal denervation should be assessed in an interdisciplinary fashion and according to current guidelines with a special focus on ruling out secondary causes for arterial hypertension. 5 - 10 % of patients with hypertension suffer from refractory hypertension, but only about 1 % of patients meet the criteria for a renal denervation. Renal denervation leads to a significant decrease in office blood pressure; however, the impact on 24-hour blood pressure

  15. Chemical Renal Denervation in the Rat

    Energy Technology Data Exchange (ETDEWEB)

    Consigny, Paul M., E-mail: paul.consigny@av.abbott.com; Davalian, Dariush, E-mail: dariush.davalian@av.abbott.com [Abbott Vascular, Innovation Incubator (United States); Donn, Rosy, E-mail: rosy.donn@av.abbott.com; Hu, Jie, E-mail: jie.hu@av.abbott.com [Abbott Vascular, Bioanalytical and Material Characterization (United States); Rieser, Matthew, E-mail: matthew.j.rieser@abbvie.com; Stolarik, DeAnne, E-mail: deanne.f.stolarik@abbvie.com [Abbvie, Analytical Pharmacology (United States)

    2013-12-03

    Introduction: The recent success of renal denervation in lowering blood pressure in drug-resistant hypertensive patients has stimulated interest in developing novel approaches to renal denervation including local drug/chemical delivery. The purpose of this study was to develop a rat model in which depletion of renal norepinephrine (NE) could be used to determine the efficacy of renal denervation after the delivery of a chemical to the periadventitial space of the renal artery. Methods: Renal denervation was performed on a single renal artery of 90 rats (n = 6 rats/group). The first study determined the time course of renal denervation after surgical stripping of a renal artery plus the topical application of phenol in alcohol. The second study determined the efficacy of periadventitial delivery of hypertonic saline, guanethidine, and salicylic acid. The final study determined the dose–response relationship for paclitaxel. In all studies, renal NE content was determined by liquid chromatography–mass spectrometry. Results: Renal NE was depleted 3 and 7 days after surgical denervation. Renal NE was also depleted by periadventitial delivery of all agents tested (hypertonic saline, salicylic acid, guanethidine, and paclitaxel). A dose response was observed after the application of 150 μL of 10{sup −5} M through 10{sup −2} M paclitaxel. Conclusion: We developed a rat model in which depletion of renal NE was used to determine the efficacy of renal denervation after perivascular renal artery drug/chemical delivery. We validated this model by demonstrating the efficacy of the neurotoxic agents hypertonic saline, salicylic acid, and guanethidine and increasing doses of paclitaxel.

  16. Chemical Renal Denervation in the Rat

    International Nuclear Information System (INIS)

    Consigny, Paul M.; Davalian, Dariush; Donn, Rosy; Hu, Jie; Rieser, Matthew; Stolarik, DeAnne

    2014-01-01

    Introduction: The recent success of renal denervation in lowering blood pressure in drug-resistant hypertensive patients has stimulated interest in developing novel approaches to renal denervation including local drug/chemical delivery. The purpose of this study was to develop a rat model in which depletion of renal norepinephrine (NE) could be used to determine the efficacy of renal denervation after the delivery of a chemical to the periadventitial space of the renal artery. Methods: Renal denervation was performed on a single renal artery of 90 rats (n = 6 rats/group). The first study determined the time course of renal denervation after surgical stripping of a renal artery plus the topical application of phenol in alcohol. The second study determined the efficacy of periadventitial delivery of hypertonic saline, guanethidine, and salicylic acid. The final study determined the dose–response relationship for paclitaxel. In all studies, renal NE content was determined by liquid chromatography–mass spectrometry. Results: Renal NE was depleted 3 and 7 days after surgical denervation. Renal NE was also depleted by periadventitial delivery of all agents tested (hypertonic saline, salicylic acid, guanethidine, and paclitaxel). A dose response was observed after the application of 150 μL of 10 −5  M through 10 −2  M paclitaxel. Conclusion: We developed a rat model in which depletion of renal NE was used to determine the efficacy of renal denervation after perivascular renal artery drug/chemical delivery. We validated this model by demonstrating the efficacy of the neurotoxic agents hypertonic saline, salicylic acid, and guanethidine and increasing doses of paclitaxel

  17. Chemical renal denervation in the rat.

    Science.gov (United States)

    Consigny, Paul M; Davalian, Dariush; Donn, Rosy; Hu, Jie; Rieser, Matthew; Stolarik, Deanne

    2014-02-01

    The recent success of renal denervation in lowering blood pressure in drug-resistant hypertensive patients has stimulated interest in developing novel approaches to renal denervation including local drug/chemical delivery. The purpose of this study was to develop a rat model in which depletion of renal norepinephrine (NE) could be used to determine the efficacy of renal denervation after the delivery of a chemical to the periadventitial space of the renal artery. Renal denervation was performed on a single renal artery of 90 rats (n = 6 rats/group). The first study determined the time course of renal denervation after surgical stripping of a renal artery plus the topical application of phenol in alcohol. The second study determined the efficacy of periadventitial delivery of hypertonic saline, guanethidine, and salicylic acid. The final study determined the dose-response relationship for paclitaxel. In all studies, renal NE content was determined by liquid chromatography-mass spectrometry. Renal NE was depleted 3 and 7 days after surgical denervation. Renal NE was also depleted by periadventitial delivery of all agents tested (hypertonic saline, salicylic acid, guanethidine, and paclitaxel). A dose response was observed after the application of 150 μL of 10(-5) M through 10(-2) M paclitaxel. We developed a rat model in which depletion of renal NE was used to determine the efficacy of renal denervation after perivascular renal artery drug/chemical delivery. We validated this model by demonstrating the efficacy of the neurotoxic agents hypertonic saline, salicylic acid, and guanethidine and increasing doses of paclitaxel.

  18. Imaging of denervation in the head and neck

    Energy Technology Data Exchange (ETDEWEB)

    Borges, Alexandra [Radiology Department, Instituto Portugues de Oncologia Francisco Gentil, Centro de Lisboa, Rua Prof. Lima Basto, 1093 Lisboa (Portugal)], E-mail: borgalexandra@gmail.com

    2010-05-15

    Denervation changes maybe the first sign of a cranial nerve injury. Recognition of denervation patterns can be used to determine the site and extent of a lesion and to tailor imaging studies according to the most likely location of an insult along the course of the affected cranial nerve(s). In addition, the extent of denervation can be used to predict functional recovery after treatment. On imaging, signs of denervation can be misleading as they often mimic recurrent neoplasm or inflammatory conditions. Imaging can both depict denervation related changes and establish its cause. This article briefly reviews the anatomy of the extracranial course of motor cranial nerves with particular emphasis on the muscles supplied by each nerve, the imaging features of the various stages of denervation, the different patterns of denervation that maybe helpful in the topographic diagnosis of nerve lesions and the most common causes of cranial nerve injuries leading to denervation.

  19. Imaging of denervation in the head and neck.

    Science.gov (United States)

    Borges, Alexandra

    2010-05-01

    Denervation changes maybe the first sign of a cranial nerve injury. Recognition of denervation patterns can be used to determine the site and extent of a lesion and to tailor imaging studies according to the most likely location of an insult along the course of the affected cranial nerve(s). In addition, the extent of denervation can be used to predict functional recovery after treatment. On imaging, signs of denervation can be misleading as they often mimic recurrent neoplasm or inflammatory conditions. Imaging can both depict denervation related changes and establish its cause. This article briefly reviews the anatomy of the extracranial course of motor cranial nerves with particular emphasis on the muscles supplied by each nerve, the imaging features of the various stages of denervation, the different patterns of denervation that maybe helpful in the topographic diagnosis of nerve lesions and the most common causes of cranial nerve injuries leading to denervation. Copyright (c) 2010 Elsevier Ireland Ltd. All rights reserved.

  20. Imaging of denervation in the head and neck

    International Nuclear Information System (INIS)

    Borges, Alexandra

    2010-01-01

    Denervation changes maybe the first sign of a cranial nerve injury. Recognition of denervation patterns can be used to determine the site and extent of a lesion and to tailor imaging studies according to the most likely location of an insult along the course of the affected cranial nerve(s). In addition, the extent of denervation can be used to predict functional recovery after treatment. On imaging, signs of denervation can be misleading as they often mimic recurrent neoplasm or inflammatory conditions. Imaging can both depict denervation related changes and establish its cause. This article briefly reviews the anatomy of the extracranial course of motor cranial nerves with particular emphasis on the muscles supplied by each nerve, the imaging features of the various stages of denervation, the different patterns of denervation that maybe helpful in the topographic diagnosis of nerve lesions and the most common causes of cranial nerve injuries leading to denervation.

  1. Renal denervation for treatment of drug-resistant hypertension.

    Science.gov (United States)

    Esler, Murray

    2015-02-01

    At the seven-year anniversary of the first catheter-based renal denervation procedure for resistant hypertension, it is timely to reflect on the past, present, and future of the development and clinical application of this treatment. Unresolved procedural and technical questions are central: How much renal denervation is optimal? How can this level of denervation be achieved? What test for denervation can be applied in renal denervation trials? Will renal denervation show a "class effect," with the different energy forms now used for renal nerve ablation producing equivalent blood pressure lowering? When I have assessed renal denervation efficacy, using measurements of the spillover of norepinephrine from the renal sympathetic nerves to plasma, the only test validated to this point, denervation was found to be incomplete and non-uniform between patients. It is probable that the degree of denervation has commonly been suboptimal in renal denervation trials; this criticism applying with special force to the Symplicity HTN-3 trial, where the proceduralists, although expert interventional cardiologists, had no prior experience with the renal denervation technique. Recently presented results from the Symplicity HTN-3 trial confirm that renal denervation was not achieved effectively or consistently. Given this, and other difficulties in the execution of the trial relating to drug adherence, an idea mooted is that the US pivotal trial of the future may be in younger, untreated patients. Copyright © 2015 Elsevier Inc. All rights reserved.

  2. [Renal denervation as treatment option for hypertension].

    Science.gov (United States)

    Blankestijn, P J; Bots, M L

    2016-01-01

    The rationale behind catheter-based renal denervation is that afferent and efferent renal nerves play a role in the pathogenesis and maintenance of high blood pressure, and that this can be prevented by blocking the function of the renal nerves. Since the introduction of catheter-based renal denervation, several observational and a small number of randomised controlled trials have been conducted. The available evidence does not allow for a definitive conclusion regarding its efficacy. There have been no serious side-effects reported. The development of this treatment concept has not been finalised; new trials have just commenced or will start in the near future.

  3. Respiratory sinus arrhythmia in the denervated heart

    Czech Academy of Sciences Publication Activity Database

    Eisenberger, M.; Halámek, Josef; Jurák, Pavel; Vítovec, J.

    2004-01-01

    Roč. 105, č. 4 (2004), s. 145 ISSN 0006-9248. [Alpe Adria Cardiology Meeting /12./. 01.05.2004, Cividale del Fuiuli] R&D Projects: GA ČR(CZ) GA102/05/0402 Keywords : denervated heart * RSA * HRV Subject RIV: FA - Cardiovascular Diseases incl. Cardiotharic Surgery

  4. Renal Sympathetic Denervation: Hibernation or Resurrection?

    Science.gov (United States)

    Papademetriou, Vasilios; Doumas, Michael; Tsioufis, Costas

    The most current versions of renal sympathetic denervation have been invented as minimally invasive approaches for the management of drug-resistant hypertension. The anatomy, physiology and pathophysiology of renal sympathetic innervation provide a strong background supporting an important role of the renal nerves in the regulation of blood pressure (BP) and volume. In addition, historical data with surgical sympathectomy and experimental data with surgical renal denervation indicate a beneficial effect on BP levels. Early clinical studies with transcatheter radiofrequency ablation demonstrated impressive BP reduction, accompanied by beneficial effects in target organ damage and other disease conditions characterized by sympathetic overactivity. However, the failure of the SYMPLICITY 3 trial to meet its primary efficacy end point raised a lot of concerns and put the field of renal denervation into hibernation. This review aims to translate basic research into clinical practice by presenting the anatomical and physiological basis for renal sympathetic denervation, critically discussing the past and present knowledge in this field, where we stand now, and also speculating about the future of the intervention and potential directions for research. © 2016 S. Karger AG, Basel.

  5. Endocrine cells in the denervated intestine

    Science.gov (United States)

    Santos, Gilda C; Zucoloto, Sérgio; Garcia, Sérgio B

    2000-01-01

    This study deals with the effects of myenteric denervation of the proximal jejunum on endocrine cell population of the crypt-villus unit, 5 months after treatment with benzalkonium chloride (BAC). Male Wistar albino rats weighing on average 100 g were allocated to two groups: the BAC group − the proximal jejunal serosa was treated with 2 mm BAC for 30 min, and the control group − treated with saline solution (0,9% NaCl). There was a significant reduction in neurone number in the jejunal myenteric plexus of the BAC group and the endocrine cell population (serotoninergic and argyrophilic cells) was significantly increased in this intestine segment. In conclusion, the present findings provide further evidence that the myenteric denervation induced by BAC may lead to the development of a local imbalance of the neurotransmitters, with a consequent induction of enteroendocrine cell (argyrophilic and serotoninergic cells) hyperplasia in the crypt and villus. PMID:10971748

  6. Renal Denervation: Intractable Hypertension and Beyond

    Science.gov (United States)

    Ariyanon, Wassawon; Mao, Huijuan; Adýbelli, Zelal; Romano, Silvia; Rodighiero, Mariapia; Reimers, Bernhard; La Vecchia, Luigi; Ronco, Claudio

    2014-01-01

    Background Hypertension continues to be a major burden of public health concern despite the recent advances and proven benefit of pharmacological therapy. A certain subset of patients has hypertension resistant to maximal medical therapy and appropriate lifestyle measures. A novel catheter-based technique for renal denervation (RDN) as a new therapeutic avenue has great promise for the treatment of refractory hypertension. Summary This review included the physiology of the renal sympathetic nervous system and the renal nerve anatomy. Furthermore, the RDN procedure, technology systems, and RDN clinical trials as well as findings besides antihypertensive effects were discussed. Findings on safety and efficacy seem to suggest that renal sympathetic denervation could be of therapeutic benefit in refractory hypertensive patients. Despite the fast pace of development in RDN therapies, only initial and very limited clinical data are available. Large gaps in knowledge concerning the long-term effects and consequences of RDN still exist, and solid, randomized data are warranted. PMID:24847331

  7. Renal denervation for resistant hypertension: yes.

    Science.gov (United States)

    Boschetti, Enrico; Alrashdi, Yahya; Schillaci, Giuseppe

    2016-06-01

    Sympathetic overactivity may have a role in triggering and maintaining resistant hypertension, and catheter-based renal denervation (RDN) has emerged as a promising treatment in refractory hypertension. Recently, the results of the Symplicity HTN-3, the first randomized, sham-controlled trial, failed to confirm the previously reported BP-lowering effects of RDN, although definitive conclusions cannot be drawn due to a number of study limitations. Consequently, although some centers halted their RDN programs, research continues and both the concept of denervation and treatment strategies are being redefined. A new generation of sham-controlled trials is currently underway with the aim of detecting which patients are expected to achieve the most beneficial effect from RDN. In this article, we examine the current data on RDN and discuss some insights and future opportunities.

  8. Does complete renal denervation translate into superior clinical outcomes? Lessons learned from denervation of accessory renal arteries

    OpenAIRE

    Mendelsohn, Farrell O.

    2014-01-01

    Pre-clinical studies of renal denervation would suggest that the extent of renal nerve injury correlates with outcomes. The “completeness” of renal nerve injury following renal denervation correlates with treatment-based variables such as the depth of ablation, the number of ablations along the length of the artery, and the number of renal arteries successfully ablated. Renal denervation techniques targeting only main renal arteries may lead to suboptimal results in patients with accessory re...

  9. Neurohumoral indicators of efficacy radiofrequency cardiac denervation

    Energy Technology Data Exchange (ETDEWEB)

    Evtushenko, A. V., E-mail: ave@cardio-tomsk.ru; Evtushenko, V. V. [National Research Tomsk State University, Tomsk (Russian Federation); Federal State Budgetary Scientific Institution “Research Institute for Cardiology”, Tomsk (Russian Federation); Saushkina, Yu. V.; Gusakova, A. M.; Suslova, T. E.; Dymbrylova, O. N.; Smyshlyaev, K. A.; Kurlov, I. O. [Federal State Budgetary Scientific Institution “Research Institute for Cardiology”, Tomsk (Russian Federation); Lishmanov, Yu. B.; Anfinogenova, Ya. D. [National Research Tomsk Polytechnic University, Tomsk (Russian Federation); Federal State Budgetary Scientific Institution “Research Institute for Cardiology”, Tomsk (Russian Federation); Sergeevichev, D. S. [Academician E.N. Meshalkin State Research Institute of Circulation Pathology, Novosibirsk (Russian Federation); Bykov, A. N.; Syryamkin, V. I.; Kistenev, Yu. V. [National Research Tomsk State University, Tomsk (Russian Federation); Lotkov, A. I. [Institute of Strength Physics and Materials Science of the Siberian Branch of the RAS, Tomsk (Russian Federation); Pokushalov, E. A.

    2015-11-17

    In this study, we compared pre- and postoperative parameters of the cardiac sympathetic innervation. The aim of the study was to examine the approaches to evaluating the quality of radiofrequency (RF)-induced cardiac denervation by using non-invasive and laboratory methods. The study included 32 people with long-lasting persistent atrial fibrillation (AF). The patients were divided into 2 groups according to the objectives of the study: group 1 (main) - 21 patients with mitral valve diseases, which simultaneously with radiofrequency ablation (RFA) AF carried out on the effects of the paraganglionic nervous plexuses by C. Pappone (2004) and N. Doll (2008) schemes. The second group (control) contained 11 patients with heart diseases in sinus rhythm (the RF denervation not been performed). All patients, who underwent surgical treatment, were received examination of cardiac sympathetic tone by using {sup 123}I-MIBG. All of them made blood analysis from ascending aorta and coronary sinus to determine the level of norepinephrine and its metabolites before and after cardiac denervation. Data of radionuclide examination are correlating with laboratory data.

  10. Reinnervation following catheter-based radio-frequency renal denervation.

    Science.gov (United States)

    Booth, Lindsea C; Nishi, Erika E; Yao, Song T; Ramchandra, Rohit; Lambert, Gavin W; Schlaich, Markus P; May, Clive N

    2015-04-20

    What is the topic of this review? Does catheter-based renal denervation effectively denervate the afferent and efferent renal nerves and does reinnervation occur? What advances does it highlight? Following catheter-based renal denervation, the afferent and efferent responses to electrical stimulation were abolished, renal sympathetic nerve activity was absent, and levels of renal noradrenaline and immunohistochemistry for tyrosine hydroxylase and calcitonin gene-related peptide were significantly reduced. By 11 months after renal denervation, both the functional responses and anatomical markers of afferent and efferent renal nerves had returned to normal, indicating reinnervation. Renal denervation reduces blood pressure in animals with experimental hypertension and, recently, catheter-based renal denervation was shown to cause a prolonged decrease in blood pressure in patients with resistant hypertension. The randomized, sham-controlled Symplicity HTN-3 trial failed to meet its primary efficacy end-point, but there is evidence that renal denervation was incomplete in many patients. Currently, there is little information regarding the effectiveness of catheter-based renal denervation and the extent of reinnervation. We assessed the effectiveness of renal nerve denervation with the Symplicity Flex catheter and the functional and anatomical reinnervation at 5.5 and 11 months postdenervation. In anaesthetized, non-denervated sheep, there was a high level of renal sympathetic nerve activity, and electrical stimulation of the renal nerve increased blood pressure and reduced heart rate (afferent response) and caused renal vasoconstriction and reduced renal blood flow (efferent response). Immediately after renal denervation, renal sympathetic nerve activity and the responses to electrical stimulation were absent, indicating effective denervation. By 11 months after denervation, renal sympathetic nerve activity was present and the responses to electrical stimulation

  11. Renal sympathetic denervation: MDCT evaluation of the renal arteries.

    LENUS (Irish Health Repository)

    Hutchinson, Barry D

    2013-08-01

    Percutaneous transluminal renal sympathetic denervation is a new treatment of refractory systemic hypertension. The purpose of this study was to assess the clinical utility of MDCT to evaluate the anatomic configuration of the renal arteries in the context of renal sympathetic denervation.

  12. Selective peripheral denervation: comparison with pallidal stimulation and literature review

    NARCIS (Netherlands)

    Contarino, Maria Fiorella; van den Munckhof, Pepijn; Tijssen, Marina A. J.; de Bie, Rob M. A.; Bosch, D. Andries; Schuurman, P. Richard; Speelman, Johannes D.

    2014-01-01

    Patients with cervical dystonia who are non-responders to Botulinum toxin qualify for surgery. Selective peripheral denervation (Bertrand's procedure, SPD) and deep brain stimulation of the globus pallidus (GPi-DBS) are available surgical options. Although peripheral denervation has potential

  13. Renal Denervation for Chronic Heart Failure: Background and Pathophysiological Rationale.

    Science.gov (United States)

    Böhm, Michael; Ewen, Sebastian; Mahfoud, Felix

    2017-01-01

    The activation of the sympathetic nervous system is associated with cardiovascular hospitalizations and death in heart failure. Renal denervation has been shown to effectively reduce sympathetic overdrive in certain patients with uncontrolled hypertension. Pilot trials investigating renal denervation as a potential treatment approach for heart failure were initiated. Heart failure comorbidities like obstructive sleep apnea, metabolic syndrome and arrhythmias could also be targets for renal denervation, because these occurrences are also mediated by the activation of the sympathetic nervous system. Therefore, renal denervation in heart failure is worthy of further investigation, although its effectiveness still has to be proven. Herein, we describe the pathophysiological rationale and the effect of renal denervation on surrogates of the heart failure syndrome.

  14. Renal Denervation for Chronic Heart Failure: Background and Pathophysiological Rationale

    Science.gov (United States)

    Ewen, Sebastian; Mahfoud, Felix

    2017-01-01

    The activation of the sympathetic nervous system is associated with cardiovascular hospitalizations and death in heart failure. Renal denervation has been shown to effectively reduce sympathetic overdrive in certain patients with uncontrolled hypertension. Pilot trials investigating renal denervation as a potential treatment approach for heart failure were initiated. Heart failure comorbidities like obstructive sleep apnea, metabolic syndrome and arrhythmias could also be targets for renal denervation, because these occurrences are also mediated by the activation of the sympathetic nervous system. Therefore, renal denervation in heart failure is worthy of further investigation, although its effectiveness still has to be proven. Herein, we describe the pathophysiological rationale and the effect of renal denervation on surrogates of the heart failure syndrome. PMID:28154583

  15. Renal denervation for resistant hypertension and beyond.

    Science.gov (United States)

    Laffin, Luke J; Bakris, George L

    2015-03-01

    Despite the availability of more than 125 approved antihypertensive medications, 36 million (48%) of 75 million people with hypertension, including 16 million treated with antihypertensive medications in the United States, do not achieve guideline blood pressure goals known to reduce cardiovascular morbidity and mortality and progression of kidney disease; 3% to 6% of these 75 million hypertensive individuals are estimated to have resistant hypertension. A major contributing factor for poor blood pressure control, besides inadequate diuretic therapy, is failure of antihypertensive agents to inhibit the sympathetic nervous system effectively. Consequently, alternative device-driven approaches have been developed. Recent technical advances targeting renal sympathetic nerves, that is, renal denervation therapy, are the focus of more invasive therapies to treat resistant hypertension. Encouraging results from the SYMPLICITY HTN-2 trial, regarding efficacy and safety of renal denervation therapy, were countered by disappointing efficacy results of SYMPLICITY HTN-3. Reasons for these divergent results and the future of the field are discussed. Copyright © 2015 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.

  16. Renal denervation: Results of a single-center cohort study

    International Nuclear Information System (INIS)

    Luetkens, J.A.; Thomas, D.; Doerner, J.; Schild, H.H.; Naehle, C.P.; Woitas, R.P.; Hundt, F.

    2015-01-01

    To investigate the effect of renal denervation on office-based and 24-h ambulatory blood pressure measurements (ABPM) in a highly selective patient population with drug-resistant hypertension. Patients with drug resistant hypertension eligible for renal denervation were included in the study population. Office blood pressure and ABPM were assessed prior to and after renal denervation. To detect procedure related renal or renal artery damage, magnetic resonance imaging (MRI) and angiography (MRA) were performed pre-interventional, one day post-interventional, and one month after renal denervation. Mean follow-up time between renal denervation and blood pressure re-assessment was 9.5 ± 3.9 months. Between August 2011 and March 2013, 17 patients prospectively underwent renal denervation. Pre-interventional mean office blood pressure and ABPM were 177.3 ± 20.3/103.8 ± 20.4 mmHg and 155.2 ± 20.5/93.7 ± 14.5 mmHg, respectively. Post-interventional, office blood pressure was significantly reduced to 144.7 ± 14.9/89.5 ± 12.1 (p 0.05). The number of prescribed antihypertensive drugs was unchanged after renal denervation (4.7 ± 2.0 vs. 4.2 ± 1.2, p = 0.18). No renovascular complications were detected in follow-up MRI. After renal denervation, no significant decrease in ABPM was observed. These results may indicate a limited impact of renal denervation for drug resistant hypertension.

  17. Renal denervation: a new therapeutic approach for resistant hypertension.

    Science.gov (United States)

    Cao, Longxing; Fu, Qiang; Wang, Binghui; Li, Zhiliang

    2014-01-01

    To review the advances in studies on renal denervation. References concerning renal denervation and resistant hypertension cited in this review were collected from PubMed published in English and those of renal denervation devices from official websites of device manufacturers up to January 2014. Articles with keywords "renal denervation" and "resistant hypertension" were selected. Renal and systemic sympathetic overactivity plays an important role in pathology of hypertension as well as other diseases characterized by sympathetic overactivity. Renal denervation is a new, catheter based procedure to reduce renal and systemic sympathetic overactivity by disruption of renal sympathetic efferent and afferent nerves through radiofrequency or ultrasound energy delivered to the endoluminal surface of both renal arteries. Although several studies have shown the efficacy and safety of renal denervation in the treatment of resistant hypertension and the potential benefit of the procedure in other diseases, Symplicity HTN 3 study, the most rigorous clinical trial of renal denervation to date, failed to meet its primary endpoint. The procedure also has other limitations such as the lack of long term, efficacy and safety data and the lack of the predictors for the blood pressure lowering response and nonresponse to the procedure. An overview of current renal denervation devices holding Conformité Européenne mark is also included in this review. Renal denervation is a promising therapeutic approach in the management of resistant hypertension and other diseases characterized by sympathetic overactivity. In its early stage of clinical application, the efficacy of the procedure is still controversial. Large scale, blind, randomized, controlled clinical trials are still necessary to address the limitations of the procedure.

  18. Renal Denervation to Modify Hypertension and the Heart Failure State.

    Science.gov (United States)

    Zhong, Ming; Kim, Luke K; Swaminathan, Rajesh V; Feldman, Dmitriy N

    2017-07-01

    Sympathetic overactivation of renal afferent and efferent nerves have been implicated in the development and maintenance of several cardiovascular disease states, including resistant hypertension and heart failure with both reduced and preserved systolic function. With the development of minimally invasive catheter-based techniques, percutaneous renal denervation has become a safe and effective method of attenuating sympathetic overactivation. Percutaneous renal denervation, therefore, has the potential to modify and treat hypertension and congestive heart failure. Although future randomized controlled studies are needed to definitively prove its efficacy, renal denervation has the potential to change the way we view and treat cardiovascular disease. Copyright © 2017 Elsevier Inc. All rights reserved.

  19. Renal denervation: Results of a single-center cohort study; Renale Denervation. Ergebnisse einer Single-Center Kohortenstudie

    Energy Technology Data Exchange (ETDEWEB)

    Luetkens, J.A.; Thomas, D.; Doerner, J.; Schild, H.H.; Naehle, C.P. [Bonn Univ. (Germany). Dept. of Radiology; Wilhelm, K. [Johanniter Hospital, Bonn (Germany). Dept. of Radiology; Duesing, R. [Hypertension Center, Bonn (Germany); Woitas, R.P.; Hundt, F. [Bonn Univ. (Germany). Dept. of Internal Medicine I

    2015-01-15

    To investigate the effect of renal denervation on office-based and 24-h ambulatory blood pressure measurements (ABPM) in a highly selective patient population with drug-resistant hypertension. Patients with drug resistant hypertension eligible for renal denervation were included in the study population. Office blood pressure and ABPM were assessed prior to and after renal denervation. To detect procedure related renal or renal artery damage, magnetic resonance imaging (MRI) and angiography (MRA) were performed pre-interventional, one day post-interventional, and one month after renal denervation. Mean follow-up time between renal denervation and blood pressure re-assessment was 9.5 ± 3.9 months. Between August 2011 and March 2013, 17 patients prospectively underwent renal denervation. Pre-interventional mean office blood pressure and ABPM were 177.3 ± 20.3/103.8 ± 20.4 mmHg and 155.2 ± 20.5/93.7 ± 14.5 mmHg, respectively. Post-interventional, office blood pressure was significantly reduced to 144.7 ± 14.9/89.5 ± 12.1 (p < 0.05). ABPM values remained unchanged (147.9 ± 20.3/90.3 ± 15.6, p > 0.05). The number of prescribed antihypertensive drugs was unchanged after renal denervation (4.7 ± 2.0 vs. 4.2 ± 1.2, p = 0.18). No renovascular complications were detected in follow-up MRI. After renal denervation, no significant decrease in ABPM was observed. These results may indicate a limited impact of renal denervation for drug resistant hypertension.

  20. Renal denervation--hypes and hopes.

    Science.gov (United States)

    Lewek, Joanna; Kaczmarek, Krzysztof; Pokushalov, Evgeniy; Romanov, Alexandr; Cygankiewicz, Iwona; Ptaszynski, Pawel

    2015-06-01

    Catheter-based renal denervation (RDN) is a novel invasive approach in the treatment of resistant hypertension. It is considered a minimally invasive and safe procedure which, as shown by initial experimental and clinical trials, is able not only to reduce blood pressure but also to modify its risk factors by modulation of autonomic nervous system. Recently published results of a randomized Symplicity HTN-3 trial, which failed to demonstrate RDN-induced reduction of blood pressure at six months, decreased the initial enthusiasm regarding RDN and raised a question about real efficacy of this procedure. Nevertheless, still there are some other conditions characterized by increased sympathetic tone such as heart failure, atrial fibrillation, or ventricular arrhythmias that may benefit from RDN. Furthermore, novel therapeutical approach toward RDN using adapted electrophysiological or new specially designed electrodes may improve effectiveness of RDN procedure. © 2015 John Wiley & Sons Ltd.

  1. Current Status of Renal Denervation in Hypertension.

    Science.gov (United States)

    Briasoulis, Alexander; Bakris, George L

    2016-11-01

    Over the past 7 years, prospective cohorts and small randomized controlled studies showed that renal denervation therapy (RDN) in patients with resistant hypertension is safe but associated with variable effects on BP which are not substantially better than medical therapy alone. The failure of the most rigorously designed randomized sham-control study, SYMPLICITY HTN-3, to meet the efficacy endpoints has raised several methodological concerns. However, recently reported studies and ongoing trials with improved procedural characteristics, identification of patients with true treatment-resistant hypertension on appropriate antihypertensive regimens further explore potential benefits of RDN. The scope of this review is to summarize evidence from currently completed studies on RDN and discuss future perspectives of RDN therapy in patients with resistant hypertension.

  2. Effect of salbutamol on innervated and denervated rat soleus muscle

    Directory of Open Access Journals (Sweden)

    ?oic-Vranic T.

    2005-01-01

    Full Text Available The objective of the present investigation was to perform a 14-day time-course study of treatment with salbutamol, a ß2 adrenoceptor agonist, on rat soleus muscle in order to assess fiber type selectivity in the hypertrophic response and fiber type composition. Male Wistar rats were divided into four groups: control (N = 10, treated with salbutamol (N = 30, denervated (N = 30, and treated with salbutamol after denervation (N = 30. Salbutamol was injected intraperitoneally in the rats of the 2nd and 4th groups at a concentration of 0.3 mg/kg twice a day for 2 weeks. The muscles were denervated using the crush method with pean. The animals were sacrificed 3, 6, 9, 12, and 14 days after treatment. Frozen cross-sections of soleus muscle were stained for myosin ATPase, pH 9.4. Cross-sectional area and percent of muscle fibers were analyzed morphometrically by computerized image analysis. Treatment with salbutamol induced hypertrophy of all fiber types and a higher percentage of type II fibers (21% in the healthy rat soleus muscle. Denervation caused marked atrophy of all fibers and conversion from type I to type II muscle fibers. Denervated muscles treated with salbutamol showed a significantly larger cross-sectional area of type I muscle fibers, 28.2% compared to the denervated untreated muscle. Moreover, the number of type I fibers was increased. These results indicate that administration of salbutamol is able to induce changes in cross-sectional area and fiber type distribution in the early phase of treatment. Since denervation-induced atrophy and conversion from type I to type II fibers were improved by salbutamol treatment we propose that salbutamol, like other ß2 adrenoceptor agonists, may have a therapeutic potential in improving the condition of skeletal muscle after denervation.

  3. Renal sympathetic denervation for resistant hypertension.

    Science.gov (United States)

    Froeschl, Michael; Hadziomerovic, Adnan; Ruzicka, Marcel

    2013-05-01

    Resistant hypertension is an increasingly prevalent health problem associated with important adverse cardiovascular outcomes. The pathophysiology that underlies this condition involves increased function of both the sympathetic nervous system and the renin-angiotensin II-aldosterone system. A crucial link between these 2 systems is the web of sympathetic fibres that course within the adventitia of the renal arteries. These nerves can be targeted by applying radiofrequency energy from the lumen of the renal arteries to renal artery walls (percutaneous renal sympathetic denervation [RSD]), an approach that has attracted great interest. This paper critically reviews the evidence supporting the use of RSD. Small studies suggest that RSD can produce dramatic blood pressure reductions: In the randomized Symplicity HTN-2 trial of 106 patients, the mean fall in blood pressure at 6 months in patients who received the treatment was 32/12 mm Hg. However, there are limitations to the evidence for RSD in the treatment of resistant hypertension. These include the small number of patients studied; the lack of any placebo-controlled evidence; the fact that blood pressure outcomes were based on office assessments, as opposed to 24-hour ambulatory monitoring; the lack of longer-term efficacy data; and the lack of long-term safety data. Some of these concerns are being addressed in the ongoing Renal Denervation in Patients With Uncontrolled Hypertension (Symplicity HTN-3) trial. The first percutaneous RSD system was approved by Health Canada in the spring of 2012. But until more and better-quality data are available, this procedure should generally be reserved for those patients whose resistant hypertension is truly uncontrolled. Copyright © 2013 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.

  4. Symplicity multi-electrode radiofrequency renal denervation system feasibility study.

    Science.gov (United States)

    Whitbourn, Robert; Harding, Scott A; Walton, Antony

    2015-05-01

    The aim of this study was to test the safety and performance of the Symplicity™ multi-electrode radio-frequency renal denervation system which was designed to reduce procedure time during renal denervation. The multi-electrode radiofrequency renal denervation system feasibility study is a prospective, non-randomised, open label, feasibility study that enrolled 50 subjects with hypertension. The study utilises a new renal denervation catheter which contains an array of four electrodes mounted in a helical configuration at 90 degrees from each other to deliver radiofrequency energy simultaneously to all four renal artery quadrants for 60 seconds. The protocol specified one renal denervation treatment towards the distal end of each main renal artery with radiofrequency energy delivered for 60 seconds per treatment. Total treatment time for both renal arteries was two minutes. The 12-month change in office systolic blood pressure (SBP) and 24-hour SBP was -19.2±25.2 mmHg, prenal artery stenosis or hypertensive emergencies occurred. The Symplicity multi-electrode radiofrequency renal denervation system was associated with a significant reduction in SBP at 12 months and minimal complications whilst it also reduced procedure time. NCT01699529.

  5. Intrapericardial Denervation: Responses to Water Immersion in Rhesus Monkeys

    Science.gov (United States)

    McKeever, Kenneth H.; Keil, Lanny C.; Sandler, Harold

    1995-01-01

    Eleven anesthetized rhesus monkeys were used to study cardiovascular, renal, and endocrine alterations associated with 120 min of head-out water immersion. Five animals underwent complete intrapericardial denervation using the Randall technique, while the remaining six monkeys served as intact controls. Each animal was chronically instrumented with an electromagnetic flow probe on the ascending aorta, a strain gauge pressure transducer implanted in the apex of the left ventricle (LV), and electrocardiogram leads anchored to the chest wall and LV. During immersion, LV end-diastolic pressure, urine flow, glomerular filtration rate, sodium excretion, and circulating atrial natriuretic peptide (ANP) each increased (P less than 0.05) for intact and denervated monkeys. There were no alterations in free water clearance in either group during immersion, yet fractional excretion of free water increased (P less than 0.05) in the intact monkeys. Plasma renin activity (PRA) decreased (P less than 0.05) during immersion in intact monkeys but not the denervated animals. Plasma vasopressin (PVP) concentration decreased (P less than 0.05) during the first 30 min of immersion in both groups but was not distinguishable from control by 60 min of immersion in denervated monkeys. These data demonstrate that complete cardiac denervation does not block the rise in plasma ANP or prevent the natriuresis associated with head-out water immersion. The suppression of PVP during the first minutes of immersion after complete cardiac denervation suggests that extracardiac sensing mechanisms associated with the induced fluid shifts may be responsible for the findings.

  6. Endpoint design for future renal denervation trials - Novel implications for a new definition of treatment response to renal denervation.

    Science.gov (United States)

    Lambert, Thomas; Nahler, Alexander; Rohla, Miklos; Reiter, Christian; Grund, Michael; Kammler, Jürgen; Blessberger, Hermann; Kypta, Alexander; Kellermair, Jörg; Schwarz, Stefan; Starnawski, Jennifer A; Lichtenauer, Michael; Weiss, Thomas W; Huber, Kurt; Steinwender, Clemens

    2016-10-01

    Defining an adequate endpoint for renal denervation trials represents a major challenge. A high inter-individual and intra-individual variability of blood pressure levels as well as a partial or total non-adherence on antihypertensive drugs hamper treatment evaluations after renal denervation. Blood pressure measurements at a single point in time as used as primary endpoint in most clinical trials on renal denervation, might not be sufficient to discriminate between patients who do or do not respond to renal denervation. We compared the traditional responder classification (defined as systolic 24-hour blood pressure reduction of -5mmHg six months after renal denervation) with a novel definition of an ideal respondership (based on a 24h blood pressure reduction at no point in time, one, or all follow-up timepoints). We were able to re-classify almost a quarter of patients. Blood pressure variability was substantial in patients traditionally defined as responders. On the other hand, our novel classification of an ideal respondership seems to be clinically superior in discriminating sustained from pseudo-response to renal denervation. Based on our observations, we recommend that the traditional response classification should be reconsidered and possibly strengthened by using a composite endpoint of 24h-BP reductions at different follow-up-visits. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  7. Functional Echomyography of the human denervated muscle: first results

    Directory of Open Access Journals (Sweden)

    Riccardo Zanato

    2011-03-01

    Full Text Available In this study we followed with ultrasound three patients with permanent denervation to evaluate changes in morphology, thickness, contraction and vascularisation of muscles undergoing the home-based electrical stimulation program of the Rise2-Italy project. During a period of 1 year for the first subject, 6 months for the second subject and 3 months for the third subject we studied with ultrasound the denervated muscle comparing it (if possible to the contralateral normal muscle. We evaluated: 1. Changes in morphology and sonographic structure of the pathologic muscle; 2. Muscular thickness in response to the electrical stimulation therapy; 3. Short-term modifications in muscle perfusion and arterial flow patterns after stimulation; 4. Contraction-relaxation kinetic induced by volitional activity or electrical stimulation. Morphology and ultrasonographic structure of the denervated muscles changed during the period of stimulation from a pattern typical of complete muscular atrophy to a pattern which might be considered “normal” when detected in an old patient. Thickness improved significantly more in the middle third than in the proximal and distal third of the denervated muscle, reaching in the last measurements of the first subject approximately the same thickness as the contralateral normal muscle. In all the measurements done within this study, arterial flow of the denervated muscle showed at rest a low-resistance pattern with Doppler Ultra Sound (US, and a pulsed pattern after electrical stimulation. The stimulation- induced pattern is similar to the trifasic high-resistance pattern of the normal muscle. Contraction- relaxation kinetic, measured by recording the muscular movements during electrical stimulation, showed an abnormal behaviour of the denervated muscle during the relaxation phase, which resulted to be significantly longer than in normal muscle (880 msec in the denervated muscle vs 240 msec in the contralateral normal one

  8. Renal denervation after Symplicity HTN-3: an update.

    Science.gov (United States)

    Persu, Alexandre; Jin, Yu; Fadl Elmula, Fadl Elmula Mohamed; Jacobs, Lotte; Renkin, Jean; Kjeldsen, Sverre

    2014-08-01

    After three years of excessive confidence, overoptimistic expectations and performance of 15 to 20,000 renal denervation procedures in Europe, the failure of a single well-designed US trial--Symplicity HTN-3--to meet its primary efficacy endpoint has cast doubt on renal denervation as a whole. The use of a sound methodology, including randomisation and blinded endpoint assessment was enough to see the typical 25-30 mmHg systolic blood pressure decrease observed after renal denervation melt down to less than 3 mmHg, the rest being likely explained by Hawthorne and placebo effects, attenuation of white coat effect, regression to the mean and other physician and patient-related biases. The modest blood pressure benefit directly assignable to renal denervation should be balanced with unresolved safety issues, such as potentially increased risk of renal artery stenosis after the procedure (more than ten cases reported up to now, most of them in 2014), unclear long-term impact on renal function and lack of morbidity-mortality data. Accordingly, there is no doubt that renal denervation is not ready for clinical use. Still, renal denervation is supported by a strong rationale and is occasionally followed by major blood pressure responses in at-risk patients who may otherwise have remained uncontrolled. Upcoming research programmes should focus on identification of those few patients with truly resistant hypertension who may derive a substantial benefit from the technique, within the context of well-designed randomised trials and independent registries. While electrical stimulation of baroreceptors and other interventional treatments of hypertension are already "knocking at the door", the premature and uncontrolled dissemination of renal denervation should remain an example of what should not be done, and trigger radical changes in evaluation processes of new devices by national and European health authorities.

  9. [Renal denervation a treatment for resistant hypertension: a French experience].

    Science.gov (United States)

    Benamer, H; Mylotte, D; Garcia-Alonso, C; Unterseeh, T; Garot, P; Louvard, Y; Lefevre, T; Morice, M-C

    2013-12-01

    Arterial hypertension is the largest single contributor to global mortality, and is poorly controlled in approximately 50% of patients despite lifestyle and pharmacologic interventions. Randomized clinical trials have demonstrated that catheter-based renal sympathetic denervation reduces blood pressure (BP) in patients with resistant hypertension. We sought to evaluate the efficacy of this novel therapy in "Real World" clinical practice. Consecutive patients with treatment-resistant primary hypertension, as defined as home BP>160 mmHg despite treatment with ≥3 antihypertensive drugs, were selected for denervation following renal artery screening. Ambulatory and home BP monitoring was performed in all patients prior to and following percutaneous renal sympathetic denervation. In total, 35 patients were selected for catheter-based renal sympathetic denervation. The mean age was 63.6 ± 11.7 years, 37.1% were women, 37.1% were diabetic, and 11.4% had renal impairment (GFRdenervation was performed in 33/35 patients (1 renal artery stenosis on angiography [not ablated], 1 patient with renal artery spasm [unilateral denervation]), with an average 5.9 ± 1.6 ablations per renal artery. No procedural complications occurred. At 6 months, blood pressure was 15.5 ± 22.37/87.76 ± 13.97 mmHg (Prenal function was observed. Catheter-based renal denervation is safe and efficacious treatment, which results in significant reductions in blood pressure in patients with treatment-resistant hypertension, stable at 2 years follow-up. These results are applicable to real-world patient populations. Copyright © 2013 Elsevier Masson SAS. All rights reserved.

  10. High incidence of secondary hypertension in patients referred for renal denervation

    DEFF Research Database (Denmark)

    Olsen, Lene Kjær; Kamper, Anne-Lise; Svendsen, Jesper Hastrup

    2014-01-01

    . Thus, 91 patients were screened, and of those 51 were found to be candidates for renal denervation. Forty patients were not candidates, of which secondary hypertension was the most common cause (n = 10). Only 51% of patients referred for renal denervation were eligible for treatment. The prevalence...... of secondary hypertension was 10% of the referred population. Secondary hypertension should therefore be considered in the evaluation of candidates for renal denervation.......Percutaneous renal denervation is a new treatment option for patients with resistant hypertension and little is known about the eligibility of patients referred. 100 consecutive patients were referred for renal denervation from March 2011 through September 2012. Clinical data were prospectively...

  11. Nandrolone reduces activation of Notch signaling in denervated muscle associated with increased Numb expression

    International Nuclear Information System (INIS)

    Liu, Xin-Hua; Yao, Shen; Qiao, Rui-Fang; Levine, Alice C.; Kirschenbaum, Alexander; Pan, Jiangping; Wu, Yong; Qin, Weiping; Bauman, William A.; Cardozo, Christopher P.

    2011-01-01

    Highlights: → Nerve transection increased Notch signaling in paralyzed muscle. → Nandrolone prevented denervation-induced Notch signaling. → Nandrolone induced the expression of an inhibitor of the Notch signaling, Numb. → Reduction of denervation-induced Notch signaling by nandrolone is likely through upregulation of Numb. -- Abstract: Nandrolone, an anabolic steroid, slows denervation-atrophy in rat muscle. The molecular mechanisms responsible for this effect are not well understood. Androgens and anabolic steroids activate Notch signaling in animal models of aging and thereby mitigate sarcopenia. To explore the molecular mechanisms by which nandrolone prevents denervation-atrophy, we investigated the effects of nandrolone on Notch signaling in denervated rat gastrocnemius muscle. Denervation significantly increased Notch activity reflected by elevated levels of nuclear Notch intracellular domain (NICD) and expression of Hey1 (a Notch target gene). Activation was greatest at 7 and 35 days after denervation but remained present at 56 days after denervation. Activation of Notch in denervated muscle was prevented by nandrolone associated with upregulated expression of Numb mRNA and protein. These data demonstrate that denervation activates Notch signaling, and that nandrolone abrogates this response associated with increased expression of Numb, suggesting a potential mechanism by which nandrolone reduces denervation-atrophy.

  12. Nandrolone reduces activation of Notch signaling in denervated muscle associated with increased Numb expression

    Energy Technology Data Exchange (ETDEWEB)

    Liu, Xin-Hua [Center of Excellence for the Medical Consequences of Spinal Cord Injury, James J. Peter VA Medical Center, Bronx, NY 10468 (United States); Department of Medicine, Mount Sinai School of Medicine, New York, NY 10029 (United States); Yao, Shen; Qiao, Rui-Fang; Levine, Alice C. [Department of Medicine, Mount Sinai School of Medicine, New York, NY 10029 (United States); Kirschenbaum, Alexander [Department of Urology, Mount Sinai School of Medicine, New York, NY 10029 (United States); Pan, Jiangping; Wu, Yong [Center of Excellence for the Medical Consequences of Spinal Cord Injury, James J. Peter VA Medical Center, Bronx, NY 10468 (United States); Qin, Weiping [Center of Excellence for the Medical Consequences of Spinal Cord Injury, James J. Peter VA Medical Center, Bronx, NY 10468 (United States); Department of Medicine, Mount Sinai School of Medicine, New York, NY 10029 (United States); Bauman, William A. [Center of Excellence for the Medical Consequences of Spinal Cord Injury, James J. Peter VA Medical Center, Bronx, NY 10468 (United States); Department of Medicine, Mount Sinai School of Medicine, New York, NY 10029 (United States); Rehabilitation Medicine, Mount Sinai School of Medicine, New York, NY 10029 (United States); Cardozo, Christopher P., E-mail: chris.cardozo@mssm.edu [Center of Excellence for the Medical Consequences of Spinal Cord Injury, James J. Peter VA Medical Center, Bronx, NY 10468 (United States); Department of Medicine, Mount Sinai School of Medicine, New York, NY 10029 (United States); Rehabilitation Medicine, Mount Sinai School of Medicine, New York, NY 10029 (United States)

    2011-10-14

    Highlights: {yields} Nerve transection increased Notch signaling in paralyzed muscle. {yields} Nandrolone prevented denervation-induced Notch signaling. {yields} Nandrolone induced the expression of an inhibitor of the Notch signaling, Numb. {yields} Reduction of denervation-induced Notch signaling by nandrolone is likely through upregulation of Numb. -- Abstract: Nandrolone, an anabolic steroid, slows denervation-atrophy in rat muscle. The molecular mechanisms responsible for this effect are not well understood. Androgens and anabolic steroids activate Notch signaling in animal models of aging and thereby mitigate sarcopenia. To explore the molecular mechanisms by which nandrolone prevents denervation-atrophy, we investigated the effects of nandrolone on Notch signaling in denervated rat gastrocnemius muscle. Denervation significantly increased Notch activity reflected by elevated levels of nuclear Notch intracellular domain (NICD) and expression of Hey1 (a Notch target gene). Activation was greatest at 7 and 35 days after denervation but remained present at 56 days after denervation. Activation of Notch in denervated muscle was prevented by nandrolone associated with upregulated expression of Numb mRNA and protein. These data demonstrate that denervation activates Notch signaling, and that nandrolone abrogates this response associated with increased expression of Numb, suggesting a potential mechanism by which nandrolone reduces denervation-atrophy.

  13. Anatomical and procedural determinants of catheter-based renal denervation

    NARCIS (Netherlands)

    Ewen, Sebastian; Ukena, Christian; Lüscher, Thomas Felix; Bergmann, Martin; Blankestijn, Peter J; Blessing, Erwin; Cremers, Bodo; Dörr, Oliver; Hering, Dagmara; Kaiser, Lukas; Nef, Holger; Noory, Elias; Schlaich, Markus; Sharif, Faisal; Sudano, Isabella; Vogel, Britta; Voskuil, Michiel; Zeller, Thomas; Tzafriri, Abraham R; Edelman, Elazer R; Lauder, Lucas; Scheller, Bruno; Böhm, Michael; Mahfoud, Felix

    2016-01-01

    BACKGROUND/PURPOSE: Catheter-based renal sympathetic denervation (RDN) can reduce blood pressure (BP) and sympathetic activity in certain patients with uncontrolled hypertension. Less is known about the impact of renal anatomy and procedural parameters on subsequent BP response. METHODS/MATERIALS: A

  14. Communication between functional and denervated muscles using radiofrequency.

    Science.gov (United States)

    Jacob, Doreen K; Stefko, Susan Tonya; Hackworth, Steven A; Lovell, Michael R; Mickle, Marlin H

    2006-05-01

    This article focuses on establishing communication between a functional muscle and a denervated muscle using a radiofrequency communications link. The ultimate objective of the project is to restore the eye blink in patients with facial nerve paralysis. Two sets of experiments were conducted using the gastrocnemius leg muscles of Sprague-Dawley rats. In the initial tests, varying magnitudes of voltages ranging from 0.85 to 2.5 V were applied directly to a denervated muscle to determine the voltage required to produce visible contraction. The second set of experiments was then conducted to determine the voltage output from an in vivo muscle contraction that could be sensed and used to coordinate a signal for actuation of a muscle in a separate limb. After designing the appropriate external communication circuitry, a third experiment was performed to verify that a signal between a functional and a denervated muscle can be generated and used as a stimulus. Voltages below 2 V at a 10-millisecond pulse width elicited a gentle, controlled contraction of the denervated muscle in vivo. It was also observed that with longer pulse widths, higher stimulation voltages were required to produce sufficient contractions. It is possible to detect contraction of a muscle, use this to generate a signal to an external base station, and subsequently cause a separate, denervated muscle to contract in response to the signal. This demonstration in vivo of a signaling system for pacing of electrical stimulation of 1 muscle to spontaneous contraction of another, separate muscle, using radiofrequency communication without direct connection, may be used in numerous ways to overcome nerve damage.

  15. The biophysics of renal sympathetic denervation using radiofrequency energy.

    Science.gov (United States)

    Patel, Hitesh C; Dhillon, Paramdeep S; Mahfoud, Felix; Lindsay, Alistair C; Hayward, Carl; Ernst, Sabine; Lyon, Alexander R; Rosen, Stuart D; di Mario, Carlo

    2014-05-01

    Renal sympathetic denervation is currently performed in the treatment of resistant hypertension by interventionists who otherwise do not typically use radiofrequency (RF) energy ablation in their clinical practice. Adequate RF lesion formation is dependent upon good electrode-tissue contact, power delivery, electrode-tissue interface temperature, target-tissue impedance and the size of the catheter's active electrode. There is significant interplay between these variables and hence an appreciation of the biophysical determinants of RF lesion formation is required to provide effective and safe clinical care to our patients. In this review article, we summarize the biophysics of RF ablation and explain why and how complications of renal sympathetic denervation may occur and discuss methods to minimise them.

  16. Increased phencyclidine-induced hyperactivity following cortical cholinergic denervation.

    Science.gov (United States)

    Mattsson, Anna; Lindqvist, Eva; Ogren, Sven Ove; Olson, Lars

    2005-11-07

    Altered cholinergic function is considered as a potential contributing factor in the pathogenesis of schizophrenia. We hypothesize that cortical cholinergic denervation may result in changes in glutamatergic activity. Therefore, we lesioned the cholinergic corticopetal projections by local infusion of 192 IgG-saporin into the nucleus basalis magnocellularis of rats. Possible effects of this lesion on glutamatergic systems were examined by phencyclidine-induced locomotor activity, and also by N-methyl-D-aspartate receptor binding. We find that cholinergic lesioning of neocortex leads to enhanced sensitivity to phencyclidine in the form of a dramatic increase in horizontal activity. Further, N-methyl-D-aspartate receptor binding is unaffected in denervated rats. These results suggest that aberrations in cholinergic function might lead to glutamatergic dysfunctions, which might be of relevance for the pathophysiology for schizophrenia.

  17. Usefulness of muscle denervation as an MRI sign of peripheral nerve pathology

    International Nuclear Information System (INIS)

    Lisle, D. A.; Johnstone, S. A.

    2007-01-01

    Full text: Peripheral nerve disorders may be classified into compressive or entrapment neuropathies and non-compressive neuropathies. Muscle denervation recognized on MRI may be a useful sign in the diagnosis of peripheral nerve disorders. Acute or subacute denervation results in prolonged T 2 relaxation time, producing increased signal in skeletal muscle on short tau inversion-recovery and fat-suppressed T 2 -weighted images. Chronic denervation produces fatty atrophy of skeletal muscles, resulting in increased muscle signal on T 1 -weighted images. This review will outline and illustrate the various ways that muscle denervation as seen on MRI may assist in the diagnosis and localization of peripheral nerve disorders

  18. A controlled trial of renal denervation for resistant hypertension.

    Science.gov (United States)

    Bhatt, Deepak L; Kandzari, David E; O'Neill, William W; D'Agostino, Ralph; Flack, John M; Katzen, Barry T; Leon, Martin B; Liu, Minglei; Mauri, Laura; Negoita, Manuela; Cohen, Sidney A; Oparil, Suzanne; Rocha-Singh, Krishna; Townsend, Raymond R; Bakris, George L

    2014-04-10

    Prior unblinded studies have suggested that catheter-based renal-artery denervation reduces blood pressure in patients with resistant hypertension. We designed a prospective, single-blind, randomized, sham-controlled trial. Patients with severe resistant hypertension were randomly assigned in a 2:1 ratio to undergo renal denervation or a sham procedure. Before randomization, patients were receiving a stable antihypertensive regimen involving maximally tolerated doses of at least three drugs, including a diuretic. The primary efficacy end point was the change in office systolic blood pressure at 6 months; a secondary efficacy end point was the change in mean 24-hour ambulatory systolic blood pressure. The primary safety end point was a composite of death, end-stage renal disease, embolic events resulting in end-organ damage, renovascular complications, or hypertensive crisis at 1 month or new renal-artery stenosis of more than 70% at 6 months. A total of 535 patients underwent randomization. The mean (±SD) change in systolic blood pressure at 6 months was -14.13±23.93 mm Hg in the denervation group as compared with -11.74±25.94 mm Hg in the sham-procedure group (Pdenervation group and -4.79±17.25 mm Hg in the sham-procedure group, for a difference of -1.96 mm Hg (95% CI, -4.97 to 1.06; P=0.98 for superiority with a margin of 2 mm Hg). There were no significant differences in safety between the two groups. This blinded trial did not show a significant reduction of systolic blood pressure in patients with resistant hypertension 6 months after renal-artery denervation as compared with a sham control. (Funded by Medtronic; SYMPLICITY HTN-3 ClinicalTrials.gov number, NCT01418261.).

  19. CT-guided percutaneous radiofrequency denervation of the sacroiliac joint

    Energy Technology Data Exchange (ETDEWEB)

    Gevargez, A.; Schirp, S.; Braun, M. [Department of Radiology and Microtherapy, University of Witten/Herdecke, Bochum (Germany); Groenemeyer, D. [Department of Radiology and Microtherapy, University of Witten/Herdecke, Bochum (Germany); EFMT Development and Research Center for Microtherapy, Bochum (Germany)

    2002-06-01

    Defining the origin of low back pain is a challenging task. Among a variety of factors the sacroiliac joint (SIJ) is a possible pain generator, although precise diagnosis is difficult. Joint blocks may reduce pain, but are, in cases, of only temporary effect. This study was conducted to evaluate CT-guided percutaneous radiofrequency denervation of the sacroiliac joint in patients with low back pain. The procedure was performed on 38 patients who only temporarily responded to CT-guided SIJ blocks. The denervation was carried out in the posterior interosseous sacroiliac ligaments and on the dorsal rami of the fifth spinal nerve. All interventions were carried out under CT guidance as out-patient therapies. Three months after the therapy, 13 patients (34.2%) were completely free of pain. Twelve patients (31.6%) reported on a substantial pain reduction, 7 patients (18.4%) had obtained a slight and 3 patients (7.9%) no pain reduction. The data of 3 patients (7.9%) was missing. There were no intra- or postoperative complications. Computed tomography-guided percutaneous radiofrequency denervation of the sacroiliac joint appears safe and effective. The procedure may be a useful therapeutic modality, especially in patients with chronic low back pain, who only temporarily respond to therapeutic blocks. (orig.)

  20. CT-guided percutaneous radiofrequency denervation of the sacroiliac joint

    International Nuclear Information System (INIS)

    Gevargez, A.; Schirp, S.; Braun, M.; Groenemeyer, D.

    2002-01-01

    Defining the origin of low back pain is a challenging task. Among a variety of factors the sacroiliac joint (SIJ) is a possible pain generator, although precise diagnosis is difficult. Joint blocks may reduce pain, but are, in cases, of only temporary effect. This study was conducted to evaluate CT-guided percutaneous radiofrequency denervation of the sacroiliac joint in patients with low back pain. The procedure was performed on 38 patients who only temporarily responded to CT-guided SIJ blocks. The denervation was carried out in the posterior interosseous sacroiliac ligaments and on the dorsal rami of the fifth spinal nerve. All interventions were carried out under CT guidance as out-patient therapies. Three months after the therapy, 13 patients (34.2%) were completely free of pain. Twelve patients (31.6%) reported on a substantial pain reduction, 7 patients (18.4%) had obtained a slight and 3 patients (7.9%) no pain reduction. The data of 3 patients (7.9%) was missing. There were no intra- or postoperative complications. Computed tomography-guided percutaneous radiofrequency denervation of the sacroiliac joint appears safe and effective. The procedure may be a useful therapeutic modality, especially in patients with chronic low back pain, who only temporarily respond to therapeutic blocks. (orig.)

  1. Twenty-Four-Hour Blood Pressure Monitoring to Predict and Assess Impact of Renal Denervation: The DENERHTN Study (Renal Denervation for Hypertension).

    Science.gov (United States)

    Gosse, Philippe; Cremer, Antoine; Pereira, Helena; Bobrie, Guillaume; Chatellier, Gilles; Chamontin, Bernard; Courand, Pierre-Yves; Delsart, Pascal; Denolle, Thierry; Dourmap, Caroline; Ferrari, Emile; Girerd, Xavier; Michel Halimi, Jean; Herpin, Daniel; Lantelme, Pierre; Monge, Matthieu; Mounier-Vehier, Claire; Mourad, Jean-Jacques; Ormezzano, Olivier; Ribstein, Jean; Rossignol, Patrick; Sapoval, Marc; Vaïsse, Bernard; Zannad, Faiez; Azizi, Michel

    2017-03-01

    The DENERHTN trial (Renal Denervation for Hypertension) confirmed the blood pressure (BP) lowering efficacy of renal denervation added to a standardized stepped-care antihypertensive treatment for resistant hypertension at 6 months. We report here the effect of denervation on 24-hour BP and its variability and look for parameters that predicted the BP response. Patients with resistant hypertension were randomly assigned to denervation plus stepped-care treatment or treatment alone (control). Average and standard deviation of 24-hour, daytime, and nighttime BP and the smoothness index were calculated on recordings performed at randomization and 6 months. Responders were defined as a 6-month 24-hour systolic BP reduction ≥20 mm Hg. Analyses were performed on the per-protocol population. The significantly greater BP reduction in the denervation group was associated with a higher smoothness index ( P =0.02). Variability of 24-hour, daytime, and nighttime BP did not change significantly from baseline to 6 months in both groups. The number of responders was greater in the denervation (20/44, 44.5%) than in the control group (11/53, 20.8%; P =0.01). In the discriminant analysis, baseline average nighttime systolic BP and standard deviation were significant predictors of the systolic BP response in the denervation group only, allowing adequate responder classification of 70% of the patients. Our results show that denervation lowers ambulatory BP homogeneously over 24 hours in patients with resistant hypertension and suggest that nighttime systolic BP and variability are predictors of the BP response to denervation. URL: https://www.clinicaltrials.gov. Unique identifier: NCT01570777. © 2017 American Heart Association, Inc.

  2. Externally Delivered Focused Ultrasound for Renal Denervation.

    Science.gov (United States)

    Neuzil, Petr; Ormiston, John; Brinton, Todd J; Starek, Zdenek; Esler, Murray; Dawood, Omar; Anderson, Thomas L; Gertner, Michael; Whitbourne, Rob; Schmieder, Roland E

    2016-06-27

    The aim of this study was to assess clinical safety and efficacy outcomes of renal denervation executed by an externally delivered, completely noninvasive focused therapeutic ultrasound device. Renal denervation has emerged as a potential treatment approach for resistant hypertension. Sixty-nine subjects received renal denervation with externally delivered focused ultrasound via the Kona Medical Surround Sound System. This approach was investigated across 3 consecutive studies to optimize targeting, tracking, and dosing. In the third study, treatments were performed in a completely noninvasive way using duplex ultrasound image guidance to target the therapy. Short- and long-term safety and efficacy were evaluated through use of clinical assessments, magnetic resonance imaging scans prior to and 3 and 24 weeks after renal denervation, and, in cases in which a targeting catheter was used to facilitate targeting, fluoroscopic angiography with contrast. All patients tolerated renal denervation using externally delivered focused ultrasound. Office blood pressure (BP) decreased by 24.6 ± 27.6/9.0 ± 15.0 mm Hg (from baseline BP of 180.0 ± 18.5/97.7 ± 13.7 mm Hg) in 69 patients after 6 months and 23.8 ± 24.1/10.3 ± 13.1 mm Hg in 64 patients with complete 1-year follow-up. The response rate (BP decrease >10 mm Hg) was 75% after 6 months and 77% after 1 year. The most common adverse event was post-treatment back pain, which was reported in 32 of 69 patients and resolved within 72 h in most cases. No intervention-related adverse events involving motor or sensory deficits were reported. Renal function was not altered, and vascular safety was established by magnetic resonance imaging (all patients), fluoroscopic angiography (n = 48), and optical coherence tomography (n = 5). Using externally delivered focused ultrasound and noninvasive duplex ultrasound, image-guided targeting was associated with substantial BP reduction without any major safety signals. Further

  3. Chemical denervation of the renal artery with vincristine for the treatment of resistant arterial hypertension: first-in-man application.

    Science.gov (United States)

    Stefanadis, Christodoulos; Toutouzas, Konstantinos; Vlachopoulos, Charalambos; Tsioufis, Costas; Synetos, Andreas; Pietri, Panagiota; Tousoulis, Dimitris; Tsiamis, Eleftherios

    2013-01-01

    Renal artery denervation has recently emerged as a novel therapy for patients with resistant hypertension. Clinical results from renal sympathetic denervation support the safety and efficacy of this method over a period of 18 months. However, several limitations have been reported. Previous studies have shown that chemical denervation by vincristine is safe and effective in an experimental model. We describe the first-in-man application of chemical denervation with vincristine in a 74-year-old male patient with resistant arterial hypertension.

  4. Next generation renal denervation: chemical “perivascular” renal denervation with alcohol using a novel drug infusion catheter

    Energy Technology Data Exchange (ETDEWEB)

    Fischell, Tim A. [Borgess Heart Institute, 1521 Gull Road, Kalamazoo, MI, 49008 (United States); Ablative Solutions, 801 Hermosa Way, Menlo Park, CA, 94025 (United States); Fischell, David R.; Ghazarossian, Vartan E. [Ablative Solutions, 801 Hermosa Way, Menlo Park, CA, 94025 (United States); Vega, Félix [Preclinical Consultation, San Francisco, CA (United States); Ebner, Adrian [Clinics, Ascension (Paraguay)

    2015-06-15

    Background/Purpose: We update the pre-clinical and early clinical results using a novel endovascular approach, to perform chemical renal denervation, via peri-adventitial injection of micro-doses of dehydrated alcohol (ethanol–EtOH). Methods/Materials: A novel, three-needle delivery device (Peregrine™) was used to denervate the renal arteries of adult swine (n = 17) and in a first-in-man feasibility study (n = 18). In the pre-clinical testing EtOH was infused bilaterally with one infusion per renal artery into to the perivascular space, using EtOH doses of 0.3 ml/artery (n = 8), and 0.6 ml/artery (n = 9), and with saline sham control (0.4 ml/artery n = 3). Renal parenchymal norepinephrine (NE) concentration (performed blindly), and safety were the primary endpoints. Data from the first-in-man study (n = 18) to evaluate device performance, safety and peri-procedural pain are reported. Results: In the pre-clinical testing renal function was unchanged at 3-month follow-up. Angiography at 90 days (n = 34 arteries) demonstrated normal appearing renal arteries, unchanged from baseline, and without stenosis or other abnormalities. The reductions in mean renal parenchymal NE reductions at 3 months were 68% and 88% at doses of 0.3 and 0.6 ml, respectively (p < 0.001 vs. controls). In the first-in-man study, there was 100% device success, no complications, a mean treatment time of 4.3 ± 3 minutes/artery, and minimal or no patient discomfort during treatment. Angiography at 6-months showed no evidence of renal artery stenosis, and evidence of a reduction of blood pressure from baseline. Conclusion: Perivascular RDN using micro-doses of alcohol is a promising alternative to energy-based systems to achieve dose-dependent, predictable, safe and essentially painless renal denervation. Further clinical evaluation is warranted. Summary: (For annotated table of contents) This paper describes the preclinical results, in a porcine model, and the early first-in-man results, using

  5. Renal denervation decreases blood pressure and renal tyrosine hydroxylase but does not augment the effect of hypotensive drugs.

    Science.gov (United States)

    Skrzypecki, Janusz; Gawlak, Maciej; Huc, Tomasz; Szulczyk, Paweł; Ufnal, Marcin

    2017-01-01

    The effect of renal denervation on the efficacy of antihypertensive drugs has not yet been elucidated. Twenty-week-old spontaneously hypertensive rats were treated with metoprolol, losartan, indapamide, or saline (controls) and assigned to renal denervation or a sham procedure. Acute hemodynamic measurements were performed ten days later. Series showing a significant interaction between renal denervation and the drugs were repeated with chronic telemetry measurements. In the saline series, denervated rats showed a significantly lower mean arterial blood pressure (blood pressure) than the sham-operated rats. In contrast, in the metoprolol series denervated rats showed a significantly higher blood pressure than sham rats. There were no differences in blood pressure between denervated and sham rats in the losartan and indapamide series. In chronic studies, a 4-week treatment with metoprolol caused a decrease in blood pressure. Renal denervation and sham denervation performed 10 days after the onset of metoprolol treatment did not affect blood pressure. Denervated rats showed markedly reduced renal nerve tyrosine hydroxylase levels. In conclusion, renal denervation decreases blood pressure in hypertensive rats. The hypotensive action of metoprolol, indapamide, and losartan is not augmented by renal denervation, suggesting the absence of synergy between renal denervation and the drugs investigated in this study.

  6. Renal denervation in a patient with Alport syndrome and rejected renal allograft

    OpenAIRE

    Raju, Narayana; Lloyd, Vincent; Yalagudri, Sachin; Das, Bharati; Ravikishore, A.G.

    2015-01-01

    Renal denervation is a new intervention to treat resistant hypertension. By applying radiofrequency (RF) to renal arteries, sympathetic nerves in adventitia layer of vascular wall can be denervated. Sympathetic hyperactivity is an important contributory factor in hypertension of hemodialysis patients. Hyperactive sympathetic nervous system aggravates hypertension and it can cause complications like left ventricular hypertrophy, heart failure, arrhythmias and atherogenesis. Our report illustra...

  7. Renal denervation beyond the bifurcation : The effect of distal ablation placement on safety and blood pressure

    NARCIS (Netherlands)

    Beeftink, Martine M A; Spiering, Wilko; De Jong, Mark R.; Doevendans, Pieter A.; Blankestijn, Peter J.; Elvan, Arif; Heeg, Jan Evert; Bots, Michiel L.; Voskuil, Michiel

    2017-01-01

    Renal denervation may be more effective if performed distal in the renal artery because of smaller distances between the lumen and perivascular nerves. The authors reviewed the angiographic results of 97 patients and compared blood pressure reduction in relation to the location of the denervation.

  8. [Expert consensus statement on interventional renal sympathetic denervation for hypertension treatment].

    Science.gov (United States)

    Mahfoud, F; Vonend, O; Bruck, H; Clasen, W; Eckert, S; Frye, B; Haller, H; Hausberg, M; Hoppe, U C; Hoyer, J; Hahn, K; Keller, T; Krämer, B K; Kreutz, R; Potthoff, S A; Reinecke, H; Schmieder, R; Schwenger, V; Kintscher, U; Böhm, M; Rump, L C

    2011-11-01

    This commentary summarizes the expert consensus and recommendations of the working group 'Herz und Niere' of the German Society of Cardiology (DGK), the German Society of Nephrology (DGfN) and the German Hypertension League (DHL) on renal denervation for antihypertensive treatment. Renal denervation is a new, interventional approach to selectively denervate renal afferent and efferent sympathetic fibers. Renal denervation has been demonstrated to reduce office systolic and diastolic blood pressure in patients with resistant hypertension, defined as systolic office blood pressure ≥ 160 mm Hg and ≥ 150 mm Hg in patients with diabetes type 2, which should currently be used as blood pressure thresholds for undergoing the procedure. Exclusion of secondary hypertension causes and optimized antihypertensive drug treatment is mandatory in every patient with resistant hypertension. In order to exclude pseudoresistance, 24-hour blood pressure measurements should be performed. Preserved renal function was an inclusion criterion in the Symplicity studies, therefore, renal denervation should be only considered in patients with a glomerular filtration rate > 45 ml/min. Adequate centre qualification in both, treatment of hypertension and interventional expertise are essential to ensure correct patient selection and procedural safety. Long-term follow-up after renal denervation and participation in the German Renal Denervation (GREAT) Registry are recommended to assess safety and efficacy after renal denervation over time. © Georg Thieme Verlag KG Stuttgart · New York.

  9. Effects of extracts of denervated muscles on the morphology of cultured muscle cells

    NARCIS (Netherlands)

    Hooisma, J.; Krijger, J.de; Groot, D.M.G. de

    1981-01-01

    Previously tropic effects of extracts from whole chick embryos and from innervated muscles on cultured muscle cells were described. The present study demonstrated similar effects of extracts from 10-days denervated chick muscles. Extracts from innervated as well as from denervated muscles

  10. Direct optical activation of skeletal muscle fibres efficiently controls muscle contraction and attenuates denervation atrophy.

    Science.gov (United States)

    Magown, Philippe; Shettar, Basavaraj; Zhang, Ying; Rafuse, Victor F

    2015-10-13

    Neural prostheses can restore meaningful function to paralysed muscles by electrically stimulating innervating motor axons, but fail when muscles are completely denervated, as seen in amyotrophic lateral sclerosis, or after a peripheral nerve or spinal cord injury. Here we show that channelrhodopsin-2 is expressed within the sarcolemma and T-tubules of skeletal muscle fibres in transgenic mice. This expression pattern allows for optical control of muscle contraction with comparable forces to nerve stimulation. Force can be controlled by varying light pulse intensity, duration or frequency. Light-stimulated muscle fibres depolarize proportionally to light intensity and duration. Denervated triceps surae muscles transcutaneously stimulated optically on a daily basis for 10 days show a significant attenuation in atrophy resulting in significantly greater contractile forces compared with chronically denervated muscles. Together, this study shows that channelrhodopsin-2/H134R can be used to restore function to permanently denervated muscles and reduce pathophysiological changes associated with denervation pathologies.

  11. Denervation-induced homeostatic dendritic plasticity in morphological granule cell models

    Directory of Open Access Journals (Sweden)

    Hermann Cuntz

    2014-03-01

    Full Text Available Neuronal death and subsequent denervation of target areas are major consequences of several neurological conditions such asischemia or neurodegeneration (Alzheimer's disease. The denervation-induced axonal loss results in reorganization of the dendritic tree of denervated neurons. The dendritic reorganization has been previously studied using entorhinal cortex lesion (ECL. ECL leads to shortening and loss of dendritic segments in the denervated outer molecular layer of the dentate gyrus. However, the functional importance of these long-term dendritic alterations is not yet understood and their impact on neuronal electrical properties remains unclear. Here we analyzed what happens to the electrotonic structure and excitability of dentate granule cells after lesion-induced alterations of their dendritic morphology, assuming all other parameters remain equal. We performed comparative electrotonic analysis in anatomically and biophysically realistic compartmental models of 3D-reconstructed healthy and denervated granule cells. Using the method of morphological modeling based on optimization principles minimizing the amount of wiring and maximizing synaptic democracy, we built artificial granule cells which replicate morphological features of their real counterparts. Our results show that somatofugal and somatopetal voltage attenuation in the passive cable model are strongly reduced in denervated granule cells. In line with these predictions, the attenuation both of simulated backpropagating action potentials and forward propagating EPSPs was significantly reduced in dendrites of denervated neurons. Intriguingly, the enhancement of action potential backpropagation occurred specifically in the denervated dendritic layers. Furthermore, simulations of synaptic f-I curves revealed a homeostatic increase of excitability in denervated granule cells. In summary, our morphological and compartmental modeling indicates that unless modified by changes of

  12. Renal denervation for the management of resistant hypertension

    Directory of Open Access Journals (Sweden)

    Patel HC

    2015-12-01

    Full Text Available Hitesh C Patel,1 Carl Hayward,1 Vassilis Vassiliou,1 Ketna Patel,2 James P Howard,3 Carlo Di Mario11NIHR Cardiovascular Biomedical Research Unit, Royal Brompton Hospital, London, UK; 2Department of Cardiology, Royal Free Hospital, London, UK; 3National Heart and Lung Institute, Imperial College, London, UKAbstract: Renal sympathetic denervation (RSD as a therapy for patients with resistant hypertension has attracted great interest. The majority of studies in this field have demonstrated impressive reductions in blood pressure (BP. However, these trials were not randomized or sham-controlled and hence, the findings may have been overinflated due to trial biases. SYMPLICITY HTN-3 was the first randomized controlled trial to use a blinded sham-control and ambulatory BP monitoring. A surprise to many was that this study was neutral. Possible reasons for this neutrality include the fact that RSD may not be effective at lowering BP in man, RSD was not performed adequately due to limited operator experience, patients’ adherence with their antihypertensive drugs may have changed during the trial period, and perhaps the intervention only works in certain subgroups that are yet to be identified. Future studies seeking to demonstrate efficacy of RSD should be designed as randomized blinded sham-controlled trials. The efficacy of RSD is in doubt, but many feel that its safety has been established through the thousands of patients in whom the procedure has been performed. Over 90% of these data, however, are for the Symplicity™ system and rarely extend beyond 12 months of follow-up. Long-term safety cannot be assumed with RSD and nor should it be assumed that if one catheter system is safe then all are. We hope that in the near future, with the benefit of well-designed clinical trials, the role of renal denervation in the management of hypertension will be established.Keywords: resistant hypertension, renal denervation, sympathetic nervous system

  13. Electromyographic permutation entropy quantifies diaphragmatic denervation and reinnervation.

    Directory of Open Access Journals (Sweden)

    Christopher Kramer

    Full Text Available Spontaneous reinnervation after diaphragmatic paralysis due to trauma, surgery, tumors and spinal cord injuries is frequently observed. A possible explanation could be collateral reinnervation, since the diaphragm is commonly double-innervated by the (accessory phrenic nerve. Permutation entropy (PeEn, a complexity measure for time series, may reflect a functional state of neuromuscular transmission by quantifying the complexity of interactions across neural and muscular networks. In an established rat model, electromyographic signals of the diaphragm after phrenicotomy were analyzed using PeEn quantifying denervation and reinnervation. Thirty-three anesthetized rats were unilaterally phrenicotomized. After 1, 3, 9, 27 and 81 days, diaphragmatic electromyographic PeEn was analyzed in vivo from sternal, mid-costal and crural areas of both hemidiaphragms. After euthanasia of the animals, both hemidiaphragms were dissected for fiber type evaluation. The electromyographic incidence of an accessory phrenic nerve was 76%. At day 1 after phrenicotomy, PeEn (normalized values was significantly diminished in the sternal (median: 0.69; interquartile range: 0.66-0.75 and mid-costal area (0.68; 0.66-0.72 compared to the non-denervated side (0.84; 0.78-0.90 at threshold p<0.05. In the crural area, innervated by the accessory phrenic nerve, PeEn remained unchanged (0.79; 0.72-0.86. During reinnervation over 81 days, PeEn normalized in the mid-costal area (0.84; 0.77-0.86, whereas it remained reduced in the sternal area (0.77; 0.70-0.81. Fiber type grouping, a histological sign for reinnervation, was found in the mid-costal area in 20% after 27 days and in 80% after 81 days. Collateral reinnervation can restore diaphragm activity after phrenicotomy. Electromyographic PeEn represents a new, distinctive assessment characterizing intramuscular function following denervation and reinnervation.

  14. Cardiac troponin T and fast skeletal muscle denervation in ageing.

    Science.gov (United States)

    Xu, Zherong; Feng, Xin; Dong, Juan; Wang, Zhong-Min; Lee, Jingyun; Furdui, Cristina; Files, Daniel Clark; Beavers, Kristen M; Kritchevsky, Stephen; Milligan, Carolanne; Jin, Jian-Ping; Delbono, Osvaldo; Zhang, Tan

    2017-10-01

    Ageing skeletal muscle undergoes chronic denervation, and the neuromuscular junction (NMJ), the key structure that connects motor neuron nerves with muscle cells, shows increased defects with ageing. Previous studies in various species have shown that with ageing, type II fast-twitch skeletal muscle fibres show more atrophy and NMJ deterioration than type I slow-twitch fibres. However, how this process is regulated is largely unknown. A better understanding of the mechanisms regulating skeletal muscle fibre-type specific denervation at the NMJ could be critical to identifying novel treatments for sarcopenia. Cardiac troponin T (cTnT), the heart muscle-specific isoform of TnT, is a key component of the mechanisms of muscle contraction. It is expressed in skeletal muscle during early development, after acute sciatic nerve denervation, in various neuromuscular diseases and possibly in ageing muscle. Yet the subcellular localization and function of cTnT in skeletal muscle is largely unknown. Studies were carried out on isolated skeletal muscles from mice, vervet monkeys, and humans. Immunoblotting, immunoprecipitation, and mass spectrometry were used to analyse protein expression, real-time reverse transcription polymerase chain reaction was used to measure gene expression, immunofluorescence staining was performed for subcellular distribution assay of proteins, and electromyographic recording was used to analyse neurotransmission at the NMJ. Levels of cTnT expression in skeletal muscle increased with ageing in mice. In addition, cTnT was highly enriched at the NMJ region-but mainly in the fast-twitch, not the slow-twitch, muscle of old mice. We further found that the protein kinase A (PKA) RIα subunit was largely removed from, while PKA RIIα and RIIβ are enriched at, the NMJ-again, preferentially in fast-twitch but not slow-twitch muscle in old mice. Knocking down cTnT in fast skeletal muscle of old mice: (i) increased PKA RIα and reduced PKA RIIα at the NMJ; (ii

  15. Imaging of muscular denervation secondary to motor cranial nerve dysfunction

    International Nuclear Information System (INIS)

    Connor, S.E.J.; Chaudhary, N.; Fareedi, S.; Woo, E.K.

    2006-01-01

    The effects of motor cranial nerve dysfunction on the computed tomography (CT) and magnetic resonance imaging (MRI) appearances of head and neck muscles are reviewed. Patterns of denervation changes are described and illustrated for V, VII, X, XI and XII cranial nerves. Recognition of the range of imaging manifestations, including the temporal changes in muscular appearances and associated muscular grafting or compensatory hypertrophy, will avoid misinterpretation as local disease. It will also prompt the radiologist to search for underlying cranial nerve pathology, which may be clinically occult. The relevant cranial nerve motor division anatomy will be described to enable a focussed search for such a structural abnormality

  16. Imaging of muscular denervation secondary to motor cranial nerve dysfunction

    Energy Technology Data Exchange (ETDEWEB)

    Connor, S.E.J. [Neuroradiology Department, Kings College Hospital, Denmark Hill, London SE5 9RS (United Kingdom)]. E-mail: sejconnor@tiscali.co.uk; Chaudhary, N. [Neuroradiology Department, Kings College Hospital, Denmark Hill, London SE5 9RS (United Kingdom); Fareedi, S. [Neuroradiology Department, Kings College Hospital, Denmark Hill, London SE5 9RS (United Kingdom); Woo, E.K. [Neuroradiology Department, Kings College Hospital, Denmark Hill, London SE5 9RS (United Kingdom)

    2006-08-15

    The effects of motor cranial nerve dysfunction on the computed tomography (CT) and magnetic resonance imaging (MRI) appearances of head and neck muscles are reviewed. Patterns of denervation changes are described and illustrated for V, VII, X, XI and XII cranial nerves. Recognition of the range of imaging manifestations, including the temporal changes in muscular appearances and associated muscular grafting or compensatory hypertrophy, will avoid misinterpretation as local disease. It will also prompt the radiologist to search for underlying cranial nerve pathology, which may be clinically occult. The relevant cranial nerve motor division anatomy will be described to enable a focussed search for such a structural abnormality.

  17. Comparative decline of the protein profiles of nebulin in response to denervation in skeletal muscle

    Energy Technology Data Exchange (ETDEWEB)

    Wei, Jih-Hua [Department of Internal Medicine, Min-Sheng General Hospital, Taoyuan, Taiwan (China); Chang, Nen-Chung [Division of Cardiology, Department of Internal Medicine, College of Medicine, Taipei Medical University Hospital, Taipei, Taiwan (China); Chen, Sy-Ping [Department of Nursing, Chang Gung University of Science and Technology, Taoyuan, Taiwan (China); Geraldine, Pitchairaj [Department of Animal Science, School of Life Sciences, Bharathidasan University, Tiruchirappalli, Tamil Nadu (India); Jayakumar, Thanasekaran, E-mail: tjaya_2002@yahoo.co.in [Department of Pharmacology and Graduate Institute of Medical Sciences, College of Medicine, Taipei Medical University, Taipei, Taiwan (China); Fong, Tsorng-Harn, E-mail: thfong@tmu.edu.tw [Department of Anatomy and Cell Biology, College of Medicine, Taipei Medical University, Taipei, Taiwan (China)

    2015-10-09

    The sliding filament model of the sarcomere was developed more than half a century ago. This model, consisting only of thin and thick filaments, has been efficacious in elucidating many, but not all, features of skeletal muscle. Work during the 1980s revealed the existence of two additional filaments: the giant filamentous proteins titin and nebulin. Nebulin, a giant myofibrillar protein, acts as a protein ruler to maintain the lattice arrays of thin filaments and plays a role in signal transduction and contractile regulation. However, the change of nebulin and its effect on thin filaments in denervation-induced atrophic muscle remains unclear. The purpose of this study is to examine the content and pattern of nebulin, myosin heavy chain (MHC), actin, and titin in innervated and denervated tibialis anterior (TA) muscles of rats using sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE), densitometry and electron microscopic (EM) analyses. The results revealed that denervation induced muscle atrophy is accompanied by decreased nebulin content in a time-dependent manner. For instant, the levels of nebulin in denervated muscles were markedly (P < 0.05) decreased, about 24.6% and 40.2% in comparison with innervated muscle after denervation of 28 and 56 days, respectively. The nebulin/MHC, nebulin/actin, and nebulin/titin ratios were decreased, suggesting a concomitant reduction of nebulin in denervated muscle. Moreover, a western blotting assay proved that nebulin declined faster than titin on 28 and 56 days of denervated muscle. In addition, EM study revealed that the disturbed arrangements of myofilaments and a disorganized contractile apparatus were also observed in denervated muscle. Overall, the present study provides evidence that nebulin is more sensitive to the effect of denervation than MHC, actin, and titin. Nebulin decline indeed resulted in disintegrate of thin filaments and shortening of sarcomeres. - Highlights: • We successfully

  18. Renal denervation in moderate treatment-resistant hypertension.

    Science.gov (United States)

    Ott, Christian; Mahfoud, Felix; Schmid, Axel; Ditting, Tilmann; Sobotka, Paul A; Veelken, Roland; Spies, Aline; Ukena, Christian; Laufs, Ulrich; Uder, Michael; Böhm, Michael; Schmieder, Roland E

    2013-11-12

    This study sought to investigate the effect of renal denervation (RDN) in patients with treatment-resistant hypertension according to the established definition (Joint National Committee VII and European Society of Hypertension/European Society of Cardiology guidelines), that is, office blood pressure (BP) ≥140/90 mm Hg (with at least three antihypertensive drugs, including a diuretic, in adequate doses) and confirmed by 24-h ambulatory BP monitoring (ABPM). RDN emerged as an innovative interventional antihypertensive therapy. However, so far, only patients with severe hypertension (systolic BP ≥160 mm Hg or ≥150 mm Hg for patients with type 2 diabetes) have been investigated. In this study, there were 54 patients with moderate treatment-resistant hypertension (office BP ≥140/90 mm Hg and who underwent catheter-based RDN using the Symplicity catheter (Medtronic Inc., Mountain View, California). Patients were treated with 5.1 ± 1.4 antihypertensive drugs on average. Office BP was significantly reduced by 13/7 mm Hg 6 months after RDN (systolic: 151 ± 6 mm Hg vs. 138 ± 21 mm Hg, p who underwent ABPM 6 months after treatment, there was a reduction in average 24-h ABPM by 14/7 mm Hg (systolic: 150 ± 16 mm Hg vs. 136 ± 16 mm Hg, p hypertension. (Renal Denervation in Treatment Resistant Hypertension; NCT01687725). Copyright © 2013 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

  19. Electrically induced release of acetylcholine from denervated Schwann cells.

    Science.gov (United States)

    Dennis, M J; Miledi, R

    1974-03-01

    1. Focal electrical stimulation of Schwann cells at the end-plates of denervated frog muscles elicited slow depolarizations of up to 30 mV in the muscle fibres. This response is referred to as a Schwann-cell end-plate potential (Schwann-e.p.p.).2. Repeated stimulation sometimes evoked further Schwann-e.p.p.s, but they were never sustained for more than 30 pulses. Successive e.p.p.s varied in amplitude and time course independently of the stimulus.3. The Schwann-e.p.p.s were reversibly blocked by curare, suggesting that they result from a release of acetylcholine (ACh) by the Schwann cells.4. ACh release by electrical stimulation did not seem to occur in quantal form and was not dependent on the presence of calcium ions in the external medium; nor was it blocked by tetrodotoxin.5. Stimulation which caused release of ACh also resulted in extensive morphological disruption of the Schwann cells, as seen with both light and electron microscopy.6. It is concluded that electrical stimulation of denervated Schwann cells causes break-down of the cell membrane and releases ACh, presumably in molecular form.

  20. Renal denervation by intravascular ultrasound: Preliminary in vivo study

    Science.gov (United States)

    Sinelnikov, Yegor; McClain, Steve; Zou, Yong; Smith, David; Warnking, Reinhard

    2012-10-01

    Ultrasound denervation has recently become a subject of intense research in connection with the treatment of complex medical conditions including neurological conditions, development of pain management, reproduction of skin sensation, neuropathic pain and spasticity. The objective of this study is to investigate the use of intravascular ultrasound to produce nerve damage in renal sympathetic nerves without significant injury to the renal artery. This technique may potentially be used to treat various medical conditions, such as hypertension. The study was approved by the Institutional Animal Care and Use Committee. Ultrasound was applied to renal nerves of the swine model for histopathological evaluation. Therapeutic ultrasound energy was delivered circumferentially by an intravascular catheter maneuvered into the renal arteries. Fluoroscopic imaging was conducted pre-and post-ultrasound treatment. Animals were recovered and euthanized up to 30 hours post procedure, followed by necropsy and tissue sample collection. Histopathological examination showed evidence of extensive damage to renal nerves, characterized by nuclear pyknosis, hyalinization of stroma and multifocal hemorrhages, with little or no damage to renal arteries. This study demonstrates the feasibility of intravascular ultrasound as a minimally invasive renal denervation technique. Further studies are necessary to evaluate the long-term safety and efficacy of this technique and its related clinical significance.

  1. Non-invasive Renal Denervation: Update on External Ultrasound Approaches.

    Science.gov (United States)

    Schmieder, Roland E; Ott, Christian; Bramlage, Peter

    2016-06-01

    In the last decade, intravenous renal denervation (RDN) has emerged as an alternative to pharmacological treatment in patients with resistant hypertension, but currently involves an invasive and technically challenging procedure. The Surround Sound™ system utilises externally delivered ultrasound to achieve RDN using a completely non-invasive, automated real-time tracking system coupled with a therapeutic delivery module thereby addressing these limitations. A brief history, technical overview and summary of preclinical and clinical studies of the KonaMedical Surround Sound™ system are presented. A literature search using the terms "renal denervation", "resistant hypertension" and "external ultrasound" was performed using PubMed, and references retrieved were selected based on relevancy and year of publication (date range 1991-2015). The Surround Sound™ system appears to be a promising approach to RDN which eliminates several of the factors currently limiting the intravenous approach. So far, it has demonstrated efficacy for reducing blood pressure in resistant hypertension patients with minimal adverse effects. Several double-blind, sham-controlled clinical trials are currently underway to confirm the validity of these findings.

  2. Renal sympathetic denervation in the treatment of resistant hypertension.

    Science.gov (United States)

    Sánchez-Álvarez, Catalina; González-Vélez, Miguel; Stilp, Erik; Ward, Charisse; Mena-Hurtado, Carlos

    2014-12-01

    Arterial hypertension (HTN) is a major health problem worldwide. Treatment-resistant hypertension (trHTN) is defined as the failure to achieve target blood pressure despite the concomitant use of maximally tolerated doses of three different antihypertensive medications, including a diuretic. trHTN is associated with considerable morbidity and mortality. Renal sympathetic denervation (RDn) is available and implemented abroad as a strategy for the treatment of trHTN and is currently under clinical investigation in the United States. Selective renal sympathectomy via an endovascular approach effectively decreases renal sympathetic nerve hyperactivity leading to a decrease in blood pressure. The Symplicity catheter, currently under investigation in the United States, is a 6-French compatible system advanced under fluoroscopic guidance via percutaneous access of the common femoral artery to the distal lumen of each of the main renal arteries. Radiofrequency (RF) energy is then applied to the endoluminal surface of the renal arteries via an electrode located at the tip of the catheter. Two clinical trials (Symplicity HTN 1 and Symplicity HTN 2) have shown the efficacy of RDn with a post-procedure decline of 27/17 mmHg at 12 months and 32/12 mmHg at 6 months, respectively, with few minor adverse events. Symplicity HTN-3 study is a, multi-center, prospective, single-blind, randomized, controlled study currently under way and will provide further insights about the safety and efficacy of renal denervation in patients with trHTN.

  3. Endovascular Renal Artery Denervation: Why, When, and How?

    International Nuclear Information System (INIS)

    Sapoval, Marc; Azizi, Michel; Bobrie, Guillaume; Cholley, Bernard; Pagny, Jean-Yves; Plouin, Pierre-François

    2012-01-01

    Endovascular renal artery denervation (ERAD) is a new procedure to reduce renal and systemic sympathetic overactivity in hypertensive patients. The role of sympathetic overactivity is recognized since a long time as being one the contributor of human hypertension. In support of this view, several studies in experimental models of hypertension in animal as well as hypertensive human subjects have demonstrated that sympathetic overactivity plays a central role in hypertension catheter based renal denervation is now possible, and this procedure may provide a useful adjunct for the management of patients with drug-resistant primary hypertension. Following a cohort study, the results of an open label randomized control trial have been published showing very encouraging results. The purpose of this paper is to help interventionalists to better understand the medical and technical issues related to this new intervention. It is most likely that as underlined in a recent editorial several other technical approaches may appear in the future, however because this is the only technique that is available today, we will focus on radiofrequency based technique.

  4. Renin angiotensin system and cardiac hypertrophy after sinoaortic denervation in rats

    Directory of Open Access Journals (Sweden)

    Aline Cristina Piratello

    2010-01-01

    Full Text Available OBJECTIVE: The aim of this study was to evaluate the role of angiotensin I, II and 1-7 on left ventricular hypertrophy of Wistar and spontaneously hypertensive rats submitted to sinoaortic denervation. METHODS: Ten weeks after sinoaortic denervation, hemodynamic and morphofunctional parameters were analyzed, and the left ventricle was dissected for biochemical analyses. RESULTS: Hypertensive groups (controls and denervated showed an increase on mean blood pressure compared with normotensive ones (controls and denervated. Blood pressure variability was higher in denervated groups than in their respective controls. Left ventricular mass and collagen content were increased in the normotensive denervated and in both spontaneously hypertensive groups compared with Wistar controls. Both hypertensive groups presented a higher concentration of angiotensin II than Wistar controls, whereas angiotensin 1-7 concentration was decreased in the hypertensive denervated group in relation to the Wistar groups. There was no difference in angiotensin I concentration among groups. CONCLUSION: Our results suggest that not only blood pressure variability and reduced baroreflex sensitivity but also elevated levels of angiotensin II and a reduced concentration of angiotensin 1-7 may contribute to the development of left ventricular hypertrophy. These data indicate that baroreflex dysfunction associated with changes in the renin angiotensin system may be predictive factors of left ventricular hypertrophy and cardiac failure.

  5. Technical aspects of renal denervation in end-stage renal disease patients with challenging anatomy.

    Science.gov (United States)

    Spinelli, Alessio; Da Ros, Valerio; Morosetti, Daniele; Onofrio, Silvia D; Rovella, Valentina; Di Daniele, Nicola; Simonetti, Giovanni

    2014-01-01

    We describe our preliminary experience with percutaneous renal denervation in end-stage renal disease patients with resistant hypertension and challenging anatomy, in terms of the feasibility, safety, and efficacy of this procedure. Four patients with end-stage renal disease patients with resistant hypertension (mean hemodialysis time, 2.3 years) who had been taking at least four antihypertensive medications underwent percutaneous renal denervation. Renal artery eligibility included the absence of prior renal artery interventions, vessel stenosis renal denervation is a feasible approach for end-stage renal disease patients with resistant hypertension with encouraging short-term preliminary results in terms of procedural efficacy and safety.

  6. Subacute mandibular and hypoglossal nerve denervation causing oedema of the masticator space and tongue

    International Nuclear Information System (INIS)

    Ho, T.; Lee, K.; Lee, H.

    2003-01-01

    We report the MRI of five patients with denervation oedema in the head and neck. Four had denervation oedema in one masticator space caused by a skull-base tumour invading the ipsilateral foramen ovale. Another case had denervation oedema confined to the half of the tongue ipsilateral to oral reconstruction surgery which involved mandibulectomy, free flap repair and wide excision of a buccal mucosal carcinoma. Inversion-recovery and/or T2-weighted spin-echo images showed increased signal in the affected areas. Contrast-enhanced T1-weighted images revealed enhancement of the muscles. There was no evidence of tumour or infection in the masticator space or tongue. It is important to differentiate denervation oedema from other disease processes causing high signal on T2-weighted images, such as tumour infiltration and soft-tissue infection. (orig.)

  7. Safety and long-term effects of renal denervation: Rationale and design of the Dutch registry

    NARCIS (Netherlands)

    Sanders, M.F.; Blankestijn, P.J.; Voskuil, M.; Spiering, W.; Vonken, E.J.; Rotmans, J.I.; Hoeven, B.L. van der; Daemen, J.; Meiracker, A.H. van den; Kroon, A.A.; Haan, M.W. de; Das, M.; Bax, M.; Meer, I.M. van der; Overhagen, H. van; Born, B.J. van den; Brussel, P.M. van; Valk, P.H. van der; Gregoor, P.J. Smak; Meuwissen, M.; Gomes, M.E.; Ophuis, T. Oude; Troe, E.; Tonino, W.A.; Konings, C.J.; Vries, P.A. de; Balen, A. van; Heeg, J.E.; Smit, J.J.; Elvan, A.; Steggerda, R.; Niamut, S.M.; Peels, J.O.; Swart, J.B. de; Wardeh, A.J.; Groeneveld, J.H.; Linden, E. van der; Hemmelder, M.H.; Folkeringa, R.; Stoel, M.G.; Kant, G.D.; Herrman, J.P.; Wissen, S. van; Deinum, J.; Westra, S.W.; Aengevaeren, W.R.; Parlevliet, K.J.; Schramm, A.; Jessurun, G.A.; Rensing, B.J.; Winkens, M.H.; Wierema, T.K.; Santegoets, E.; Lipsic, E.; Houwerzijl, E.; Kater, M.; Allaart, C.P.; Nap, A.; Bots, M.L.

    2016-01-01

    BACKGROUND: Percutaneous renal denervation (RDN) has recently been introduced as a treatment for therapyresistant hypertension. Also, it has been suggested that RDN may be beneficial for other conditions characterised by increased sympathetic nerve activity. There are still many uncertainties with

  8. Renal denervation beyond the bifurcation: The effect of distal ablation placement on safety and blood pressure.

    Science.gov (United States)

    Beeftink, Martine M A; Spiering, Wilko; De Jong, Mark R; Doevendans, Pieter A; Blankestijn, Peter J; Elvan, Arif; Heeg, Jan-Evert; Bots, Michiel L; Voskuil, Michiel

    2017-04-01

    Renal denervation may be more effective if performed distal in the renal artery because of smaller distances between the lumen and perivascular nerves. The authors reviewed the angiographic results of 97 patients and compared blood pressure reduction in relation to the location of the denervation. No significant differences in blood pressure reduction or complications were found between patient groups divided according to their spatial distribution of the ablations (proximal to the bifurcation in both arteries, distal to the bifurcation in one artery and distal in the other artery, or distal to the bifurcation in both arteries), but systolic ambulatory blood pressure reduction was significantly related to the number of distal ablations. No differences in adverse events were observed. In conclusion, we found no reason to believe that renal denervation distal to the bifurcation poses additional risks over the currently advised approach of proximal denervation, but improved efficacy remains to be conclusively established. ©2017 Wiley Periodicals, Inc.

  9. Renal denervation in a patient with Alport syndrome and rejected renal allograft

    Directory of Open Access Journals (Sweden)

    Narayana Raju

    2015-12-01

    Full Text Available Renal denervation is a new intervention to treat resistant hypertension. By applying radiofrequency (RF to renal arteries, sympathetic nerves in adventitia layer of vascular wall can be denervated. Sympathetic hyperactivity is an important contributory factor in hypertension of hemodialysis patients. Hyperactive sympathetic nervous system aggravates hypertension and it can cause complications like left ventricular hypertrophy, heart failure, arrhythmias and atherogenesis. Our report illustrates the use of renal denervation using conventional RF catheter for uncontrolled hypertension in a patient with Alport syndrome and rejected renal allograft. Progressive and sustained reduction of blood pressure was obtained post-procedure and at 24 months follow-up with antihypertensives decreased from 6 to 2 per day, thereby demonstrating the safety, feasibility, and efficacy of the procedure. There are some reports available on the usefulness of this technique in hemodialysis patients; however, there are no studies of renal denervation in patients with Alport syndrome and failed allograft situation.

  10. MRI diagnosis of muscle denervation from herpes zoster with discordant distribution of the skin rash

    Energy Technology Data Exchange (ETDEWEB)

    Gupta, Amit; Sundaram, Murali [Cleveland Clinic, Section of Musculoskeletal Radiology, Imaging Institute, Cleveland, OH (United States); Winalski, Carl S. [Cleveland Clinic, Section of Musculoskeletal Radiology, Imaging Institute, Cleveland, OH (United States); Cleveland Clinic, Department of Biomedical Engineering, Lerner Research Institute, Cleveland, OH (United States)

    2014-10-15

    Herpes zoster is a common disorder characterized by a painful rash along a dermatome caused by reactivation of the varicella zoster virus (VZV). Muscle denervation injury from motor involvement is an uncommon phenomenon. Discordant distribution of the skin rash and motor nerve involvement, presenting as a skin rash in one body part and muscle weakness or pain from nerve involvement in another body part is an even more uncommonly reported finding. We present an unusual case of muscle denervation injury resulting from motor involvement of a peripheral nerve by VZV diagnosed by magnetic resonance imaging with cutaneous manifestations in a different dermatomal distribution. To the best of our knowledge, there has been no similar case reported in the English radiology literature. We suggest that whenever a radiologist notices MRI findings suggesting denervation injury and a cause not readily identified, VZV-related denervation injury should be included in the differential diagnosis, especially in an older immunocompromised patient. (orig.)

  11. Adrenergic receptors are a fallible index of adrenergic denervation hypersensitivity

    DEFF Research Database (Denmark)

    Dejgaard, Anders; Liggett, S B; Christensen, N J

    1991-01-01

    In view of evidence that neither interindividual nor induced intra-individual variations of adrenergic receptor status are related to metabolic or haemodynamic sensitivity to adrenaline in vivo, we took an alternative approach to assessment of the relevance of adrenergic receptor measurement...... by measuring these in a group of subjects with well-documented adrenergic denervation hypersensitivity, patients with diabetic autonomic neuropathy. Mononuclear leukocyte beta 2-adrenergic receptor densities (and binding affinities), measured with 125I-labelled pindolol, and isoproterenol-stimulated cyclic AMP...... accumulation, in samples from patients with insulin-dependent diabetes mellitus (IDDM) with diabetic autonomic neuropathy (n = 8), were no different from those in samples from patients with IDDM without neuropathy (n = 8), or from non-diabetic subjects (n = 8). In addition, platelet alpha 2-adrenergic receptor...

  12. Magnetic resonance imaging patterns of mononeuropathic denervation in muscles with dual innervation

    Energy Technology Data Exchange (ETDEWEB)

    Sneag, Darryl B.; Lee, Susan C.; Melisaratus, Darius P. [Hospital for Special Surgery, Department of Radiology and Imaging, New York, NY (United States); Feinberg, Joseph H. [Physical Medicine and Rehabilitation, Hospital for Special Surgery, New York, NY (United States); Amber, Ian [MedStar Georgetown University Hospital, Department of Radiology, DC, Washington (United States)

    2017-12-15

    Magnetic resonance imaging (MRI) of mononeuropathy in muscles with dual innervation depicts geographic denervation corresponding to the affected nerve. Knowledge of the normal distribution of a muscle's neural supply is clinically relevant as partial muscle denervation represents a potential imaging pitfall that can be confused with other pathology, such as muscle strain. This article reviews the normal innervation pattern of extremity muscles with dual supply, providing illustrative examples of mononeuropathy affecting such muscles. (orig.)

  13. Magnetic resonance imaging patterns of mononeuropathic denervation in muscles with dual innervation

    International Nuclear Information System (INIS)

    Sneag, Darryl B.; Lee, Susan C.; Melisaratus, Darius P.; Feinberg, Joseph H.; Amber, Ian

    2017-01-01

    Magnetic resonance imaging (MRI) of mononeuropathy in muscles with dual innervation depicts geographic denervation corresponding to the affected nerve. Knowledge of the normal distribution of a muscle's neural supply is clinically relevant as partial muscle denervation represents a potential imaging pitfall that can be confused with other pathology, such as muscle strain. This article reviews the normal innervation pattern of extremity muscles with dual supply, providing illustrative examples of mononeuropathy affecting such muscles. (orig.)

  14. Carotid body denervation prevents fasting hyperglycemia during chronic intermittent hypoxia.

    Science.gov (United States)

    Shin, Mi-Kyung; Yao, Qiaoling; Jun, Jonathan C; Bevans-Fonti, Shannon; Yoo, Doo-Young; Han, Woobum; Mesarwi, Omar; Richardson, Ria; Fu, Ya-Yuan; Pasricha, Pankaj J; Schwartz, Alan R; Shirahata, Machiko; Polotsky, Vsevolod Y

    2014-10-01

    Obstructive sleep apnea causes chronic intermittent hypoxia (IH) and is associated with impaired glucose metabolism, but mechanisms are unknown. Carotid bodies orchestrate physiological responses to hypoxemia by activating the sympathetic nervous system. Therefore, we hypothesized that carotid body denervation would abolish glucose intolerance and insulin resistance induced by chronic IH. Male C57BL/6J mice underwent carotid sinus nerve dissection (CSND) or sham surgery and then were exposed to IH or intermittent air (IA) for 4 or 6 wk. Hypoxia was administered by decreasing a fraction of inspired oxygen from 20.9% to 6.5% once per minute, during the 12-h light phase (9 a.m.-9 p.m.). As expected, denervated mice exhibited blunted hypoxic ventilatory responses. In sham-operated mice, IH increased fasting blood glucose, baseline hepatic glucose output (HGO), and expression of a rate-liming hepatic enzyme of gluconeogenesis phosphoenolpyruvate carboxykinase (PEPCK), whereas the whole body glucose flux during hyperinsulinemic euglycemic clamp was not changed. IH did not affect glucose tolerance after adjustment for fasting hyperglycemia in the intraperitoneal glucose tolerance test. CSND prevented IH-induced fasting hyperglycemia and increases in baseline HGO and liver PEPCK expression. CSND trended to augment the insulin-stimulated glucose flux and enhanced liver Akt phosphorylation at both hypoxic and normoxic conditions. IH increased serum epinephrine levels and liver sympathetic innervation, and both increases were abolished by CSND. We conclude that chronic IH induces fasting hyperglycemia increasing baseline HGO via the CSN sympathetic output from carotid body chemoreceptors, but does not significantly impair whole body insulin sensitivity. Copyright © 2014 the American Physiological Society.

  15. Renal denervation for the management of resistant hypertension

    Science.gov (United States)

    Patel, Hitesh C; Hayward, Carl; Vassiliou, Vassilis; Patel, Ketna; Howard, James P; Di Mario, Carlo

    2015-01-01

    Renal sympathetic denervation (RSD) as a therapy for patients with resistant hypertension has attracted great interest. The majority of studies in this field have demonstrated impressive reductions in blood pressure (BP). However, these trials were not randomized or sham-controlled and hence, the findings may have been overinflated due to trial biases. SYMPLICITY HTN-3 was the first randomized controlled trial to use a blinded sham-control and ambulatory BP monitoring. A surprise to many was that this study was neutral. Possible reasons for this neutrality include the fact that RSD may not be effective at lowering BP in man, RSD was not performed adequately due to limited operator experience, patients’ adherence with their anti-hypertensive drugs may have changed during the trial period, and perhaps the intervention only works in certain subgroups that are yet to be identified. Future studies seeking to demonstrate efficacy of RSD should be designed as randomized blinded sham-controlled trials. The efficacy of RSD is in doubt, but many feel that its safety has been established through the thousands of patients in whom the procedure has been performed. Over 90% of these data, however, are for the Symplicity™ system and rarely extend beyond 12 months of follow-up. Long-term safety cannot be assumed with RSD and nor should it be assumed that if one catheter system is safe then all are. We hope that in the near future, with the benefit of well-designed clinical trials, the role of renal denervation in the management of hypertension will be established. PMID:26672761

  16. Renal sympathetic denervation for treatment of resistant hypertension: Egyptian experience.

    Science.gov (United States)

    Hamza, Mohamed; Khamis, Hazem

    2014-08-01

    Among the Egyptian population with essential hypertension, a minority are under control (systolic pressure renal artery radiofrequency (RF) ablation. To evaluate the feasibility, efficacy, and safety of catheter-based radiofrequency renal sympathetic denervation for treatment of resistant hypertension in Egyptian patients. Patients with essential hypertension unresponsive to at least 3 types of antihypertensive medical therapy (baseline office systolic blood pressure ≥160 mmHg) (n = 55) were enrolled between February 2012 and June 2013 and received percutaneous RF ablation. Patients were followed up for 6 months after treatment to detect any change in office-based measurement of blood pressure. Urine and blood samples were taken to evaluate the effects on renal function. A reduction of mean office blood pressure was seen from 174/103 ± 9/5 mmHg at baseline to 150/91 ± 8/5 mmHg at 6 months follow-up (P = 0.001). Also, we noted a significant decrease in plasma renin activity (3.66 ± 0.64 vs. 3.37 ± 0.47 ng/mL per hour; P = 0.003), and there were no periprocedural complications, no adverse events, and no change in renal function during the follow-up period. Also, no change was noted in the number of medications after 6 months (3.95 ± 1.64 vs. 3.67 ± 0.72; P = 0.27). In this observational study, catheter-based renal denervation causes sustained blood pressure reduction in patients with resistant hypertension, without serious adverse events. © 2014, Wiley Periodicals, Inc.

  17. Renal sympathetic nervous system and the effects of denervation on renal arteries.

    Science.gov (United States)

    Kannan, Arun; Medina, Raul Ivan; Nagajothi, Nagapradeep; Balamuthusamy, Saravanan

    2014-08-26

    Resistant hypertension is associated with chronic activation of the sympathetic nervous system resulting in various comorbidities. The prevalence of resistant hypertension is often under estimated due to various reasons. Activation of sympathetic nervous system at the renal- as well as systemic- level contributes to the increased level of catecholamines and resulting increase in the blood pressure. This increased activity was demonstrated by increased muscle sympathetic nerve activity and renal and total body noradrenaline spillover. Apart from the hypertension, it is hypothesized to be associated with insulin resistance, congestive heart failure and obstructive sleep apnea. Renal denervation is a novel procedure where the sympathetic afferent and efferent activity is reduced by various techniques and has been used successfully to treat drug-resistant hypertension improvement of various metabolic derangements. Renal denervation has the unique advantage of offering the denervation at the renal level, thus mitigating the systemic side effects. Renal denervation can be done by various techniques including radiofrequency ablation, ultrasound guided ablation and chemical ablation. Various trials evaluated the role of renal denervation in the management of resistant hypertension and have found promising results. More studies are underway to evaluate the role of renal denervation in patients presenting with resistant hypertension in different scenarios. Appropriate patient selection might be the key in determining the effectiveness of the procedure.

  18. Radiofrequency Denervation Improves Health-Related Quality of Life in Patients with Thoracic Zygapophyseal Joint Pain.

    Science.gov (United States)

    Hambraeus, Johan; Hambraeus, Kjerstin S; Persson, Jan

    2018-05-01

    To describe a practical approach for the diagnosis and treatment of thoracic zygapophyseal joint pain and to present preliminary clinical data on the effects of this treatment approach on health-related quality of life. An observational study. Specialist outpatient pain clinic in northern Sweden. Patients with long-term thoracic pain. We describe a method of radiofrequency denervation of thoracic zygapophyseal joints. We compared health-related quality of life between patients who underwent radiofrequency denervation of thoracic zygapophyseal joints and patients who underwent radiofrequency denervation for lumbar and cervical zygapophyseal joint pain. Treatment according to the Spine Intervention Society Guidelines was performed on the lumbar region in 178 patients and in the cervical region in 55 patients. Another 82 patients were treated in the thoracic region with our proposed technique. A survival plot of improvements in health-related quality of life revealed that all three treatments were effective in 65% or more of patients. The improvement in health-related quality of life was maintained for 12 or more months after treatment in 47% to 51% of patients. Our results suggest that radiofrequency denervation of thoracic zygapophyseal joint pain is as effective as radiofrequency denervation, the standard treatment, for lumbar and cervical zygapophyseal joint pain. If these results can be confirmed by other centers, radiofrequency denervation is likely to become more widely available for the treatment of thoracic zygapophyseal joint pain.

  19. High incidence of secondary hypertension in patients referred for renal denervation--the Copenhagen experience.

    Science.gov (United States)

    Olsen, Lene Kjær; Kamper, Anne-Lise; Svendsen, Jesper Hastrup; Bang, Lia Evi; Frimodt-Møller, Marie; Kelbæk, Henning; Sander, Mikael; Feldt-Rasmussen, Bo

    2014-08-01

    Percutaneous renal denervation is a new treatment option for patients with resistant hypertension and little is known about the eligibility of patients referred. 100 consecutive patients were referred for renal denervation from March 2011 through September 2012. Clinical data were prospectively extracted from letters and documents from referring clinics and from our physical examination. Of the 100 patients included, 68 were men and the mean age was 60 (± 12) years. Office blood pressure was 176 (± 28)/99 (± 19) mmHg and 24-h ambulatory blood pressure 156 (± 20)/88 (± 13) mmHg. The mean number of antihypertensive agents was 4.0 (± 1.6). Nearly four-fifths (82%) of the patients were categorized as having resistant hypertension based on the criteria stated by The American Heart Association's stated criteria. Nine patients declined interest in renal denervation before completing the clinical workup program. Thus, 91 patients were screened, and of those 51 were found to be candidates for renal denervation. Forty patients were not candidates, of which secondary hypertension was the most common cause (n = 10). Only 51% of patients referred for renal denervation were eligible for treatment. The prevalence of secondary hypertension was 10% of the referred population. Secondary hypertension should therefore be considered in the evaluation of candidates for renal denervation.

  20. HDAC4 preserves skeletal muscle structure following long-term denervation by mediating distinct cellular responses.

    Science.gov (United States)

    Pigna, Eva; Renzini, Alessandra; Greco, Emanuela; Simonazzi, Elena; Fulle, Stefania; Mancinelli, Rosa; Moresi, Viviana; Adamo, Sergio

    2018-02-24

    Denervation triggers numerous molecular responses in skeletal muscle, including the activation of catabolic pathways and oxidative stress, leading to progressive muscle atrophy. Histone deacetylase 4 (HDAC4) mediates skeletal muscle response to denervation, suggesting the use of HDAC inhibitors as a therapeutic approach to neurogenic muscle atrophy. However, the effects of HDAC4 inhibition in skeletal muscle in response to long-term denervation have not been described yet. To further study HDAC4 functions in response to denervation, we analyzed mutant mice in which HDAC4 is specifically deleted in skeletal muscle. After an initial phase of resistance to neurogenic muscle atrophy, skeletal muscle with a deletion of HDAC4 lost structural integrity after 4 weeks of denervation. Deletion of HDAC4 impaired the activation of the ubiquitin-proteasome system, delayed the autophagic response, and dampened the OS response in skeletal muscle. Inhibition of the ubiquitin-proteasome system or the autophagic response, if on the one hand, conferred resistance to neurogenic muscle atrophy; on the other hand, induced loss of muscle integrity and inflammation in mice lacking HDAC4 in skeletal muscle. Moreover, treatment with the antioxidant drug Trolox prevented loss of muscle integrity and inflammation in in mice lacking HDAC4 in skeletal muscle, despite the resistance to neurogenic muscle atrophy. These results reveal new functions of HDAC4 in mediating skeletal muscle response to denervation and lead us to propose the combined use of HDAC inhibitors and antioxidant drugs to treat neurogenic muscle atrophy.

  1. Regional sympathetic denervation after myocardial infarction in humans detected noninvasively using I-123-metaiodobenzylguanidine

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    Stanton, M.S.; Tuli, M.M.; Radtke, N.L.; Heger, J.J.; Miles, W.M.; Mock, B.H.; Burt, R.W.; Wellman, H.N.; Zipes, D.P. (Indiana Univ. School of Medicine, IN (USA))

    1989-11-15

    Transmural myocardial infarction in dogs produces denervation of sympathetic nerves in viable myocardium apical to the infarct that may be arrhythmogenic. It is unknown whether sympathetic denervation occurs in humans. The purpose of this study was to use iodine-123-metaiodobenzylguanidine (MIBG), a radiolabeled guanethidine analog that is actively taken up by sympathetic nerve terminals, to image noninvasively the cardiac sympathetic nerves in patients with and without ventricular arrhythmias after myocardial infarction. Results showed that 10 of 12 patients with spontaneous ventricular tachyarrhythmias after myocardial infarction exhibited regions of thallium-201 uptake indicating viable perfused myocardium, with no MIBG uptake. Such a finding is consistent with sympathetic denervation. One patient had frequent episodes of nonsustained ventricular tachycardia induced at exercise testing that was eliminated by beta-adrenoceptor blockade. Eleven of the 12 patients had ventricular tachycardia induced at electrophysiologic study and metoprolol never prevented induction. Sympathetic denervation was also detected in two of seven postinfarction patients without ventricular arrhythmias. Normal control subjects had no regions lacking MIBG uptake. This study provides evidence that regional sympathetic denervation occurs in humans after myocardial infarction and can be detected noninvasively by comparing MIBG and thallium-201 images. Although the presence of sympathetic denervation may be related to the onset of spontaneous ventricular tachyarrhythmias in some patients, it does not appear to be related to sustained ventricular tachycardia induced at electrophysiologic study.

  2. Does the presence of accessory renal arteries affect the efficacy of renal denervation?

    Science.gov (United States)

    Id, Dani; Kaltenbach, Benjamin; Bertog, Stefan C; Hornung, Marius; Hofmann, Ilona; Vaskelyte, Laura; Sievert, Horst

    2013-10-01

    This study sought to assess the efficacy of catheter-based renal sympathetic denervation in patients with accessory renal arteries and to compare the blood pressure (BP)-lowering effect with that observed in patients with bilateral single renal arteries after renal denervation. Catheter-based renal sympathetic denervation causes significant BP reductions in patients with resistant hypertension. Seventy-four patients were included in this study. Patients were assigned to 2 main groups: a bilateral single renal arteries group I (n = 54) and an accessory renal arteries group II (n = 20). Group II consisted of 9 patients whose accessory renal arteries were all denervated (group IIa), and 11 patients whose accessory renal arteries were not, or only incompletely, denervated (group IIb). The primary endpoint was the change in office systolic BP after 6 months. The procedure was successful in all patients. Group I: mean BP at baseline was 166.2/89.4 ± 20.5/14.6 mm Hg and decreased by -16.6 (p renal denervation in patients with accessory renal arteries is less pronounced than in patients with bilateral single renal arteries. Copyright © 2013 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

  3. Diagnostic signs of motor neuropathy in MR neurography: Nerve lesions and muscle denervation

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    Schwarz, Daniel; Pham, Mirko; Bendszus, Martin; Baeumer, Philipp; Weiler, Markus; Heiland, Sabine

    2015-01-01

    To investigate the diagnostic contribution of T2-w nerve lesions and of muscle denervation in peripheral motor neuropathies by magnetic resonance neurography (MRN). Fifty-one patients with peripheral motor neuropathies underwent high-resolution MRN by large coverage axial T2-w sequences of the upper arm, elbow, and forearm. Images were evaluated by two blinded readers for T2-w signal alterations of median, ulnar, and radial nerves, and for denervation in respective target muscle groups. All 51 patients displayed nerve lesions in at least one of three nerves, and 43 out of 51 patients showed denervation in at least one target muscle group of these nerves. In 21 out of 51 patients, the number of affected nerves matched the number of affected target muscle groups. In the remaining 30 patients, T2-w lesions were encountered more frequently than target muscle group denervation. In 153 nerve-muscle pairs, 72 showed denervation, but only one had increased muscle signal without a lesion in the corresponding nerve. MRN-based diagnosis of peripheral motor neuropathies is more likely by visualization of peripheral nerve lesions than by denervation in corresponding target muscles. Increased muscular T2-w signal without concomitant nerve lesions should raise suspicion of an etiology other than peripheral neuropathy. (orig.)

  4. Diagnostic signs of motor neuropathy in MR neurography: Nerve lesions and muscle denervation

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    Schwarz, Daniel; Pham, Mirko; Bendszus, Martin; Baeumer, Philipp [Heidelberg University Hospital, Department of Neuroradiology, Heidelberg (Germany); Weiler, Markus [Heidelberg University Hospital, Department of Neurology, Heidelberg (Germany); German Cancer Research Center (DKFZ), Clinical Cooperation Unit Neurooncology, Heidelberg (Germany); Heiland, Sabine [Heidelberg University Hospital, Section of Experimental Radiology, Department of Neuroradiology, Heidelberg (Germany)

    2015-05-01

    To investigate the diagnostic contribution of T2-w nerve lesions and of muscle denervation in peripheral motor neuropathies by magnetic resonance neurography (MRN). Fifty-one patients with peripheral motor neuropathies underwent high-resolution MRN by large coverage axial T2-w sequences of the upper arm, elbow, and forearm. Images were evaluated by two blinded readers for T2-w signal alterations of median, ulnar, and radial nerves, and for denervation in respective target muscle groups. All 51 patients displayed nerve lesions in at least one of three nerves, and 43 out of 51 patients showed denervation in at least one target muscle group of these nerves. In 21 out of 51 patients, the number of affected nerves matched the number of affected target muscle groups. In the remaining 30 patients, T2-w lesions were encountered more frequently than target muscle group denervation. In 153 nerve-muscle pairs, 72 showed denervation, but only one had increased muscle signal without a lesion in the corresponding nerve. MRN-based diagnosis of peripheral motor neuropathies is more likely by visualization of peripheral nerve lesions than by denervation in corresponding target muscles. Increased muscular T2-w signal without concomitant nerve lesions should raise suspicion of an etiology other than peripheral neuropathy. (orig.)

  5. Endovascular ultrasound for renal sympathetic denervation in patients with therapy-resistant hypertension not responding to radiofrequency renal sympathetic denervation.

    Science.gov (United States)

    Stiermaier, Thomas; Okon, Thomas; Fengler, Karl; Mueller, Ulrike; Hoellriegel, Robert; Schuler, Gerhard; Desch, Steffen; Lurz, Philipp

    2016-06-12

    Recent studies have reported a considerable number of non-responders after renal sympathetic de-nervation (RSD) with radiofrequency technology. Here we report our results of repeat RSD using ultrasound in these patients. A cohort study was performed in patients who underwent ultrasound RSD after non-response to RSD with radiofrequency. Non-response was defined as mean daytime systolic blood pressure ≥140 mmHg and/or a reduction of ≤10 mmHg in ambulatory blood pressure measurement (ABPM) ≥6 months after radiofrequency denervation. ABPM was recorded at baseline, post radiofrequency RSD as well as at three and six months post ultrasound RSD. A total of 24 non-responders underwent retreatment with the ultrasound device at a mean 15.3±8.2 months after radiofrequency RSD. Ultrasound RSD was performed successfully in all patients without severe adverse events. Mean daytime systolic blood pressure changed from 161.7±14.6 mmHg at baseline to 158.5±9.5 mmHg post radiofrequency RSD and to 150.5±10.4 mmHg and 151.6±11.0 mmHg at three and six months, respectively, post ultrasound RSD (pmeasures analysis of variance). The main results of post hoc testing were as follows: baseline versus post radiofrequency RSD, p=0.83; baseline versus three months post ultrasound RSD, p=0.01; and baseline versus six months post ultrasound RSD, p=0.04. Ultrasound RSD appears to be safe and an effective therapeutic approach in patients not responding to previous RSD with radiofrequency technology.

  6. Beneficial Effects of Renal Denervation on Pulmonary Vascular Remodeling in Experimental Pulmonary Artery Hypertension.

    Science.gov (United States)

    Qingyan, Zhao; Xuejun, Jiang; Yanhong, Tang; Zixuan, Dai; Xiaozhan, Wang; Xule, Wang; Zongwen, Guo; Wei, Hu; Shengbo, Yu; Congxin, Huang

    2015-07-01

    Activation of both the sympathetic nervous system and the renin-angiotensin-aldosterone system is closely associated with pulmonary arterial hypertension. We hypothesized that renal denervation decreases renin-angiotensin-aldosterone activity and inhibits the progression of pulmonary arterial hypertension. Twenty-two beagles were randomized into 3 groups. The dogs' pulmonary dynamics were measured before and 8 weeks after injection of 0.1mL/kg dimethylformamide (control dogs) or 2mg/kg dehydromonocrotaline (pulmonary arterial hypertension and pulmonary arterial hypertension + renal denervation dogs). Eight weeks after injection, neurohormone levels and pulmonary tissue morphology were measured. Levels of plasma angiotensin II and endothelin-1 were significantly increased after 8 weeks in the pulmonary arterial hypertension dogs and were higher in the lung tissues of these dogs than in those of the control and renal denervation dogs (mean [standard deviation] angiotensin II: 65 [9.8] vs 38 [6.7], 46 [8.1]; endothelin-1: 96 [10.3] vs 54 [6.2], 67 [9.4]; P < .01). Dehydromonocrotaline increased the mean pulmonary arterial pressure (16 [3.4] mmHg vs 33 [7.3] mmHg; P < .01), and renal denervation prevented this increase. Pulmonary smooth muscle cell proliferation was higher in the pulmonary arterial hypertension dogs than in the control and pulmonary arterial hypertension + renal denervation dogs. Renal denervation attenuates pulmonary vascular remodeling and decreases pulmonary arterial pressure in experimental pulmonary arterial hypertension. The effect of renal denervation may contribute to decreased neurohormone levels. Copyright © 2014 Sociedad Española de Cardiología. Published by Elsevier España, S.L.U. All rights reserved.

  7. Degradation rate of acetylcholine receptors inserted into denervated vertebrate neuromuscular junctions

    International Nuclear Information System (INIS)

    Shyng, S.L.; Salpeter, M.M.

    1989-01-01

    Many studies exist on the effect of denervation on the degradation of acetylcholine receptors (AChRs) at the vertebrate neuromuscular junction (nmj). These studies have described the behavior of either the total population of junctional receptors at different times after denervation, or of the receptors present at the time of denervation. No experimental studies yet exist on the degradation rate of the receptors newly inserted into denervated junctions. In the previous studies, the original receptors of mouse sternomastoid muscles were found to retain the slow degradation (t 1/2) of approximately 8-10 d of innervated junctional receptors for up to 10 d after denervation before accelerating to a t 1/2 of approximately 3 d. The total junctional receptors, on the other hand, showed a progressive increase in degradation rate from a t 1/2 of 8-10 d to a t 1/2 of 1 d. To reconcile these earlier observations, the present study examines the degradation of new receptors inserted into the nmj after denervation. To avoid possible contamination of the data with postdenervation extrajunctional receptors, we used transmission electron microscope autoradiography to study only receptors located at the postjunctional fold of the nmj. We established that the new receptors inserted into denervated junctions have a t 1/2 of approximately 1 d, considerably faster than that of the original receptors and equivalent to that of postdenervation extrajunctional receptors. Both original and new receptors are interspersed at the top of the junctional folds. Thus, until all the original receptors are degraded, the postjunctional membrane contains two populations of AChRs that maintain a total steady-state site density but degrade at different rates

  8. Denervation in murine fast-twitch muscle: short-term physiological changes and temporal expression profiling.

    Science.gov (United States)

    Raffaello, Anna; Laveder, Paolo; Romualdi, Chiara; Bean, Camilla; Toniolo, Luana; Germinario, Elena; Megighian, Aram; Danieli-Betto, Daniela; Reggiani, Carlo; Lanfranchi, Gerolamo

    2006-03-13

    Denervation deeply affects muscle structure and function, the alterations being different in slow and fast muscles. Because the effects of denervation on fast muscles are still controversial, and high-throughput studies on gene expression in denervated muscles are lacking, we studied gene expression during atrophy progression following denervation in mouse tibialis anterior (TA). The sciatic nerve was cut close to trochanter in adult CD1 mice. One, three, seven, and fourteen days after denervation, animals were killed and TA muscles were dissected out and utilized for physiological experiments and gene expression studies. Target cDNAs from TA muscles were hybridized on a dedicated cDNA microarray of muscle genes. Seventy-one genes were found differentially expressed. Microarray results were validated, and the expression of relevant genes not probed on our array was monitored by real-time quantitative PCR (RQ-PCR). Nuclear- and mitochondrial-encoded genes implicated in energy metabolism were consistently downregulated. Among genes implicated in muscle contraction (myofibrillar and sarcoplasmic reticulum), genes typical of fast fibers were downregulated, whereas those typical of slow fibers were upregulated. Electrophoresis and Western blot showed less pronounced changes in myofibrillar protein expression, partially confirming changes in gene expression. Isometric tension of skinned fibers was little affected by denervation, whereas calcium sensitivity decreased. Functional studies in mouse extensor digitorum longus muscle showed prolongation in twitch time parameters and shift to the left in force-frequency curves after denervation. We conclude that, if studied at the mRNA level, fast muscles appear not less responsive than slow muscles to the interruption of neural stimulation.

  9. Dynamic changes in the mouse skeletal muscle proteome during denervation-induced atrophy

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    Franziska Lang

    2017-07-01

    Full Text Available Loss of neuronal stimulation enhances protein breakdown and reduces protein synthesis, causing rapid loss of muscle mass. To elucidate the pathophysiological adaptations that occur in atrophying muscles, we used stable isotope labelling and mass spectrometry to quantify protein expression changes accurately during denervation-induced atrophy after sciatic nerve section in the mouse gastrocnemius muscle. Additionally, mice were fed a stable isotope labelling of amino acids in cell culture (SILAC diet containing 13C6-lysine for 4, 7 or 11 days to calculate relative levels of protein synthesis in denervated and control muscles. Ubiquitin remnant peptides (K-ε-GG were profiled by immunoaffinity enrichment to identify potential substrates of the ubiquitin-proteasomal pathway. Of the 4279 skeletal muscle proteins quantified, 850 were differentially expressed significantly within 2 weeks after denervation compared with control muscles. Moreover, pulse labelling identified Lys6 incorporation in 4786 proteins, of which 43 had differential Lys6 incorporation between control and denervated muscle. Enrichment of diglycine remnants identified 2100 endogenous ubiquitination sites and revealed a metabolic and myofibrillar protein diglycine signature, including myosin heavy chains, myomesins and titin, during denervation. Comparative analysis of these proteomic data sets with known atrogenes using a random forest approach identified 92 proteins subject to atrogene-like regulation that have not previously been associated directly with denervation-induced atrophy. Comparison of protein synthesis and proteomic data indicated that upregulation of specific proteins in response to denervation is mainly achieved by protein stabilization. This study provides the first integrated analysis of protein expression, synthesis and ubiquitin signatures during muscular atrophy in a living animal.

  10. The effect of renal denervation in an experimental model of chronic renal insufficiency, The REmnant kidney Denervation In Pigs study (REDIP study

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    Jean-Claude Lubanda

    2017-10-01

    Full Text Available Abstract Background Renal denervation (RDN is a promising therapeutic method in cardiology. Its currently most investigated indication is resistant hypertension. Other potential indications are atrial fibrillation, type 2 diabetes mellitus and chronic renal insufficiency among others. Previous trials showed conflicting but promising results, but the real benefits of RDN are still under investigation. Patients with renal insufficiency and resistant hypertension are proposed to be a good target for this therapy due to excessive activation of renal sympathetic drive. However, only limited number of studies showed benefits for these patients. We hypothesize that in our experimental model of chronic kidney disease (CKD due to ischemia with increased activity of the renin–angiotensin–aldosterone system (RAAS, renal denervation can have protective effects by slowing or blocking the progression of renal injury. Methods An experimental biomodel of chronic renal insufficiency induced by ischemia was developed using selective renal artery embolization (remnant kidney porcine model. 27 biomodels were assessed. Renal denervation was performed in 19 biomodels (denervated group, and the remaining were used as controls (n = 8. The extent of renal injury and reparative process between the two groups were compared and assessed using biochemical parameters and histological findings. Results Viable remnant kidney biomodels were achieved and maintained in 27 swine. There were no significant differences in biochemical parameters between the two groups at baseline. Histological assessment proved successful RDN procedure in all biomodels in the denervated group. Over the 7-week period, there were significant increases in serum urea, creatinine, and aldosterone concentration in both groups. The difference in urea and creatinine levels were not statistically significant between the two groups. However, the level of aldosterone in the denervated was significantly

  11. Impact of renal denervation on 24-hour ambulatory blood pressure: results from SYMPLICITY HTN-3.

    Science.gov (United States)

    Bakris, George L; Townsend, Raymond R; Liu, Minglei; Cohen, Sidney A; D'Agostino, Ralph; Flack, John M; Kandzari, David E; Katzen, Barry T; Leon, Martin B; Mauri, Laura; Negoita, Manuela; O'Neill, William W; Oparil, Suzanne; Rocha-Singh, Krishna; Bhatt, Deepak L

    2014-09-16

    Prior studies of catheter-based renal artery denervation have not systematically performed ambulatory blood pressure monitoring (ABPM) to assess the efficacy of the procedure. SYMPLICITY HTN-3 (Renal Denervation in Patients With Uncontrolled Hypertension) was a prospective, blinded, randomized, sham-controlled trial. The current analysis details the effect of renal denervation or a sham procedure on ABPM measurements 6 months post-randomization. Patients with resistant hypertension were randomized 2:1 to renal denervation or sham control. Patients were on a stable antihypertensive regimen including maximally tolerated doses of at least 3 drugs including a diuretic before randomization. The powered secondary efficacy endpoint was a change in mean 24-h ambulatory systolic blood pressure (SBP). Nondipper to dipper (nighttime blood pressure [BP] 10% to 20% lower than daytime BP) conversion was calculated at 6 months. The 24-h ambulatory SBP changed -6.8 ± 15.1 mm Hg in the denervation group and -4.8 ± 17.3 mm Hg in the sham group: difference of -2.0 mm Hg (95% confidence interval [CI]: -5.0 to 1.1; p = 0.98 with a 2 mm Hg superiority margin). The daytime ambulatory SBP change difference between groups was -1.1 (95% CI: -4.3 to 2.2; p = 0.52). The nocturnal ambulatory SBP change difference between groups was -3.3 (95 CI: -6.7 to 0.1; p = 0.06). The percent of nondippers converted to dippers was 21.2% in the denervation group and 15.0% in the sham group (95% CI: -3.8% to 16.2%; p = 0.30). Change in 24-h heart rate was -1.4 ± 7.4 in the denervation group and -1.3 ± 7.3 in the sham group; (95% CI: -1.5 to 1.4; p = 0.94). This trial did not demonstrate a benefit of renal artery denervation on reduction in ambulatory BP in either the 24-h or day and night periods compared with sham (Renal Denervation in Patients With Uncontrolled Hypertension [SYMPLICITY HTN-3]; NCT01418261). Copyright © 2014 American College of Cardiology Foundation. Published by

  12. Cooled radiofrequency denervation for treatment of sacroiliac joint pain: two-year results from 20 cases

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    Ho, Kok-Yuen; Hadi, Mohamed Abdul; Pasutharnchat, Koravee; Tan, Kian-Hian

    2013-01-01

    Background Sacroiliac joint pain is a common cause of chronic low back pain. Different techniques for radiofrequency denervation of the sacroiliac joint have been used to treat this condition. However, results have been inconsistent because the variable sensory supply to the sacroiliac joint is difficult to disrupt completely using conventional radiofrequency. Cooled radiofrequency is a novel technique that uses internally cooled radiofrequency probes to enlarge lesion size, thereby increasing the chance of completely denervating the sacroiliac joint. The objective of this study was to evaluate the efficacy of cooled radiofrequency denervation using the SInergy™ cooled radiofrequency system for sacroiliac joint pain. Methods The charts of 20 patients with chronic sacroiliac joint pain who had undergone denervation using the SInergy™ cooled radiofrequency system were reviewed at two years following the procedure. Outcome measures included the Numeric Rating Scale for pain intensity, Patient Global Impression of Change, and Global Perceived Effect for patient satisfaction. Results Fifteen of 20 patients showed a significant reduction in pain (a decrease of at least three points on the Numeric Rating Scale). Mean Numeric Rating Scale for pain decreased from 7.4 ± 1.4 to 3.1 ± 2.5, mean Patient Global Impression of Change was “improved” (1.4 ± 1.5), and Global Perceived Effect was reported to be positive in 16 patients at two years following the procedure. Conclusion Cooled radiofrequency denervation showed long-term efficacy for up to two years in the treatment of sacroiliac joint pain. PMID:23869175

  13. Interaction of thyroid state and denervation on skeletal myosin heavy chain expression

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    Haddad, F.; Arnold, C.; Zeng, M.; Baldwin, K.

    1997-01-01

    The goal of this study was to examine the effects of altered thyroid state and denervation (Den) on skeletal myosin heavy chain (MHC) expression in the plantaris and soleus muscles. Rats were subjected to unilateral denervation (Den) and randomly assigned to one of three groups: (1) euthyroid; (2) hyperthyroid; (3) and hypothyroid. Denervation caused severe muscle atrophy and muscle-type specific MHC transformation. Denervation transformed the soleus to a faster muscle, and its effects required the presence of circulating thyroid hormone. In contrast, denervation transformed the plantaris to a slower muscle independently of thyroid state. Furthermore, thyroid hormone effects did not depend upon innervation status in the soleus, while they required the presence of the nerve in the plantaris. Collectively, these findings suggest that both thyroid hormone and intact nerve (a) differentially affect MHC transformations in fast and slow muscle; and (b) are important factors in regulating the optimal expression of both type I and IIB MHC genes. This research suggests that for patients with nerve damage and/or paralysis, both muscle mass and biochemical properties can also be affected by the thyroid state.

  14. Functional recovery of denervated skeletal muscle with sensory or mixed nerve protection: a pilot study.

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    Qing Tian Li

    Full Text Available Functional recovery is usually poor following peripheral nerve injury when reinnervation is delayed. Early innervation by sensory nerve has been indicated to prevent atrophy of the denervated muscle. It is hypothesized that early protection with sensory axons is adequate to improve functional recovery of skeletal muscle following prolonged denervation of mixed nerve injury. In this study, four groups of rats received surgical denervation of the tibial nerve. The proximal and distal stumps of the tibial nerve were ligated in all animals except for those in the immediate repair group. The experimental groups underwent denervation with nerve protection of peroneal nerve (mixed protection or sural nerve (sensory protection. The experimental and unprotected groups had a stage II surgery in which the trimmed proximal and distal tibial nerve stumps were sutured together. After 3 months of recovery, electrophysiological, histological and morphometric parameters were assessed. It was detected that the significant muscle atrophy and a good preserved structure of the muscle were observed in the unprotected and protective experimental groups, respectively. Significantly fewer numbers of regenerated myelinated axons were observed in the sensory-protected group. Enhanced recovery in the mixed protection group was indicated by the results of the muscle contraction force tests, regenerated myelinated fiber, and the results of the histological analysis. Our results suggest that early axons protection by mixed nerve may complement sensory axons which are required for promoting functional recovery of the denervated muscle natively innervated by mixed nerve.

  15. Diffusion-weighted MRI of denervated muscle: a clinical and experimental study

    International Nuclear Information System (INIS)

    Holl, Nathalie; Bierry, Guillaume; Moser, Thomas; Dietemann, Jean-Louis; Kremer, Stephane; Echaniz-Laguna, Andoni; Mohr, Michel; Loeffler, Jean-Philippe

    2008-01-01

    The aim of this study was to investigate skeletal muscle denervation using diffusion-weighted magnetic resonance imaging (DWMRI). Sciatic nerve axotomy was performed in a group of nine New Zealand White rabbits, and electromyographic (EMG), pathological, and DWMRI studies were conducted on ipsilateral hamstring muscles 1 and 8 days after axotomy. In addition, DWMRI studies were carried out on leg muscles of ten patients with acute and subacute lumbosacral radiculopathy. High intensity signals on short tau inversion recovery (STIR) magnetic resonance imaging and an increased apparent diffusion coefficient (ADC) were observed in denervated muscles of the animals 1 and 8 days after axotomy as well as in denervated muscles of the patients with radiculopathy. In the clinical study, ADC was 1.26±0.18 x 10 -9 m 2 /s in normal muscle and increased to 1.56±0.23 x 10 -9 m 2 /s in denervated muscles (p =0.0016). In animals, EMG and muscle pathological studies were normal 1 day after axotomy, and the muscles demonstrated spontaneous activity on EMG and neurogenic atrophy on histological studies 7 days later. This DWMRI study demonstrates that enlargement of extracellular fluid space in muscle denervation is an early phenomenon occurring several days before the appearance of EMG and histological abnormalities. (orig.)

  16. Parasympathetic denervation increases responses to VIP in isolated rat parotid acini

    International Nuclear Information System (INIS)

    McMillian, M.K.; Talamo, B.R.

    1989-01-01

    Vasoactive intestinal peptide (VIP) is a putative neurotransmitter found in the salivary glands of many species, including the rat parotid gland. Parasympathetic denervation has been reported to deplete VIP in the rat parotid gland and to lead to supersensitivity to this peptide in vivo. We have compared the effects of VIP on acini isolated from parasympathetically denervated and unoperated parotid glands to examine possible supersensitivity to the peptide in vitro. VIP normally produced responses similar to those obtained with a low concentration of the beta adrenergic agonist isoproterenol (ISO), but strikingly different from the effects obtained with the muscarinic agonist carbachol (CARB). In parotid membrane preparations, VIP stimulated adenylate cyclase activity. Dissociated acini treated with VIP showed increases in cAMP accumulation and amylase release which were potentiated by forskolin and also by inhibition of phosphodiesterase. After parasympathetic denervation, maximal effects of VIP on adenylate cyclase, cAMP accumulation and amylase release in intact cells were increased two- to five-fold over contralateral control (or unoperated) parotid responses. The increase in adenylate cyclase-mediated responses after denervation was specific to VIP; there was no increased response nor increased sensitivity of any of these responses to ISO. Specific [125I]VIP binding to parotid acini increased two-fold per gland and three-fold per mg of protein after denervation; this probably explains the observed increases in the response to VIP

  17. Renal denervation therapy for hypertension: Current and future perspectives

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    Mohd Aslam Khan

    2016-01-01

    Full Text Available Hypertension (HTN is the most common chronic cardiovascular disease with increasing prevalence and morbidity in India as well as worldwide. Despite the availability of different effective subgroups of antihypertensive drugs, few patients may not respond and causes significant morbidity. Resistant HTN is defined as blood pressure above target goals in patients using three different antihypertensive drugs in maximum tolerated doses, including a diuretic. Prevalence of resistant HTN varies from 8% to 18% of all hypertensives. Increased sympathetic nervous system activity has been identified as one potential cause for resistant HTN. Catheter-based renal denervation (RDN has been studied in different subgroups of patients for the treatment of resistant HTN. Clinical data for usefulness of RDN till date show mixed results, and overall indications for procedure are unclear. Different observational studies and randomized, controlled trials (Symplicity HTN-2, Prague-15, RSD-LEIPZIG, and DENERHTN support both safety and efficacy of procedure, whereas some smaller studies and large Symplicity HTN-3 trial failed to show the superiority of RDN when compared to medical therapy alone. The aim of the present review is to provide an overview of RDN therapy in the treatment of HTN and current status of this procedure in management of such patients.

  18. Feasibility of catheter ablation renal denervation in "mild" resistant hypertension.

    Science.gov (United States)

    Chen, Shaojie; Kiuchi, Marcio Galindo; Acou, Willem-Jan; Derndorfer, Michael; Wang, Jiazhi; Li, Ruotian; Kollias, Georgios; Martinek, Martin; Kiuchi, Tetsuaki; Pürerfellner, Helmut; Liu, Shaowen

    2017-04-01

    Renal denervation (RDN) has been proposed as a novel interventional antihypertensive technique. However, existing evidence was mainly from patients with severe resistant hypertension. The authors aimed to evaluate the efficacy of RDN in patients with resistant hypertension with mildly elevated blood pressure (BP). Studies of RDN in patients with mild resistant hypertension (systolic office BP 140-160 mm Hg despite treatment with three antihypertensive drugs including one diuretic, or mean systolic BP by 24-hour ambulatory BP measurement [ABPM] 135-150 mm Hg) were included. Two observational and one randomized cohort were identified (109 patients in the RDN group and 36 patients in the control group). Overall, the mean age of patients was 62±10 years, and 69.7% were male. Before-after comparison showed that RDN significantly reduced ABPM as compared with the baseline systolic ABPM, from 146.3±13 mm Hg at baseline to 134.6±14.7 mm Hg at 6-month follow-up and diastolic ABPM from 80.8±9.4 mm Hg at baseline to 75.5±9.8 mm Hg at 6-month follow up (both Phypertension. ©2017 Wiley Periodicals, Inc.

  19. Suppressed serum prolactin in sinoaortic-denervated rats

    International Nuclear Information System (INIS)

    Alexander, N.; Melmed, S.; Morris, M.

    1987-01-01

    The authors investigated the effect of arterial baroreceptor deafferentation on serum and pituitary prolactin (PRL) and on catecholamines in median eminence (ME) and anterior and posterior pituitaries. Male Wistar rats were sinoaortic denervated (SAD) or sham operated (SO). Three days after surgery serum prolactin, measured by radioimmunoassay, was suppressed in SAD rats, and dopamine (DA) and norepinephrine (NE) concentrations, measured by radioenzymatic or high-performance liquid chromatography electron capture methods, were significantly reduced in ME of SAD rats. Simultaneously, anterior pituitary of SAD rats had significant increases in both catecholamines, whereas posterior pituitary showed no changes. Four hours after surgery serum PRL was also reduced in SAD rats, but no changes in ME catecholamines were found. Mean arterial pressure (MAP) and heart rate were measured before and after injection of bromocriptine in SAD and SO rats 3 days after surgery. Bromocriptine markedly suppressed serum PRL in both groups and reduced MAP from 144 +/- 10 to 84 +/- 5 and from 116 +/- 2 to 99 +/- 3 in SAD and SO rats, respectively; heart rate was reduced in SAD rats. They conclude that the SAD rat is a model of hypertension with suppressed serum PRL and that interruption of arterial baroreceptor nerves suppresses PRL secretion probably by modulating tuberoinfundibular turnover of catecholamines

  20. Functional Echomyography: thickness, ecogenicity, contraction and perfusion of the LMN denervated human muscle before and during h-bFES

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    Riccardo Zanato

    2010-03-01

    Full Text Available Permanent denervated muscles were evaluated by ultrasound to monitor changes in morphology, thickness, contraction-relaxation kinetics and perfusion due to the electrical stimulation program of the Rise2-Italy project. In a case of monolateral lesion, morphology and ultrasonographic structure of the denervated muscles changed during the period of stimulation from a pattern typical of complete denervation-induced muscle atrophy to a pattern which might be considered “normal” when detected in an old patient. Thickness improved significantly more in the middle third of the denervated muscle, reaching the same value as the contralateral innervated muscle. Contraction-relaxation kinetics, measured by recording the muscle movements during electrical stimulation, showed an abnormal behavior of the chronically denervated muscle during the relaxation phase, which resulted to be significantly longer than in normal muscle. The long-term denervated muscles analyzed with Echo Doppler showed at rest a low resistance arterial flow that became pulsed during and after electrical stimulation. As expected, the ultra sound measured electrical stimulation-induced hyperemia lasted longer than the stimulation period. The higher than normal energy of the delivered electrical stimuli of the Vienna home-based Functional Electrical Stimulation strategy (h-b FES demonstrate that the explored muscles were still almost completely denervated during the one-year of training. In conclusion, this pilot study confirms the usefulness of Functional Echomyography in the follow-up and the positive effects of h-b FES of denervated muscles.

  1. Renal denervation and hypertension - The need to investigate unintended effects and neural control of the human kidney.

    Science.gov (United States)

    Grisk, Olaf

    2017-05-01

    Increased renal sympathetic nerve activity (RSNA) is present in human and experimental forms of arterial hypertension. Experimental denervation studies showed that renal nerves contribute to the development of hypertension. Clinical trials provided equivocal results on the antihypertensive efficacy of renal denervation in patients spurring discussions on technical aspects of renal denervation and further research on the role of renal nerves for the regulation of kidney function as well as the pathophysiology of hypertension. This review summarizes recent findings on adrenoceptor expression and function in the human kidney, adrenoceptor-dependent regulation of sodium chloride transport in the distal nephron, experimental data on chronic RSNA and the development of high arterial pressure and consequences of renal denervation that may limit its antihypertensive efficacy. Future research needs to reduce the gap between our knowledge on neural control of renal function in animals vs. humans to facilitate translation of experimental animal data to humans. More experimental studies on the temporal relationship between RSNA and arterial pressure in the chronic setting are needed to better define the pathogenetic role of heightened RSNA in different forms of arterial hypertension in order to improve the rational basis for renal denervation in antihypertensive therapy. Finally, research on unintended consequences of renal denervation including but not limited to reinnervation and denervation supersensitivity needs to be intensified to further assess the potential of renal denervation to slow the progression of renal disease and hypertension. Copyright © 2016 Elsevier B.V. All rights reserved.

  2. Renal Denervation for Treating Resistant Hypertension: Current Evidence and Future Insights from a Global Perspective

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    Y. Castro Torres

    2013-01-01

    Full Text Available Adequate blood pressure control represents an important goal for all physicians due to the complications of hypertension which reduce patients' quality of life. A new interventional strategy to reduce blood pressure has been developed for patients with resistant hypertension. Catheter-based renal denervation has demonstrated excellent results in recent investigations associated with few side effects. With the growing diffusion of this technique worldwide, some medical societies have published consensus statements to guide physicians how to best apply this procedure. Questions remain to be answered such as the long-term durability of renal denervation, the efficacy in patients with other sympathetically mediated diseases, and whether renal denervation would benefit patients with stage 1 hypertension.

  3. Randomized sham-controlled trial of renal sympathetic denervation in mild resistant hypertension.

    Science.gov (United States)

    Desch, Steffen; Okon, Thomas; Heinemann, Diana; Kulle, Konrad; Röhnert, Karoline; Sonnabend, Melanie; Petzold, Martin; Müller, Ulrike; Schuler, Gerhard; Eitel, Ingo; Thiele, Holger; Lurz, Philipp

    2015-06-01

    Few data are available with regard to the effectiveness of renal sympathetic denervation in patients with resistant hypertension yet only mildly elevated blood pressure (BP). Patients with resistant hypertension and slightly elevated BP (day-time systolic pressure, 135-149 and diastolic pressure, 90-94 mm Hg on 24-hour ambulatory measurement) were randomized in a 1:1 ratio to renal sympathetic denervation with the Symplicity Flex Catheter (Medtronic) or an invasive sham procedure. The primary efficacy end point was the change in 24-hour systolic BP at 6 months between groups in the intention to treat population. A total of 71 patients underwent randomization. Baseline day-time systolic BP was 144.4±4.8 mm Hg in patients assigned to denervation and 143.0±4.7 mm Hg in patients randomized to the sham procedure. The mean change in 24-hour systolic BP in the intention to treat cohort at 6 months was -7.0 mm Hg (95% confidence interval, -10.8 to -3.2) for patients undergoing denervation and -3.5 mm Hg (95% confidence interval, -6.7 to -0.2) in the sham group (P=0.15). In the per protocol population, the change in 24-hour systolic BP at 6 months was -8.3 mm Hg (95% confidence interval, -11.7 to -5.0) for patients undergoing denervation and -3.5 mm Hg (95% confidence interval, -6.8 to -0.2) in the sham group (P=0.042). In patients with mild resistant hypertension, renal sympathetic denervation failed to show a significant reduction in the primary end point of 24-hour systolic BP at 6 months between groups in the intention to treat analysis. URL: http://www.clinicaltrials.gov. Unique identifier: NCT01656096. © 2015 American Heart Association, Inc.

  4. Improved sphincter contractility after allogenic muscle-derived progenitor cell injection into the denervated rat urethra.

    Science.gov (United States)

    Cannon, Tracy W; Lee, Ji Youl; Somogyi, George; Pruchnic, Ryan; Smith, Christopher P; Huard, Johnny; Chancellor, Michael B

    2003-11-01

    To study the physiologic outcome of allogenic transplant of muscle-derived progenitor cells (MDPCs) in the denervated female rat urethra. MDPCs were isolated from muscle biopsies of normal 6-week-old Sprague-Dawley rats and purified using the preplate technique. Sciatic nerve-transected rats were used as a model of stress urinary incontinence. The experimental group was divided into three subgroups: control, denervated plus 20 microL saline injection, and denervated plus allogenic MDPCs (1 to 1.5 x 10(6) cells) injection. Two weeks after injection, urethral muscle strips were prepared and underwent electrical field stimulation. The pharmacologic effects of d-tubocurare, phentolamine, and tetrodotoxin on the urethral strips were assessed by contractions induced by electrical field stimulation. The urethral tissues also underwent immunohistochemical staining for fast myosin heavy chain and CD4-activated lymphocytes. Urethral denervation resulted in a significant decrease of the maximal fast-twitch muscle contraction amplitude to only 8.77% of the normal urethra and partial impairment of smooth muscle contractility. Injection of MDPCs into the denervated sphincter significantly improved the fast-twitch muscle contraction amplitude to 87.02% of normal animals. Immunohistochemistry revealed a large amount of new skeletal muscle fiber formation at the injection site of the urethra with minimal inflammation. CD4 staining showed minimal lymphocyte infiltration around the MDPC injection sites. Urethral denervation resulted in near-total abolishment of the skeletal muscle and partial impairment of smooth muscle contractility. Allogenic MDPCs survived 2 weeks in sciatic nerve-transected urethra with minimal inflammation. This is the first report of the restoration of deficient urethral sphincter function through muscle-derived progenitor cell tissue engineering. MDPC-mediated cellular urethral myoplasty warrants additional investigation as a new method to treat stress urinary

  5. Adherence to Antihypertensive Treatment and the Blood Pressure-Lowering Effects of Renal Denervation in the Renal Denervation for Hypertension (DENERHTN) Trial.

    Science.gov (United States)

    Azizi, Michel; Pereira, Helena; Hamdidouche, Idir; Gosse, Philippe; Monge, Matthieu; Bobrie, Guillaume; Delsart, Pascal; Mounier-Véhier, Claire; Courand, Pierre-Yves; Lantelme, Pierre; Denolle, Thierry; Dourmap-Collas, Caroline; Girerd, Xavier; Michel Halimi, Jean; Zannad, Faiez; Ormezzano, Olivier; Vaïsse, Bernard; Herpin, Daniel; Ribstein, Jean; Chamontin, Bernard; Mourad, Jean-Jacques; Ferrari, Emile; Plouin, Pierre-François; Jullien, Vincent; Sapoval, Marc; Chatellier, Gilles

    2016-09-20

    The DENERHTN trial (Renal Denervation for Hypertension) confirmed the blood pressure-lowering efficacy of renal denervation added to a standardized stepped-care antihypertensive treatment for resistant hypertension at 6 months. We report the influence of adherence to antihypertensive treatment on blood pressure control. One hundred six patients with hypertension resistant to 4 weeks of treatment with indapamide 1.5 mg/d, ramipril 10 mg/d (or irbesartan 300 mg/d), and amlodipine 10 mg/d were randomly assigned to renal denervation plus standardized stepped-care antihypertensive treatment, or the same antihypertensive treatment alone. For standardized stepped-care antihypertensive treatment, spironolactone 25 mg/d, bisoprolol 10 mg/d, prazosin 5 mg/d, and rilmenidine 1 mg/d were sequentially added at monthly visits if home blood pressure was ≥135/85 mm Hg after randomization. We assessed adherence to antihypertensive treatment at 6 months by drug screening in urine/plasma samples from 85 patients. The numbers of fully adherent (20/40 versus 21/45), partially nonadherent (13/40 versus 20/45), or completely nonadherent patients (7/40 versus 4/45) to antihypertensive treatment were not different in the renal denervation and the control groups, respectively (P=0.3605). The difference in the change in daytime ambulatory systolic blood pressure from baseline to 6 months between the 2 groups was -6.7 mm Hg (P=0.0461) in fully adherent and -7.8 mm Hg (P=0.0996) in nonadherent (partially nonadherent plus completely nonadherent) patients. The between-patient variability of daytime ambulatory systolic blood pressure was greater for nonadherent than for fully adherent patients. In the DENERHTN trial, the prevalence of nonadherence to antihypertensive drugs at 6 months was high (≈50%) but not different in the renal denervation and control groups. Regardless of adherence to treatment, renal denervation plus standardized stepped-care antihypertensive treatment resulted in

  6. Glucose turnover during insulin-induced hypoglycemia in liver-denervated rats

    DEFF Research Database (Denmark)

    Mikines, K J; Sonne, B; Richter, Erik

    1985-01-01

    The role of hepatic autonomic nerves in glucose production during hypoglycemia was studied. Selective, surgical denervation of the liver was performed in rats, which reduced hepatic norepinephrine concentrations by 96%. Hypoglycemia was induced by 250 mU of insulin intra-arterially in anesthetized...... as well as in chronically catheterized, awake rats. Half of the anesthetized denervated or sham-operated rats had previously been adrenodemedullated. Glucose turnover was measured by primed, constant intravenous infusion of [3-3H]glucose. Before as well as during hypoglycemia the arterial glucose...

  7. Leucine minimizes denervation-induced skeletal muscle atrophy of rats through akt/mtor signaling pathways

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    Carolina Barbosa Ribeiro

    2015-03-01

    Full Text Available The aim of the present study was to evaluate the effect of leucine treatment (0.30 mM on muscle weight and signaling of myoproteins related to synthesis and degradation pathways of soleus muscle following seven days of complete sciatic nerve lesion.Wistar rats (n=24 of 3 to 4 months of age (192 ± 23 g were used. The animals were randomly distributed into four experimental groups (n=6/group: control, treated with leucine (L, denervated (D and denervated treated with leucine (DL.Dependent measures were proteins levels of AKT, AMPK, mTOR, and ACC performed by Western blot. Leucine induced a reduction in the phosphorylation of AMPK (p<0.05 by 16% in the L and by 68% in the DL groups as compared with control group. Denervation increased AMPK by 24% in the D group as compared with the control group (p<0.05. AKT was also modulated by denervation and leucine treatment, highlighted by the elevation of AKT phosphorylation in the D (65%, L (98% and DL (146% groups as compared with the control group (p<0.05. AKT phosphorylation was 49% higher in the D group as compared with the DL group.Furthermore, denervation decreased mTOR phosphorylation by 29% in the D group as compared with the control group. However, leucine treatment induced an increase of 49% in the phosphorylation of mTOR in the L group as compared with the control group, and an increase of 154% in the DL as compared with the D group ( p<0.05. ACC phosphorylation was 20% greater in the D group than the control group. Furthermore, ACC in the soleus was 22% lower in the in the L group and 50% lower in the DL group than the respective control group (p<0.05.In conclusion, leucine treatment minimized the deleterious effects of denervation on rat soleus muscle by increasing anabolic (AKT and mTOR and decreasing catabolic (AMPK pathways. These results may be interesting for muscle recovery following acute denervation, which may contribute to musculoskeletal rehabilitation after denervation.

  8. Cholinergic denervation of the hippocampal formation does not produce long-term changes in glucose metabolism

    International Nuclear Information System (INIS)

    Harrell, L.E.; Davis, J.N.

    1984-01-01

    Decreased glucose metabolism is found in Alzheimer's disease associated with a loss of cholinergic neurons. The relationship between the chronic cholinergic denervation produced by medial septal lesions and glucose metabolism was studied using 2-deoxy-D-[ 3 H]glucose in the rat hippocampal formation. Hippocampal glucose metabolism was increased 1 week after medial septal lesions. Three weeks after lesions, glucose metabolism was profoundly suppressed in all regions. By 3 months, intraregional hippocampal glucose metabolism had returned to control values. Our results demonstrate that chronic cholinergic denervation of the hippocampal formation does not result in permanent alterations of metabolic activity

  9. Does Renal Artery Supply Indicate Treatment Success of Renal Denervation?

    International Nuclear Information System (INIS)

    Schmid, Axel; Ditting, Tilmann; Sobotka, Paul A.; Veelken, Roland; Schmieder, Roland E.; Uder, Michael; Ott, Christian

    2013-01-01

    PurposeRenal denervation (RDN) emerged as an innovative interventional antihypertensive therapy. With the exception of pretreatment blood pressure (BP) level, no other clear predictor for treatment efficacy is yet known. We analyzed whether the presence of multiple renal arteries has an impact on BP reduction after RDN.MethodsFifty-three patients with treatment-resistant hypertension (office BP ≥ 140/90 mmHg and 24-h ambulatory BP monitoring (≥130/80 mmHg) underwent bilateral catheter-based RDN. Patients were stratified into one-vessel (OV) (both sides) and at least multivessel (MV) supply at one side. Both groups were treated on one vessel at each side; in case of multiple arteries, only the dominant artery was treated on each side.ResultsBaseline clinical characteristics (including BP, age, and estimated glomerular filtration rate) did not differ between patients with OV (n = 32) and MV (n = 21). Office BP was significantly reduced in both groups at 3 months (systolic: OV −15 ± 23 vs. MV −16 ± 20 mmHg; diastolic: OV −10 ± 12 vs. MV −8 ± 11 mmHg, both p = NS) as well as 6 months (systolic: OV −18 ± 18 vs. MV −17 ± 22 mmHg; diastolic: OV −10 ± 10 vs. −10 ± 12 mmHg, both p = NS) after RDN. There was no difference in responder rate (rate of patients with office systolic BP reduction of at least 10 mmHg after 6 months) between the groups.ConclusionIn patients with multiple renal arteries, RDN of one renal artery—namely, the dominant one—is sufficient to induce BP reduction in treatment-resistant hypertension

  10. Does Renal Artery Supply Indicate Treatment Success of Renal Denervation?

    Energy Technology Data Exchange (ETDEWEB)

    Schmid, Axel, E-mail: axel.schmid@uk-erlangen.de [University of Erlangen-Nuremberg, Department of Radiology (Germany); Ditting, Tilmann, E-mail: tilmann.ditting@uk-erlangen.de [University of Erlangen-Nuremberg, Department of Nephrology and Hypertension (Germany); Sobotka, Paul A., E-mail: sobotka@alumni.stanford.edu [Ohio State University (United States); Veelken, Roland, E-mail: roland.veelken@uk-erlangen.de; Schmieder, Roland E., E-mail: roland.schmieder@uk-erlangen.de [University of Erlangen-Nuremberg, Department of Nephrology and Hypertension (Germany); Uder, Michael, E-mail: michael.uder@uk-erlangen.de [University of Erlangen-Nuremberg, Department of Radiology (Germany); Ott, Christian, E-mail: christian.ott@uk-erlangen.de [University of Erlangen-Nuremberg, Department of Nephrology and Hypertension (Germany)

    2013-08-01

    PurposeRenal denervation (RDN) emerged as an innovative interventional antihypertensive therapy. With the exception of pretreatment blood pressure (BP) level, no other clear predictor for treatment efficacy is yet known. We analyzed whether the presence of multiple renal arteries has an impact on BP reduction after RDN.MethodsFifty-three patients with treatment-resistant hypertension (office BP {>=} 140/90 mmHg and 24-h ambulatory BP monitoring ({>=}130/80 mmHg) underwent bilateral catheter-based RDN. Patients were stratified into one-vessel (OV) (both sides) and at least multivessel (MV) supply at one side. Both groups were treated on one vessel at each side; in case of multiple arteries, only the dominant artery was treated on each side.ResultsBaseline clinical characteristics (including BP, age, and estimated glomerular filtration rate) did not differ between patients with OV (n = 32) and MV (n = 21). Office BP was significantly reduced in both groups at 3 months (systolic: OV -15 {+-} 23 vs. MV -16 {+-} 20 mmHg; diastolic: OV -10 {+-} 12 vs. MV -8 {+-} 11 mmHg, both p = NS) as well as 6 months (systolic: OV -18 {+-} 18 vs. MV -17 {+-} 22 mmHg; diastolic: OV -10 {+-} 10 vs. -10 {+-} 12 mmHg, both p = NS) after RDN. There was no difference in responder rate (rate of patients with office systolic BP reduction of at least 10 mmHg after 6 months) between the groups.ConclusionIn patients with multiple renal arteries, RDN of one renal artery-namely, the dominant one-is sufficient to induce BP reduction in treatment-resistant hypertension.

  11. Integrative Blood Pressure Response to Upright Tilt Post Renal Denervation

    Science.gov (United States)

    Howden, Erin J.; East, Cara; Lawley, Justin S.; Stickford, Abigail S.L.; Verhees, Myrthe; Fu, Qi

    2017-01-01

    Abstract BACKGROUND Whether renal denervation (RDN) in patients with resistant hypertension normalizes blood pressure (BP) regulation in response to routine cardiovascular stimuli such as upright posture is unknown. We conducted an integrative study of BP regulation in patients with resistant hypertension who had received RDN to characterize autonomic circulatory control. METHODS Twelve patients (60 ± 9 [SD] years, n = 10 males) who participated in the Symplicity HTN-3 trial were studied and compared to 2 age-matched normotensive (Norm) and hypertensive (unmedicated, HTN) control groups. BP, heart rate (HR), cardiac output (Qc), muscle sympathetic nerve activity (MSNA), and neurohormonal variables were measured supine, and 30° (5 minutes) and 60° (20 minutes) head-up-tilt (HUT). Total peripheral resistance (TPR) was calculated from mean arterial pressure and Qc. RESULTS Despite treatment with RDN and 4.8 (range, 3–7) antihypertensive medications, the RDN had significantly higher supine systolic BP compared to Norm and HTN (149 ± 15 vs. 118 ± 6, 108 ± 8 mm Hg, P < 0.001). When supine, RDN had higher HR, TPR, MSNA, plasma norepinephrine, and effective arterial elastance compared to Norm. Plasma norepinephrine, Qc, and HR were also higher in the RDN vs. HTN. During HUT, BP remained higher in the RDN, due to increases in Qc, plasma norepinephrine, and aldosterone. CONCLUSION We provide evidence of a possible mechanism by which BP remains elevated post RDN, with the observation of increased Qc and arterial stiffness, as well as plasma norepinephrine and aldosterone levels at approximately 2 years post treatment. These findings may be the consequence of incomplete ablation of sympathetic renal nerves or be related to other factors. PMID:28338768

  12. Persistent muscle fiber regeneration in long term denervation. Past, present, future

    Directory of Open Access Journals (Sweden)

    Ugo Carraro

    2015-03-01

    Full Text Available Despite the ravages of long term denervation there is structural and ultrastructural evidence for survival of muscle fibers in mammals, with some fibers surviving at least ten months in rodents and 3-6 years in humans. Further, in rodents there is evidence that muscle fibers may regenerate even after repeated damage in the absence of the nerve, and that this potential is maintained for several months after denervation. While in animal models permanently denervated muscle sooner or later loses the ability to contract, the muscles may maintain their size and ability to function if electrically stimulated soon after denervation. Whether in mammals, humans included, this is a result of persistent de novo formation of muscle fibers is an open issue we would like to explore in this review. During the past decade, we have studied muscle biopsies from the quadriceps muscle of Spinal Cord Injury (SCI patients suffering with Conus and Cauda Equina syndrome, a condition that fully and irreversibly disconnects skeletal muscle fibers from their damaged innervating motor neurons. We have demonstrated that human denervated muscle fibers survive years of denervation and can be rescued from severe atrophy by home-based Functional Electrical Stimulation (h-bFES. Using immunohistochemistry with both non-stimulated and the h-bFES stimulated human muscle biopsies, we have observed the persistent presence of muscle fibers which are positive to labeling by an antibody which specifically recognizes the embryonic myosin heavy chain (MHCemb. Relative to the total number of fibers present, only a small percentage of these MHCemb positive fibers are detected, suggesting that they are regenerating muscle fibers and not pre-existing myofibers re-expressing embryonic isoforms. Although embryonic isoforms of acetylcholine receptors are known to be re-expressed and to spread from the end-plate to the sarcolemma of muscle fibers in early phases of muscle denervation, we suggest

  13. miRNA targeted signaling pathway in the early stage of denervated fast and slow muscle atrophy

    Directory of Open Access Journals (Sweden)

    Gang Li

    2016-01-01

    Full Text Available Denervation often results in skeletal muscle atrophy. Different mechanisms seem to be involved in the determination between denervated slow and fast skeletal muscle atrophy. At the epigenetic level, miRNAs are thought to be highly involved in the pathophysiological progress of denervated muscles. We used miRNA microarrays to determine miRNA expression profiles from a typical slow muscle (soleus muscle and a typical fast muscle (tibialis anterior muscle at an early denervation stage in a rat model. Results showed that miR-206, miR-195, miR-23a, and miR-30e might be key factors in the transformation process from slow to fast muscle in denervated slow muscles. Additionally, certain miRNA molecules (miR-214, miR-221, miR-222, miR-152, miR-320, and Let-7e could be key regulatory factors in the denervated atrophy process involved in fast muscle. Analysis of signaling pathway networks revealed the miRNA molecules that were responsible for regulating certain signaling pathways, which were the final targets (e.g., p38 MAPK pathway; Pax3/Pax7 regulates Utrophin and follistatin by HDAC4; IGF1/PI3K/Akt/mTOR pathway regulates atrogin-1 and MuRF1 expression via FoxO phosphorylation. Our results provide a better understanding of the mechanisms of denervated skeletal muscle pathophysiology.

  14. Expression of TGF-β1 and CTGF Is Associated with Fibrosis of Denervated Sternocleidomastoid Muscles in Mice.

    Science.gov (United States)

    Liu, Fei; Tang, Weifang; Chen, Donghui; Li, Meng; Gao, Yinna; Zheng, Hongliang; Chen, Shicai

    2016-01-01

    Injury to the recurrent laryngeal nerve often leads to permanent vocal cord paralysis, which has a significant negative impact on the quality of life. Long-term denervation can induce laryngeal muscle fibrosis, which obstructs the muscle recovery after laryngeal reinnervation. However, the mechanisms of fibrosis remain unclear. In this study, we aimed to analyze the changes in the expression of fibrosis-related factors, including transforming growth factor-β1 (TGF-β1), connective tissue growth factor (CTGF), and α-smooth muscle actin (α-SMA) in denervated skeletal muscles using a mouse model of accessory nerve transection. Because of the small size, we used sternocleidomastoid muscles instead of laryngeal muscles for denervation experiments. Masson's trichrome staining showed that the grade of atrophy and fibrosis of muscles became more severe with time, but showed a plateau at 4 weeks after denervation, followed by a slow decrease. Quantitative assessment and immunohistochemistry showed that TGF-β1 expression peaked at 1 week after denervation (p muscle cells were detected at 1 week after denervation, peaked at 2 weeks (p muscle fibrosis. They may induce the differentiation of myoblasts into myofibroblasts, as characterized by the activation of α-SMA. These findings may provide insights on key pathological processes in denervated skeletal muscle fibrosis and develop novel therapeutic strategies.

  15. Does dysfunction of the autonomic nervous system affect success of renal denervation in reducing blood pressure?

    Science.gov (United States)

    Fricke, Lisa; Petroff, David; Desch, Steffen; Lurz, Philipp; Reinhardt, Sebastian; Sonnabend, Melanie; Classen, Joseph; Baum, Petra

    2017-01-01

    Renal denervation is an interventional approach aiming to reduce high blood pressure. Its efficacy is subject of controversial debate. We analyzed autonomic function in patients undergoing renal denervation to identify responders. A total of 21 patients with treatment-resistant hypertension scheduled for renal denervation were included. Heart rate variability, pupillary function and sympathetic skin response were examined prior to intervention. Before and 1 or 3 months after intervention, 24-h ambulatory blood pressure readings were taken. Patients were stratified according to sympathetic nervous system function. Sympathetic activity was reduced in 12 participants (group 1) and normal or enhanced in nine patients (group 2). The mean of daytime systolic blood pressure decreased in groups 1 and 2 from 168 to 157 mmHg (95% confidence interval for difference, 1-21 mmHg, p = 0.035) and from 166 to 145 mmHg (8-34 mmHg, p = 0.005), respectively. In a linear model, blood pressure reduction was 11.3 mmHg (0.3-22 mmHg) greater in group 2 than in group 1 (p = 0.045). Patients with preexisting reduced activity of the sympathetic nervous system benefited less from renal denervation.

  16. Renal sympathetic denervation for treatment of patients with heart failure: summary of the available evidence.

    Science.gov (United States)

    Nammas, Wail; Koistinen, Juhani; Paana, Tuomas; Karjalainen, Pasi P

    2017-08-01

    Heart failure syndrome results from compensatory mechanisms that operate to restore - back to normal - the systemic perfusion pressure. Sympathetic overactivity plays a pivotal role in heart failure; norepinephrine contributes to maintenance of the systemic blood pressure and increasing preload. Cardiac norepinephrine spillover increases in patients with heart failure; norepinephrine exerts direct toxicity on cardiac myocytes resulting in a decrease of synthetic activity and/or viability. Importantly, cardiac norepinephrine spillover is a powerful predictor of mortality in patients with moderate to severe HF. This provided the rationale for trials that demonstrated survival benefit associated with the use of beta adrenergic blockers in heart failure with reduced ejection fraction. Nevertheless, the MOXCON trial demonstrated that rapid uptitration of moxonidine (inhibitor of central sympathetic outflow) in patients with heart failure was associated with excess mortality and morbidity, despite reduction of plasma norepinephrine. Interestingly, renal norepinephrine spillover was the only independent predictor of adverse outcome in patients with heart failure, in multivariable analysis. Recently, renal sympathetic denervation has emerged as a novel approach for control of blood pressure in patients with treatment-resistant hypertension. This article summarizes the available evidence for the effect of renal sympathetic denervation in the setting of heart failure. Key messages Experimental studies supported a beneficial effect of renal sympathetic denervation in heart failure with reduced ejection fraction. Clinical studies demonstrated improvement of symptoms, and left ventricular function. In heart failure and preserved ejection fraction, renal sympathetic denervation is associated with improvement of surrogate endpoints.

  17. Denervation syndromes of the shoulder girdle: MR imaging with electrophysiologic correlation

    International Nuclear Information System (INIS)

    Bredella, M.A.; Wischer, T.K.; Stork, A.; Genant, H.K.; Tirman, P.F.J.; Fritz, R.C.

    1999-01-01

    Objective. To investigate the use of MR imaging in the characterization of denervated muscle of the shoulder correlated with electrophysiologic studies.Design and patients. We studied with MR imaging five patients who presented with shoulder weakness and pain and who underwent electrophysiologic studies. On MR imaging the distribution of muscle edema and fatty infiltration was recorded, as was the presence of masses impinging on a regional nerve.Results. Acute/subacute denervation was best seen on T2-weighted fast spin-echo images with fat saturation, showing increased SI related to neurogenic edema. Chronic denervation was best seen on T1-weighted spin-echo images, demonstrating loss of muscle bulk and diffuse areas of increased signal intensity within the muscle. Three patients showed MR imaging and electrophysiologic findings of Parsonage Turner syndrome. One patient demonstrated an arteriovenous malformation within the spinoglenoid notch, impinging on the suprascapular nerve with associated atrophy of the infraspinatus muscle. The fifth patient demonstrated fatty atrophy of the teres minor muscle caused by compression by a cyst of the axillary nerve and electrophysiologic findings of an incomplete axillary nerve block.Conclusion. MR imaging is useful in detecting and characterizing denervation atrophy and neurogenic edema in shoulder muscles. MR imaging can provide additional information to electrophysiologic studies by estimating the age (acute/chronic) and identifying morphologic causes for shoulder pain and atrophy. (orig.)

  18. An Update on Renal Artery Denervation and Its Clinical Impact on Hypertensive Disease

    Directory of Open Access Journals (Sweden)

    Aditya Bhat

    2015-01-01

    Full Text Available Hypertension is a globally prevalent condition, with a heavy clinical and economic burden. It is the predominant risk factor for premature cardiovascular and cerebrovascular disease, and is associated with a variety of clinical disorders including stroke, congestive cardiac failure, ischaemic heart disease, chronic renal failure, and peripheral arterial disease. A significant subset of hypertensive patients have resistant hypertensive disease. In this group of patients, catheter-based renal artery denervation has emerged as a potential therapy, with favourable clinical efficacy and safety in early trials. Additional benefits of this therapy are also being identified and include effects on left ventricular remodeling, cardiac performance, and symptom status in congestive cardiac failure. Utility of renal denervation for the management of resistant hypertension, however, has become controversial since the release of the Symplicity HTN-3 trial, the first large-scale blinded randomised study investigating the efficacy and safety of renal artery denervation. The aim of this paper is to evaluate the history, utility, and clinical efficacy of renal artery denervation technology, including an in-depth appraisal of the current literature and principal trials.

  19. Rationale and design of a large registry on renal denervation: the Global SYMPLICITY registry.

    Science.gov (United States)

    Böhm, Michael; Mahfoud, Felix; Ukena, Christian; Bauer, Axel; Fleck, Eckart; Hoppe, Uta C; Kintscher, Ulrich; Narkiewicz, Krzysztof; Negoita, Manuela; Ruilope, Luis; Rump, L Christian; Schlaich, Markus; Schmieder, Roland; Sievert, Horst; Weil, Joachim; Williams, Bryan; Zeymer, Uwe; Mancia, Giuseppe

    2013-08-22

    Hypertension is a global healthcare concern associated with a wide range of comorbidities. The recognition that elevated sympathetic drive plays an important role in the pathogenesis of hypertension led to the use of renal artery denervation to interrupt the efferent and afferent sympathetic nerves between the brain and kidneys to lower blood pressure. Clinical trials of the Symplicity™ renal denervation system have demonstrated that radiofrequency ablation of renal artery nerves is safe and significantly lowers blood pressure in patients with severe resistant (systolic BP >160 mmHg) hypertension. Smaller ancillary studies in hypertensive patients suggest a benefit from renal denervation in a variety of conditions such as chronic kidney disease, glucose intolerance, sleep apnoea and heart failure. The Global SYMPLICITY registry, which incorporates the GREAT SYMPLICITY registry initiated in Germany, is being conducted worldwide to evaluate the safety and efficacy of treatment with the Symplicity renal denervation system in real-world uncontrolled hypertensive patients, looking first at subjects with severe resistant hypertension to confirm the results of prior clinical trials, but then also subjects with a wider range of baseline blood pressure and coexisting comorbidities. The rationale, design and first baseline data from the Global SYMPLICITY registry are presented.

  20. Does dysfunction of the autonomic nervous system affect success of renal denervation in reducing blood pressure?

    Directory of Open Access Journals (Sweden)

    Lisa Fricke

    2017-04-01

    Full Text Available Objectives: Renal denervation is an interventional approach aiming to reduce high blood pressure. Its efficacy is subject of controversial debate. We analyzed autonomic function in patients undergoing renal denervation to identify responders. Methods: A total of 21 patients with treatment-resistant hypertension scheduled for renal denervation were included. Heart rate variability, pupillary function and sympathetic skin response were examined prior to intervention. Before and 1 or 3 months after intervention, 24-h ambulatory blood pressure readings were taken. Results: Patients were stratified according to sympathetic nervous system function. Sympathetic activity was reduced in 12 participants (group 1 and normal or enhanced in nine patients (group 2. The mean of daytime systolic blood pressure decreased in groups 1 and 2 from 168 to 157 mmHg (95% confidence interval for difference, 1–21 mmHg, p = 0.035 and from 166 to 145 mmHg (8–34 mmHg, p = 0.005, respectively. In a linear model, blood pressure reduction was 11.3 mmHg (0.3–22 mmHg greater in group 2 than in group 1 (p = 0.045. Conclusion: Patients with preexisting reduced activity of the sympathetic nervous system benefited less from renal denervation.

  1. An Update on Renal Artery Denervation and Its Clinical Impact on Hypertensive Disease

    Science.gov (United States)

    Kuang, Ye Min; Gan, Gary C. H.; Burgess, David; Denniss, Alan Robert

    2015-01-01

    Hypertension is a globally prevalent condition, with a heavy clinical and economic burden. It is the predominant risk factor for premature cardiovascular and cerebrovascular disease, and is associated with a variety of clinical disorders including stroke, congestive cardiac failure, ischaemic heart disease, chronic renal failure, and peripheral arterial disease. A significant subset of hypertensive patients have resistant hypertensive disease. In this group of patients, catheter-based renal artery denervation has emerged as a potential therapy, with favourable clinical efficacy and safety in early trials. Additional benefits of this therapy are also being identified and include effects on left ventricular remodeling, cardiac performance, and symptom status in congestive cardiac failure. Utility of renal denervation for the management of resistant hypertension, however, has become controversial since the release of the Symplicity HTN-3 trial, the first large-scale blinded randomised study investigating the efficacy and safety of renal artery denervation. The aim of this paper is to evaluate the history, utility, and clinical efficacy of renal artery denervation technology, including an in-depth appraisal of the current literature and principal trials. PMID:26495305

  2. Cost-effectiveness of renal denervation therapy for the treatment of resistant hypertension in the Netherlands

    NARCIS (Netherlands)

    Henry, Thea L.; De Brouwer, Bonnie F E; Van Keep, Marjolijn M L; Blankestijn, Peter J.; Bots, Michiel L.; Koffijberg, Hendrik

    2015-01-01

    Objectives: Safety and efficacy data for catheter-based renal denervation (RDN) in the treatment of resistant hypertension have been used to estimate the cost-effectiveness of this approach. However, there are no Dutch-specific analyses. This study examined the cost-effectiveness of RDN from the

  3. Renal denervation in the management of resistant hypertension: current evidence and perspectives.

    Science.gov (United States)

    Jin, Yu; Persu, Alexandre; Staessen, Jan A

    2013-09-01

    Catheter-based renal denervation has emerged as a novel treatment modality for resistant hypertension. This review summarizes the current evidence on this procedure in treatment of resistant hypertension, limitations of available evidence and questions to be answered. The SYMPLICITY studies showed that renal denervation is feasible in treating resistant hypertension, but failed to provide conclusive evidence on the size and durability of the antihypertensive, renal and sympatholytic effects, as well as the long-term safety. The definition of resistant hypertension was loose in the SYMPLICITY studies and the management of resistant hypertension was suboptimal. Future studies should have a randomized design and enroll truly resistant hypertension patients by excluding secondary hypertension, white-coat hypertension and nonadherent patients. Questions to be addressed by the ongoing and future trials include the long-term efficacy and safety of this procedure, identification of responders and uncovering of the underlying mechanisms. Only well-designed, randomized clinical trials addressing the limitations of the SYMPLICITY studies will be able to demonstrate whether renal denervation is an efficacious treatment modality in resistant hypertension and in which patients. For now, renal denervation remains an experimental procedure and should only be offered to truly resistant hypertensive patients in a research context after careful selection.

  4. Safety and long-term effects of renal denervation : Rationale and design of the Dutch registry

    NARCIS (Netherlands)

    Sanders, M. F.; Blankestijn, P. J.; Voskuil, M.; Spiering, W.; Vonken, E. J.; Rotmans, J. I.; van der Hoeven, B. L.; Daemen, J.; van den Meiracker, A. H.; Kroon, A. A.; de Haan, M.W.; Das, M.; Bax, M.; van der Meer, I. M.; van Overhagen, H.; van den Born, B. J H; van Brussel, P. M.; van der Valk, P.H.M.; Smak Gregoor, P. J H; Meuwissen, M.; Gomes, M. E R; Oude Ophuis, T.; Troe, E.; Tonino, W. A L; Konings, C. J A M; de Vries, P. A M; van Balen, A.; Heeg, J. E.; Smit, J. J J; Elvan, A.; Steggerda, R.; Niamut, S. M L; Peels, J. O J; de Swart, J. B R M; Wardeh, A. J.; Groeneveld, J. H M; van der Linden, E.; Hemmelder, M. H.; Folkeringa, R.; Stoel, M. G.; Kant, G. D.; Herrman, J. P R; van Wissen, S.; Deinum, J.; Westra, S. W.; Aengevaeren, W. R M; Parlevliet, K. J.; Schramm, A.; Jessurun, G. A J; Rensing, B. J W M; Winkens, M. H M; Wierema, T. K A; Santegoets, E.; Lipsic, E.; Houwerzijl, E.; Kater, M.; Allaart, C. P.; Nap, A.; Bots, M. L.

    BACKGROUND: Percutaneous renal denervation (RDN) has recently been introduced as a treatment for therapy-resistant hypertension. Also, it has been suggested that RDN may be beneficial for other conditions characterised by increased sympathetic nerve activity. There are still many uncertainties with

  5. Safety and long-term effects of renal denervation : Rationale and design of the Dutch registry

    NARCIS (Netherlands)

    Sanders, M. F.; Blankestijn, P. J.; Voskuil, M.; Spiering, W.; Vonken, E. J.; Rotmans, J. I.; van der Hoeven, B. L.; Daemen, J.; van den Meiracker, A. H.; Kroon, A. A.; de Haan, M. W.; Das, M.; Bax, M.; van der Meer, I. M.; van Overhagen, H.; van den Born, B. J. H.; van Brussel, P. M.; van der Valk, P. H. M.; Gregoor, P. J. H. Smak; Meuwissen, M.; Gomes, M. E. R.; Ophuis, T. Oude; Troe, E.; Tonino, W. A. L.; Konings, C. J. A. M.; de Vries, P. A. M.; van Balen, A.; Heeg, J. E.; Smit, J. J. J.; Elvan, A.; Steggerda, R.; Niamut, S. M. L.; Peels, J. O. J.; de Swart, J. B. R. M.; Wardeh, A. J.; Groeneveld, J. H. M.; van der Linden, E.; Hemmelder, M. H.; Folkeringa, R.; Stoel, M. G.; Kant, G. D.; Herrman, J. P. R.; van Wissen, S.; Deinum, J.; Westra, S. W.; Aengevaeren, W. R. M.; Parlevliet, K. J.; Schramm, A.; Jessurun, G. A. J.; Rensing, B. J. W. M.; Winkens, M. H. M.; Wierema, T. K. A.; Santegoets, E.; Lipsic, E.; Houwerzijl, E.; Kater, M.; Allaart, C. P.; Nap, A.; Bots, M. L.

    Background: Percutaneous renal denervation (RDN) has recently been introduced as a treatment for therapy-resistant hypertension. Also, it has been suggested that RDN may be beneficial for other conditions characterised by increased sympathetic nerve activity. There are still many uncertainties with

  6. Renal Denervation, Hope or Hype? : Studies on patient selection and mechanisms

    NARCIS (Netherlands)

    Vink, E.E.

    2014-01-01

    The general objective of this thesis was to determine which patients are most likely to benefit most from treatment with RDN and to study the effects of renal denervation (RDN). This thesis is subdivided into three parts. Part I focused on pathophysiologic studies on renal oxygenation and the

  7. Safety and long-term effects of renal denervation: Rationale and design of the Dutch registry

    NARCIS (Netherlands)

    Sanders, M. F.; Blankestijn, P. J.; Voskuil, M.; Spiering, W.; Vonken, E. J.; Rotmans, J. I.; van der Hoeven, B. L.; Daemen, J.; van den Meiracker, A. H.; Kroon, A. A.; de Haan, M. W.; Das, M.; Bax, M.; van der Meer, I. M.; van Overhagen, H.; van den Born, B. J. H.; van Brussel, P. M.; van der Valk, P. H. M.; Smak Gregoor, P. J. H.; Meuwissen, M.; Gomes, M. E. R.; Oude Ophuis, T.; Troe, E.; Tonino, W. A. L.; Konings, C. J. A. M.; de Vries, P. A. M.; van Balen, A.; Heeg, J. E.; Smit, J. J. J.; Elvan, A.; Steggerda, R.; Niamut, S. M. L.; Peels, J. O. J.; de Swart, J. B. R. M.; Wardeh, A. J.; Groeneveld, J. H. M.; van der Linden, E.; Hemmelder, M. H.; Folkeringa, R.; Stoel, M. G.; Kant, G. D.; Herrman, J. P. R.; van Wissen, S.; Deinum, J.; Westra, S. W.; Aengevaeren, W. R. M.; Parlevliet, K. J.; Schramm, A.; Jessurun, G. A. J.; Rensing, B. J. W. M.; Winkens, M. H. M.; Wierema, T. K. A.; Santegoets, E.; Lipsic, E.; Houwerzijl, E.; Kater, M.; Allaart, C. P.; Nap, A.; Bots, M. L.

    2016-01-01

    Percutaneous renal denervation (RDN) has recently been introduced as a treatment for therapy-resistant hypertension. Also, it has been suggested that RDN may be beneficial for other conditions characterised by increased sympathetic nerve activity. There are still many uncertainties with regard to

  8. Joint UK societies’ 2014 consensus statement on renal denervation for resistant hypertension

    Science.gov (United States)

    Lobo, Melvin D; de Belder, Mark A; Cleveland, Trevor; Collier, David; Dasgupta, Indranil; Deanfield, John; Kapil, Vikas; Knight, Charles; Matson, Matthew; Moss, Jonathan; Paton, Julian F R; Poulter, Neil; Simpson, Iain; Williams, Bryan; Caulfield, Mark J

    2015-01-01

    Resistant hypertension continues to pose a major challenge to clinicians worldwide and has serious implications for patients who are at increased risk of cardiovascular morbidity and mortality with this diagnosis. Pharmacological therapy for resistant hypertension follows guidelines-based regimens although there is surprisingly scant evidence for beneficial outcomes using additional drug treatment after three antihypertensives have failed to achieve target blood pressure. Recently there has been considerable interest in the use of endoluminal renal denervation as an interventional technique to achieve renal nerve ablation and lower blood pressure. Although initial clinical trials of renal denervation in patients with resistant hypertension demonstrated encouraging office blood pressure reduction, a large randomised control trial (Symplicity HTN-3) with a sham-control limb, failed to meet its primary efficacy end point. The trial however was subject to a number of flaws which must be taken into consideration in interpreting the final results. Moreover a substantial body of evidence from non-randomised smaller trials does suggest that renal denervation may have an important role in the management of hypertension and other disease states characterised by overactivation of the sympathetic nervous system. The Joint UK Societies does not recommend the use of renal denervation for treatment of resistant hypertension in routine clinical practice but remains committed to supporting research activity in this field. A number of research strategies are identified and much that can be improved upon to ensure better design and conduct of future randomised studies. PMID:25431461

  9. Renal denervation in a patient with Alport syndrome and rejected renal allograft.

    Science.gov (United States)

    Raju, Narayana; Lloyd, Vincent; Yalagudri, Sachin; Das, Bharati; Ravikishore, A G

    2015-12-01

    Renal denervation is a new intervention to treat resistant hypertension. By applying radiofrequency (RF) to renal arteries, sympathetic nerves in adventitia layer of vascular wall can be denervated. Sympathetic hyperactivity is an important contributory factor in hypertension of hemodialysis patients. Hyperactive sympathetic nervous system aggravates hypertension and it can cause complications like left ventricular hypertrophy, heart failure, arrhythmias and atherogenesis. Our report illustrates the use of renal denervation using conventional RF catheter for uncontrolled hypertension in a patient with Alport syndrome and rejected renal allograft. Progressive and sustained reduction of blood pressure was obtained post-procedure and at 24 months follow-up with antihypertensives decreased from 6 to 2 per day, thereby demonstrating the safety, feasibility, and efficacy of the procedure. There are some reports available on the usefulness of this technique in hemodialysis patients; however, there are no studies of renal denervation in patients with Alport syndrome and failed allograft situation. Copyright © 2015 Cardiological Society of India. Published by Elsevier B.V. All rights reserved.

  10. EFFECT OF LIVER DENERVATION ON GLUCOSE-PRODUCTION DURING RUNNING IN GUINEA-PIGS

    NARCIS (Netherlands)

    WIERSMA, MML; VISSING, J; MIKINES, KJ; STEFFENS, AB; GALBO, H

    Activity in sympathetic liver nerves has been proposed to be important for glucose production in exercising humans. However, liver denervation does not influence the exercise-induced increase in glucose production in the rat and dog. These species have a poor sympathetic liver innervation in

  11. Effects of renal denervation on end organ damage in hypertensive patients

    NARCIS (Netherlands)

    Verloop, WL; Vink, Eva E.; Spiering, Wilko; Blankestijn, PJ; Doevendans, Pieter A.; Bots, Michiel L.; Vonken, EPA; Voskuil, Michiel; Leiner, Tim

    Background: Renal denervation (RDN) is believed to reduce sympathetic nerve activity and is a potential treatment for resistant hypertension. The present study investigated the effects of RDN on end organ damage (EOD). Design: The present study was a prospective cohort study (registered as

  12. Evaluation of cardiac denervation in patients with long-standing diabetes

    International Nuclear Information System (INIS)

    Khurram, M.; Khar, Hamama-tul-Bushra; Malik, M.F. Fazal-ur-Rehman; Javed, S.; Hassan, Z.; Minhas, Z.; Goraya, M.F.; Shakoor, A.

    2002-01-01

    Objective: Evaluation of cardiac autonomic dysfunction in long-standing diabetics, comparing patients treated with insulin and oral hypo glycemic agents. Design: Observational and comparative study between two treatment groups. Place and Duration of Study: At department of Medicine, Pakistan Institute of Medical Sciences, Islamabad, for 6 months. Subjects and Methods: Fifty diabetic patients of about 10 years illness were studied. Patients were divided into two groups, Group 1(13 males, 12 females; mean age 33.08 years) included those who received insulin, and Group II patients (12 males, 13 females; mean age 54.68 years) who received oral hypo glycemic agents for their diabetic illness. Evaluation of cardiac denervation in both the groups was done in terms of presence of resting tachycardia, loss of sinus arrhythmia and abnormalities of Valsava response. Results: At least some form of cardiac denervation was present in 62% of total subjects. 48% of Group I and 76 % of Group II patients. A significantly high number of patients treated with oral hypo glycemic agents had evidence of cardiac denervation when compared with patients who were treated with insulin (p < 0.05). Conclusion: Cardiac denervation is common in long-standing diabetics specifically in those treated with oral hypo glycemic agents. (author)

  13. Renal denervation attenuates NADPH oxidase-mediated oxidative stress and hypertension in rats with hydronephrosis.

    Science.gov (United States)

    Peleli, Maria; Al-Mashhadi, Ammar; Yang, Ting; Larsson, Erik; Wåhlin, Nils; Jensen, Boye L; G Persson, A Erik; Carlström, Mattias

    2016-01-01

    Hydronephrosis is associated with the development of salt-sensitive hypertension. Studies have suggested that increased sympathetic nerve activity and oxidative stress play important roles in hypertension and the modulation of salt sensitivity. The present study primarily aimed to examine the role of renal sympathetic nerve activity in the development of hypertension in rats with hydronephrosis. In addition, we aimed to investigate if NADPH oxidase (NOX) function could be affected by renal denervation. Partial unilateral ureteral obstruction (PUUO) was created in 3-wk-old rats to induce hydronephrosis. Sham surgery or renal denervation was performed at the same time. Blood pressure was measured during normal, high-, and low-salt diets. The renal excretion pattern, NOX activity, and expression as well as components of the renin-angiotensin-aldosterone system were characterized after treatment with the normal salt diet. On the normal salt diet, rats in the PUUO group had elevated blood pressure compared with control rats (115 ± 3 vs. 87 ± 1 mmHg, P < 0.05) and displayed increased urine production and lower urine osmolality. The blood pressure change in response to salt loading (salt sensitivity) was more pronounced in the PUUO group compared with the control group (15 ± 2 vs. 5 ± 1 mmHg, P < 0.05). Renal denervation in PUUO rats attenuated both hypertension (97 ± 3 mmHg) and salt sensitivity (5 ± 1 mmHg, P < 0.05) and normalized the renal excretion pattern, whereas the degree of renal fibrosis and inflammation was not changed. NOX activity and expression as well as renin and ANG II type 1A receptor expression were increased in the renal cortex from PUUO rats and normalized by denervation. Plasma Na(+) and K(+) levels were elevated in PUUO rats and normalized after renal denervation. Finally, denervation in PUUO rats was also associated with reduced NOX expression, superoxide production, and fibrosis in the heart. In conclusion, renal denervation attenuates

  14. Persistent Thalamic Sound Processing Despite Profound Cochlear Denervation

    Directory of Open Access Journals (Sweden)

    Anna R. Chambers

    2016-08-01

    Full Text Available Neurons at higher stages of sensory processing can partially compensate for a sudden drop in input from the periphery through a homeostatic plasticity process that increases the gain on weak afferent inputs. Even after a profound unilateral auditory neuropathy where > 95% of synapses between auditory nerve fibers and inner hair cells have been eliminated with ouabain, central gain can restore the cortical processing and perceptual detection of basic sounds delivered to the denervated ear. In this model of profound auditory neuropathy, cortical processing and perception recover despite the absence of an auditory brainstem response (ABR or brainstem acoustic reflexes, and only a partial recovery of sound processing at the level of the inferior colliculus (IC, an auditory midbrain nucleus. In this study, we induced a profound cochlear neuropathy with ouabain and asked whether central gain enabled a compensatory plasticity in the auditory thalamus comparable to the full recovery of function previously observed in the auditory cortex (ACtx, the partial recovery observed in the IC, or something different entirely. Unilateral ouabain treatment in adult mice effectively eliminated the ABR, yet robust sound-evoked activity persisted in a minority of units recorded from the contralateral medial geniculate body (MGB of awake mice. Sound-driven MGB units could decode moderate and high-intensity sounds with accuracies comparable to sham-treated control mice, but low-intensity classification was near chance. Pure tone receptive fields and synchronization to broadband pulse trains also persisted, albeit with significantly reduced quality and precision, respectively. MGB decoding of temporally modulated pulse trains and speech tokens were both greatly impaired in ouabain-treated mice. Taken together, the absence of an ABR belied a persistent auditory processing at the level of the MGB that was likely enabled through increased central gain. Compensatory

  15. Effects of local cardiac denervation on cardiac innervation and ventricular arrhythmia after chronic myocardial infarction.

    Directory of Open Access Journals (Sweden)

    Xudong Liu

    Full Text Available Modulation of the autonomic nervous system (ANS has already been demonstrated to display antiarrhythmic effects in patients and animals with MI. In this study, we investigated whether local cardiac denervation has any beneficial effects on ventricular electrical stability and cardiac function in the chronic phase of MI.Twenty-one anesthetized dogs were randomly assigned into the sham-operated, MI and MI-ablation groups, respectively. Four weeks after local cardiac denervation, LSG stimulation was used to induce VPCs and VAs. The ventricular fibrillation threshold (VFT and the incidence of inducible VPCs were measured with electrophysiological protocol. Cardiac innervation was determined with immunohistochemical staining of growth associated protein-43 (GAP43 and tyrosine hydroxylase (TH. The global cardiac and regional ventricular function was evaluated with doppler echocardiography in this study.Four weeks after operation, the incidence of inducible VPC and VF in MI-ablation group were significantly reduced compared to the MI dogs (p<0.05. Moreover, local cardiac denervation significantly improved VFT in the infarcted border zone (p<0.05. The densities of GAP43 and TH-positive nerve fibers in the infarcted border zone in the MI-ablation group were lower than those in the MI group (p<0.05. However, the local cardiac denervation did not significantly improve cardiac function in the chronic phase of MI, determined by the left ventricle diameter (LV, left atrial diameter (LA, ejection fraction (EF.Summarily, in the chronic phase of MI, local cardiac denervation reduces the ventricular electrical instability, and attenuates spatial heterogeneity of sympathetic nerve reconstruction. Our study suggests that this methodology might decrease malignant ventricular arrhythmia in chronic MI, and has a great potential for clinical application.

  16. Altered Satellite Cell Responsiveness and Denervation Implicated in Progression of Rotator-Cuff Injury.

    Directory of Open Access Journals (Sweden)

    Deanna Gigliotti

    Full Text Available Rotator-cuff injury (RCI is common and painful; even after surgery, joint stability and function may not recover. Relative contributions to atrophy from disuse, fibrosis, denervation, and satellite-cell responsiveness to activating stimuli are not known.Potential contributions of denervation and disrupted satellite cell responses to growth signals were examined in supraspinatus (SS and control (ipsilateral deltoid muscles biopsied from participants with RCI (N = 27. Biopsies were prepared for explant culture (to study satellite cell activity, immunostained to localize Pax7, BrdU, and Semaphorin 3A in satellite cells, sectioning to study blood vessel density, and western blotting to measure the fetal (γ subunit of acetylcholine receptor (γ-AchR. Principal component analysis (PCA for 35 parameters extracted components identified variables that contributed most to variability in the dataset. γ-AchR was higher in SS than control, indicating denervation. Satellite cells in SS had a low baseline level of activity (Pax7+ cells labelled in S-phase versus control; only satellite cells in SS showed increased proliferative activity after nitric oxide-donor treatment. Interestingly, satellite cell localization of Semaphorin 3A, a neuro-chemorepellent, was greater in SS (consistent with fiber denervation than control muscle at baseline. PCAs extracted components including fiber atrophy, satellite cell activity, fibrosis, atrogin-1, smoking status, vascular density, γAchR, and the time between symptoms and surgery. Use of deltoid as a control for SS was supported by PCA findings since "muscle" was not extracted as a variable in the first two principal components. SS muscle in RCI is therefore atrophic, denervated, and fibrotic, and has satellite cells that respond to activating stimuli.Since SS satellite cells can be activated in culture, a NO-donor drug combined with stretching could promote muscle growth and improve functional outcome after RCI. PCAs

  17. Renal denervation for the treatment of resistant hypertension: review and clinical perspective.

    Science.gov (United States)

    Iliescu, Radu; Lohmeier, Thomas E; Tudorancea, Ionut; Laffin, Luke; Bakris, George L

    2015-10-01

    When introduced clinically 6 years ago, renal denervation was thought to be the solution for all patients whose blood pressure could not be controlled by medication. The initial two studies, SYMPLICITY HTN-1 and HTN-2, demonstrated great magnitudes of blood pressure reduction within 6 mo of the procedure and were based on a number of assumptions that may not have been true, including strict adherence to medication and absence of white-coat hypertension. The SYMPLICITY HTN-3 trial controlled for all possible factors believed to influence the outcome, including the addition of a sham arm, and ultimately proved the demise of the initial overly optimistic expectations. This trial yielded a much lower blood pressure reduction compared with the previous SYMPLICITY trials. Since its publication in 2014, there have been many analyses to try and understand what accounted for the differences. Of all the variables examined that could influence blood pressure outcomes, the extent of the denervation procedure was determined to be inadequate. Beyond this, the physiological mechanisms that account for the heterogeneous fall in arterial pressure following renal denervation remain unclear, and experimental studies indicate dependence on more than simply reduced renal sympathetic activity. These and other related issues are discussed in this paper. Our perspective is that renal denervation works if done properly and used in the appropriate patient population. New studies with new approaches and catheters and appropriate controls will be starting later this year to reassess the efficacy and safety of renal denervation in humans. Copyright © 2015 the American Physiological Society.

  18. Renal Denervation for Treatment of Hypertension: a Second Start and New Challenges.

    Science.gov (United States)

    Persu, Alexandre; Kjeldsen, Sverre; Staessen, Jan A; Azizi, Michel

    2016-01-01

    Following the publication of the randomized controlled but open-label trial Symplicity HTN-2, catheter-based renal sympathetic denervation was proposed as a novel treatment for drug-resistant hypertension. Thousands of procedures were routinely performed in Europe, Australia and Asia, and many observational studies were published. A sudden shift from overoptimistic views to radical scepticism occurred later, when the large US randomized sham-controlled trial Symplicity HTN-3 failed to meet its primary blood pressure lowering efficacy endpoint. Experts are divided on the reasons accounting for the large discrepancy between the results of initial studies and those of Symplicity HTN-3. Indeed, the blood pressure lowering effect associated with renal denervation was overestimated in initial trials due to various patient and physician-related biases, whereas it could have been underestimated in Symplicity HTN-3, which was well designed but not rigorously executed. Still, there is a large consensus on the need to further study catheter-based renal denervation in more controlled conditions, with particular emphasis on identification of predictors of blood pressure response. US and European experts have recently issued very similar recommendations on design of upcoming trials, procedural aspects, drug treatment, patient population and inclusion-exclusion criteria. Application of these new standards may represent a second chance for renal denervation to demonstrate--or not--its efficacy and safety in various patient populations. With its highly standardized treatment regimen, the French trial DENERHTN paved the way for this new approach and may inspire upcoming studies testing novel renal denervation systems in different populations.

  19. Ultra structure of the denervated vocal muscle mechanically in hogs (sus scrofa domestica

    Directory of Open Access Journals (Sweden)

    Leão, Henrique Zaquia

    2010-03-01

    Full Text Available Introduction: The literature is not clear in the ultra-structural manifestations of the vocal wrinkles after neural wound. Objective: To verify the alterations that occur in a vocal fold mechanically denervated. Method: In this prospective study, it were utilized 15 hogs of commercial race (Sus scrofa domesticates, with age of 4 to 12 weeks. The animals were distributed in three groups, chosen at random. Everybody was submitted to the denervation of the right vocal fold, with surgical removal of a segment with three centimeters of the recurring right laryngeal nerve. After 45, 90 and 180 days of the operations, it was proceeded the biopsy of the vocal muscles, it was prosecuted the samples for transmission electron microscopy and, for the ultra-structural study, utilized the transmission electron microscopy Philips, model EM208S. Results: The biopsied groups with 45 and 90 days after operation of mechanical denervation, presented disorganization miofibrilar, only vestigial lines Z in many samples, as well like altered mithochondrions presenting limited sizes, and matrix mithocondrial rarefied with rare mithocondrial cristae present. The biopsied group with 180 days after operation of denervation, presented regular sarcomeres, mithocondrions with sizes and regular number with correct positioning between the sarcomerical units. Conclusion: The finds in the ultra-structure of the vocal muscles suggest to re enervation of the muscle being that the muscular mithochondrions were the most sensible structures to the denervated condition, successions by the cytoarchiteture of the miofibrilas; the finds in the ultra-structure of the vocal muscles suggests to reinervation of the muscle in the period of approximately six months.

  20. Altered Satellite Cell Responsiveness and Denervation Implicated in Progression of Rotator-Cuff Injury.

    Science.gov (United States)

    Gigliotti, Deanna; Leiter, Jeff R S; MacDonald, Peter B; Peeler, Jason; Anderson, Judy E

    Rotator-cuff injury (RCI) is common and painful; even after surgery, joint stability and function may not recover. Relative contributions to atrophy from disuse, fibrosis, denervation, and satellite-cell responsiveness to activating stimuli are not known. Potential contributions of denervation and disrupted satellite cell responses to growth signals were examined in supraspinatus (SS) and control (ipsilateral deltoid) muscles biopsied from participants with RCI (N = 27). Biopsies were prepared for explant culture (to study satellite cell activity), immunostained to localize Pax7, BrdU, and Semaphorin 3A in satellite cells, sectioning to study blood vessel density, and western blotting to measure the fetal (γ) subunit of acetylcholine receptor (γ-AchR). Principal component analysis (PCA) for 35 parameters extracted components identified variables that contributed most to variability in the dataset. γ-AchR was higher in SS than control, indicating denervation. Satellite cells in SS had a low baseline level of activity (Pax7+ cells labelled in S-phase) versus control; only satellite cells in SS showed increased proliferative activity after nitric oxide-donor treatment. Interestingly, satellite cell localization of Semaphorin 3A, a neuro-chemorepellent, was greater in SS (consistent with fiber denervation) than control muscle at baseline. PCAs extracted components including fiber atrophy, satellite cell activity, fibrosis, atrogin-1, smoking status, vascular density, γAchR, and the time between symptoms and surgery. Use of deltoid as a control for SS was supported by PCA findings since "muscle" was not extracted as a variable in the first two principal components. SS muscle in RCI is therefore atrophic, denervated, and fibrotic, and has satellite cells that respond to activating stimuli. Since SS satellite cells can be activated in culture, a NO-donor drug combined with stretching could promote muscle growth and improve functional outcome after RCI. PCAs suggest

  1. Effects of nerve growth factor on the neurotization of denervated muscles.

    Science.gov (United States)

    Menderes, Adnan; Yilmaz, Mustafa; Vayvada, Haluk; Ozer, Erdener; Barutçu, Ali

    2002-04-01

    Studies on surgical repair techniques of the peripheral nerve are still trying to improve the outcome. There are many studies on the effects of various neurotrophic factors on the transected peripheral nerve. Muscular neurotization, which is the direct implantation of the nerve to the target denervated skeletal muscle, is one of the techniques used when the primary repair of the peripheral nerves is not possible. The effects of nerve growth factor (NGF), which is one of the primary neurotrophic factors, on the reinnervation of denervated muscles by neurotization is investigated in this experimental study. The denervated soleus muscle was neurotized via peroneal nerve implantation (group 1), and NGF was administered to the neurotized muscle (group 2). All animals were evaluated at weeks 8, 10, and 12 using electromyography. Muscle contractility, muscle weight, and histological morphometric tests were performed at week 12. The experimental groups were compared with each other and normal control values. Electromyographically, group 2 (direct nerve implantation + NGF) demonstrated better reinnervation in all evaluations. The study of muscle weight showed that the muscle mass was 75% of the normal soleus muscle in group 1 and was 85% of the normal side in group 2 at the end of week 12. In group 1, the twitch force was 56% of the normal soleus muscle and was 71% in group 2. Tetanic force was 53% of the normal soleus muscle in group 1 and 68% in group 2. Histological morphometric studies revealed that there was a decrease in the density of the motor end plates in group 1, but there was no statistically significant difference between the normal soleus muscles and the NGF applied to group 2. The positive effects of NGF on the neurotization of denervated muscles seen in this study suggest that it may be useful for treating some difficult reconstructions caused by denervation.

  2. Side-To-Side Nerve Bridges Support Donor Axon Regeneration Into Chronically Denervated Nerves and Are Associated With Characteristic Changes in Schwann Cell Phenotype.

    Science.gov (United States)

    Hendry, J Michael; Alvarez-Veronesi, M Cecilia; Snyder-Warwick, Alison; Gordon, Tessa; Borschel, Gregory H

    2015-11-01

    Chronic denervation resulting from long nerve regeneration times and distances contributes greatly to suboptimal outcomes following nerve injuries. Recent studies showed that multiple nerve grafts inserted between an intact donor nerve and a denervated distal recipient nerve stump (termed "side-to-side nerve bridges") enhanced regeneration after delayed nerve repair. To examine the cellular aspects of axon growth across these bridges to explore the "protective" mechanism of donor axons on chronically denervated Schwann cells. In Sprague Dawley rats, 3 side-to-side nerve bridges were placed over a 10-mm distance between an intact donor tibial (TIB) nerve and a recipient denervated common peroneal (CP) distal nerve stump. Green fluorescent protein-expressing TIB axons grew across the bridges and were counted in cross section after 4 weeks. Immunofluorescent axons and Schwann cells were imaged over a 4-month period. Denervated Schwann cells dedifferentiated to a proliferative, nonmyelinating phenotype within the bridges and the recipient denervated CP nerve stump. As donor TIB axons grew across the 3 side-to-side nerve bridges and into the denervated CP nerve, the Schwann cells redifferentiated to the myelinating phenotype. Bridge placement led to an increased mass of hind limb anterior compartment muscles after 4 months of denervation compared with muscles whose CP nerve was not "protected" by bridges. This study describes patterns of donor axon regeneration and myelination in the denervated recipient nerve stump and supports a mechanism where these donor axons sustain a proregenerative state to prevent deterioration in the face of chronic denervation.

  3. 12-month blood pressure results of catheter-based renal artery denervation for resistant hypertension: the SYMPLICITY HTN-3 trial.

    Science.gov (United States)

    Bakris, George L; Townsend, Raymond R; Flack, John M; Brar, Sandeep; Cohen, Sidney A; D'Agostino, Ralph; Kandzari, David E; Katzen, Barry T; Leon, Martin B; Mauri, Laura; Negoita, Manuela; O'Neill, William W; Oparil, Suzanne; Rocha-Singh, Krishna; Bhatt, Deepak L

    2015-04-07

    Results of the SYMPLICITY HTN-3 (Renal Denervation in Patients With Uncontrolled Hypertension) trial confirmed the safety but not the efficacy of renal denervation for treatment-resistant hypertension at 6 months post procedure. This study sought to analyze the 12-month SYMPLICITY HTN-3 results for the original denervation group, the sham subjects who underwent denervation after the 6-month endpoint (crossover group), and the sham subjects who did not undergo denervation after 6 months (non-crossover group). Eligible subjects were randomized 2:1 to denervation or sham procedure. Subjects were unblinded to their treatment group after the 6-month primary endpoint was ascertained; subjects in the sham group meeting eligibility requirements could undergo denervation. Change in blood pressure (BP) at 12 months post randomization (6 months for crossover subjects) was analyzed. The 12-month follow-up was available for 319 of 361 denervation subjects and 48 of 101 non-crossover subjects; 6-month denervation follow-up was available for 93 of 101 crossover subjects. In denervation subjects, the 12-month office systolic BP (SBP) change was greater than that observed at 6 months (-15.5 ± 24.1 mm Hg vs. -18.9 ± 25.4 mm Hg, respectively; p = 0.025), but the 24-h SBP change was not significantly different at 12 months (p = 0.229). The non-crossover group office SBP decreased by -32.9 ± 28.1 mm Hg at 6 months, but this response regressed to -21.4 ± 19.9 mm Hg (p = 0.01) at 12 months, increasing to 11.5 ± 29.8 mm Hg. These data support no further reduction in office or ambulatory BP after 1-year follow-up. Loss of BP reduction in the non-crossover group may reflect decreased medication adherence or other related factors. (Renal Denervation in Patients With Uncontrolled Hypertension [SYMPLICITY HTN-3]; NCT01418261). Copyright © 2015 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

  4. Advanced age-related denervation and fiber-type grouping in skeletal muscle of SOD1 knockout mice.

    Science.gov (United States)

    Kostrominova, Tatiana Y

    2010-11-30

    In this study skeletal muscles from 1.5- and 10-month-old Cu/Zn superoxide dismutase (SOD1) homozygous knockout (JLSod1(-/-)) mice obtained from The Jackson Laboratory (C57Bl6/129SvEv background) were compared with muscles from age- and sex-matched heterozygous (JLSod1(+/-)) littermates. The results of this study were compared with previously published data on two different strains of Sod1(-/-) mice: one from Dr. Epstein's laboratory (ELSod1(-/-); C57Bl6 background) and the other from Cephalon, Inc. (CSod1(-/-); 129/CD-1 background). Grouping of succinate dehydrogenase-positive fibers characterized muscles of Sod1(-/-) mice from all three strains. The 10-month-old Sod1(-/-)C and JL mice displayed pronounced denervation of the gastrocnemius muscle, whereas the ELSod1(-/-) mice displayed a small degree of denervation at this age, but developed accelerated age-related denervation later on. Denervation markers were up-regulated in skeletal muscle of 10-month-old JLSod1(-/-) mice. This study is the first to show that metallothionein mRNA and protein expression was up-regulated in the skeletal muscle of 10-month-old JLSod1(-/-) mice and was mostly localized to the small atrophic muscle fibers. In conclusion, all three strains of Sod1(-/-) mice develop accelerated age-related muscle denervation, but the genetic background has significant influence on the progress of denervation. Copyright © 2010 Elsevier Inc. All rights reserved.

  5. Blood pressure response to catheter-based renal sympathetic denervation in severe resistant hypertension: data from the Greek Renal Denervation Registry.

    Science.gov (United States)

    Tsioufis, C; Ziakas, A; Dimitriadis, K; Davlouros, P; Marketou, M; Kasiakogias, A; Thomopoulos, C; Petroglou, D; Tsiachris, D; Doumas, M; Skalidis, E; Karvounis, C; Alexopoulos, D; Vardas, P; Kallikazaros, I; Stefanadis, C; Papademetriou, V; Tousoulis, D

    2017-05-01

    The efficacy of catheter-based renal sympathetic denervation (RDN) in terms of blood pressure (BP) reduction has been questioned, while "real-world" data from registries are needed. In this study, we report the complete set of 12-month data on office and ambulatory BP changes as well as the predictors for BP response to RDN from a national registry. In 4 Greek hospital centers, 79 patients with severe drug-resistant hypertension (age 59 ± 10 years, 53 males, body mass index 33 ± 5 kg/m 2 ; office BP and 24-h ambulatory BP were 176 ± 15/95 ± 13 and 155 ± 14/90 ± 12 mmHg, respectively, 4.4 ± 0.9 antihypertensive drugs) underwent RDN and were followed-up for 12 months in the Greek Renal Denervation Registry. Bilateral RDN was performed using percutaneous femoral approach and standardized techniques. Reduction in office systolic/diastolic BP at 6 and 12 months from baseline was -30/-12 and -29/-12 mmHg, while the reduction in 24-h ambulatory BP was -16/-9 and -15/-9 mmHg, respectively (p renal function and any new serious device or procedure-related adverse events. In our "real-world" multicenter national registry, the efficacy of renal denervation in reducing BP as well as safety is confirmed during a 12-month follow-up. Moreover, younger age, obesity, and higher levels of baseline systolic BP are independently related to better BP response to RDN.

  6. Effect of denervation and ischemia reperfusion injury on serum nitricoxide levels in rats

    International Nuclear Information System (INIS)

    Ozsoy, U.; Sindel, S.; Oygur, N.; Akbas, H.; Mutluay, R.

    2008-01-01

    Objective was to evaluate the effect of renal denervation and serumnitric oxide level with a different time course of renal ischemia-reperfusioninjury. Thirty-six male Wistar rats were randomized into 6 groups. All ratsunderwent right nephrectomy to create a single kidney model. Renal denervatedand innerved rats were subjected to renal clamping for 30-60 minutes. Thestudy was performed in the Department of Anatomy, Akdeniz University,Antalya, Turkey, between June and November 2005. Combined effects ofdenervation and ischemia may cause significant increase in serum nitric oxidelevels and decrease in glomerular filtration rates. Our results indicate thatkidney denervation did not cause any changes in renal functions, but withischemia it worsens the deleterious effect of ischemia-reperfusion injury andcauses a significant increase in serum nitric oxide levels. (author)

  7. Improvement of Myocardial Function Following Catheter-Based Renal Denervation in Heart Failure

    Directory of Open Access Journals (Sweden)

    Song-Yan Liao, MD

    2017-06-01

    Full Text Available Summary: Renal denervation (RD is a potential novel nonpharmacological therapy for heart failure (HF. We performed bilateral catheter-based RD in 10 adult pigs and compared them with 10 control subjects after induction of HF to investigate the long-term beneficial effects of RD on left ventricular (LV function and regional norepinephrine gradient after conventional HF pharmacological therapy. Compared with control subjects, animals treated with RD demonstrated an improvement in LV function and reduction of norepinephrine gradients over the myocardium and kidney at 10-week follow-up. Our results demonstrated that effective bilateral RD decrease regional norepinephrine gradients and improve LV contractile function compared with medical therapy alone. Key Words: heart failure, left ventricular function, norepinephrine, renal denervation

  8. Transcatheter renal denervation for the treatment of resistant arterial hypertension: the Swiss expert consensus.

    Science.gov (United States)

    Wuerzner, Gregoire; Muller, Olivier; Erne, Paul; Cook, Stéphane; Sudano, Isabella; Lüscher, Thomas F; Noll, Georg; Kaufmann, Urs; Rickli, Hans; Waeber, Bernard; Kaiser, Christophe; Sticherling, Christian; Pechère-Bertschi, Antoinette; Baumgartner, Iris; Jacob, Augustinus L; Burnier, Michel; Qanadli, Salah D

    2014-03-20

    Transcatheter (or percutaneous) renal denervation is a novel technique developed for the treatment of resistant hypertension. So far, only one randomised controlled trial has been published, which has shown a reduction of office blood pressure. The Swiss Society of Hypertension, the Swiss Society of Cardiology, The Swiss Society of Angiology and the Swiss Society of Interventional Radiology decided to establish recommendations to practicing physicians and specialists for good clinical practice. The eligibility of patients for transcatheter renal denervation needs (1.) confirmation of truly resistant hypertension, (2.) exclusion of secondary forms of hypertension, (3.) a multidisciplinary decision confirming the eligibility, (4.) facilities that guarantee procedural safety and (5.) a long-term follow-up of the patients, if possible in cooperation with a hypertension specialist. These steps are essential until long-term data on safety and efficacy are available.

  9. Functional reinnervation of vocal folds after selective laryngeal adductor denervation-reinnervation surgery for spasmodic dysphonia.

    Science.gov (United States)

    DeConde, Adam S; Long, Jennifer L; Armin, Bob B; Berke, Gerald S

    2012-09-01

    Selective laryngeal adductor denervation-reinnervation surgery (SLAD-R) offers a viable surgical alternative for patients with adductor spasmodic dysphonia refractory to botulinum toxin injections. SLAD-R selectively denervates the symptomatic thyroarytenoid muscle by dividing the distal adductor branch of the recurrent laryngeal nerve (RLN), and preventing reinnervation, by the proximal RLN and maintaining vocal fold bulk and tone by reinnervating the distal RLN with the ansa cervicalis. We present a patient who had previously undergone successful SLAD-R but presented 10 years postoperatively with a new regional dystonia involving his strap muscles translocated to his reinnervated larynx by his previous ansa-RLN neurorraphy. The patient's symptomatic vocal fold adduction resolved completely on division of the ansa-RLN neurorraphy confirming successful selective functional reinnervation of vocal fold adductors by the ansa cervicalis. Copyright © 2012 The Voice Foundation. Published by Mosby, Inc. All rights reserved.

  10. Renal Denervation Using an Irrigated Catheter in Patients with Resistant Hypertension: A Promising Strategy?

    International Nuclear Information System (INIS)

    Armaganijan, Luciana; Staico, Rodolfo; Moraes, Aline; Abizaid, Alexandre; Moreira, Dalmo; Amodeo, Celso; Sousa, Márcio; Borelli, Flávio; Armaganijan, Dikran; Sousa, J. Eduardo; Sousa, Amanda

    2014-01-01

    Systemic hypertension is an important public health problem and a significant cause of cardiovascular mortality. Its high prevalence and the low rates of blood pressure control have resulted in the search for alternative therapeutic strategies. Percutaneous renal sympathetic denervation emerged as a perspective in the treatment of patients with resistant hypertension. To evaluate the feasibility and safety of renal denervation using an irrigated catheter. Ten patients with resistant hypertension underwent the procedure. The primary endpoint was safety, as assessed by periprocedural adverse events, renal function and renal vascular abnormalities at 6 months. The secondary endpoints were changes in blood pressure levels (office and ambulatory monitoring) and in the number of antihypertensive drugs at 6 months. The mean age was 47.3 (± 12) years, and 90% of patients were women. In the first case, renal artery dissection occurred as a result of trauma due to the long sheath; no further cases were observed after technical adjustments, thus showing an effect of the learning curve. No cases of thrombosis/renal infarction or death were reported. Elevation of serum creatinine levels was not observed during follow-up. At 6 months, one case of significant renal artery stenosis with no clinical consequences was diagnosed. Renal denervation reduced office blood pressure levels by 14.6/6.6 mmHg, on average (p = 0.4 both for systolic and diastolic blood pressure). Blood pressure levels on ambulatory monitoring decreased by 28/17.6 mmHg (p = 0.02 and p = 0.07 for systolic and diastolic blood pressure, respectively). A mean reduction of 2.1 antihypertensive drugs was observed. Renal denervation is feasible and safe in the treatment of resistant systemic arterial hypertension. Larger studies are required to confirm our findings

  11. Denervation-Induced Activation of the Ubiquitin-Proteasome System Reduces Skeletal Muscle Quantity Not Quality.

    Science.gov (United States)

    Baumann, Cory W; Liu, Haiming M; Thompson, LaDora V

    2016-01-01

    It is well known that the ubiquitin-proteasome system is activated in response to skeletal muscle wasting and functions to degrade contractile proteins. The loss of these proteins inevitably reduces skeletal muscle size (i.e., quantity). However, it is currently unknown whether activation of this pathway also affects function by impairing the muscle's intrinsic ability to produce force (i.e., quality). Therefore, the purpose of this study was twofold, (1) document how the ubiquitin-proteasome system responds to denervation and (2) identify the physiological consequences of these changes. To induce soleus muscle atrophy, C57BL6 mice underwent tibial nerve transection of the left hindlimb for 7 or 14 days (n = 6-8 per group). At these time points, content of several proteins within the ubiquitin-proteasome system were determined via Western blot, while ex vivo whole muscle contractility was specifically analyzed at day 14. Denervation temporarily increased several key proteins within the ubiquitin-proteasome system, including the E3 ligase MuRF1 and the proteasome subunits 19S, α7 and β5. These changes were accompanied by reductions in absolute peak force and power, which were offset when expressed relative to physiological cross-sectional area. Contrary to peak force, absolute and relative forces at submaximal stimulation frequencies were significantly greater following 14 days of denervation. Taken together, these data represent two keys findings. First, activation of the ubiquitin-proteasome system is associated with reductions in skeletal muscle quantity rather than quality. Second, shortly after denervation, it appears the muscle remodels to compensate for the loss of neural activity via changes in Ca2+ handling.

  12. Excitation-contraction coupling and mechano-sensitivity in denervated skeletal muscles

    Directory of Open Access Journals (Sweden)

    Fabio Francini

    2010-09-01

    Full Text Available Skeletal muscle atrophy can be defined as a wasting or decrease in muscle mass and muscle force generation owing lack of use, ageing, injury or disease. Thus, the etiology of atrophy can be different. Atrophy in denervated muscle is a consequence of two factors: 1 the complete lack of motoneuron activity inducing the deficiency of neurotransmitter release and 2 the muscles disuse. The balance of the muscular functions depends on extra- and intra-muscular signals. In the balance are involved the excitation-contraction coupling (ECC, local growth factors, Ca2+-dependent and independent intracellular signals, mechano-sensitivity and mechano-transduction that activate Ca2+-dependent signaling proteins and cytoskeleton- nucleus pathways to the nucleus, that regulate the gene expression. Moreover, retrograde signal from intracellular compartments and cytoskeleton to the sarcolemma are additional factors that regulate the muscle function. Proteolytic systems that operate in atrophic muscles progressively reduce the muscle protein content and so the sarcolemma, ECC and the force generation. In this review we will focus on the more relevant changes of the sarcolemma, excitation-contraction coupling, ECC and mechano-transduction evaluated by electrophysiological methods and observed from early- to long-term denervated skeletal muscles. This review put in particular evidence that long-term denervated muscle maintain a sub-population of fibers with ECC and contractile machinery able to be activated, albeit in lesser amounts, by electrical and mechanical stimulation. Accordingly, this provides a potential molecular explanation of the muscle recovery that occurs in response to rehabilitation strategy as transcutaneous electrical stimulation and passive stretching of denervated muscles, which wre developed as a result of empirical clinical observations.

  13. Implantable microencapsulated dopamine (DA): prolonged functional release of DA in denervated striatal tissue.

    Science.gov (United States)

    McRae, A; Hjorth, S; Mason, D; Dillon, L; Tice, T

    1990-01-01

    Biodegradable controlled-release microcapsule systems made with the biocompatible biodegradable polyester excipient poly [DL-lactide-co-gly-colide] constitute an exciting new technology for drug delivery to the central nervous system (CNS). The present study describes functional observations indicating that implantation of dopamine (DA) microcapsules encapsulated within two different polymer excipients into denervated striatal tissue assures a prolonged release of the transmitter in vivo. This technology has a considerable potential for basic and possibly clinical research.

  14. Renal Denervation Using an Irrigated Catheter in Patients with Resistant Hypertension: A Promising Strategy?

    Energy Technology Data Exchange (ETDEWEB)

    Armaganijan, Luciana, E-mail: luciana-va@hotmail.com; Staico, Rodolfo; Moraes, Aline; Abizaid, Alexandre; Moreira, Dalmo; Amodeo, Celso; Sousa, Márcio; Borelli, Flávio; Armaganijan, Dikran; Sousa, J. Eduardo; Sousa, Amanda [Instituto Dante Pazzanese de Cardiologia, São Paulo, SP (Brazil)

    2014-04-15

    Systemic hypertension is an important public health problem and a significant cause of cardiovascular mortality. Its high prevalence and the low rates of blood pressure control have resulted in the search for alternative therapeutic strategies. Percutaneous renal sympathetic denervation emerged as a perspective in the treatment of patients with resistant hypertension. To evaluate the feasibility and safety of renal denervation using an irrigated catheter. Ten patients with resistant hypertension underwent the procedure. The primary endpoint was safety, as assessed by periprocedural adverse events, renal function and renal vascular abnormalities at 6 months. The secondary endpoints were changes in blood pressure levels (office and ambulatory monitoring) and in the number of antihypertensive drugs at 6 months. The mean age was 47.3 (± 12) years, and 90% of patients were women. In the first case, renal artery dissection occurred as a result of trauma due to the long sheath; no further cases were observed after technical adjustments, thus showing an effect of the learning curve. No cases of thrombosis/renal infarction or death were reported. Elevation of serum creatinine levels was not observed during follow-up. At 6 months, one case of significant renal artery stenosis with no clinical consequences was diagnosed. Renal denervation reduced office blood pressure levels by 14.6/6.6 mmHg, on average (p = 0.4 both for systolic and diastolic blood pressure). Blood pressure levels on ambulatory monitoring decreased by 28/17.6 mmHg (p = 0.02 and p = 0.07 for systolic and diastolic blood pressure, respectively). A mean reduction of 2.1 antihypertensive drugs was observed. Renal denervation is feasible and safe in the treatment of resistant systemic arterial hypertension. Larger studies are required to confirm our findings.

  15. Joint UK societies' 2014 consensus statement on renal denervation for resistant hypertension.

    Science.gov (United States)

    Lobo, Melvin D; de Belder, Mark A; Cleveland, Trevor; Collier, David; Dasgupta, Indranil; Deanfield, John; Kapil, Vikas; Knight, Charles; Matson, Matthew; Moss, Jonathan; Paton, Julian F R; Poulter, Neil; Simpson, Iain; Williams, Bryan; Caulfield, Mark J

    2015-01-01

    Resistant hypertension continues to pose a major challenge to clinicians worldwide and has serious implications for patients who are at increased risk of cardiovascular morbidity and mortality with this diagnosis. Pharmacological therapy for resistant hypertension follows guidelines-based regimens although there is surprisingly scant evidence for beneficial outcomes using additional drug treatment after three antihypertensives have failed to achieve target blood pressure. Recently there has been considerable interest in the use of endoluminal renal denervation as an interventional technique to achieve renal nerve ablation and lower blood pressure. Although initial clinical trials of renal denervation in patients with resistant hypertension demonstrated encouraging office blood pressure reduction, a large randomised control trial (Symplicity HTN-3) with a sham-control limb, failed to meet its primary efficacy end point. The trial however was subject to a number of flaws which must be taken into consideration in interpreting the final results. Moreover a substantial body of evidence from non-randomised smaller trials does suggest that renal denervation may have an important role in the management of hypertension and other disease states characterised by overactivation of the sympathetic nervous system. The Joint UK Societies does not recommend the use of renal denervation for treatment of resistant hypertension in routine clinical practice but remains committed to supporting research activity in this field. A number of research strategies are identified and much that can be improved upon to ensure better design and conduct of future randomised studies. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

  16. Renal Denervation for Treating Resistant Hypertension: Current Evidence and Future Insights from a Global Perspective

    OpenAIRE

    Castro Torres, Y.; Katholi, Richard E.

    2013-01-01

    Adequate blood pressure control represents an important goal for all physicians due to the complications of hypertension which reduce patients' quality of life. A new interventional strategy to reduce blood pressure has been developed for patients with resistant hypertension. Catheter-based renal denervation has demonstrated excellent results in recent investigations associated with few side effects. With the growing diffusion of this technique worldwide, some medical societies have published...

  17. Does sensory stimulation threshold affect lumbar facet radiofrequency denervation outcomes? A prospective clinical correlational study.

    Science.gov (United States)

    Cohen, Steven P; Strassels, Scott A; Kurihara, Connie; Lesnick, Ivan K; Hanling, Steven R; Griffith, Scott R; Buckenmaier, Chester C; Nguyen, Conner

    2011-11-01

    Radiofrequency facet denervation is one of the most frequently performed procedures for chronic low back pain. Although sensory stimulation is generally used as a surrogate measure to denote sufficient proximity of the electrode to the nerve, no study has examined whether stimulation threshold influences outcome. We prospectively recorded data in 61 consecutive patients undergoing lumbar facet radiofrequency denervation who experienced significant pain relief after medial branch blocks. For each nerve lesioned, multiple attempts were made to maximize sensory stimulation threshold (SST). Mean SST was calculated on the basis of the lowest stimulation perceived at 0.1-V increments for each medial branch. A positive outcome was defined as a ≥50% reduction in back pain coupled with a positive satisfaction score lasting ≥3 months. The relationship between mean SST and denervation outcomes was evaluated via a receiver's operating characteristic (ROC) curve, and stratifying outcomes on the basis of various cutoff values. No correlation was noted between mean SST and pain relief at rest (Pearson's r=-0.01, 95% confidence interval [CI]: -0.24 to 0.23, P=0.97), with activity (r=-0.17, 95% CI: -0.40 to 0.07, P=0.20), or a successful outcome. No optimal SST could be identified. There is no significant relationship between mean SST during lumbar facet radiofrequency denervation and treatment outcome, which may be due to differences in general sensory perception. Because stimulation threshold was optimized for each patient, these data cannot be interpreted to suggest that sensory testing should not be performed, or that high sensory stimulation thresholds obtained on the first attempt should be deemed acceptable.

  18. Diffusion tensor imaging and T2 mapping in early denervated skeletal muscle in rats.

    Science.gov (United States)

    Ha, Dong-Ho; Choi, Sunseob; Kang, Eun-Ju; Park, Hwan Tae

    2015-09-01

    To evaluate the temporal changes of diffusion tensor imaging (DTI) indices, T2 values, and visual signal intensity on various fat suppression techniques in the early state of denervated skeletal muscle in a rat model. Institutional Animal Care and Use Committee approval was obtained. Sciatic nerves of eight rats were transected for irreversible neurotmesis model. We examined normal lower leg and denervated muscles at 3 days, 1 week, and 2 weeks on a 3 Tesla MR. fractional anisotropy (FA), mean apparent diffusion coefficient (mADC), and T2 values were measured by using DTI and T2 mapping scan. We subjectively classified the signal intensity change on various fat suppression images into the following three grades: negative, suspicious, and definite change. Wilcoxon-sign rank test and Kruskal-Wallis test were used for the comparison of FA, mADC, T2 values. McNemar's test was used for comparing signal intensity change among fat suppression techniques. FA values of denervated muscles at 3 days (0.35 ± 0.06), 1 week (0.29 ± 0.04), and 2 weeks (0.34 ± 0.05) were significantly (P  0.05) change. T2 values were significantly increased at 1 week (38.11 ± 6.42 ms, P = 0.017) and markedly increased at 2 weeks (46.53 ± 5.17 ms, P = 0.012). The grade of visual signal intensity change on chemical shift selective fat saturation, STIR and IDEAL images were identical in all cases (P = 1.000). FA and T2 values can demonstrate the early temporal changes in denervated rat skeletal muscle. © 2014 Wiley Periodicals, Inc.

  19. Effects of renal denervation on tubular sodium handling in rats with CBL-induced liver cirrhosis

    DEFF Research Database (Denmark)

    Jonassen, T.E.; Brond, L.; Torp, M.

    2003-01-01

    This study was designed to examine the effect of bilateral renal denervation (DNX) on thick ascending limb of Henle's loop (TAL) function in rats with liver cirrhosis induced by common bile duct ligation (CBL). The CBL rats had, as previously shown, sodium retention associated with hypertrophy...... renal sympathetic nerve activity known to be present in CBL rats plays a significant role in the formation of sodium retention by stimulating sodium reabsorption in the TAL via increased renal abundance of NKCC2....

  20. Myenteric denervation differentially reduces enteroendocrine serotonin cell population in rats during postnatal development.

    Science.gov (United States)

    Hernandes, Luzmarina; Fernandes, Marilda da Cruz; Pereira, Lucieni Cristina Marques da Silva; Freitas, Priscila de; Gama, Patrícia; Alvares, Eliana Parisi

    2006-05-01

    The enteric nervous and enteroendocrine systems regulate different processes in the small intestine. Ablation of myenteric plexus with benzalkonium chloride (BAC) stimulates epithelial cell proliferation, whereas endocrine serotonin cells may inhibit the process. To evaluate the connection between the systems and the influence of myenteric plexus on serotoninergic cells in rats during postnatal development, the ileal plexus was partially removed with BAC. Rats were treated at 13 or 21 days and sacrificed after 15 days. The cell bodies of myenteric neurons were stained by beta NADH-diaphorase to detect the extension of denervation. The number of enteroendocrine cells in the ileum was estimated in crypts and villi in paraffin sections immunostained for serotonin. The number of neurons was reduced by 27.6 and 45% in rats treated on the 13th and 21st days, respectively. We tried to establish a correlation of denervation and the serotonin population according to the age of treatment. We observed a reduction of immunolabelled cells in the crypts of rats treated at 13 days, whereas this effect was seen in the villi of rats denervated at 21 days. These results suggest that the enteric nervous system might control the enteroendocrine cell population and this complex mechanism could be correlated to changes in cell proliferation.

  1. Is Tadpole Pupil in an Adolescent Girl Caused by Denervation Hypersensitivity?

    Science.gov (United States)

    Hansen, Jonas Kjeldbjerg; Møller, Hans Ulrik

    2017-06-01

    Tadpole pupil is a rarely encountered phenomenon caused by episodic, segmental iris dilator muscle spasm of short duration (2-15 minutes), occurring in clusters without a known precipitating factor. It has most commonly been described in women aged 28 to 48 years. A few hypotheses on pathogenesis have been discussed but none has been proved. Here, we present an adolescent girl with bilateral tadpole pupil that appeared during physical exercise. This is the first pediatric case of tadpole pupil, not caused by preceding surgery, to be published. Based on (1) this case in which tadpole pupil developed when the norepinephrine level rose during exercise, (2) the high ratio of patients with tadpole pupil who concurrently have or later develop Horner syndrome, in which denervation hypersensitivity is well described, (3) a previous report of a patient with both tadpole pupil and Horner syndrome who had denervation hypersensitivity on pharmacological testing, (4) a 29-year-old man with unilateral tadpole pupil induced by exercise, and (5) a 19-year-old man with bilateral tadpole pupil and possible autonomic neuropathy, we suggest denervation hypersensitivity as a probable pathogenic mechanism causing tadpole pupil. In addition, a suggestion for investigations to be performed in future pediatric cases is provided. Georg Thieme Verlag KG Stuttgart · New York.

  2. Single strip lesions radiofrequency denervation for treatment of sacroiliac joint pain: two years' results.

    Science.gov (United States)

    Bellini, Martina; Barbieri, Massimo

    2016-01-01

    Sacroiliac joint pain can be managed by intra-articular injections or radiofrequency of its innervation. Single strip lesions radiofrequency denervation is a new system. The objective of this study was to present one of the first utilizations of this innovative technique. 60 patients who met the diagnostic criteria for sacroiliac joint syndrome were enrolled in the study. In total, 102 single strip lesions radiofrequency denervations were performed. Pain intensity was measured with the Oswestry low back pain disability questionnaire and the Oswestry Disability Index whose scores were assessed at 1, 3, 6 and 12 months after the procedure. 91.8 % of the 102 radiofrequency treatments resulted in a reduction of more than 50% pain intensity relief at 1 month, 81.6% at 3 months and 59.16% at 6 months. In 35.7% of cases, the relief was continuative up to 1 year. No relief was observed in 12.24% of cases. The ODI scores improved significantly 1 month after the procedure, compared with the baseline scores. The ODI scores after 6 months improved very clearly compared with the baseline scores and with the 3-month scores. Single strip lesions radiofrequency denervation using the Simplicity III probe is a potential modality for intermediate term relief for patients with sacroiliac pain.

  3. Transcatheter Alcohol-Mediated Perivascular Renal Denervation With the Peregrine System: First-in-Human Experience.

    Science.gov (United States)

    Fischell, Tim A; Ebner, Adrian; Gallo, Santiago; Ikeno, Fumiaki; Minarsch, Laura; Vega, Félix; Haratani, Nicole; Ghazarossian, Vartan E

    2016-03-28

    This study evaluated the first clinical use of a new endovascular approach to renal denervation, using chemical neurolysis, via periadventitial infusion of dehydrated alcohol (ethanol) to perform "perivascular" renal artery sympathetic denervation. Renal denervation remains a promising technology for the treatment of hypertension and other disorders. A novel 3-needle delivery device (Peregrine System Infusion Catheter, Ablative Solutions, Inc., Kalamazoo, Michigan) was introduced into the renal arteries of 18 subjects with refractory hypertension. Microdoses of alcohol were infused bilaterally via the 3 needles into to the adventitial space (0.30 ml/artery, 37 arteries). Renal artery angiography was performed at the time of the procedure and at 6 months (n = 16). The primary safety endpoints were complications associated with the catheter insertion and delivery of the neurolytic agent or any major vascular access complications. The secondary performance endpoint was a reduction in office-based systolic blood pressure at 6 months compared with baseline. Procedural success was achieved in 100% of subjects (N = 18) and arteries (N = 37). There were no study-related adverse clinical events at follow-up. One death of a subject was recorded but determined by the investigator and an independent medical monitor to be non-study related. There were no angiographic observations of renal artery stenosis, aneurysms, or other renal artery abnormalities at 6 months (32 renal arteries). Sixteen of the 18 subjects had a 6-month follow-up. The mean office systolic blood pressure decreased from 175 ± 17 mm Hg to 151 ± 26 mm Hg (-24 mm Hg). There was an average reduction of antihypertensive medications from 3.4 (baseline) to 2.0 per subject at 6 months. Chemical renal denervation using the infusion of very low doses of alcohol directly into the adventitial space appears to be feasible and safe. This approach may be a promising alternative approach to perform catheter-based renal

  4. Neurogenic myopathies and imaging of muscle denervation; Neurogene Myopathien und Bildgebung der Muskeldenervation

    Energy Technology Data Exchange (ETDEWEB)

    Wolf, M. [Universitaetsklinikum Heidelberg, Abteilung fuer Neuroradiologie, Heidelberg (Germany); Wolf, C. [Reha-Zentrum Gernsbach, Neurologie, Gernsbach (Germany); Weber, M.A. [Universitaetsklinikum Heidelberg, Abteilung fuer Diagnostische und Interventionelle Radiologie, Heidelberg (Germany)

    2017-12-15

    Neurogenic myopathies are primary diseases of the nervous system, which secondarily result in denervation of the target musculature. The spectrum of potential causes is manifold ranging from acute traumatic injuries and chronic compression to neurodegenerative, inflammatory, metabolic and neoplastic processes. The medical history, clinical neurological examination, and electrophysiological tests including electromyography and nerve conduction studies are crucial in diagnosing neuropathic myopathies. Electromyography is the gold standard for diagnosing muscle denervation. Additional imaging methods and magnetic resonance imaging (MRI) in particular, are capable of contributing valuable information. The MRI examination of denervated musculature shows edema, an increase in the apparent diffusion coefficient (ADC) and hyperperfusion. Chronic denervation results in fatty degeneration and atrophy of affected muscles, which are also detectable by MRI. Although the MRI findings in muscle denervation are relatively unspecific, they show a high sensitivity, comparable to electromyography. Dedicated MR neurography may often visualize the underlying lesion(s) of the innervating nerve(s). Besides high sensitivity, comparable to electromyography, MRI is capable of evaluating muscles which are inaccessible for needle electromyography. Due to its non-invasive character, MRI is ideal for follow-up examinations. The use of MRI is often a meaningful addition to the diagnostics of neurogenic myopathies. The extent and distribution pattern of muscular alterations often provide information on the localization of the causative nerve damage. A correct diagnosis or at least a narrowing down of possible differential diagnoses can often be achieved using MRI. (orig.) [German] Neurogene Myopathien sind Erkrankungen des Nervensystems, die sekundaer zur Denervierung der Zielmuskulatur fuehren. Das Spektrum potenzieller Ursachen ist vielfaeltig und umfasst akute traumatische Verletzungen

  5. Peripheral denervation participates in heterotopic ossification in a spinal cord injury model.

    Directory of Open Access Journals (Sweden)

    Charlotte Debaud

    Full Text Available We previously reported the development of a new acquired neurogenic HO (NHO mouse model, combining spinal cord transection (SCI and chemical muscle injury. Pathological mechanisms responsible for ectopic osteogenesis after central neurological damage are still to be elucidated. In this study, we first hypothesized that peripheral nervous system (PNS might convey pathological signals from injured spinal cord to muscles in NHO mouse model. Secondly, we sought to determine whether SCI could lead to intramuscular modifications of BMP2 signaling pathways. Twenty one C57Bl6 mice were included in this protocol. Bilateral cardiotoxin (CTX injection in hamstring muscles was associated with a two-stage surgical procedure, combining thoracic SCI with unilateral peripheral denervation. Volumes of HO (Bone Volume, BV were measured 28 days after surgery using micro-computed tomography imaging techniques and histological analyses were made to confirm intramuscular osteogenesis. Volume comparisons were conducted between right and left hind limb of each animal, using a Wilcoxon signed rank test. Quantitative polymerase chain reaction (qPCR was performed to explore intra muscular expression of BMP2, Alk3 and Id1. Nineteen mice survive the complete SCI and peripheral denervation procedure. When CTX injections were done right after surgery (n = 7, bilateral HO were detected in all animals after 28 days. Micro-CT measurements showed significantly increased BV in denervated paws (1.47 mm3 +/- 0.5 compared to contralateral sides (0.56 mm3 +/-0.4, p = 0.03. When peripheral denervation and CTX injections were performed after sham SCI surgery (n = 6, bilateral HO were present in three mice at day 28. Quantitative PCR analyses showed no changes in intra muscular BMP2 expression after SCI as compared to control mice (shamSCI. Peripheral denervation can be reliably added to spinal cord transection in NHO mouse model. This new experimental design confirms that neuro

  6. Muscular hypertrophy and atrophy in normal rats provoked by the administration of normal and denervated muscle extracts.

    Science.gov (United States)

    Agüera, Eduardo; Castilla, Salvador; Luque, Evelio; Jimena, Ignacio; Leiva-Cepas, Fernando; Ruz-Caracuel, Ignacio; Peña, José

    2016-12-01

    This study was conducted to determine the effects of extracts obtained from both normal and denervated muscles on different muscle types. Wistar rats were used and were divided into a control group and four experimental groups. Each experimental group was treated intraperitoneally during 10 consecutive days with a different extract. These extracts were obtained from normal soleus muscle, denervated soleus, normal extensor digitorum longus, and denervated extensor digitorum longus. Following treatment, the soleus and extensor digitorum longus muscles were obtained for study under optic and transmission electron microscope; morphometric parameters and myogenic responses were also analyzed. The results demonstrated that the treatment with normal soleus muscle and denervated soleus muscle extracts provoked hypertrophy and increased myogenic activity. In contrast, treatment with extracts from the normal and denervated EDL had a different effect depending on the muscle analyzed. In the soleus muscle it provoked hypertrophy of type I fibers and increased myogenic activity, while in the extensor digitorum longus atrophy of the type II fibers was observed without changes in myogenic activity. This suggests that the muscular responses of atrophy and hypertrophy may depend on different factors related to the muscle type which could be related to innervation.

  7. Renal denervation in an animal model of diabetes and hypertension: Impact on the autonomic nervous system and nephropathy

    Directory of Open Access Journals (Sweden)

    Machado Ubiratan F

    2011-04-01

    Full Text Available Abstract Background The effects of renal denervation on cardiovascular reflexes and markers of nephropathy in diabetic-hypertensive rats have not yet been explored. Methods Aim: To evaluate the effects of renal denervation on nephropathy development mechanisms (blood pressure, cardiovascular autonomic changes, renal GLUT2 in diabetic-hypertensive rats. Forty-one male spontaneously hypertensive rats (SHR ~250 g were injected with STZ or not; 30 days later, surgical renal denervation (RD or sham procedure was performed; 15 days later, glycemia and albuminuria (ELISA were evaluated. Catheters were implanted into the femoral artery to evaluate arterial pressure (AP and heart rate variability (spectral analysis one day later in conscious animals. Animals were killed, kidneys removed, and cortical renal GLUT2 quantified (Western blotting. Results Higher glycemia (p vs. nondiabetics (p vs. SHR. Conclusions Renal denervation in diabetic-hypertensive rats improved previously reduced heart rate variability. The GLUT2 equally overexpressed by diabetes and renal denervation may represent a maximal derangement effect of each condition.

  8. Denervation atrophy is independent from Akt and mTOR activation and is not rescued by myostatin inhibition

    Directory of Open Access Journals (Sweden)

    Elizabeth M. MacDonald

    2014-04-01

    Full Text Available The purpose of our study was to compare two acquired muscle atrophies and the use of myostatin inhibition for their treatment. Myostatin naturally inhibits skeletal muscle growth by binding to ActRIIB, a receptor on the cell surface of myofibers. Because blocking myostatin in an adult wild-type mouse induces profound muscle hypertrophy, we applied a soluble ActRIIB receptor to models of disuse (limb immobilization and denervation (sciatic nerve resection atrophy. We found that treatment of immobilized mice with ActRIIB prevented the loss of muscle mass observed in placebo-treated mice. Our results suggest that this protection from disuse atrophy is regulated by serum and glucocorticoid-induced kinase (SGK rather than by Akt. Denervation atrophy, however, was not protected by ActRIIB treatment, yet resulted in an upregulation of the pro-growth factors Akt, SGK and components of the mTOR pathway. We then treated the denervated mice with the mTOR inhibitor rapamycin and found that, despite a reduction in mTOR activation, there is no alteration of the atrophy phenotype. Additionally, rapamycin prevented the denervation-induced upregulation of the mTORC2 substrates Akt and SGK. Thus, our studies show that denervation atrophy is not only independent from Akt, SGK and mTOR activation but also has a different underlying pathophysiological mechanism than disuse atrophy.

  9. Skeletal muscles of hibernating brown bears are unusually resistant to effects of denervation.

    Science.gov (United States)

    Lin, David C; Hershey, John D; Mattoon, John S; Robbins, Charles T

    2012-06-15

    Hibernating bears retain most of their skeletal muscle strength despite drastically reduced weight-bearing activity. Regular neural activation of muscles is a potential mechanism by which muscle atrophy could be limited. However, both mechanical loading and neural activity are usually necessary to maintain muscle size. An alternative mechanism is that the signaling pathways related to the regulation of muscle size could be altered so that neither mechanical nor neural inputs are needed for retaining strength. More specifically, we hypothesized that muscles in hibernating bears are resistant to a severe reduction in neural activation. To test this hypothesis, we unilaterally transected the common peroneal nerve, which innervates ankle flexor muscles, in hibernating and summer-active brown bears (Ursus arctos). In hibernating bears, the long digital extensor (LDE) and cranial tibial (CT) musculotendon masses on the denervated side decreased after 11 weeks post-surgery by 18 ± 11 and 25 ± 10%, respectively, compared with those in the intact side. In contrast, decreases in musculotendon masses of summer-active bears after denervation were 61 ± 4 and 58 ± 5% in the LDE and CT, respectively, and significantly different from those of hibernating bears. The decrease due to denervation in summer-active bears was comparable to that occurring in other mammals. Whole-muscle cross-sectional areas (CSAs) measured from ultrasound images and myofiber CSAs measured from biopsies decreased similarly to musculotendon mass. Thus, hibernating bears alter skeletal muscle catabolic pathways regulated by neural activity, and exploration of these pathways may offer potential solutions for disuse atrophy of muscles.

  10. How long does denervation take in poliomyelitis? Or is it a lifetime?”

    Directory of Open Access Journals (Sweden)

    Mehmet Guney Senol

    2017-01-01

    Full Text Available Background and Objective: This study aims to determine the period of reinnervation in patients with poliomyelitis. This research was conducted to identify the appearance of denervation potentials in patients with poliomyelitis as indicators for reinnervation. Materials and Methods: A total of 246 male patients with poliomyelitis were assessed electrophysiologically between 1988 and 2007. The mean age was 22.8 (18–42. It has been an average of 19.9 ± 4.9 years since the beginning of complaints from the patients. Results: The patients had no complaints of newly developing muscle weakness, fatigue, muscle and joint pain, and difficulties in breathing and swallowing. Neurological examinations revealed the absence of myotomal pain and sensory loss. Upon assessment of the patients' limbs, the following findings were revealed: two patients had left upper and lower limb involvement, two patients had left upper and right lower limb involvement, 6 patients had left upper limb involvement, 12 patients had both lower limb involvement, 105 patients had left lower limb involvement, 1 patient had both upper limb involvement, 2 patients had right lower and upper limb involvement, 12 patients had right upper limb involvement, 6 patients had both lower limb involvement, 95 patients had right lower limb involvement, and 3 had all the three extremities affected. The needle electromyography revealed the presence of denervation potentials in 25.2% (62 of the patients. Conclusion: When poliovirus attacks the motor neuron, this neuron may be completely destroyed, damaged, or unaffected. Reinnervation occurs when nearby functioning motor units send out terminal axon sprouts to reinnervate the damaged muscle fibers. As a consequence of poliomyelitis, several muscle fibers become atrophic and fibrotic, but others continue to survive. This study showed that patients with a history of poliomyelitis experienced denervation with subsequent reinnervation for many years.

  11. Electrical stimulation attenuates morphological alterations and prevents atrophy of the denervated cranial tibial muscle.

    Science.gov (United States)

    Bueno, Cleuber Rodrigo de Souza; Pereira, Mizael; Favaretto, Idvaldo Aparecido; Bortoluci, Carlos Henrique Fachin; Santos, Thais Caroline Pereira Dos; Dias, Daniel Ventura; Daré, Letícia Rossi; Rosa, Geraldo Marco

    2017-01-01

    To investigate if electrical stimulation through Russian current is able to maintain morphology of the cranial tibial muscle of experimentally denervated rats. Thirty-six Wistar rats were divided into four groups: the Initial Control Group, Final Control Group, Experimental Denervated and Treated Group, Experimental Denervated Group. The electrostimulation was performed with a protocol of Russian current applied three times per week, for 45 days. At the end, the animals were euthanized and histological and morphometric analyses were performed. Data were submitted to statistical analysis with a significance level of pprotocolo de corrente russa aplicada três vezes por semanas, durante 45 dias. Ao final, os animais foram eutanasiados e, em seguida, foram realizadas as análises histológica e morfométrica. Os dados foram submetidos à análise estatística, com nível de significância de p<0,05. Os Grupos Experimental Desnervado e o Grupo Experimental Desnervado Tratado apresentaram área de secção transversal da fibra menor quando comparados ao Grupo Controle Final. Entretanto, constatou-se diferença significativa entre o Grupo Experimental Desnervado e o Grupo Experimental Desnervado Tratado, mostrando que a estimulação elétrica minimizou atrofia muscular. Ainda, observou-se que o Grupo Experimental Desnervado Tratado apresentou resultados semelhantes ao Grupo Controle Inicial. A estimulação elétrica por meio da corrente russa foi favorável na manutenção da morfologia do músculo tibial cranial desnervado experimentalmente, minimizando a atrofia muscular.

  12. Impaired growth of denervated muscle contributes to contracture formation following neonatal brachial plexus injury.

    Science.gov (United States)

    Nikolaou, Sia; Peterson, Elizabeth; Kim, Annie; Wylie, Christopher; Cornwall, Roger

    2011-03-02

    The etiology of shoulder and elbow contractures following neonatal brachial plexus injury is incompletely understood. With use of a mouse model, the current study tests the novel hypothesis that reduced growth of denervated muscle contributes to contractures following neonatal brachial plexus injury. Unilateral brachial plexus injuries were created in neonatal mice by supraclavicular C5-C6 nerve root excision. Shoulder and elbow range of motion was measured four weeks after injury. Fibrosis, cross-sectional area, and functional length of the biceps, brachialis, and subscapularis muscles were measured over four weeks following injury. Muscle satellite cells were cultured from denervated and control biceps muscles to assess myogenic capability. In a comparison group, shoulder motion and subscapularis length were assessed following surgical excision of external rotator muscles. Shoulder internal rotation and elbow flexion contractures developed on the involved side within four weeks following brachial plexus injury. Excision of the biceps and brachialis muscles relieved the elbow flexion contractures. The biceps muscles were histologically fibrotic, whereas fatty infiltration predominated in the brachialis and rotator cuff muscles. The biceps and brachialis muscles displayed reduced cross-sectional and longitudinal growth compared with the contralateral muscles. The upper subscapularis muscle similarly displayed reduced longitudinal growth, with the subscapularis shortening correlating with internal rotation contracture. However, excision of the external rotators without brachial plexus injury caused no contractures or subscapularis shortening. Myogenically capable satellite cells were present in denervated biceps muscles despite impaired muscle growth in vivo. Injury of the upper trunk of the brachial plexus leads to impaired growth of the biceps and brachialis muscles, which are responsible for elbow flexion contractures, and impaired growth of the subscapularis

  13. Anatomic Patterns of Renal Arterial Sympathetic Innervation: New Aspects for Renal Denervation.

    Science.gov (United States)

    Imnadze, Guram; Balzer, Stefan; Meyer, Baerbel; Neumann, Joerg; Krech, Rainer Horst; Thale, Joachim; Franz, Norbert; Warnecke, Henning; Awad, Khaled; Hayek, Salim S; Devireddy, Chandan

    2016-12-01

    Initial studies of catheter-based renal arterial sympathetic denervation to lower blood pressure in resistant hypertensive patients renewed interest in the sympathetic nervous system's role in the pathogenesis of hypertension. However, the SYMPLICITY HTN-3 study failed to meet its prespecified blood pressure lowering efficacy endpoint. To date, only a limited number of studies have described the microanatomy of renal nerves, of which, only two involve humans. Renal arteries were harvested from 15 cadavers from the Klinikum Osnabruck and Schuchtermann Klinik, Bad Rothenfelde. Each artery was divided longitudinally in equal thirds (proximal, middle, and distal), with each section then divided into equal superior, inferior, anterior, and posterior quadrants, which were then stained. Segments containing no renal nerves were given a score value = 0, 1-2 nerves with diameter 4 nerves or nerve diameter ≥600 µm a score = 3. A total of 22 renal arteries (9 right-sided, 13 left-sided) were suitable for examination. Overall, 691 sections of 5 mm thickness were prepared. Right renal arteries had significantly higher mean innervation grade (1.56 ± 0.85) compared to left renal arteries (1.09 ± 0.87) (P renal artery has significantly higher innervation scores than the left. The anterior and superior quadrants of the renal arteries scored higher in innervation than the posterior and inferior quadrants did. The distal third of the renal arteries are more innervated than the more proximal segments. These findings warrant further evaluation of the spatial innervation patterns of the renal artery in order to understand how it may enhance catheter-based renal arterial denervation procedural strategy and outcomes. The SYMPLICITY HTN-3 study dealt a blow to the idea of the catheter-based renal arterial sympathetic denervation. We investigated the location and patterns of periarterial renal nerves in cadaveric human renal arteries. To quantify the density of the

  14. Denervation of the lateral humeral epicondyle for treatment of chronic lateral epicondylitis.

    Science.gov (United States)

    Rose, Nicholas E; Forman, Scott K; Dellon, A Lee

    2013-02-01

    Chronic lateral epicondylitis remains a treatment challenge. Traditional surgical treatments for lateral epicondylitis involve variations of the classic Nirschl lateral release. Anatomic studies reveal that the posterior branch or branches of the posterior cutaneous nerve of the forearm consistently innervate the lateral humeral epicondyle. We undertook the present study to determine the effectiveness of denervation of the lateral humeral epicondyle in treating chronic lateral epicondylitis. An institutional review board-approved prospective study included 30 elbows in 26 patients. Inclusion criteria included failure to respond to nonoperative treatment for more than 6 months and improvement in grip strength and in visual analog pain scale after diagnostic nerve block of the posterior branches of the posterior cutaneous nerve of the forearm proximal to the lateral humeral epicondyle. We excluded patients who had undergone previous surgery for lateral epicondylitis. Outcome measures included visual analog pain scale and grip strength testing. Denervation surgery involved identification and transection of the posterior cutaneous nerve of the forearm branches with implantation into the triceps. The presence of radial tunnel syndrome was noted but did not affect inclusion criteria; if it was present, we did not correct it surgically. We used no postoperative splinting and permitted immediate return to activities of daily living. At a mean of 28 months of follow-up, the average visual analog scale score decreased from 7.9 to 1.9. Average grip strength with the elbow extended improved from 13 to 24 kg. A total of 80% of patients had good or excellent results, as defined by an improvement of 5 or more points on the visual analog scale for pain. Denervation of the lateral epicondyle was effective in relieving pain in 80% of patients with chronic lateral epicondylitis who had a positive response to a local anesthetic block of the posterior branches of the posterior

  15. Renal denervation attenuates NADPH oxidase-mediated oxidative stress and hypertension in rats with hydronephrosis

    DEFF Research Database (Denmark)

    Peleli, Maria; Al-Mashhadi, Ammar; Yang, Ting

    2016-01-01

    Hydronephrosis is associated with development of salt-sensitive hypertension. Studies suggest that increased sympathetic nerve activity (SNA) and oxidative stress play important roles in renovascular hypertension. This study aimed to investigate the link between renal SNA and NADPH oxidase (NOX......) regulation in the development of hypertension in rats with hydronephrosis. Hydronephrosis was induced by partial unilateral ureteral obstruction (PUUO) in young rats. Sham surgery or renal denervation was performed at the same time. Blood pressure was measured during normal, high and low salt diets. Renal...

  16. [Renal denervation in resistant hypertension: proposal for a common multidisciplinary attitude].

    Science.gov (United States)

    Muller, Olivier; Qanadli, Salah D; Waeber, Bernard; Wuerzner, Grégoire

    2012-05-30

    The prevalence of resistant hypertension ranges between 5-30%. Patients with resistant hypertension are at increased risk of cardiovascular events. Radiofrequency renal denervation is a recent and promising technique that can be used in the setting of resistant hypertension. However, long-term safety and efficacy data are lacking and evidence to use this procedure outside the strict setting of resistant hypertension is missing. The aim of the article is to propose a common work-up for nephrologists, hypertensiologists, cardiologists and interventional radiologists in order to avoid inappropriate selection of patients and a possible misuse of this procedure.

  17. Catheter-Based Renal Denervation for Resistant Hypertension: Will It Ever Be Ready for "Prime Time"?

    Science.gov (United States)

    Laffin, Luke J; Bakris, George L

    2017-09-01

    The year 2014 was a turning point for the field of renal denervation (RDN) and its potential use to treat resistant hypertension. Tremendous enthusiasm shifted to sober reflection on the efficacy of a technology once touted as the cure to resistant hypertension. The following review highlights 2 major questions: First, does catheter-based RDN lower blood pressure and, second, will RDN using catheter-directed therapy for the treatment of resistant hypertension ever become more than an investigational technology. © American Journal of Hypertension, Ltd 2016. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  18. Revisiting renovascular imaging for renal sympathetic denervation: current techniques and applications

    Energy Technology Data Exchange (ETDEWEB)

    Pua, Uei; Tan, Cher Heng [Tan Tock Seng Hospital, Department of Diagnostic Radiology, Singapore (Singapore); Ho, Hee Hwa; Tan, Julian Ko Beng; Ong, Paul Jau Leong [Tan Tock Seng Hospital, Department of Cardiology, Singapore (Singapore)

    2014-08-28

    Renal sympathetic denervation (RDN) is an emerging technique in the treatment of resistant hypertension, most commonly performed using an endovascular approach. Clinical and anatomical criteria for RDN are well established and imaging plays an integral role in selecting patients with suitable anatomy, procedural planning and device selection. Nevertheless, the current body of literature surrounding imaging related to RDN remains limited. The purpose of this article is to illustrate the expectations and limitations of various imaging techniques, including Doppler ultrasound, CT angiography, MR angiography and newer techniques such as non-contrast MR angiography, in the context of RDN. (orig.)

  19. Revisiting renovascular imaging for renal sympathetic denervation: current techniques and applications

    International Nuclear Information System (INIS)

    Pua, Uei; Tan, Cher Heng; Ho, Hee Hwa; Tan, Julian Ko Beng; Ong, Paul Jau Leong

    2015-01-01

    Renal sympathetic denervation (RDN) is an emerging technique in the treatment of resistant hypertension, most commonly performed using an endovascular approach. Clinical and anatomical criteria for RDN are well established and imaging plays an integral role in selecting patients with suitable anatomy, procedural planning and device selection. Nevertheless, the current body of literature surrounding imaging related to RDN remains limited. The purpose of this article is to illustrate the expectations and limitations of various imaging techniques, including Doppler ultrasound, CT angiography, MR angiography and newer techniques such as non-contrast MR angiography, in the context of RDN. (orig.)

  20. Renal Sympathetic Denervation by CT-scan-Guided Periarterial Ethanol Injection in Sheep

    International Nuclear Information System (INIS)

    Firouznia, Kavous; Hosseininasab, Sayed jaber; Amanpour, Saeid; Haj-Mirzaian, Arya; Miri, Roza; Muhammadnejad, Ahad; Muhammadnejad, Samad; Jalali, Amir H.; Ahmadi, Farrokhlagha; Rokni-Yazdi, Hadi

    2015-01-01

    BackgroundRenal nerves are a recent target in the treatment of hypertension. Renal sympathetic denervation (RSD) is currently performed using catheter-based radiofrequency ablation (RFA) and because this method has limitations, percutaneous magnetic resonance (MR)-guided periarterial ethanol injection is a suggested alternative. However, few studies have been conducted on the effectiveness of percutaneous ethanol injection for RSD.AimTo evaluate the feasibility, efficacy, and complications of computed tomography (CT)-guided periarterial ethanol injection.MethodsEthanol (10 ml, 99.6 %) was injected around the right renal artery in six sheep under CT guidance with the left kidney serving as a control. Before and after the intervention, the sheep underwent MR imaging studies and the serum creatinine level was measured. One month after the intervention, the sheep were euthanized and norepinephrine (NE) concentration in the renal parenchyma was measured to evaluate the efficacy of the procedure. The treated tissues were also examined histopathologically to evaluate vascular, parenchymal, and neural injury.ResultsThe right kidney parenchymal NE concentration decreased significantly compared with the left kidney after intervention (average reduction: 40 %, P = 0.0016). Histologic examination revealed apparent denervation with no other vascular or parenchymal injuries observed in the histological and imaging studies.ConclusionEffective and feasible RSD was achieved using CT-guided periarterial ethanol injection. This technique may be a potential alternative to catheter-based RFA in the treatment of hypertension

  1. MR-guided Periarterial Ethanol Injection for Renal Sympathetic Denervation: A Feasibility Study in Pigs

    International Nuclear Information System (INIS)

    Streitparth, F.; Walter, A.; Stolzenburg, N.; Heckmann, L.; Breinl, J.; Rinnenthal, J. L.; Beck, A.; De Bucourt, M.; Schnorr, J.; Bernhardt, U.; Gebauer, B.; Hamm, B.; Günther, R. W.

    2013-01-01

    Purpose. To evaluate the feasibility and efficacy of image-guided periarterial ethanol injection as an alternative to transluminal radiofrequency ablation. Methods. Unilateral renal periarterial ethanol injection was performed under general anesthesia in 6 pigs with the contralateral kidney serving as control. All interventions were performed in an open 1.0 T MRI system under real-time multiplanar guidance. The injected volume was 5 ml (95 % ethanol labelled marked MR contrast medium) in 2 pigs and 10 ml in 4 pigs. Four weeks after treatment, the pigs underwent MRI including MRA and were killed. Norepinephrine (NE) concentration in the renal parenchyma served as a surrogate parameter to analyze the efficacy of sympathetic denervation. In addition, the renal artery and sympathetic nerves were examined histologically to identify evidence of vascular and neural injury. Results. In pigs treated with 10 ml ethanol, treatment resulted in neural degeneration. We found a significant reduction of NE concentration in the kidney parenchyma of 53 % (p < 0.02) compared with the untreated contralateral kidney. In pigs treated with 5 ml ethanol, no significant changes in histology or NE were observed. There was no evidence of renal arterial stenosis in MRI, macroscopy or histology in any pig. Conclusion. MR-guided periarterial ethanol injection was feasible and efficient for renal sympathetic denervation in a swine model. This technique may be a promising alternative to the catheter-based approach in the treatment of resistant arterial hypertension.

  2. Renal Sympathetic Denervation by CT-scan-Guided Periarterial Ethanol Injection in Sheep

    Energy Technology Data Exchange (ETDEWEB)

    Firouznia, Kavous, E-mail: k-firouznia@yahoo.com; Hosseininasab, Sayed jaber, E-mail: dr.hosseininasab@gmail.com [Tehran University of Medical Sciences (TMUS), Advanced Diagnostic and Interventional Radiology Research Center (ADIR), Imam Khomeini Hospital Complex (Iran, Islamic Republic of); Amanpour, Saeid, E-mail: saeidamanpour@yahoo.com [Tehran University of Medical Science, Cancer Models Research Center, Cancer Institute of Iran (Iran, Islamic Republic of); Haj-Mirzaian, Arya, E-mail: arya.mirzaian@gmail.com [Tehran University of Medical Science, Department of Radiology and Imaging, MIC, Imam Khomeini Hospital (Iran, Islamic Republic of); Miri, Roza, E-mail: rosa.miri@yahoo.com [Tehran University of Medical Science, Department of Pathology, Imam Khomeini Hospital Complex (Iran, Islamic Republic of); Muhammadnejad, Ahad, E-mail: mohamadnejad@yahoo.com [Tehran University of Medical Science, Cancer Research Center, Cancer Institute of Iran (Iran, Islamic Republic of); Muhammadnejad, Samad, E-mail: s-muhammadnejad@sina.tums.ac.ir [Tehran University of Medical Sciences, Research Center for Molecular and Cellular Imaging (Iran, Islamic Republic of); Jalali, Amir H., E-mail: amirjalali51@yahoo.com [Tehran University of Medical Sciences (TMUS), Advanced Diagnostic and Interventional Radiology Research Center (ADIR), Imam Khomeini Hospital Complex (Iran, Islamic Republic of); Ahmadi, Farrokhlagha, E-mail: ahmadi@tums.ac.ir [Tehran University of Medical Sciences, Nephrology Research Center, Imam Khomeini Hospital Complex (Iran, Islamic Republic of); Rokni-Yazdi, Hadi, E-mail: rokniyaz@tums.ac.ir [Tehran University of Medical Sciences (TMUS), Advanced Diagnostic and Interventional Radiology Research Center (ADIR), Imam Khomeini Hospital Complex (Iran, Islamic Republic of)

    2015-08-15

    BackgroundRenal nerves are a recent target in the treatment of hypertension. Renal sympathetic denervation (RSD) is currently performed using catheter-based radiofrequency ablation (RFA) and because this method has limitations, percutaneous magnetic resonance (MR)-guided periarterial ethanol injection is a suggested alternative. However, few studies have been conducted on the effectiveness of percutaneous ethanol injection for RSD.AimTo evaluate the feasibility, efficacy, and complications of computed tomography (CT)-guided periarterial ethanol injection.MethodsEthanol (10 ml, 99.6 %) was injected around the right renal artery in six sheep under CT guidance with the left kidney serving as a control. Before and after the intervention, the sheep underwent MR imaging studies and the serum creatinine level was measured. One month after the intervention, the sheep were euthanized and norepinephrine (NE) concentration in the renal parenchyma was measured to evaluate the efficacy of the procedure. The treated tissues were also examined histopathologically to evaluate vascular, parenchymal, and neural injury.ResultsThe right kidney parenchymal NE concentration decreased significantly compared with the left kidney after intervention (average reduction: 40 %, P = 0.0016). Histologic examination revealed apparent denervation with no other vascular or parenchymal injuries observed in the histological and imaging studies.ConclusionEffective and feasible RSD was achieved using CT-guided periarterial ethanol injection. This technique may be a potential alternative to catheter-based RFA in the treatment of hypertension.

  3. Modulation of the Neuregulin 1/ErbB system after skeletal muscle denervation and reinnervation.

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    Morano, Michela; Ronchi, Giulia; Nicolò, Valentina; Fornasari, Benedetta Elena; Crosio, Alessandro; Perroteau, Isabelle; Geuna, Stefano; Gambarotta, Giovanna; Raimondo, Stefania

    2018-03-22

    Neuregulin 1 (NRG1) is a growth factor produced by both peripheral nerves and skeletal muscle. In muscle, it regulates neuromuscular junction gene expression, acetylcholine receptor number, muscle homeostasis and satellite cell survival. NRG1 signalling is mediated by the tyrosine kinase receptors ErbB3 and ErbB4 and their co-receptors ErbB1 and ErbB2. The NRG1/ErbB system is well studied in nerve tissue after injury, but little is known about this system in skeletal muscle after denervation/reinnervation processes. Here, we performed a detailed time-course expression analysis of several NRG1 isoforms and ErbB receptors in the rat superficial digitorum flexor muscle after three types of median nerve injuries of different severities. We found that ErbB receptor expression was correlated with the innervated state of the muscle, with upregulation of ErbB2 clearly associated with the denervation state. Interestingly, the NRG1 isoforms were differently regulated depending on the nerve injury type, leading to the hypothesis that both the NRG1α and NRG1β isoforms play a key role in the muscle reaction to injury. Indeed, in vitro experiments with C2C12 atrophic myotubes revealed that both NRG1α and NRG1β treatment influences the best-known atrophic pathways, suggesting that NRG1 might play an anti-atrophic role.

  4. Efficacy and safety of catheter-based radiofrequency renal denervation in stented renal arteries.

    Science.gov (United States)

    Mahfoud, Felix; Tunev, Stefan; Ruwart, Jennifer; Schulz-Jander, Daniel; Cremers, Bodo; Linz, Dominik; Zeller, Thomas; Bhatt, Deepak L; Rocha-Singh, Krishna; Böhm, Michael; Melder, Robert J

    2014-12-01

    In selected patients with hypertension, renal artery (RA) stenting is used to treat significant atherosclerotic stenoses. However, blood pressure often remains uncontrolled after the procedure. Although catheter-based renal denervation (RDN) can reduce blood pressure in certain patients with resistant hypertension, there are no data on the feasibility and safety of RDN in stented RA. We report marked blood pressure reduction after RDN in a patient with resistant hypertension who underwent previous stenting. Subsequently, radiofrequency ablation was investigated within the stented segment of porcine RA, distal to the stented segment, and in nonstented RA and compared with stent only and untreated controls. There were neither observations of thrombus nor gross or histological changes in the kidneys. After radiofrequency ablation of the nonstented RA, sympathetic nerves innervating the kidney were significantly reduced, as indicated by significant decreases in sympathetic terminal axons and reduction of norepinephrine in renal tissue. Similar denervation efficacy was found when RDN was performed distal to a renal stent. In contrast, when radiofrequency ablation was performed within the stented segment of the RA, significant sympathetic nerve ablation was not seen. Histological observation showed favorable healing in all arteries. Radiofrequency ablation of previously stented RA demonstrated that RDN provides equally safe experimental procedural outcomes in a porcine model whether the radiofrequency treatment is delivered within, adjacent, or without the stent struts being present in the RA. However, efficacious RDN is only achieved when radiofrequency ablation is delivered to the nonstented RA segment distal to the stent. © 2014 American Heart Association, Inc.

  5. MR-guided Periarterial Ethanol Injection for Renal Sympathetic Denervation: A Feasibility Study in Pigs

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    Streitparth, F., E-mail: florian.streitparth@charite.de; Walter, A.; Stolzenburg, N.; Heckmann, L.; Breinl, J. [Charite, Humboldt University, Department of Radiology (Germany); Rinnenthal, J. L. [Charite, Humboldt University, Department of Neuropathology (Germany); Beck, A.; De Bucourt, M.; Schnorr, J. [Charite, Humboldt University, Department of Radiology (Germany); Bernhardt, U. [InnoRa GmbH (Germany); Gebauer, B.; Hamm, B.; Guenther, R. W. [Charite, Humboldt University, Department of Radiology (Germany)

    2013-06-15

    Purpose. To evaluate the feasibility and efficacy of image-guided periarterial ethanol injection as an alternative to transluminal radiofrequency ablation. Methods. Unilateral renal periarterial ethanol injection was performed under general anesthesia in 6 pigs with the contralateral kidney serving as control. All interventions were performed in an open 1.0 T MRI system under real-time multiplanar guidance. The injected volume was 5 ml (95 % ethanol labelled marked MR contrast medium) in 2 pigs and 10 ml in 4 pigs. Four weeks after treatment, the pigs underwent MRI including MRA and were killed. Norepinephrine (NE) concentration in the renal parenchyma served as a surrogate parameter to analyze the efficacy of sympathetic denervation. In addition, the renal artery and sympathetic nerves were examined histologically to identify evidence of vascular and neural injury. Results. In pigs treated with 10 ml ethanol, treatment resulted in neural degeneration. We found a significant reduction of NE concentration in the kidney parenchyma of 53 % (p < 0.02) compared with the untreated contralateral kidney. In pigs treated with 5 ml ethanol, no significant changes in histology or NE were observed. There was no evidence of renal arterial stenosis in MRI, macroscopy or histology in any pig. Conclusion. MR-guided periarterial ethanol injection was feasible and efficient for renal sympathetic denervation in a swine model. This technique may be a promising alternative to the catheter-based approach in the treatment of resistant arterial hypertension.

  6. Radiofrequency denervation of the hip joint for pain management: case report and literature review.

    Science.gov (United States)

    Gupta, Gaurav; Radhakrishna, Mohan; Etheridge, Paul; Besemann, Markus; Finlayson, Robert J

    2014-01-01

    A 55-year-old male presented with severe pain and functional limitations as a result of left hip osteoarthritis. He had failed multiple treatments while waiting for a hip arthroplasty, including physical therapy, medications, and various intra-articular injections. Thermal radiofrequency lesioning of the obturator and femoral articular branches to the hip joint was offered in the interim. To our knowledge, this is the first report to describe an inferior-lateral approach for lesioning the obturator branch, the clinical application of successive lesions to increase denervation area, and outcomes in a patient receiving a second treatment with previously good results. To discuss relevant and technical factors for this specific case, we reviewed previous literature on hip joint radiofrequency and critically evaluated previous anatomic studies in the context of radiofrequency. The first treatment provided significant benefit for a period of 6 months. A second treatment was employed providing only mild to moderate benefit until his joint replacement surgery 4 months later. Literature review revealed studies of low quality secondary to small sample sizes, patient selection methodology, inclusion of patients with heterogenous etiologies for pain, variable needle placement techniques, and lack of measurement of functional outcomes. Case report and low quality studies in existing literature. Hip joint radiofrequency denervation is a promising avenue for adjunctive treatment of hip pain. Further cadaveric studies are required to clarify a multitude of technical parameters. Once these are well defined, future clinical studies should consider pain, functional, and economic outcomes in their design.

  7. Reduction of Blood Pressure Following After Renal Artery Adventitia Stripping During Total Nephroureterectomy: Potential Effect of Renal Sympathetic Denervation.

    Science.gov (United States)

    Okamura, Keisuke; Satou, Shunsuke; Setojima, Keita; Shono, Shinjiro; Miyajima, Shigero; Ishii, Tatsu; Shirai, Kazuyuki; Urata, Hidenori

    2018-05-16

    BACKGROUND Catheter-based renal sympathetic denervation has been reported to be effective for treatment resistance hypertension in Australia and Europe. However, in the blinded SYMPLICITY HTN-3 trial, renal denervation did not achieve a significant decrease in blood pressure (BP) in comparison to sham controls. There have been various discussions on the factors that influenced this result. CASE REPORT Two men on antihypertensive therapy underwent unilateral radical nephroureterectomy for cancer of the renal pelvis. When the renal artery adventitia was stripped and cauterized just before renal artery ligation, the measured BP of the 2 men increased after stripping adventitia and decreased gradually after cauterization of the renal artery. This was presumably due to removal of renal artery sympathetic nerves, similar to the mechanism of catheter-based renal sympathetic denervation, although anesthesia, fluid infusion, and/or mesenteric traction may have had an influence. CONCLUSIONS A similar strategy involving thoracolumbar sympathectomy was reported about 50 years ago. The clinically significant blood pressure reduction in these patients suggests renal denervation is effective.

  8. Effects of renal sympathetic denervation on cardiac sympathetic activity and function in patients with therapy resistant hypertension

    NARCIS (Netherlands)

    van Brussel, Peter M.; Eeftinck Schattenkerk, Daan W.; Dobrowolski, Linn C.; de Winter, Robbert J.; Reekers, Jim A.; Verberne, Hein J.; Vogt, Liffert; van den Born, Bert-Jan H.

    2016-01-01

    Renal sympathetic denervation (RSD) is currently being investigated in multiple studies of sympathetically driven cardiovascular diseases such as heart failure and arrhythmias. Our aim was to assess systemic and cardiac sympatholytic effects of RSD by the measurement of cardiac sympathetic activity

  9. Electrical Stimulation of Denervated Rat Skeletal Muscle Retards Capillary and Muscle Loss in Early Stages of Disuse Atrophy

    Directory of Open Access Journals (Sweden)

    Kouki Nakagawa

    2017-01-01

    Full Text Available The purpose of the present study is to investigate the effects of low-frequency electrical muscle stimulation (ES on the decrease in muscle mass, fiber size, capillary supply, and matrix metalloproteinase (MMP immunoreactivity in the early stages of denervation-induced limb disuse. Direct ES was performed on the tibialis anterior muscle following denervation in seven-week-old male rats. The rats were divided into the following groups: control (CON, denervation (DN, and denervation with direct ES (DN + ES. Direct ES was performed at an intensity of 16 mA and a frequency of 10 Hz for 30 min per day, six days a week, for one week. We performed immunohistochemical staining to determine the expression of dystrophin, CD34, and MMP-2 in transverse sections of TA muscles. The weight, myofiber cross-sectional area (FCSA, and capillary-to-fiber (C/F ratio of the tibialis anterior (TA muscle were significantly reduced in the DN group compared to the control and DN + ES groups. The MMP-2 positive area was significantly greater in DN and DN + ES groups compared to the control group. These findings suggest beneficial effects of direct ES in reducing muscle atrophy and capillary regression without increasing MMP-2 immunoreactivity in the early stages of DN-induced muscle disuse in rat hind limbs.

  10. Electrical Stimulation of Denervated Rat Skeletal Muscle Retards Capillary and Muscle Loss in Early Stages of Disuse Atrophy

    Science.gov (United States)

    Nakagawa, Kouki; Hayao, Keishi; Yotani, Kengo; Ogita, Futoshi; Yamamoto, Noriaki; Onishi, Hideaki

    2017-01-01

    The purpose of the present study is to investigate the effects of low-frequency electrical muscle stimulation (ES) on the decrease in muscle mass, fiber size, capillary supply, and matrix metalloproteinase (MMP) immunoreactivity in the early stages of denervation-induced limb disuse. Direct ES was performed on the tibialis anterior muscle following denervation in seven-week-old male rats. The rats were divided into the following groups: control (CON), denervation (DN), and denervation with direct ES (DN + ES). Direct ES was performed at an intensity of 16 mA and a frequency of 10 Hz for 30 min per day, six days a week, for one week. We performed immunohistochemical staining to determine the expression of dystrophin, CD34, and MMP-2 in transverse sections of TA muscles. The weight, myofiber cross-sectional area (FCSA), and capillary-to-fiber (C/F) ratio of the tibialis anterior (TA) muscle were significantly reduced in the DN group compared to the control and DN + ES groups. The MMP-2 positive area was significantly greater in DN and DN + ES groups compared to the control group. These findings suggest beneficial effects of direct ES in reducing muscle atrophy and capillary regression without increasing MMP-2 immunoreactivity in the early stages of DN-induced muscle disuse in rat hind limbs. PMID:28497057

  11. The morphological substrate for Renal Denervation : Nerve distribution patterns and parasympathetic nerves. A post-mortem histological study

    NARCIS (Netherlands)

    van Amsterdam, Wouter A C; Blankestijn, Peter J; Goldschmeding, Roel; Bleys, Ronald L A W

    2015-01-01

    BACKGROUND: Renal Denervation as a possible treatment for hypertension has been studied extensively, but knowledge on the distribution of nerves surrounding the renal artery is still incomplete. While sympathetic and sensory nerves have been demonstrated, there is no mention of the presence of

  12. Antifibrillatory effects of renal denervation on ventricular fibrillation in a canine model of pacing-induced heart failure.

    Science.gov (United States)

    Luo, Qingzhi; Jin, Qi; Zhang, Ning; Huang, Shangwei; Han, Yanxin; Lin, Changjian; Ling, Tianyou; Chen, Kang; Pan, Wenqi; Wu, Liqun

    2018-01-01

    What is the central question of this study? In the present study, we investigated the effects of renal denervation on the vulnerability to ventricular fibrillation and the ventricular electrical properties in a rapid pacing-induced heart failure canine model. What is the main finding and its importance? Renal denervation significantly attenuated the process of heart failure and improved left ventricular systolic dysfunction, stabilized ventricular electrophysiological properties and decreased the vulnerability of the heart to ventricular fibrillation during heart failure. Thus, renal denervation can attenuate ventricular electrical remodelling and exert a potential antifibrillatory action in a pacing-induced heart failure canine model. In this study, we investigated the effects of renal denervation (RDN) on the vulnerability to ventricular fibrillation (VF) and the ventricular electrical properties in a canine model of pacing-induced heart failure (HF). Eighteen beagles were divided into the following three groups: control (n = 6), HF (n = 6) and HF+RDN (n = 6). Heart failure was induced by rapid right ventricular pacing. Renal denervation was performed simultaneously with the pacemaker implantation in the HF+RDN group. A 64-unipolar basket catheter was used to perform global endocardial mapping of the left ventricle. The restitution properties and dispersion of refractoriness were estimated from the activation recovery intervals (ARIs) by a pacing protocol. The VF threshold (VFT) was defined as the maximal pacing cycle length required to induce VF using a specific pacing protocol. The defibrillation threshold (DFT) was measured by an up-down algorithm. Renal denervation partly restored left ventricular systolic function and attenuated the process of HF. Compared with the control group, the VFT in the HF group was decreased by 27% (106 ± 8.0 versus 135 ± 10 ms, P Renal denervation significantly flattened the ventricular ARI restitution curve by 15% (1

  13. Differential alterations in gene expression profiles contribute to time-dependent effects of nandrolone to prevent denervation atrophy

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    Bauman William A

    2010-10-01

    Full Text Available Abstract Background Anabolic steroids, such as nandrolone, slow muscle atrophy, but the mechanisms responsible for this effect are largely unknown. Their effects on muscle size and gene expression depend upon time, and the cause of muscle atrophy. Administration of nandrolone for 7 days beginning either concomitantly with sciatic nerve transection (7 days or 29 days later (35 days attenuated denervation atrophy at 35 but not 7 days. We reasoned that this model could be used to identify genes that are regulated by nandrolone and slow denervation atrophy, as well as genes that might explain the time-dependence of nandrolone effects on such atrophy. Affymetrix microarrays were used to profile gene expression changes due to nandrolone at 7 and 35 days and to identify major gene expression changes in denervated muscle between 7 and 35 days. Results Nandrolone selectively altered expression of 124 genes at 7 days and 122 genes at 35 days, with only 20 genes being regulated at both time points. Marked differences in biological function of genes regulated by nandrolone at 7 and 35 days were observed. At 35, but not 7 days, nandrolone reduced mRNA and protein levels for FOXO1, the mTOR inhibitor REDD2, and the calcineurin inhibitor RCAN2 and increased those for ApoD. At 35 days, correlations between mRNA levels and the size of denervated muscle were negative for RCAN2, and positive for ApoD. Nandrolone also regulated genes for Wnt signaling molecules. Comparison of gene expression at 7 and 35 days after denervation revealed marked alterations in the expression of 9 transcriptional coregulators, including Ankrd1 and 2, and many transcription factors and kinases. Conclusions Genes regulated in denervated muscle after 7 days administration of nandrolone are almost entirely different at 7 versus 35 days. Alterations in levels of FOXO1, and of genes involved in signaling through calcineurin, mTOR and Wnt may be linked to the favorable action of nandrolone on

  14. Abdominal Aortic Calcifications Influences the Systemic and Renal Hemodynamic Response to Renal Denervation in the DENERHTN (Renal Denervation for Hypertension) Trial.

    Science.gov (United States)

    Courand, Pierre-Yves; Pereira, Helena; Del Giudice, Costantino; Gosse, Philippe; Monge, Matthieu; Bobrie, Guillaume; Delsart, Pascal; Mounier-Vehier, Claire; Lantelme, Pierre; Denolle, Thierry; Dourmap, Caroline; Halimi, Jean Michel; Girerd, Xavier; Rossignol, Patrick; Zannad, Faiez; Ormezzano, Olivier; Vaisse, Bernard; Herpin, Daniel; Ribstein, Jean; Bouhanick, Beatrice; Mourad, Jean-Jacques; Ferrari, Emile; Chatellier, Gilles; Sapoval, Marc; Azarine, Arshid; Azizi, Michel

    2017-10-10

    The DENERHTN (Renal Denervation for Hypertension) trial confirmed the efficacy of renal denervation (RDN) in lowering daytime ambulatory systolic blood pressure when added to standardized stepped-care antihypertensive treatment (SSAHT) for resistant hypertension at 6 months. This post hoc exploratory analysis assessed the impact of abdominal aortic calcifications (AAC) on the hemodynamic and renal response to RDN at 6 months. In total, 106 patients with resistant hypertension were randomly assigned to RDN plus SSAHT or to the same SSAHT alone (control group). Total AAC volume was measured, with semiautomatic software and blind to randomization, from the aortic hiatus to the iliac bifurcation using the prerandomization noncontrast abdominal computed tomography scans of 90 patients. Measurements were expressed as tertiles. The baseline-adjusted difference in the change in daytime ambulatory systolic blood pressure from baseline to 6 months between the RDN and control groups was -10.1 mm Hg ( P =0.0462) in the lowest tertile and -2.5 mm Hg ( P =0.4987) in the 2 highest tertiles of AAC volume. Estimated glomerular filtration rate remained stable at 6 months for the patients in the lowest tertile of AAC volume who underwent RDN (+2.5 mL/min per 1.73 m 2 ) but decreased in the control group (-8.0 mL/min per 1.73 m 2 , P =0.0148). In the 2 highest tertiles of AAC volume, estimated glomerular filtration rate decreased similarly in the RDN and control groups ( P =0.2640). RDN plus SSAHT resulted in a larger decrease in daytime ambulatory systolic blood pressure than SSAHT alone in patients with a lower AAC burden than in those with a higher AAC burden. This larger decrease in daytime ambulatory systolic blood pressure was not associated with a decrease in estimated glomerular filtration rate. URL: http://www.clinicaltrials.gov. Unique identifier: NCT01570777. © 2017 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.

  15. [Endovascular radiofrequency denervation of renal arteries as an innovation method of treatment of refractory arterial hypertension. First experience in Russia].

    Science.gov (United States)

    Danilov, N M; Matchin, Iu G; Chazova, I E

    2012-01-01

    Excessive activation of the sympathetic nervous system forms the basis of pathogenesis of essential arterial hypertension (AH). The present work was aimed at evaluating efficacy and safety of endovascular radiofrequency denervation of renal arteries in patients with AH refractory AH based on the initial first experience in with using this methodology in the Russian Federation. The interventions were carried out on December 14-15th, 2011 in the first five patients presenting with AH refractory to antihypertensive therapy consisting of three and more drugs in therapeutic doses, one of which was a diuretic. The selection criteria were systolic arterial pressure (SAP) ≥160 mm Hg or ≥150 mm Hg in the presence of type 2 diabetes mellitus. The obligatory conditions for selection were the preserved renal function [glomerular filtration rate (GFR) ≥45 ml/min] and the absence of the secondary form of AH. The procedure of denervation was performed in the conditions of roentgen-operating room using special Medtronic Ardian Simplicity Catheter System™. In all cases we managed to perform bilateral denervation of renal arteries with the radiofrequency effect in not less than 4 zones of each of vessels. Efficacy of each of the effect was registered with due regard for reaching certain temperature and values of impedance. The interventions were not accompanied by the development of any complications either in the area of manipulations or the site of puncture. Neither were there any complications from the side of the cardiovascular or excretory systems of the body. Diurnal monitoring of AP (DMAP) registered a significant decrease in SAP averagely from 174±12 to 145±10 mm Hg three days after the intervention. A persistent antihypertensive effect was confirmed by the DMAP findings one month after denervation - the SAP level averagely amounted to 131±6 mm Hg. Endovascular radiofrequency denervation of renal arteries is a safe and efficient method of treatment of AH resistant

  16. Renal denervation therapy for the treatment of resistant hypertension: a position statement by the Canadian Hypertension Education Program.

    Science.gov (United States)

    Khan, Nadia A; Herman, Robert J; Quinn, Robert R; Rabkin, Simon W; Ravani, Pietro; Tobe, Sheldon W; Feldman, Ross D; Wijeysundera, Harindra C; Padwal, Raj S

    2014-01-01

    Renal denervation is a novel catheter-based, percutaneous procedure using radiofrequency energy to ablate nerves within the renal arteries. This procedure might help to significantly lower blood pressure (BP) in patients with resistant hypertension, defined as BP > 140/90 mm Hg (> 130/80 mm Hg for those with diabetes) despite use of ≥ 3 optimally dosed antihypertensive agents, ideally including 1 diuretic agent. The Canadian Hypertension Education Program Recommendations Task Force reviewed the current evidence on safety and efficacy of this procedure. Eleven studies on renal denervation were examined and most of the evidence evaluating renal denervation was derived from the Symplicity studies. In patients with systolic BP ≥ 160 mm Hg (≥ 150 mm Hg for patients with type 2 diabetes) despite use of ≥ 3 antihypertensive agents, bilateral renal denervation was associated with significantly lower BP (-22/11 to -34/13 mm Hg) at 6 months with a low periprocedural complication rate. Few patients underwent 24-hour ambulatory BP monitoring and ambulatory BP monitoring showed more modest BP lowering (0 to -11/7 mm Hg). Although early results on short-term safety and blood pressure-lowering are encouraging, there are no long-term efficacy and safety data, or hard cardiovascular end point data. The discrepancy between office BP reductions and 24-hour ambulatory BP monitor reductions needs to be further investigated. Until more data are available, renal sympathetic denervation should be considered as a treatment option of last resort for patients with resistant hypertension who have exhausted all other available medical management options. Copyright © 2014 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.

  17. Permanent LMN denervation of human skeletal muscle and recovery by h-b FES: management and monitoring

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    Helmut Kern

    2010-09-01

    Full Text Available Denervation of a defined skeletal muscle is due to lower motor neuron (LMN or peripheral nerve lesions that have major consequences on the muscle tissue. After early atrophy, the mid- and late-phases presents two very contrasting myofibers populations: beside those severely atrophic with internalized groups of myonuclei, large fast-type muscle fibers continue to be present 4 to 6 years after Spinal Cord Injury (SCI. Recent results of rat experiments provides the rational basis for understanding the residual functional characteristics of the long-term denervated muscle and the molecular explanation of its ability to respond to home-base functional electrical stimulation (h-b FES using custom-designed electrodes and stimulators. Further outcomes of the Vienna-Padova ten-year collaboration are: 1. a world-unique Myo- Bank of muscle biopsies and 2. improved imaging procedures (Color Computer Tomography (CT scan and Functional Echomyography, all demonstrating that h-b FES induces improvements in muscle contractility, tissue composition and mass, despite permanent LMN denervation. The benefits of h-b FES could be extended from patents suffering with complete Conus-Cauda Syndrome to the numerous patients with incomplete LMN denervation of skeletal muscles to determine whether h-b FES reduces secondary complications related to disuse and impaired blood perfusion (reduction in bone density, risk of bone fracture, decubitus ulcers, and pulmonary thromboembolism. We are confident that translation of the results of a clinical experiment, the EU Project RISE, to the larger cohort of incomplete LMN denervated muscles will provide the wanted results.

  18. Mr 40,000 and Mr 39,000 pertussis toxin substrates are increased in surgically denervated dog ventricular myocardium

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    Hershberger, R.E.; Feldman, A.M.; Anderson, F.L.; Kimball, J.A.; Wynn, J.R.; Bristow, M.R. (Univ. of Utah School of Medicine, Salt Lake City (USA))

    1991-04-01

    To test the general hypothesis that cardiac innervation may participate in myocardial G protein regulation, we examined the effects of complete intrapericardial surgical denervation or sham operation in dogs. In particulate fractions of dog left ventricular (LV) myocardium harvested 28-33 days after denervation or sham operation, Mr 40,000 and Mr 39,000 pertussis toxin-sensitive substrates (G proteins) were increased by 31% (1.31 +/- 0.084 vs 1.00 +/- 0.058 OD, arbitrary units, p less than 0.01) and 40% (1.40 +/- 0.117 vs. 1.000 +/- 0.084 OD, arbitrary units, p less than 0.02), respectively, as compared with sham-operated controls. The Mr 40,000 pertussis toxin-sensitive band comigrated with a pertussis toxin-sensitive substrate in human erythrocyte membranes known to contain an alpha Gi species. In these same preparations basal, GTP and GppNHp stimulated adenylate cyclase activities were decreased in denervated heart by 20, 26, and 19%, respectively, consistent with increased activity of an inhibitory G protein. In contrast, Gs function was not altered, because cyc(-) membranes reconstituted with membrane extracts and fluoride and beta-receptor-stimulated adenylate cyclase activity were not different between groups. Furthermore, adenylate cyclase catalytic subunit function as assessed with forskolin and manganese stimulation was not different between preparations of control and denervated heart. We conclude that in preparations of surgically denervated dog myocardium Mr 40,000 and Mr 39,000 pertussis toxin-sensitive G proteins are increased by 31 and 40%, respectively, and that functional alterations in adenylate cyclase activity exist, consistent with increased inhibitory G-protein function.

  19. Mr 40,000 and Mr 39,000 pertussis toxin substrates are increased in surgically denervated dog ventricular myocardium

    International Nuclear Information System (INIS)

    Hershberger, R.E.; Feldman, A.M.; Anderson, F.L.; Kimball, J.A.; Wynn, J.R.; Bristow, M.R.

    1991-01-01

    To test the general hypothesis that cardiac innervation may participate in myocardial G protein regulation, we examined the effects of complete intrapericardial surgical denervation or sham operation in dogs. In particulate fractions of dog left ventricular (LV) myocardium harvested 28-33 days after denervation or sham operation, Mr 40,000 and Mr 39,000 pertussis toxin-sensitive substrates (G proteins) were increased by 31% (1.31 +/- 0.084 vs 1.00 +/- 0.058 OD, arbitrary units, p less than 0.01) and 40% (1.40 +/- 0.117 vs. 1.000 +/- 0.084 OD, arbitrary units, p less than 0.02), respectively, as compared with sham-operated controls. The Mr 40,000 pertussis toxin-sensitive band comigrated with a pertussis toxin-sensitive substrate in human erythrocyte membranes known to contain an alpha Gi species. In these same preparations basal, GTP and GppNHp stimulated adenylate cyclase activities were decreased in denervated heart by 20, 26, and 19%, respectively, consistent with increased activity of an inhibitory G protein. In contrast, Gs function was not altered, because cyc(-) membranes reconstituted with membrane extracts and fluoride and beta-receptor-stimulated adenylate cyclase activity were not different between groups. Furthermore, adenylate cyclase catalytic subunit function as assessed with forskolin and manganese stimulation was not different between preparations of control and denervated heart. We conclude that in preparations of surgically denervated dog myocardium Mr 40,000 and Mr 39,000 pertussis toxin-sensitive G proteins are increased by 31 and 40%, respectively, and that functional alterations in adenylate cyclase activity exist, consistent with increased inhibitory G-protein function

  20. The Effect of Patellar Denervation by Circumpatellar Electrocautery on Anterior Knee Pain Following Total Knee Replacement – An Experimental Study

    Directory of Open Access Journals (Sweden)

    Balaji Zacharia

    2017-07-01

    Full Text Available ABSTRACT OBJECTIVES Anterior knee pain is a common problem in patients who have undergone TKR which causes dissatisfaction among them. There are Various methods for prevention of anterior knee pain following TKR .The  objective of this study is to determine the  effect of circumpatellar electrocautery on anterior knee pain following TKR and to compare the results with that of those patients who have undergone TKR without circumpatellar denervation. METHODS This is a cohort study conducted in Dept. of Orthopedics, Govt. Medical College, Kozhikode,kerala, 2014. Total sample size was 90.out of which 2 patients died during the study period. We lost follow up of 7 patients.  Among the remaining 81 patients 42 had undergone TKR with circumpatellar denervation using electocautery and 39 without circumpatellar denervation. They were kept under follow up. Patients were followed up postoperatively at 1 month, 3 months, 6 months and at one year. At all postoperative visits, a clinical score was determined using the Knee Society score and the clinical anterior knee pain rating system described by Waters and Bentley RESULTS There is no statistically significant difference in AKP score between both groups.There is a statistically significant difference in the knee society score at 1st month(p value <.001.  But there is no difference on further follow up visits . CONCLUSION There is no statistically significant difference between final outcome of patients who underwent patella denervation using circumpatellar electrocauterisation and those without denervation  with respect to anterior knee pain among patients who have undergone TKR.

  1. Effect of renal sympathetic denervation on atrial substrate remodeling in ambulatory canines with prolonged atrial pacing.

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    Xule Wang

    Full Text Available We have previously demonstrated that catheter-based renal sympathetic denervation (RSD could suppress atrial fibrillation (AF in canines with short-time rapid right atrial pacing (RAP. However, the role of renal denervation on atrial remodeling is unclear. The aim of the present study was to explore the long-term effect of RSD on the atrial remodeling during prolonged RAP. Twenty mongrel dogs were implanted with a high-frequency cardiac pacemaker with a transvenous lead inserted into the right atrial appendage. The dogs were divided into three groups: a sham-operated group (n = 6, the chronic RAP (CRAP group (n = 7, and the CRAP+RSD group (n = 7. In the CRAP+RSD group, a pacemaker was implanted 6 weeks after RSD was performed bilaterally for recovery. RAP was maintained for 5 weeks in CRAP group and CRAP+RSD group. The plasma levels of Angiotensin II and aldosterone were significantly increased in CRAP group compared with sham-operated group, but the increasing trend was inhibited in CRAP+RSD group compared with CRAP group (P<0.05. Similarly, RSD suppressed the increasing trend that prolonged RAP produced in the left atrial levels of ANP, TNF-α and IL-6. Compared with the sham-operated group, the CRAP group had significantly increased levels of caspase-3, bax and Cx40 whereas the level of Bcl-2 decreased (P<0.05. RSD markedly reduced the upregulation of caspase-3, bax and Cx40 and the downregulation of Bcl-2 expression compared with the CRAP group (P<0.05. Picric acid-sirius red staining study suggested that RSD could markedly alleviate the lesion degree of cardic fibrosis induced by CRAP (P<0.05. Immunohistochemistry results showed that the densities of TH- and GAP43- positive nerves were significantly elevated in the CRAP group compared with the sham-operated group, while RSD operation signicantly inhibited the these changes produced by CRAP. These findings suggest that renal denervation could suppress the atrial remodeling after

  2. Renal sympathetic denervation attenuates hypertension and vascular remodeling in renovascular hypertensive rats.

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    Li, Peng; Huang, Pei-Pei; Yang, Yun; Liu, Chi; Lu, Yan; Wang, Fang; Sun, Wei; Kong, Xiang-Qing

    2017-01-01

    Li P, Huang P, Yang Y, Liu C, Lu Y, Wang F, Sun W, Kong X. Renal sympathetic denervation attenuates hypertension and vascular remodeling in renovascular hypertensive rats. J Appl Physiol 122: 121-129, 2017. First published October 14, 2016; doi:10.1152/japplphysiol.01019.2015-Sympathetic activity is enhanced in patients with essential or secondary hypertension, as well as in various hypertensive animal models. Therapeutic targeting of sympathetic activation is considered an effective antihypertensive strategy. We hypothesized that renal sympathetic denervation (RSD) attenuates hypertension and improves vascular remodeling and renal disease in the 2-kidney, 1-clip (2K1C) rat model. Rats underwent 2K1C modeling or sham surgery; then rats underwent RSD or sham surgery 4 wk later, thus resulting in four groups (normotensive-sham, normotensive-RSD, 2K1C-sham, and 2K1C-RSD). Norepinephrine was measured by ELISA. Echocardiography was used to assess heart function. Fibrosis and apoptosis were assessed by Masson and TUNEL staining. Changes in mean arterial blood pressure in response to hexamethonium and plasma norepinephrine levels were used to evaluate basal sympathetic nerve activity. The 2K1C modeling success rate was 86.8%. RSD reversed the elevated systolic blood pressure induced by 2K1C, but had no effect on body weight. Compared with rats in the 2K1C-sham group, rats in the 2K1C-RSD group showed lower left ventricular mass/body weight ratio, interventricular septal thickness in diastole, left ventricular end-systolic diameter, and left ventricular posterior wall thickness in systole, whereas fractional shortening and ejection fraction were higher. Right kidney apoptosis and left kidney hypertrophy were not changed by RSD. Arterial fibrosis was lower in animals in the 2K1C-RSD group compared with those in the 2K1C-sham group. RSD reduced plasma norepinephrine and basal sympathetic activity in rats in the 2K1C-RSD group compared with rats in the 2K1C-sham group. These

  3. The Effects of Renal Denervation on Renal Hemodynamics and Renal Vasculature in a Porcine Model.

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    Willemien L Verloop

    Full Text Available Recently, the efficacy of renal denervation (RDN has been debated. It is discussed whether RDN is able to adequately target the renal nerves.We aimed to investigate how effective RDN was by means of functional hemodynamic measurements and nerve damage on histology.We performed hemodynamic measurements in both renal arteries of healthy pigs using a Doppler flow and pressure wire. Subsequently unilateral denervation was performed, followed by repeated bilateral hemodynamic measurements. Pigs were terminated directly after RDN or were followed for 3 weeks or 3 months after the procedure. After termination, both treated and control arteries were prepared for histology to evaluate vascular damage and nerve damage. Directly after RDN, resting renal blood flow tended to increase by 29±67% (P = 0.01. In contrast, renal resistance reserve increased from 1.74 (1.28 to 1.88 (1.17 (P = 0.02 during follow-up. Vascular histopathology showed that most nerves around the treated arteries were located outside the lesion areas (8±7 out of 55±25 (14% nerves per pig were observed within a lesion area. Subsequently, a correlation was noted between a more impaired adventitia and a reduction in renal resistance reserve (β: -0.33; P = 0.05 at three weeks of follow-up.Only a small minority of renal nerves was targeted after RDN. Furthermore, more severe adventitial damage was related to a reduction in renal resistance in the treated arteries at follow-up. These hemodynamic and histological observations may indicate that RDN did not sufficiently target the renal nerves. Potentially, this may explain the significant spread in the response after RDN.

  4. The Effects of Renal Denervation on Renal Hemodynamics and Renal Vasculature in a Porcine Model

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    Verloop, Willemien L.; Hubens, Lisette E. G.; Spiering, Wilko; Doevendans, Pieter A.; Goldschmeding, Roel; Bleys, Ronald L. A. W.; Voskuil, Michiel

    2015-01-01

    Rationale Recently, the efficacy of renal denervation (RDN) has been debated. It is discussed whether RDN is able to adequately target the renal nerves. Objective We aimed to investigate how effective RDN was by means of functional hemodynamic measurements and nerve damage on histology. Methods and Results We performed hemodynamic measurements in both renal arteries of healthy pigs using a Doppler flow and pressure wire. Subsequently unilateral denervation was performed, followed by repeated bilateral hemodynamic measurements. Pigs were terminated directly after RDN or were followed for 3 weeks or 3 months after the procedure. After termination, both treated and control arteries were prepared for histology to evaluate vascular damage and nerve damage. Directly after RDN, resting renal blood flow tended to increase by 29±67% (P = 0.01). In contrast, renal resistance reserve increased from 1.74 (1.28) to 1.88 (1.17) (P = 0.02) during follow-up. Vascular histopathology showed that most nerves around the treated arteries were located outside the lesion areas (8±7 out of 55±25 (14%) nerves per pig were observed within a lesion area). Subsequently, a correlation was noted between a more impaired adventitia and a reduction in renal resistance reserve (β: -0.33; P = 0.05) at three weeks of follow-up. Conclusion Only a small minority of renal nerves was targeted after RDN. Furthermore, more severe adventitial damage was related to a reduction in renal resistance in the treated arteries at follow-up. These hemodynamic and histological observations may indicate that RDN did not sufficiently target the renal nerves. Potentially, this may explain the significant spread in the response after RDN. PMID:26587981

  5. Renal denervation in the era of HTN-3. Comprehensive review and glimpse into the future.

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    Silva, Joana Delgado; Costa, Marco; Gersh, Bernard J; Gonçalves, Lino

    2016-08-01

    The pathophysiological role of sympathetic overactivity in conditions such as hypertension has been well documented. Catheter-based renal denervation (RDN) is a minimally invasive percutaneous procedure which aims to disrupt sympathetic nerve afferent and efferent activity through the application of radiofrequency energy directly within the renal artery wall. This technique has emerged as a very promising treatment with dramatic effects on refractory hypertension but also in other conditions in which a sympathetic influence is present. Several studies have evaluated the safety and efficacy of this procedure, presently surrounded by controversy since the recent outcome of Symplicity HTN-3, the first randomized, sham-control trial, which failed to confirm RDN previous reported benefits on BP and cardiovascular risk lowering. Consequently, although some centers halted their RDN programs, research continues and both the concept of denervation and treatment strategies are being redefined to identify patients who can drive the most benefit from this technology. In the United States, the Food and Drug Administration (FDA) has appropriately mandated that RDN remains an investigative procedure and a new generation of sham-controlled trials are ongoing and aimed to assess not only its efficacy against pharmacotherapy but also trials in drug free patients with the objective of demonstrating once and for all whether the procedure actually does lower BP in comparison to a placebo arm. In this article, we present an overview of the sympathetic nervous system and its role in hypertension, examine the current data on RDN, and share some insights and future expectations. Copyright © 2016 American Society of Hypertension. All rights reserved.

  6. Selective Denervation for Persistent Knee Pain After Total Knee Arthroplasty: A Report of 50 Cases.

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    Shi, Shao-Min; Meister, David W; Graner, Kelly C; Ninomiya, James T

    2017-03-01

    Despite the general success of total knee arthroplasty (TKA), up to 20% of patients report dissatisfaction following surgery. One potential cause of this dissatisfaction is residual pain secondary to neuroma formation in the sensory nerve branches that innervate the knee. We found, after performing a retrospective review, that up to 9.7% of patients following primary TKA and up to 21% of revision cases exhibited persistent knee pain attributable to neuroma formation. Despite the high incidence of this pathology, little is known about the effective diagnosis or treatment of neuroma formation following TKA. Between 2011 and 2014, 50 patients with persistent symptomatic neuroma pain following TKA underwent selective denervation. These patients had demonstrated the appropriate selection criteria and had failed conservative management. Patients were evaluated by the visual analog scale pain score and the Knee Society Score to determine the outcome of the described treatment. Thirty-two patients (64%) rated their outcome as excellent, 10 (20%) as good, 3 (6%) as fair, and 2 (4%) reported no change. The mean visual analog scale pain score was improved from 9.4 ± 0.8 to 1.1 ± 1.6 following surgery (P ≤ .001). The mean Knee Society Scores increased from 45.5 ± 14.3 to 94.1 ± 8.6 points (P ≤ .0001). Three patients (6%) required the second neurectomy due to recurrent pain and received excellent pain relief postoperatively. There were 2 complications of superficial skin peri-incisional hyperemia related to dressings. Average follow-up duration was 24 months (range, 16-38 months). Our study suggests that selective denervation provides an effective and long-lasting option for the management of this pathology. Copyright © 2016 Elsevier Inc. All rights reserved.

  7. Skin denervation and its clinical significance in late-stage chronic kidney disease.

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    Chao, Chi-Chao; Wu, Vin-Cent; Tan, Chun-Hsiang; Wang, Yi-Mei; Tseng, Ming-Tsung; Wu, Pei-Chen; Lin, Yea-Huey; Lin, Whei-Min; Wu, Kwan-Dun; Hsieh, Sung-Tsang

    2011-02-01

    To investigate the skin innervation and its clinical significance in late-stage chronic kidney disease (CKD). Case series. National Taiwan University Hospital, Taipei, Taiwan. Forty consecutive nondiabetic patients with late-stage CKD (14 female and 26 male; mean [SD] age, 60.7 [12.3] years), including 2 cases with stage 3 CKD, 6 with stage 4 CKD, and 32 with stage 5 CKD, ie, end-stage kidney disease. Clinical evaluation of neurological deficits, nerve conduction study, autonomic function tests, and a 3-mm-diameter skin biopsy specimen taken from the distal leg. Quantitation of epidermal innervation, parameters of nerve conduction study, R-R interval variability, and sympathetic skin response. Clinically, 21 patients (52.5%) were symptomatic with paresthesia over the limbs or autonomic symptoms. The intraepidermal nerve fiber (IENF) density was markedly reduced in patients with CKD compared with age- and sex-matched controls (mean [SD], 2.8 [2.0] vs 8.6 [2.8] fibers/mm; P Skin denervation was observed in 27 patients (67.5%). Fifteen patients (37.5%) had abnormalities on nerve conduction studies, and 29 patients (72.5%) had abnormal results on autonomic function tests. By analysis with multiple regression models, the IENF density was negatively correlated with the duration of renal disease (P = .02). Additionally, the R-R interval variability at rest was linearly correlated with the IENF density (P = .02) and the absence of sympathetic skin responses at the soles was associated with reduced IENF density (P = .03). Small-fiber sensory and autonomic neuropathies constitute the major form of neuropathy in late-stage CKD. Furthermore, skin denervation was associated with the duration of renal disease.

  8. Comparison between neurectomy and botulinum toxin A injection for denervated skeletal muscle.

    Science.gov (United States)

    Tsai, Feng-Chou; Hsieh, Ming-Shium; Chou, Chih-Ming

    2010-08-01

    Neurectomy and botulinum toxin A (BoNT-A) injection cause denervated muscle atrophy, but questions remain about their clinical utility. We investigated time-series alterations of rat muscle weight, functional deficits, signaling pathways, and microscopic structures, to gain an understanding of the clinical implications. Between 2008 and 2009, the maximal calf circumference of patients for calf reduction either by neurectomy or BoNT-A injections were recorded for study. A rat skeletal muscle model was established through repeated or dose-adjusted BoNT-A injections and neurectomy. The survival, apoptosis pathways, functional deficits, and microscopic structures were investigated using Western blot, sciatic functional index (SFI), and transmission electron microscopy (TEM), respectively. The rat muscle weight ratio of the BoNT-A group had recovered to 89.3 +/- 3.8% by week 58, but it never recovered in the neurectomy group. Muscle weight reduction by BoNT-A not only depended on the dose, but additive effects were also obtained through repeated injections. Rat SFI demonstrated rapid recovery in both groups. Molecular expressions showed a coherent and biphasic pattern. p-Akt and apoptosis-inducing factor (AIF) were upregulated significantly, with a peak at 8 weeks in the neurectomy group (p structure disruption and sarcomere discontinuity in the neurectomy and BoNT-A groups, respectively. We demonstrated that denervation induced lasting muscle weight and structural changes of different degrees. Muscle weight reduction by BoNT-A was related to frequency and dose. AIF-mediated caspase-independent apoptosis was significantly different for neurectomy and BoNT-A injection.

  9. Degree of skin denervation and its correlation to objective thermal sensory test in leprosy patients.

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    Ismael Alves Rodrigues Júnior

    Full Text Available BACKGROUND: Leprosy is an infectious disease affecting skin and peripheral nerves resulting in increased morbidity and physical deformities. Early diagnosis provides opportune treatment and reduces its complications, relying fundamentally on the demonstration of impaired sensation in suggestive cutaneous lesions. The loss of tactile sensitivity in the lesions is preceded by the loss of thermal sensitivity, stressing the importance of the thermal test in the suspicious lesions approach. The gold-standard method for the assessment of thermal sensitivity is the quantitative sensory test (QST. Morphological study may be an alternative approach to access the thin nerve fibers responsible for thermal sensitivity transduction. The few studies reported in leprosy patients pointed out a rarefaction of thin dermo-epidermal fibers in lesions, but used semi-quantitative evaluation methods. METHODOLOGY/PRINCIPAL FINDINGS: This work aimed to study the correlation between the degree of thermal sensitivity impairment measured by QST and the degree of denervation in leprosy skin lesions, evaluated by immunohistochemistry anti-PGP 9.5 and morphometry. Twenty-two patients were included. There were significant differences in skin thermal thresholds among lesions and contralateral skin (cold, warm, cold induced pain and heat induced pain. The mean reduction in the density of intraepidermal and subepidermal fibers in lesions was 79.5% (SD = 19.6 and 80.8% (SD = 24.9, respectively. CONCLUSIONS/SIGNIFICANCE: We observed a good correlation between intraepidermal and subepidermal fibers deficit, but no correlation between these variables and those accounting for the degree of impairment in thermal thresholds, since the thin fibers rarefaction was homogeneously intense in all patients, regardless of the degree of sensory deficit. We believe that the homogeneously intense denervation in leprosy lesions should be objective of further investigations focused on its

  10. Predictors of Renal Denervation Efficacy in the Treatment of Resistant Hypertension.

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    Ripp, Tatiana M; Mordovin, Victor F; Pekarskiy, Stanislav E; Ryabova, Tamara R; Zlobina, Marina V; Baev, Andrei E; Anfinogenova, Yana; Popov, Sergey V

    2015-12-01

    The aims of the study were to evaluate the effects of renal sympathetic denervation (RSD) on the heart and to identify the predictors of RSD efficacy in patients with resistant arterial hypertension. The study comprised 60 RSD patients (54.6 ± 9.5 years) who received full-dose antihypertensive therapy (4.1 drugs) including diuretics. Initially, 58.6% of patients had abnormal left ventricular (LV) diastolic function. All patients received echocardiography before and 24 weeks after RSD. Renal sympathetic denervation was achieved through the endovascular radiofrequency ablation (RFA) of the renal arteries. Drug therapy continued for the entire period of observation. After RSD, all patients were retrospectively assigned to two groups: group 1 comprised patients (n = 22; 36.7%) in whom the myocardial mass (MM) of the left ventricle decreased by more than 10 g after RSD; group 2 comprised patients (n = 38; 63.3%) in whom LV MM increased or decreased by less than 10 g. Anthropometry, arterial blood pressure, heart rate, therapy, and LV end-diastolic dimensions (EDD) were comparable in these groups. After RSD, the values of office blood pressure significantly decreased and MM regressed by more than 10 g in 36.7% of patients; LV diastolic function normalized in 31% of patients, and diastolic dysfunction improved in 14% of patients. The study found the associations between the initial LV wall dimensions and LV MM changes. Unlike LV EDD, arterial blood pressure, or heart rate, the initial values of LV wall thickness predicted LV MM regress. #NCT01499810 https://clinicaltrials.gov/ct2/show/NCT01499810.

  11. Efficacy and safety of renal denervation in elderly patients with resistant hypertension.

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    Ziegler, Ann-Kathrin; Bertog, Stefan; Kaltenbach, Benjamin; Id, Dani; Franke, Jennifer; Hofmann, Ilona; Vaskelyte, Laura; Sievert, Horst

    2015-08-01

    Catheter-based renal sympathetic denervation (RD) causes significant blood pressure (BP) reductions in patients with resistant hypertension (rHTN). However, hypertensive elderly patients reportedly have a lower sympathetic tone than younger patients and a BP lowering effect of RD in this population has not yet been demonstrated. The purpose of this study was to assess the efficacy and safety of RD in elderly patients. We reviewed all consecutive patients aged ≥ 75 years (mean: 78 years) with rHTN treated with RD. Twenty-four patients were included in this prospective study. Office and ambulatory BPs were assessed at baseline and 6-months follow-up. Primary endpoint was the change in office systolic BP at 6 months. Baseline mean office BP was 173/86 ± 21/13 mm Hg. Baseline 24-hr mean ambulatory BP, available in 22 patients, was 158/80 ± 20/13 mm Hg. Baseline creatinine was 1.0 ± 0.18 mg/dl and mean number of antihypertensive agents at baseline 4.3 ± 1.4. No device- or procedure-related adverse events occurred. At 6-months follow-up, the mean office BP decreased by 19/11 ± 29/16 mm Hg (P renal function was not impaired. According to our findings, a similar magnitude of BP reduction as reported in previous trials can be expected in elderly patients. Elderly patients with rHTN should not be excluded from renal denervation. © 2015 Wiley Periodicals, Inc.

  12. Renal denervation prevents long-term sequelae of ischemic renal injury

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    Kim, Jinu; Padanilam, Babu J.

    2014-01-01

    Signals that drive interstitial fibrogenesis after renal ischemia reperfusion injury remain undefined. Sympathetic activation is manifest even in the early clinical stages of chronic kidney disease and is directly related to disease severity. A role for renal nerves in renal interstitial fibrogenesis in the setting of ischemia reperfusion injury has not been studied. In male 129S1/SvImJ mice, ischemia reperfusion injury induced tubulointerstitial fibrosis as indicated by collagen deposition and profibrotic protein expression 4 to 16 days after the injury.. Leukocyte influx, proinflammatory protein expression, oxidative stress, apoptosis, and cell cycle arrest at G2/M phase were enhanced after ischemia reperfusion injury. Renal denervation at the time of injury or up to 1 day post-injury improved histology, decreased proinflammatory/profibrotic responses and apoptosis, and prevented G2/M cell cycle arrest in the kidney. Treatment with afferent nerve-derived calcitonin gene-related peptide (CGRP) or efferent nerve-derived norepinephrine in denervated and ischemia reperfusion injury-induced kidneys mimicked innervation, restored inflammation and fibrosis, induced G2/M arrest, and enhanced TGF-β1 activation. Blocking norepinephrine or CGRP function using respective receptor blockers prevented these effects. Consistent with the in vivo study, treatment with either norepinephrine or CGRP induced G2/M cell cycle arrest in HK-2 proximal tubule cells, whereas antagonists against their respective receptors prevented G2/M arrest. Thus, renal nerve stimulation is a primary mechanism and renal nerve-derived factors drive epithelial cell cycle arrest and the inflammatory cascade causing interstitial fibrogenesis after ischemia reperfusion injury. PMID:25207878

  13. [Renal denervation for treating hypertension: experience at the University Hospital in Lyon].

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    Courand, P-Y; Dauphin, R; Rouvière, O; Paget, V; Khettab, F; Bergerot, C; Harbaoui, B; Bricca, G; Fauvel, J-P; Lantelme, P

    2014-06-01

    We report the first experience of Lyon's university hospital regarding renal denervation to treat patients with resistant essential hypertension. Over a one-year period, 17 patients were treated (12 men, 5 women) with renal denervation. Baseline characteristics were as follows: age 56.5±11.5 years, BMI 33±5kg/m(2) and ambulatory blood pressure 157±16/87±13mmHg with 4.2±1.5 anti-hypertensive treatment. We did not observe intra-operative or early complications. After a median follow-up of 3 months and with the same anti-hypertensive treatment, office systolic blood pressure (SBP) and diastolic blood pressure (DBP) decrease respectively of 20±15 (P<0.001) and 10±13mmHg (P=0.014) (n=17). After six months of follow-up, ambulatory blood pressure (ABPM) decrease of 17.5±14.9mmHg (P=0.027) for SBP and of 10.5±9.6mmHg (P=0.029) for DBP (n=6). Among these patients, five of them were controlled (ABPM inferior to 130/80mmHg) and electrical left ventricular hypertrophy indexes decreased: R wave in aVL lead of 4±3mm (P=0.031), Sokolow index of 3±3mm (P=0.205), Cornell voltage criterion of 9±7mm (P=0.027) and Cornell product of 1310±1104 (P=0.027). Our results are in accordance with data from other centers. On average blood pressure decreases significantly but important inter individual variations are observed. The procedure seems safe. Copyright © 2014. Published by Elsevier SAS.

  14. Spleen vagal denervation inhibits the production of antibodies to circulating antigens.

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    Ruud M Buijs

    Full Text Available BACKGROUND: Recently the vagal output of the central nervous system has been shown to suppress the innate immune defense to pathogens. Here we investigated by anatomical and physiological techniques the communication of the brain with the spleen and provided evidence that the brain has the capacity to stimulate the production of antigen specific antibodies by its parasympathetic autonomic output. METHODOLOGY/PRINCIPAL FINDINGS: This conclusion was reached by successively demonstrating that: 1. The spleen receives not only sympathetic input but also parasympathetic input. 2. Intravenous trinitrophenyl-ovalbumin (TNP-OVA does not activate the brain and does not induce an immune response. 3. Intravenous TNP-OVA with an inducer of inflammation; lipopolysaccharide (LPS, activates the brain and induces TNP-specific IgM. 4. LPS activated neurons are in the same areas of the brain as those that provide parasympathetic autonomic information to the spleen, suggesting a feed back circuit between brain and immune system. Consequently we investigated the interaction of the brain with the spleen and observed that specific parasympathetic denervation but not sympathetic denervation of the spleen eliminates the LPS-induced antibody response to TNP-OVA. CONCLUSIONS/SIGNIFICANCE: These findings not only show that the brain can stimulate antibody production by its autonomic output, it also suggests that the power of LPS as adjuvant to stimulate antibody production may also depend on its capacity to activate the brain. The role of the autonomic nervous system in the stimulation of the adaptive immune response may explain why mood and sleep have an influence on antibody production.

  15. Effect of Radiofrequency Denervation on Pain Intensity Among Patients With Chronic Low Back Pain: The Mint Randomized Clinical Trials.

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    Juch, Johan N S; Maas, Esther T; Ostelo, Raymond W J G; Groeneweg, J George; Kallewaard, Jan-Willem; Koes, Bart W; Verhagen, Arianne P; van Dongen, Johanna M; Huygen, Frank J P M; van Tulder, Maurits W

    2017-07-04

    Radiofrequency denervation is a commonly used treatment for chronic low back pain, but high-quality evidence for its effectiveness is lacking. To evaluate the effectiveness of radiofrequency denervation added to a standardized exercise program for patients with chronic low back pain. Three pragmatic multicenter, nonblinded randomized clinical trials on the effectiveness of minimal interventional treatments for participants with chronic low back pain (Mint study) were conducted in 16 multidisciplinary pain clinics in the Netherlands. Eligible participants were included between January 1, 2013, and October 24, 2014, and had chronic low back pain, a positive diagnostic block at the facet joints (facet joint trial, 251 participants), sacroiliac joints (sacroiliac joint trial, 228 participants), or a combination of facet joints, sacroiliac joints, or intervertebral disks (combination trial, 202 participants) and were unresponsive to conservative care. All participants received a 3-month standardized exercise program and psychological support if needed. Participants in the intervention group received radiofrequency denervation as well. This is usually a 1-time procedure, but the maximum number of treatments in the trial was 3. The primary outcome was pain intensity (numeric rating scale, 0-10; whereby 0 indicated no pain and 10 indicated worst pain imaginable) measured 3 months after the intervention. The prespecified minimal clinically important difference was defined as 2 points or more. Final follow-up was at 12 months, ending October 2015. Among 681 participants who were randomized (mean age, 52.2 years; 421 women [61.8%], mean baseline pain intensity, 7.1), 599 (88%) completed the 3-month follow-up, and 521 (77%) completed the 12-month follow-up. The mean difference in pain intensity between the radiofrequency denervation and control groups at 3 months was -0.18 (95% CI, -0.76 to 0.40) in the facet joint trial; -0.71 (95% CI, -1.35 to -0.06) in the sacroiliac joint

  16. Accessory renal arteries: Prevalence in resistant hypertension and an important role in nonresponse to radiofrequency renal denervation

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    VonAchen, Paige [Minneapolis Heart Institute and Foundation at Abbott Northwestern Hospital, Minneapolis, MN (United States); Hamann, Jason [Boston Scientific Corporation, Maple Grove, MN (United States); Houghland, Thomas; Lesser, John R.; Wang, Yale; Caye, David; Rosenthal, Kristi; Garberich, Ross F. [Minneapolis Heart Institute and Foundation at Abbott Northwestern Hospital, Minneapolis, MN (United States); Daniels, Mary [Vital Images/Toshiba, Minnetonka, MN (United States); Schwartz, Robert S., E-mail: rss@rsschwartz.com [Minneapolis Heart Institute and Foundation at Abbott Northwestern Hospital, Minneapolis, MN (United States)

    2016-10-15

    Objective: The aim of this study was to understand the role of accessory renal arteries in resistant hypertension, and to establish their role in nonresponse to radiofrequency renal denervation (RDN) procedures. Background: Prior studies suggest a role for accessory renal arteries in hypertensive syndromes, and recent clinical trials of renal denervation report that these anomalies are highly prevalent in resistant hypertension. This study evaluated the relationships among resistant hypertension, accessory renal arteries, and the response to radiofrequency (RF) renal denervation. Methods: Computed Tomography Angiography (CTA) and magnetic resonance imaging (MRI) scans from 58 patients with resistant hypertension undergoing RF renal denervation (RDN) were evaluated. Results were compared with CT scans in 57 healthy, normotensive subjects undergoing screening as possible renal transplant donors. All scans were carefully studied for accessory renal arteries, and were correlated with long term blood pressure reduction. Results: Accessory renal arteries were markedly more prevalent in the hypertensive patients than normotensive renal donors (59% vs 32% respectively, p = 0.004). RDN had an overall nonresponse rate of 29% (response rate 71%). Patients without accessory vessels had a borderline higher response rate to RDN than those with at least one accessory vessel (83% vs 62% respectively, p = 0.076) and a higher RDN response than patients with untreated accessory arteries (83% vs 55%; p = 0.040). For accessory renal arteries and nonresponse, the sensitivity was 76%, specificity 49%, with positive and negative predictive values 38% and 83% respectively. Conclusions: Accessory renal arteries were markedly over-represented in resistant hypertensives compared with healthy controls. While not all patients with accessory arteries were nonresponders, nonresponse was related to both the presence and non-treatment of accessory arteries. Addressing accessory renal arteries in

  17. Accessory renal arteries: Prevalence in resistant hypertension and an important role in nonresponse to radiofrequency renal denervation

    International Nuclear Information System (INIS)

    VonAchen, Paige; Hamann, Jason; Houghland, Thomas; Lesser, John R.; Wang, Yale; Caye, David; Rosenthal, Kristi; Garberich, Ross F.; Daniels, Mary; Schwartz, Robert S.

    2016-01-01

    Objective: The aim of this study was to understand the role of accessory renal arteries in resistant hypertension, and to establish their role in nonresponse to radiofrequency renal denervation (RDN) procedures. Background: Prior studies suggest a role for accessory renal arteries in hypertensive syndromes, and recent clinical trials of renal denervation report that these anomalies are highly prevalent in resistant hypertension. This study evaluated the relationships among resistant hypertension, accessory renal arteries, and the response to radiofrequency (RF) renal denervation. Methods: Computed Tomography Angiography (CTA) and magnetic resonance imaging (MRI) scans from 58 patients with resistant hypertension undergoing RF renal denervation (RDN) were evaluated. Results were compared with CT scans in 57 healthy, normotensive subjects undergoing screening as possible renal transplant donors. All scans were carefully studied for accessory renal arteries, and were correlated with long term blood pressure reduction. Results: Accessory renal arteries were markedly more prevalent in the hypertensive patients than normotensive renal donors (59% vs 32% respectively, p = 0.004). RDN had an overall nonresponse rate of 29% (response rate 71%). Patients without accessory vessels had a borderline higher response rate to RDN than those with at least one accessory vessel (83% vs 62% respectively, p = 0.076) and a higher RDN response than patients with untreated accessory arteries (83% vs 55%; p = 0.040). For accessory renal arteries and nonresponse, the sensitivity was 76%, specificity 49%, with positive and negative predictive values 38% and 83% respectively. Conclusions: Accessory renal arteries were markedly over-represented in resistant hypertensives compared with healthy controls. While not all patients with accessory arteries were nonresponders, nonresponse was related to both the presence and non-treatment of accessory arteries. Addressing accessory renal arteries in

  18. Nikolaus Rüdinger (1832-1896), His Description of Joint Innervation in 1857, and the History of Surgical Joint Denervation.

    Science.gov (United States)

    Gohritz, Andreas; Kaiser, Erich; Guggenheim, Merlin; Dellon, Arnold Lee

    2018-01-01

     Selective joint denervation has become a reliable palliative treatment, especially for painful joints in the upper and lower extremity.  This article highlights the life and work of Nikolaus Rüdinger (1832-1896) who first described joint innervation which became the basis of later techniques of surgical joint denervation. The historical evolution of this method is outlined.  Rüdinger made a unique career from apprentice barber to military surgeon and anatomy professor in Munich, Germany. His first description of articular innervation of temporomandibular, shoulder, elbow, wrist, finger, sacroiliac, hip, knee, ankle, foot, and toe joints in 1857 stimulated the subsequent history of surgical joint denervation. Comparing his investigations with modern joint denervation methods, developed by pioneers like Albrecht Wilhelm or A. Lee Dellon, shows his great exactitude and anatomical correspondence despite different current terminology. Clinical series of modern surgical joint denervations reveal success rates of up to 80% with reliable long-term results.  The history of joint denervation with Rüdinger as its important protagonist offers inspiring insights into the evolution of surgical techniques and exemplifies the value of descriptive functional anatomy, even if surgical application may not have been realized until a century later. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

  19. Short-Term Motor Compensations to Denervation of Feline Soleus and Lateral Gastrocnemius Result in Preservation of Ankle Mechanical Output during Locomotion

    Science.gov (United States)

    Prilutsky, Boris I.; Maas, Huub; Bulgakova, Margarita; Hodson-Tole, Emma F.; Gregor, Robert J.

    2011-01-01

    Denervation of selected ankle extensors in animals results in locomotor changes. These changes have been suggested to permit preservation of global kinematic characteristics of the hindlimb during stance. The peak ankle joint moment is also preserved immediately after denervation of several ankle extensors in the cat, suggesting that the animal's response to peripheral nerve injury may also be aimed at preserving ankle mechanical output. We tested this hypothesis by comparing joint moments and power patterns during walking before and after denervation of soleus and lateral gastrocnemius muscles. Hindlimb kinematics, ground reaction forces and electromyographic activity of selected muscles were recorded during level, downslope (−50%) and upslope (50%) walking before and 1–3 weeks after nerve denervation. Denervation resulted in increased activity of the intact medial gastrocnemius and plantaris muscles, greater ankle dorsiflexion, smaller knee flexion, and the preservation of the peak ankle moment during stance. Surprisingly, ankle positive power generated in the propulsion phase of stance was increased (up to 50%) after denervation in all walking conditions (p ankle. The additional mechanical energy generated at the ankle during propulsion can result, in part, from increased activity of intact synergists, the use of passive tissues around the ankle and by the tendon action of ankle two-joint muscles and crural fascia. PMID:21411965

  20. The effects of denervation, reinnervation, and muscle imbalance on functional muscle length and elbow flexion contracture following neonatal brachial plexus injury.

    Science.gov (United States)

    Weekley, Holly; Nikolaou, Sia; Hu, Liangjun; Eismann, Emily; Wylie, Christopher; Cornwall, Roger

    2012-08-01

    The pathophysiology of paradoxical elbow flexion contractures following neonatal brachial plexus injury (NBPI) is incompletely understood. The current study tests the hypothesis that this contracture occurs by denervation-induced impairment of elbow flexor muscle growth. Unilateral forelimb paralysis was created in mice in four neonatal (5-day-old) BPI groups (C5-6 excision, C5-6 neurotomy, C5-6 neurotomy/repair, and C5-T1 global excision), one non-neonatal BPI group (28-day-old C5-6 excision), and two neonatal muscle imbalance groups (triceps tenotomy ± C5-6 excision). Four weeks post-operatively, motor function, elbow range of motion, and biceps/brachialis functional lengths were assessed. Musculocutaneous nerve (MCN) denervation and reinnervation were assessed immunohistochemically. Elbow flexion motor recovery and elbow flexion contractures varied inversely among the neonatal BPI groups. Contracture severity correlated with biceps/brachialis shortening and MCN denervation (relative axon loss), with no contractures occurring in mice with MCN reinnervation (presence of growth cones). No contractures or biceps/brachialis shortening occurred following non-neonatal BPI, regardless of denervation or reinnervation. Neonatal triceps tenotomy did not cause contractures or biceps/brachialis shortening, nor did it worsen those following neonatal C5-6 excision. Denervation-induced functional shortening of elbow flexor muscles leads to variable elbow flexion contractures depending on the degree, permanence, and timing of denervation, independent of muscle imbalance. Copyright © 2012 Orthopaedic Research Society.

  1. Redo renal denervation using a multi-electrode radiofrequency system in patients with persistent therapy-resistant hypertension.

    Science.gov (United States)

    Daemen, J; Feyz, L; Van Zandvoort, L; Van Mieghem, N M

    2017-06-01

    Renal sympathetic denervation has been studied as a potential therapeutic option for patients with therapy-resistant hypertension; however, a significant proportion of patients do not show a significant reduction in blood pressure and are classified as non-responders. The objective of the present study was to assess whether a redo renal denervation procedure increases response rates. We present a case series of three consecutive renal denervation non-responders treated with the multi-electrode radiofrequency St. Jude EnligHTN catheter after an average of 22 months. Patients were followed for 6 months. Mean age was 66 years and two patients were male. Patients were previously treated using either ReCor's Paradise system, the Vessix V2 system or the Covidien OneShot system. Mean office blood pressure one year after the initial procedure was 187/102 mm Hg with a mean 24 h ambulatory blood pressure of 166/102 mm Hg. All patients underwent a successful redo procedure using the EnligHTN system because of persistent therapy-resistant hypertension. At 6 months a significant drop in both office and ambulatory blood pressure of -27/-6 mm Hg and -15/-13 mm Hg, respectively, was observed. No significant renal artery stenosis was observed at 6 months. In patients with therapy-resistant hypertension who do not respond to an initial renal denervation procedure, a redo procedure using the St. Jude EnligHTN system may help to significantly improve blood pressure control.

  2. Improved neurological outcome by intramuscular injection of human amniotic fluid derived stem cells in a muscle denervation model.

    Directory of Open Access Journals (Sweden)

    Chun-Jung Chen

    Full Text Available The skeletal muscle develops various degrees of atrophy and metabolic dysfunction following nerve injury. Neurotrophic factors are essential for muscle regeneration. Human amniotic fluid derived stem cells (AFS have the potential to secrete various neurotrophic factors necessary for nerve regeneration. In the present study, we assess the outcome of neurological function by intramuscular injection of AFS in a muscle denervation and nerve anastomosis model.Seventy two Sprague-Dawley rats weighing 200-250 gm were enrolled in this study. Muscle denervation model was conducted by transverse resection of a sciatic nerve with the proximal end sutured into the gluteal muscle. The nerve anastomosis model was performed by transverse resection of the sciatic nerve followed by four stitches reconnection. These animals were allocated to three groups: control, electrical muscle stimulation, and AFS groups.NT-3 (Neurotrophin 3, BDNF (Brain derived neurotrophic factor, CNTF (Ciliary neurotrophic factor, and GDNF (Glia cell line derived neurotrophic factor were highly expressed in AFS cells and supernatant of culture medium. Intra-muscular injection of AFS exerted significant expression of several neurotrophic factors over the distal end of nerve and denervated muscle. AFS caused high expression of Bcl-2 in denervated muscle with a reciprocal decrease of Bad and Bax. AFS preserved the muscle morphology with high expression of desmin and acetylcholine receptors. Up to two months, AFS produced significant improvement in electrophysiological study and neurological functions such as SFI (sciatic nerve function index and Catwalk gait analysis. There was also significant preservation of the number of anterior horn cells and increased nerve myelination as well as muscle morphology.Intramuscular injection of AFS can protect muscle apoptosis and likely does so through the secretion of various neurotrophic factors. This protection furthermore improves the nerve

  3. Intracellular uptake and degradation of extracellular tracers in mouse skeletal muscle in vitro: the effect of denervation

    International Nuclear Information System (INIS)

    Libelius, R.; Lundquist, I.; Templeton, W.; Thesleff, S.

    1978-01-01

    Innervated and chronically denervated mouse skeletal muscles have been incubated under various conditions in a Ringer solution containing one of the three macromolecules [ 3 H] α-neurotoxin, [ 3 H]inulin and horseradish peroxidase. Following extensive wash-out for 4 h of the extracellular compartment, the amount of each macromolecule retained intracellularly was obtained. Intracellular uptake of a [ 3 H]monoacetylated α-neurotoxin in vitro at 37 C was found to be increased in denervated mouse extensor digitorum longus muscles compared to innervated control muscles. Similarly, the uptake in vitro at 37 C of [ 3 H] inulin and horseradish peroxidase was also increased in denervated muscles. At 4 C the uptake of [ 3 H]inulin and horseradish peroxidase was markedly reduced. Protamine was found to stimulate the uptake of [ 3 H]inulin at 37 C, but not at 4 C. Reduction in specific activity by addition of 50-fold excess of unlabelled inulin failed to affect the uptake of [ 3 H]inulin suggesting that this uptake process obeyed bulk kinetics. Furthermore, the endocytized [ 3 H]inulin was found to be strongly retained in the muscles since prolonged washing or addition of unlabelled inulin to the washing solution did not reduce the uptake. Characterization of [ 3 H]inulin taken up by the muscles was performed by gel chromatography on Sephadex G-25. Using a purified [ 3 H]inulin solution it was observed that about 45% of the total radioactivity remaining in the muscles was eluted as [ 3 H]inulin. Additional radioactivity consisted of lower molecular weight compounds. These degradation products of [ 3 H]inulin were only present in the muscle homogenate and were not detected in the incubation solution. The results suggest that intracellular uptake of different macromolecules by endocytosis in skeletal muscles increases following denervation, and that following uptake, degradation of the endocytized material may occur. (author)

  4. Plasticity of the transverse tubules following denervation and subsequent reinnervation in rat slow and fast muscle fibres.

    Science.gov (United States)

    Takekura, Hiroaki; Tamaki, Hiroyuki; Nishizawa, Tomie; Kasuga, Norikatsu

    2003-01-01

    We have studied the effects of short term denervation followed by reinnervation on the ultrastructure of the membrane systems and on the content of and distribution of key proteins involved in calcium regulation of fast-twitch (FT) extensor digitorum longus (EDL) and slow-twitch (ST) soleus (SOL) muscle fibres. Ischiadic nerve freezing resulted in total lack of neuromuscular transmission for 3 days followed by a slow recovery, but no decline in twitch force elicited by direct stimulation. The latter measurements indicate no significant atrophy within this time frame. The membrane systems of skeletal muscle fibres were visualized using Ca92+)-K3Fe(CN)6-OsO4 techniques and observed using a high voltage electron microscope. [3H]nitrendipine binding was used to detect levels of dihydropyridine receptor (DHPR) expression. The Ca2+ pumping free sarcoplasmic reticulum domains were not affected by the denervation, but the Ca2+ release domains were dramatically increased, particularly in the FT-EDL muscle fibres. The increase is evidenced by a doubling up of the areas of contacts between SR and transverse (t-) tubules, so that in place of the normal triadic arrangement, pentadic and heptadic junctions, formed by multiple interacting layers of ST and t-tubules are seen. Frequency of pentads and heptads increases and declines in parallel to the denervation and reinnervation but with a delay. Immunofluorecence and electron microscopy observations show presence of DHPR and ryanodine receptor clusters at pentads and heptads junctions. A significant (P muscle fibres indicating that overexpression of DHPRs accompanies the build up extra junctional contacts. The results indicate that denervation reversibly affects the domains of the membrane systems involved in excitation-contraction coupling.

  5. Intracellular uptake and degradation of extracellular tracers in mouse skeletal muscle in vitro: the effect of denervation

    Energy Technology Data Exchange (ETDEWEB)

    Libelius, R; Lundquist, I; Templeton, W; Thesleff, S [Lund Univ. (Sweden)

    1978-01-01

    Innervated and chronically denervated mouse skeletal muscles have been incubated under various conditions in a Ringer solution containing one of the three macromolecules (/sup 3/H) ..cap alpha..-neurotoxin, (/sup 3/H)inulin and horseradish peroxidase. Following extensive wash-out for 4 h of the extracellular compartment, the amount of each macromolecule retained intracellularly was obtained. Intracellular uptake of a (/sup 3/H)monoacetylated ..cap alpha..-neurotoxin in vitro at 37 C was found to be increased in denervated mouse extensor digitorum longus muscles compared to innervated control muscles. Similarly, the uptake in vitro at 37 C of (/sup 3/H) inulin and horseradish peroxidase was also increased in denervated muscles. At 4 C the uptake of (/sup 3/H)inulin and horseradish peroxidase was markedly reduced. Protamine was found to stimulate the uptake of (/sup 3/H)inulin at 37 C, but not at 4 C. Reduction in specific activity by addition of 50-fold excess of unlabelled inulin failed to affect the uptake of (/sup 3/H)inulin suggesting that this uptake process obeyed bulk kinetics. Furthermore, the endocytized (/sup 3/H)inulin was found to be strongly retained in the muscles since prolonged washing or addition of unlabelled inulin to the washing solution did not reduce the uptake. Characterization of (/sup 3/H)inulin taken up by the muscles was performed by gel chromatography on Sephadex G-25. Using a purified (/sup 3/H)inulin solution it was observed that about 45% of the total radioactivity remaining in the muscles was eluted as (/sup 3/H)inulin. Additional radioactivity consisted of lower molecular weight compounds. Degradation products of (/sup 3/H)inulin were only present in the muscle homogenate and were not detected in the incubation solution. Results suggest that intracellular uptake of different macromolecules by endocytosis in skeletal muscles increases following denervation, and that following uptake, degradation of the endocytized material may occur.

  6. Accessory renal arteries: Prevalence in resistant hypertension and an important role in nonresponse to radiofrequency renal denervation.

    Science.gov (United States)

    VonAchen, Paige; Hamann, Jason; Houghland, Thomas; Lesser, John R; Wang, Yale; Caye, David; Rosenthal, Kristi; Garberich, Ross F; Daniels, Mary; Schwartz, Robert S

    The aim of this study was to understand the role of accessory renal arteries in resistant hypertension, and to establish their role in nonresponse to radiofrequency renal denervation (RDN) procedures. Prior studies suggest a role for accessory renal arteries in hypertensive syndromes, and recent clinical trials of renal denervation report that these anomalies are highly prevalent in resistant hypertension. This study evaluated the relationships among resistant hypertension, accessory renal arteries, and the response to radiofrequency (RF) renal denervation. Computed Tomography Angiography (CTA) and magnetic resonance imaging (MRI) scans from 58 patients with resistant hypertension undergoing RF renal denervation (RDN) were evaluated. Results were compared with CT scans in 57 healthy, normotensive subjects undergoing screening as possible renal transplant donors. All scans were carefully studied for accessory renal arteries, and were correlated with long term blood pressure reduction. Accessory renal arteries were markedly more prevalent in the hypertensive patients than normotensive renal donors (59% vs 32% respectively, p=0.004). RDN had an overall nonresponse rate of 29% (response rate 71%). Patients without accessory vessels had a borderline higher response rate to RDN than those with at least one accessory vessel (83% vs 62% respectively, p=0.076) and a higher RDN response than patients with untreated accessory arteries (83% vs 55%; p=0.040). For accessory renal arteries and nonresponse, the sensitivity was 76%, specificity 49%, with positive and negative predictive values 38% and 83% respectively. Accessory renal arteries were markedly over-represented in resistant hypertensives compared with healthy controls. While not all patients with accessory arteries were nonresponders, nonresponse was related to both the presence and non-treatment of accessory arteries. Addressing accessory renal arteries in future clinical trials may improve RDN therapeutic efficacy

  7. Cutaneous collateral axonal sprouting re-innervates the skin component and restores sensation of denervated Swine osteomyocutaneous alloflaps.

    Directory of Open Access Journals (Sweden)

    Zuhaib Ibrahim

    Full Text Available Reconstructive transplantation such as extremity and face transplantation is a viable treatment option for select patients with devastating tissue loss. Sensorimotor recovery is a critical determinant of overall success of such transplants. Although motor function recovery has been extensively studied, mechanisms of sensory re-innervation are not well established. Recent clinical reports of face transplants confirm progressive sensory improvement even in cases where optimal repair of sensory nerves was not achieved. Two forms of sensory nerve regeneration are known. In regenerative sprouting, axonal outgrowth occurs from the transected nerve stump while in collateral sprouting, reinnervation of denervated tissue occurs through growth of uninjured axons into the denervated tissue. The latter mechanism may be more important in settings where transected sensory nerves cannot be re-apposed. In this study, denervated osteomyocutaneous alloflaps (hind- limb transplants from Major Histocompatibility Complex (MHC-defined MGH miniature swine were performed to specifically evaluate collateral axonal sprouting for cutaneous sensory re-innervation. The skin component of the flap was externalized and serial skin sections extending from native skin to the grafted flap were biopsied. In order to visualize regenerating axonal structures in the dermis and epidermis, 50 um frozen sections were immunostained against axonal and Schwann cell markers. In all alloflaps, collateral axonal sprouts from adjacent recipient skin extended into the denervated skin component along the dermal-epidermal junction from the periphery towards the center. On day 100 post-transplant, regenerating sprouts reached 0.5 cm into the flap centripetally. Eight months following transplant, epidermal fibers were visualized 1.5 cm from the margin (rate of regeneration 0.06 mm per day. All animals had pinprick sensation in the periphery of the transplanted skin within 3 months post

  8. Minimally Invasive Sacroiliac Joint Fusion, Radiofrequency Denervation, and Conservative Management for Sacroiliac Joint Pain: 6-Year Comparative Case Series.

    Science.gov (United States)

    Vanaclocha, Vicente; Herrera, Juan Manuel; Sáiz-Sapena, Nieves; Rivera-Paz, Marlon; Verdú-López, Francisco

    2018-01-01

    Sacroiliac joint (SIJ) pain is an under-recognized condition. Substantial information supports the safety and effectiveness of SIJ fusion (SIJF). Long-term follow-up after SIJF has not been reported. To determine responses to conservative management (CM), SIJ denervation, and SIJF in patients with SIJ pain unresponsive to CM. Retrospective study with long-term (up to 6 yr) follow-up of 137 patients with SIJ pain seen in an outpatient neurosurgery clinic who received either CM (n = 63), sacroiliac denervation (n = 47), or minimally invasive SIJF (n = 27). At each routine clinic visit, patients completed pain scores and Oswestry Disability Index. Additional data were extracted from medical charts. Patients treated with continued CM had no long-term improvement in pain (mean worsening of 1 point) or disability (mean Oswestry Disability Index worsened by 4-6 points), increased their use of opioids, and had poor long-term work status. SIJF patients had large improvements in SIJ pain (mean 6 points), large improvements in disability (mean 25 points), a decrease in opioid use, and good final work status. Sacroiliac denervation patients had intermediate responses (0-1 and 1-2 points, respectively). In patients with SIJ pain unresponsive to CM, SIJF resulted in excellent long-term clinical responses, with low opioid use and better work status compared to other treatments. Copyright © 2017 by the Congress of Neurological Surgeons

  9. Sensory nerve cross-anastomosis and electrical muscle stimulation synergistically enhance functional recovery of chronically denervated muscle.

    Science.gov (United States)

    Willand, Michael P; Holmes, Michael; Bain, James R; de Bruin, Hubert; Fahnestock, Margaret

    2014-11-01

    Long-term muscle denervation leads to severe and irreversible atrophy coupled with loss of force and motor function. These factors contribute to poor functional recovery following delayed reinnervation. The authors' previous work demonstrated that temporarily suturing a sensory nerve to the distal motor stump (called sensory protection) significantly reduces muscle atrophy and improves function following reinnervation. The authors have also shown that 1 month of electrical stimulation of denervated muscle significantly improves function and reduces atrophy. In this study, the authors tested whether a combination of sensory protection and electrical stimulation would enhance functional recovery more than either treatment alone. Rat gastrocnemius muscles were denervated by cutting the tibial nerve. The peroneal nerve was then sutured to the distal tibial stump following 3 months of treatment (i.e., electrical stimulation, sensory protection, or both). Three months after peroneal repair, functional and histologic measurements were taken. All treatment groups had significantly higher muscle weight (pstimulation or sensory protection alone. The combined treatment also produced motor unit counts significantly greater than sensory protection alone (p<0.05). The combination treatment synergistically reduces atrophy and improves reinnervation and functional measures following delayed nerve repair, suggesting that these approaches work through different mechanisms. The authors' research supports the clinical use of both modalities together following peripheral nerve injury.

  10. Renal Sympathetic Denervation System via Intraluminal Ultrasonic Ablation: Therapeutic Intravascular Ultrasound Design and Preclinical Evaluation.

    Science.gov (United States)

    Chernin, Gil; Szwarcfiter, Iris; Bausback, Yvonne; Jonas, Michael

    2017-05-01

    To assess the safety and performance of a nonfocused and nonballooned ultrasonic (US) catheter-based renal sympathetic denervation (RDN) system in normotensive swine. RDN with the therapeutic intravascular US catheter was evaluated in 3 experiments: (i) therapeutic intravascular US RDN vs a control group of untreated animals with follow-up of 30, 45, and 90 days (n = 6; n = 12 renal arteries for each group); (ii) therapeutic intravascular US RDN vs radiofrequency (RF) RDN in the contralateral artery in the same animal (n = 2; n = 4 renal arteries); and (iii) therapeutic intravascular US RDN in a recently stent-implanted renal artery (n = 2; n = 4 renal arteries). In the first experiment, therapeutic intravascular US RDN was safe, without angiographic evidence of dissection or renal artery stenosis. Neuronal tissue vacuolization, nuclei pyknosis, and perineuronal inflammation were evident after RDN, without renal artery wall damage. Norepinephrine levels were significantly lower after therapeutic intravascular US RDN after 30, 45, and 90 days compared with the control group (200.17 pg/mg ± 63.35, 184.75 pg/mg ± 44.51, and 203.43 pg/mg ± 58.54, respectively, vs 342.42 pg/mg ± 79.97). In the second experiment, deeper neuronal ablation penetrance was found with therapeutic intravascular US RDN vs RF RDN (maximal penetrance from endothelium of 7.0 mm vs 3.5 mm, respectively). There was less damage to the artery wall after therapeutic intravascular US RDN than with RF RDN, after which edema and injured endothelium were seen. In the third experiment, denervation inside the stent-implanted segments was feasible without damage to the renal artery wall or stent. The therapeutic intravascular US system performed safely and reduced norepinephrine levels. Deeper penetrance and better preservation of vessel wall were observed with therapeutic intravascular US RDN vs RF RDN. Neuronal ablations were observed in stent-implanted renal arteries. Copyright © 2017 SIR. Published

  11. Effects of renal sympathetic denervation on blood pressure and glycaemic control in patients with true resistant hypertension: results of Polish Renal Denervation Registry (RDN-POL Registry).

    Science.gov (United States)

    Kądziela, Jacek; Prejbisz, Aleksander; Kostka-Jeziorny, Katarzyna; Dudek, Dariusz; Narkiewicz, Krzysztof; Sadowski, Jerzy; Lekston, Andrzej; Gziut, Aneta; Więcek, Andrzej; Buszman, Paweł; Kleinrok, Andrzej; Kochman, Janusz; Czarnecka, Danuta; Januszewicz, Andrzej; Witkowski, Adam

    2016-01-01

    The assessment of percutaneous renal sympathetic denervation (RDN) efficacy in patients with true-resistant hypertension (true-RH) in a newly established net of Polish centres (RDN-POL Registry). Forty-four patients with true-RH (23 men, mean age 52.3 years) with daytime systolic blood pressure (SBP) in ambulatory blood pressure monitoring (ABPM) ≥ 135 mm Hg, on ≥ three antihypertensive agents, including diuretic, underwent RDN and completed 12-month follow-up. Mean reductions of office SBP/diastolic blood pressure were -23.8/-10.0, -12.5/-4.6, and -12.6/-6.1 mm Hg at 3, 6, and 12 months, respectively (all significant except diastolic at 6 months). Diabetes was the only predictor of office SBP reduction at 6 months (OR 9.6, 95% CI 1.4-66.5, p < 0.05). Mean 24-h SBP change was -8.3 mm Hg at 6 months and -4.6 mm Hg at 12 months. Increased 2 h-glucose in oral glucose tolerance test was the only predictor of 24-h SBP reduction at 6 months (OR 1.24 for 10 mg/dL glucose increase, 95% CI 1.04-1.48, p < 0.05). At 12 months, 24-h SBP change predictors were: baseline office SBP (OR 4.93 for 10 mm Hg SBP increment, 95% CI 1.01-24.1, p < 0.05) and 2 h-glucose (OR 1.47, 95% CI 1.08-2.00, p < 0.05). In ABPM responders, significant reduction of 2 h glucose was found as compared to the non-responders (-45.8 vs. -7.7 mg/dL, p < 0.005). The RDN-POL Registry demonstrated moderate blood pressure decrease after RDN. The predictors of blood pressure reduction were diabetes, 2 h-glucose, and baseline office SBP. Analysis of ABPM responders indicates a probable positive impact of RDN on glycaemic control.

  12. Invasive assessment of renal artery atherosclerotic disease and resistant hypertension before renal sympathetic denervation.

    Science.gov (United States)

    Ribichini, Flavio; Pighi, Michele; Zivelonghi, Carlo; Gambaro, Alessia; Valvo, Enrico; Lupo, Antonio; Vassanelli, Corrado

    2013-01-01

    Renal sympathetic denervation (RSD) is emerging as a new therapeutic option for patients with severe hypertension refractory to medical therapy. The presence of a renal artery stenosis may be both a cause of secondary hypertension and a contraindication to RSD if a renal artery stent is implanted; therefore, the definition of the functional importance of a renal artery stenosis in a patient with refractory hypertension is crucial. We describe the imaging and functional intravascular assessment of an angiographically severe stenosis of the renal artery in a patient with severe refractory hypertension, by means of intravascular ultrasound (IVUS), and measurement of the translesional pressure gradient with a pressure wire. Pressure wire examination excluded any severity of the stenosis, and IVUS showed the presence of a dissected plaque that resolved spontaneously after 3 months of intensive medical therapy and high-dose statin. Subsequently the patient was treated with RSD, achieving a significant effect on blood pressure control. Intravascular imaging and functional assessment of renal artery anatomy in patients with atherosclerotic disease may prove particularly suited to patients with refractory hypertension and multilevel vascular disease who are considered for endovascular therapies, either renal artery stenting or RSD.

  13. [Economic efficiency of renal denervation in patients with resistant hypertension: results of Markov modeling].

    Science.gov (United States)

    Kontsevaia, A V; Suvorova, E I; Khudiakov, M B

    2014-01-01

    Aim of this study was to evaluate the cost-effectiveness of renal denervation (RD) in resistant arterial hypertension (AH) in Russia. Modeling of Markov conducted economic impact of RD on the Russian population of patients with resistant hypertension in combination with optimal medical therapy (OMT) compared with OMT using a model developed by American researchers based on the results of international research. The model contains data on Russian mortality, and costs of major complications of hypertension. The simulation results showed a significant reduction in relative risk reduction of adverse outcomes in patients with resistant hypertension for 10 years (risk of stroke is reduced by 30%, myocardial infarction - 32%). RD saves 0.9 years of quality-adjusted life (QALY) by an average of 1 patient with resistant hypertension. Costs for 1 year stored in the application of quality of life amounted to RD 203 791.6 rubles. Which is below the 1 gross domestic product and therefore indicates the feasibility of this method in Russia.

  14. Preventive effect of dietary quercetin on disuse muscle atrophy by targeting mitochondria in denervated mice.

    Science.gov (United States)

    Mukai, Rie; Matsui, Naoko; Fujikura, Yutaka; Matsumoto, Norifumi; Hou, De-Xing; Kanzaki, Noriyuki; Shibata, Hiroshi; Horikawa, Manabu; Iwasa, Keiko; Hirasaka, Katsuya; Nikawa, Takeshi; Terao, Junji

    2016-05-01

    Quercetin is a major dietary flavonoid in fruits and vegetables. We aimed to clarify the preventive effect of dietary quercetin on disuse muscle atrophy and the underlying mechanisms. We established a mouse denervation model by cutting the sciatic nerve in the right leg (SNX surgery) to lack of mobilization in hind-limb. Preintake of a quercetin-mixed diet for 14days before SNX surgery prevented loss of muscle mass and atrophy of muscle fibers in the gastrocnemius muscle (GM). Phosphorylation of Akt, a key phosphorylation pathway of suppression of protein degradation, was activated in the quercetin-mixed diet group with and without SNX surgery. Intake of a quercetin-mixed diet suppressed the generation of hydrogen peroxide originating from mitochondria and elevated mitochondrial peroxisome proliferator-activated receptor-γ coactivator 1α mRNA expression as well as NADH dehydrogenase 4 expression in the GM with SNX surgery. Quercetin and its conjugated metabolites reduced hydrogen peroxide production in the mitochondrial fraction obtained from atrophied muscle. In C2C12 myotubes, quercetin reached the mitochondrial fraction. These findings suggest that dietary quercetin can prevent disuse muscle atrophy by targeting mitochondria in skeletal muscle tissue through protecting mitochondria from decreased biogenesis and reducing mitochondrial hydrogen peroxide release, which can be related to decreased hydrogen peroxide production and/or improvements on antioxidant capacity of mitochondria. Copyright © 2016 Elsevier Inc. All rights reserved.

  15. Sympathetic Denervation Accelerates Wound Contraction but Inhibits Reepithelialization and Pericyte Proliferation in Diabetic Mice

    Directory of Open Access Journals (Sweden)

    Zhifang Zheng

    2017-01-01

    Full Text Available Previous studies focused on the effects of sympathetic denervation with 6-hydroxydopamine (6-OHDA on nondiabetic wounds, but the effects of 6-OHDA on diabetic wounds have not been previously reported. In this study, treated mice received intraperitoneal 6-OHDA, and control mice received intraperitoneal injections of normal saline. Full-thickness wounds were established on the backs of mice. The wounds were sectioned (four mice per group for analysis at 2, 5, 7, 10, 14, 17, and 21 days after injury. The wound areas in the control group were larger than those in the treatment group. Histological scores for epidermal and dermal regeneration were reduced in the 6-OHDA-treated group on day 21. The mast cells (MCs in each field decreased after sympathectomy on days 17 and 21. The expression levels of norepinephrine, epidermal growth factor (EGF, interleukin-1 beta, NG2 proteoglycan, and desmin in the treatment group were less than those in the control group. In conclusion, 6-OHDA delays reepithelialization during wound healing in diabetic mice by decreasing EGF, but increases wound contraction by reducing IL-1β levels and the number of MCs. Besides, 6-OHDA led to reduced pericyte proliferation in diabetic wounds, which might explain the vascular dysfunction after sympathetic nerve loss in diabetic wounds.

  16. Renal artery and parenchymal changes after renal denervation: assessment by magnetic resonance angiography

    Energy Technology Data Exchange (ETDEWEB)

    Sanders, Margreet F.; Vink, Eva E.; Blankestijn, Peter J. [University Medical Center Utrecht, Department of Nephrology and Hypertension, PO Box 85500, Utrecht (Netherlands); Doormaal, Pieter Jan van; Habets, Jesse; Vonken, Evert-Jan; Leiner, Tim [University Medical Center Utrecht, Department of Radiology, Utrecht (Netherlands); Beeftink, Martine M.A.; Verloop, Willemien L.; Voskuil, Michiel [University Medical Center Utrecht, Department of Cardiology, Utrecht (Netherlands); Bots, Michiel L. [University Medical Center Utrecht, Julius Center for Health Sciences and Primary Care, Utrecht (Netherlands); Fadl Elmula, Fadl Elmula M. [Oslo University Hospital, Department of Internal Medicine and Department of Cardiology, Ullevaal, Oslo (Norway); Hammer, Frank [Cliniques Universitaires Saint-Luc, Universite Catholique de Louvain, Department of Radiology, Brussels (Belgium); Hoffmann, Pavel [Oslo University Hospital, Section for Interventional Cardiology, Department of Cardiology, Ullevaal, Oslo (Norway); Jacobs, Lotte; Staessen, Jan A. [University of Leuven, Studies Coordinating Centre, Research Unit Hypertension and Cardiovascular Epidemiology, KU Leuven Department of Cardiovascular Sciences, Leuven (Belgium); Mark, Patrick B.; Taylor, Alison H. [University of Glasgow, Institute of Cardiovascular and Medical Sciences, Glasgow, Scotland (United Kingdom); Persu, Alexandre; Renkin, Jean [Universite Catholique de Louvain, Pole of Cardiovascular Research, Institut de Recherche Experimentale et Clinique, Brussels (Belgium); Cliniques Universitaires Saint-Luc, Universite Catholique de Louvain, Cardiology Department, Brussels (Belgium); Roditi, Giles [Glasgow Royal Infirmary, Department of Radiology, Glasgow (United Kingdom); Spiering, Wilko [University Medical Centre Utrecht, Department of Vascular Medicine, Utrecht (Netherlands); Collaboration: on behalf of the European Network COordinating research on Renal Denervation (ENCOReD) Consortium

    2017-09-15

    Relatively little is known about the incidence of long-term renal damage after renal denervation (RDN), a potential new treatment for hypertension. In this study the incidence of renal artery and parenchymal changes, assessed with contrast-enhanced magnetic resonance angiography (MRA) after RDN, is investigated. This study is an initiative of ENCOReD, a collaboration of hypertension expert centres. Patients in whom an MRA was performed before and after RDN were included. Scans were evaluated by two independent, blinded radiologists. Primary outcome was the change in renal artery morphology and parenchyma. MRAs from 96 patients were analysed. Before RDN, 41 renal anomalies were observed, of which 29 mostly mild renal artery stenoses. After a median time of 366 days post RDN, MRA showed a new stenosis (25-49% lumen reduction) in two patients and progression of pre-existing lumen reduction in a single patient. No other renal changes were observed and renal function remained stable. We observed new or progressed renal artery stenosis in three out of 96 patients, after a median time of 12 months post RDN (3.1%). Procedural angiographies showed that ablations were applied near the observed stenosis in only one of the three patients. (orig.)

  17. Cost-effectiveness of renal denervation therapy for the treatment of resistant hypertension in The Netherlands.

    Science.gov (United States)

    Henry, Thea L; De Brouwer, Bonnie F E; Van Keep, Marjolijn M L; Blankestijn, Peter J; Bots, Michiel L; Koffijberg, Hendrik

    2015-01-01

    Safety and efficacy data for catheter-based renal denervation (RDN) in the treatment of resistant hypertension have been used to estimate the cost-effectiveness of this approach. However, there are no Dutch-specific analyses. This study examined the cost-effectiveness of RDN from the perspective of the healthcare payer in The Netherlands. A previously constructed Markov state-transition model was adapted and updated with costs and utilities relevant to the Dutch setting. The cost-effectiveness of RDN was compared with standard of care (SoC) for patients with resistant hypertension. The efficacy of RDN treatment was modeled as a reduction in the risk of cardiovascular events associated with a lower systolic blood pressure (SBP). Treatment with RDN compared to SoC gave an incremental quality-adjusted life year (QALY) gain of 0.89 at an additional cost of €1315 over a patient's lifetime, resulting in a base case incremental cost-effectiveness ratio (ICER) of €1474. Deterministic and probabilistic sensitivity analyses (PSA) showed that treatment with RDN therapy was cost-effective at conventional willingness-to-pay thresholds (€10,000-80,000/QALY). RDN is a cost-effective intervention for patients with resistant hypertension in The Netherlands.

  18. Single-side renal sympathetic denervation to treat malignant refractory hypertension in a solitary kidney patient.

    Science.gov (United States)

    Ribichini, Flavio; Ferrara, Angela; Pighi, Michele; Pesarini, Gabriele; Gambaro, Alessia; Valvo, Enrico; Lupo, Antonio; Vassanelli, Corrado

    2014-12-01

    Renal sympathetic denervation (RSD) is emerging as a new therapeutic option for patients with severe hypertension refractory to medical therapy. Patients affected by renovascular or anatomical abnormalities have hitherto been systematically excluded from clinical trials with RSD because of concern about safety and the unknown efficacy of the procedure in this subgroup of patients. We describe the management of a case of RSD in a single-kidney patient with refractory hypertension; the patient had had a previous surgical right nephrectomy for renal cell carcinoma that subsequently required no other oncologic treatment. After multidisciplinary assessment, the patient underwent RSD. The procedure was performed through a 6F femoral access using the Symplicity™ RSD system (Medtronic, Mountain View, CA, USA). Radiofrequency was applied to the renal artery wall in 6 different points under general sedation with midazolam to control back pain caused by the procedure, that was performed without periprocedural complications. The patient was discharged 2 days later after a control of the vascular access site and routine biochemical examinations. The following 9-month follow up showed a significant reduction in blood pressure and stable renal function, without signs of renal damage. Our report confirms the feasibility of RSD in this delicate context, without evident negative effects on kidney function and with a significant reduction in blood pressure. Future studies are needed to fully clarify the value of RSD in single-kidney patients.

  19. Renal Nerve Stimulation-Induced Blood Pressure Changes Predict Ambulatory Blood Pressure Response After Renal Denervation.

    Science.gov (United States)

    de Jong, Mark R; Adiyaman, Ahmet; Gal, Pim; Smit, Jaap Jan J; Delnoy, Peter Paul H M; Heeg, Jan-Evert; van Hasselt, Boudewijn A A M; Lau, Elizabeth O Y; Persu, Alexandre; Staessen, Jan A; Ramdat Misier, Anand R; Steinberg, Jonathan S; Elvan, Arif

    2016-09-01

    Blood pressure (BP) response to renal denervation (RDN) is highly variable and its effectiveness debated. A procedural end point for RDN may improve consistency of response. The objective of the current analysis was to look for the association between renal nerve stimulation (RNS)-induced BP increase before and after RDN and changes in ambulatory BP monitoring (ABPM) after RDN. Fourteen patients with drug-resistant hypertension referred for RDN were included. RNS was performed under general anesthesia at 4 sites in the right and left renal arteries, both before and immediately after RDN. RNS-induced BP changes were monitored and correlated to changes in ambulatory BP at a follow-up of 3 to 6 months after RDN. RNS resulted in a systolic BP increase of 50±27 mm Hg before RDN and systolic BP increase of 13±16 mm Hg after RDN (Pefficacy of RDN and predict BP response to RDN. © 2016 American Heart Association, Inc.

  20. [Safety and short-term efficacy of renal sympathetic denervation in the treatment of resistant hypertension].

    Science.gov (United States)

    Jiang, Xiong-jing; Liang, Tuo; Dong, Hui; Peng, Meng; Ma, Wen-jun; Guan, Ting; Zhang, Hui-min; Bian, Jin; Xu, Bo; Gao, Run-lin

    2012-12-11

    Transcatheter renal sympathetic denervation (RDN) is a novel technology/therapy in treating resistant hypertension. The present study aims to evaluate the safety and short-term efficacy of RDN for the treatment of resistant hypertension in a Chinese population. This prospective single-center pilot study was the first one conducted in China with Medtronic Ardian Symplicity Catheter System. Eight patients (6 males and 2 females) with resistant hypertension underwent RDN at our hospital from February to April 2012. All patients were followed up at one month and three months post-RDN. Blood pressure, use of antihypertensive medications, renal function and complications were recorded and analyzed. At one month and three months post-RDN, 24-hour ambulatory blood pressure monitoring showed mean systolic blood pressure and diastolic blood pressure decreased 10 (0 - 18) 13 (3 - 19) and 8 (-2 - 15), 9 (2 - 16) mm Hg throughout 24 hours respectively (P renal function (P > 0.05). No complications were observed. The preliminary results revealed that RDN was safe and effective for the treatment of resistant hypertension in the Chinese population during a 3-month follow-up. Further large and long-term studies are warranted.

  1. EFFECTIVENESS OF RADIOFREQUENCY DENERVATION FOR PAIN RELIEF IN HIP DEGENERATIVE DISEASES

    Directory of Open Access Journals (Sweden)

    G. I. Nazarenko

    2014-01-01

    Full Text Available Objective - to compare the effectiveness of radiofrequency denervation (RFD and conservative treatment of patients with hip degenerative diseases. Material and methods. 66 patients with various stages of hip degeneration were followed up for 12 months, including 36 patients who underwent RFD and 30 patients of control group with conservative treatment. Treatment results were assessed using Visual Analogue Scale (VAS and Harris Hip Score before treatment, during the first day, 2 days later, as well as at 1, 6 and 12 months. Results: RFD patients demonstrated significantly better results compared with conservative group. Patients with coxarthrosis stage I and II, besides higher efficiency had prolonged period of remission, while patients with coxarthrosis stage III returned to the near-baseline level of pain only in 3-6 months. Conclusions: RFD is an effective treatment modality for patients with initial coxarthrosis stages, which helps to reduce significantly the disability period compared with conservative therapy. RFD is the only method of effective hip pain relieve in patients with severe comorbidities allowing to reduce analgesic consumption. This method is minimally invasive, has low cost, permits repeated procedures, making it attractive for both physicians and patients.

  2. Renal artery anatomy affects the blood pressure response to renal denervation in patients with resistant hypertension.

    Science.gov (United States)

    Hering, Dagmara; Marusic, Petra; Walton, Antony S; Duval, Jacqueline; Lee, Rebecca; Sata, Yusuke; Krum, Henry; Lambert, Elisabeth; Peter, Karlheinz; Head, Geoff; Lambert, Gavin; Esler, Murray D; Schlaich, Markus P

    2016-01-01

    Renal denervation (RDN) has been shown to reduce blood pressure (BP), muscle sympathetic nerve activity (MSNA) and target organ damage in patients with resistant hypertension (RH) and bilateral single renal arteries. The safety and efficacy of RDN in patients with multiple renal arteries remains unclear. We measured office and 24-hour BP at baseline, 3 and 6 months following RDN in 91 patients with RH, including 65 patients with single renal arteries bilaterally (group 1), 16 patients with dual renal arteries on either one or both sides (group 2) and 10 patients with other anatomical constellations or structural abnormalities (group 3). Thirty nine out of 91 patients completed MSNA at baseline and follow-up. RDN significantly reduced office and daytime SBP in group 1 at both 3 and 6 months follow-up (Pkidney function in any group. While RDN can be performed safely irrespective of the underlying renal anatomy, the presence of single renal arteries with or without structural abnormalities is associated with a more pronounced BP and MSNA lowering effect than the presence of dual renal arteries in patients with RH. However, when patients with dual renal arteries received renal nerve ablation in all arteries there was trend towards a greater BP reduction. Insufficient renal sympathetic nerve ablation may account for these differences. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  3. Patellar denervation with electrocautery in total knee arthroplasty without patellar resurfacing: a meta-analysis.

    Science.gov (United States)

    Cheng, Tao; Zhu, Chen; Guo, Yongyuan; Shi, Sifeng; Chen, Desheng; Zhang, Xianlong

    2014-11-01

    The impact of patellar denervation with electrocautery in total knee arthroplasty (TKA) on post-operative outcomes has been under debate. This study aims to conduct a meta-analysis and systematic review to compare the benefits and risks of circumpatellar electrocautery with those of non-electrocautery in primary TKAs. Comparative and randomized clinical studies were identified by conducting an electronic search of articles dated up to September 2012 in PubMed, EMBASE, Scopus, and the Cochrane databases. Six studies that focus on a total of 849 knees were analysed. A random-effects model was conducted using the inverse-variance method for continuous variables and the Mantel-Haenszel method for dichotomous variables. There was no significant difference in the incidence of anterior knee pain between the electrocautery and non-electrocautery groups. In term of patellar score and Knee Society Score, circumpatellar electrocautery improved clinical outcomes compared with non-electrocautery in TKAs. The statistical differences were in favour of the electrocautery group but have minimal clinical significance. In addition, the overall complications indicate no statistical significance between the two groups. This study shows no strong evidence either for or against electrocautery compared with non-electrocautery in TKAs. Therapeutic study (systematic review and meta-analysis), Level III.

  4. The response of denervated muscle to long-term stimulation (1985, revisited here in 2014

    Directory of Open Access Journals (Sweden)

    Terje Lomo

    2014-03-01

    Full Text Available In 1985, at a meeting in Abano, I presented results showing that direct stimulation of skeletal muscles with appropriate stimulus patterns prevents the effects of denervation on non-junctional properties of muscle fibers. Hence, it appeared unnecessary to postulate that unknown nerve-derived trophic factors control such properties, as posited by the (anterograde neurotrophic hypothesis. Here I discuss this conclusion in the light of what we know today, particularly with respect to the many lines of evidence that were then taken to support the trophic hypothesis, but which today have alternative interpretations consistent with control by evoked impulse activity. Despite much effort, no one has yet identified any nerve-derived factor consistent with the neurotrophic hypothesis. Reports favoring the existence of neurotrophic factors were numerous before 2000. Now they have essentially disappeared from the literature, including original research papers, textbooks and handbooks, suggesting that the hypothesis is no longer arguable. Thus, the results that I presented in our paper in 1985 seem to have held up rather well.

  5. Safety and performance of the next generation EnligHTN™ renal denervation system in patients with drug-resistant, uncontrolled hypertension: The EnligHTN III first-in-human multicentre study

    Directory of Open Access Journals (Sweden)

    Stephen G. Worthley

    2015-08-01

    Conclusions: Renal sympathetic denervation using the next generation EnligHTN renal denervation system resulted in safe, rapid, and significant mean office blood pressure reduction that was sustained through 6 months. Future studies will need to address the utility of this system against an appropriate placebo based comparator.

  6. Renal artery denervation for treating resistant hypertension : definition of the disease, patient selection and description of the procedure.

    Science.gov (United States)

    Volpe, Massimo; Rosei, Enrico Agabiti; Ambrosioni, Ettore; Cottone, Santina; Cuspidi, Cesare; Borghi, Claudio; De Luca, Nicola; Fallo, Francesco; Ferri, Claudio; Mancia, Giuseppe; Morganti, Alberto; Muiesan, Maria Lorenza; Sarzani, Riccardo; Sechi, Leonardo; Tocci, Giuliano; Virdis, Agostino

    2012-12-01

    Arterial hypertension is responsible for a significant burden of cardiovascular morbidity and mortality, worldwide. Although several rational and integrated pharmacological strategies are available, the control of high blood pressure still remains largely unsatisfactory. Failure to achieve effective blood pressure control in treated hypertensive patients may have a substantial impact on individual global cardiovascular risk, since it significantly increases the risk of developing hypertension-related macrovascular and microvascular complications. Arterial hypertension is arbitrarily defined as 'resistant' or 'refractory' when the recommended blood pressure goals (clinic blood pressure below 140/90 mmHg or below 130/80 mmHg in patients with type 2 diabetes mellitus or nephropathy) are not achieved in the presence of a therapeutic strategy that includes lifestyle changes and at least three classes of antihypertensive drugs, including a diuretic, at adequate doses. Recently, an innovative non-pharmacological option has become available for treating resistant hypertension. Sympathetic denervation of renal arteries is a minimally invasive procedure that is performed via percutaneous access from the femoral artery. It consists of radiofrequency ablation of the afferent and efferent nerves of the renal sympathetic nervous system, with consequent isolation of renal parenchymal and juxtaglomerular structures from abnormal stimulation of the efferent adrenergic system. The present position paper of the Italian Society of Hypertension (SIIA) offers a diagnostic and therapeutic approach for the proper identification and effective clinical management of patients with resistant hypertension, who are candidates for renal artery denervation. These indications may have important implications not only from a clinical point of view, but also from an economic point of view, since a proper identification of patients with true resistant hypertension and an accurate selection of patients

  7. Retrospective morphometric study of the suitability of renal arteries for renal denervation according to the Symplicity HTN2 trial criteria

    Science.gov (United States)

    Schönherr, Elisabeth; Rehwald, Rafael; Nasseri, Parinaz; Luger, Anna K; Grams, Astrid E; Kerschbaum, Julia; Rehder, Peter; Petersen, Johannes; Glodny, Bernhard

    2016-01-01

    Objective The aim of this study was to describe the renal arteries of humans in vivo, as precisely as possible, and to formulate an expected value for the exclusion of renal denervation due to the anatomical situation based on the criteria of the Symplicity HTN trials. Design and setting In a retrospective cohort study, the renal arteries of 126 patients (57 women, 69 men, mean age 60±17.2 years (CI 57.7 to 63.6)) were segmented semiautomatically from high-contrast CT angiographies. Results Among the 300 renal arteries, there were three arteries with fibromuscular dysplasia and one with ostial renal artery stenosis. The first left renal artery was shorter than the right (34±11.4 mm (CI 32 to 36) vs 45.9±15 mm (CI 43.2 to 48.6); p0.05). The first left renal arteries were 1.1±0.4 mm (CI 0.9 to 1.3), and the first right renal arteries were 0.3±0.6 mm (CI 0.1 to 0.5) thinner in women than in men (p4 mm. Some 46% of the patients, or 58.7% when variants and diseases were taken into consideration, were theoretically not suitable for denervation. Conclusions Based on these precise measurements, the anatomical situation as a reason for ruling out denervation appears to be significantly more common than previously suspected. Since this can be the cause of the failure of treatment in some cases, further development of catheters or direct percutaneous approaches may improve success rates. PMID:26729385

  8. Renal Sympathetic Denervation by CT-Guided Ethanol Injection: A Phase II Pilot Trial of a Novel Technique

    International Nuclear Information System (INIS)

    Ricke, J.; Seidensticker, M.; Becker, S.; Schiefer, J.; Adamchic, I.; Lohfink, K.; Kandulski, M.; Heller, A.; Mertens, P. R.

    2016-01-01

    ObjectivesCT-guided ethanol-mediated renal sympathetic denervation in treatment of therapy-resistant hypertension was performed to assess patient safety and collect preliminary data on treatment efficacy.Materials and MethodsEleven patients with therapy-resistant hypertension (blood pressure of >160 mmHg despite three different antihypertensive drugs including a diuretic) and following screening for secondary causes were enrolled in a phase II single arm open label pilot trial of CT-guided neurolysis of sympathetic renal innervation. Primary endpoint was safety, and secondary endpoint was a decrease of the mean office as well as 24-h systolic blood pressure in follow-up. Follow-up visits at 4 weeks, 3, and 6 months included 24-h blood pressure assessments, office blood pressure, laboratory values, as well as full clinical and quality of life assessments.ResultsNo toxicities ≥3° occurred. Three patients exhibited worsened kidney function in follow-up analyses. When accounting all patients, office systolic blood pressure decreased significantly at all follow-up visits (maximal mean decrease −41.2 mmHg at 3 months). The mean 24-h systolic blood pressure values decreased significantly at 3 months, but not at 6 months (mean: −9.7 and −6.3 mmHg, respectively). Exclusion of five patients who had failed catheter-based endovascular denervation and/or were incompliant for antihypertensive drug intake revealed a more pronounced decrease of 24-h systolic blood pressure (mean: −18.3 and −15.2 mmHg at 3 and 6 months, p = 0.03 and 0.06).ConclusionCT-guided sympathetic denervation proved to be safe and applicable under various anatomical conditions with more renal arteries and such of small diameter

  9. Renal Sympathetic Denervation by CT-Guided Ethanol Injection: A Phase II Pilot Trial of a Novel Technique

    Energy Technology Data Exchange (ETDEWEB)

    Ricke, J., E-mail: jens.ricke@med.ovgu.de; Seidensticker, M.; Becker, S. [Otto-von-Guericke University Magdeburg, Department of Radiology and Nuclear Medicine, Universitätsklinikum Magdeburg AöR (Germany); Schiefer, J. [Universitätsklinikum Magdeburg AöR, Department of Nephrology and Hypertension, Diabetes and Endocrinology (Germany); Adamchic, I.; Lohfink, K. [Otto-von-Guericke University Magdeburg, Department of Radiology and Nuclear Medicine, Universitätsklinikum Magdeburg AöR (Germany); Kandulski, M.; Heller, A.; Mertens, P. R. [Universitätsklinikum Magdeburg AöR, Department of Nephrology and Hypertension, Diabetes and Endocrinology (Germany)

    2016-02-15

    ObjectivesCT-guided ethanol-mediated renal sympathetic denervation in treatment of therapy-resistant hypertension was performed to assess patient safety and collect preliminary data on treatment efficacy.Materials and MethodsEleven patients with therapy-resistant hypertension (blood pressure of >160 mmHg despite three different antihypertensive drugs including a diuretic) and following screening for secondary causes were enrolled in a phase II single arm open label pilot trial of CT-guided neurolysis of sympathetic renal innervation. Primary endpoint was safety, and secondary endpoint was a decrease of the mean office as well as 24-h systolic blood pressure in follow-up. Follow-up visits at 4 weeks, 3, and 6 months included 24-h blood pressure assessments, office blood pressure, laboratory values, as well as full clinical and quality of life assessments.ResultsNo toxicities ≥3° occurred. Three patients exhibited worsened kidney function in follow-up analyses. When accounting all patients, office systolic blood pressure decreased significantly at all follow-up visits (maximal mean decrease −41.2 mmHg at 3 months). The mean 24-h systolic blood pressure values decreased significantly at 3 months, but not at 6 months (mean: −9.7 and −6.3 mmHg, respectively). Exclusion of five patients who had failed catheter-based endovascular denervation and/or were incompliant for antihypertensive drug intake revealed a more pronounced decrease of 24-h systolic blood pressure (mean: −18.3 and −15.2 mmHg at 3 and 6 months, p = 0.03 and 0.06).ConclusionCT-guided sympathetic denervation proved to be safe and applicable under various anatomical conditions with more renal arteries and such of small diameter.

  10. The efficacy of conventional radiofrequency denervation in patients with chronic low back pain originating from the facet joints: a meta-analysis of randomized controlled trials.

    Science.gov (United States)

    Lee, Chang-Hyun; Chung, Chun Kee; Kim, Chi Heon

    2017-11-01

    Radiofrequency denervation is commonly used for the treatment of chronic facet joint pain that has been refractory to more conservative treatments, although the evidence supporting this treatment has been controversial. We aimed to elucidate the precise effects of radiofrequency denervation in patients with low back pain originating from the facet joints relative to those obtained using control treatments, with particular attention to consistency in the denervation protocol. A meta-analysis of randomized controlled trials was carried out. Adult patients undergoing radiofrequency denervation or control treatments (sham or epidural block) for facet joint disease of the lumbar spine comprised the patient sample. Visual analog scale (VAS) pain scores were measured and stratified by response of diagnostic block procedures. We searched PubMed, Embase, Web of Science, and the Cochrane Database for randomized controlled trials regarding radiofrequency denervation and control treatments for back pain. Changes in VAS pain scores of the radiofrequency group were compared with those of the control group as well as the minimal clinically important difference (MCID) for back pain VAS. Meta-regression model was developed to evaluate the effect of radiofrequency treatment according to responses of diagnostic block while controlling for other variables. We then calculated mean differences and 95% confidence intervals (CIs) using random-effects models. We included data from seven trials involving 454 patients who had undergone radiofrequency denervation (231 patients) and control treatments such as sham or epidural block procedures (223 patients). The radiofrequency group exhibited significantly greater improvements in back pain score when compared with the control group for 1-year follow-up. Although the average improvement in VAS scores exceeded the MCID, the lower limit of the 95% CI encompassed the MCID. A subgroup of patients who responded very well to diagnostic block

  11. [Renal denervation in refractory hypertension: joint statement of the German hypertension league DHL eV and the German societies of cardiology, angiology, nephrology and radiology].

    Science.gov (United States)

    Vonend, Oliver; Böhm, Michael; Eckert, Siegfried; Hausberg, Martin; Rittger, Harald; Rump, Lars-Christian; Schmieder, Roland; Schulte, Karl-Ludwig; Schunkert, Heribert; Uder, Michael; Veelken, Roland; Vorwerk, Dierk; Weil, Joachim; Wenzel, Ulrich; Mahfoud, Felix

    2015-03-01

    Arterial hypertension is a major risk factor for cardiovascular mortality and remains insufficiently controlled in Germany. The sham controlled Symplicity HTN-3 trial did meet its primary safety endpoint but failed to meet its primary efficacy endpoint. Renal denervation can not replace established, well-proven therapies. It can only be used in selected truly resistant hypertensive patients as an additive approach and should be performed by specialized centers only. Randomized controlled trials are needed to further evaluate renal denervation. © Georg Thieme Verlag KG Stuttgart · New York.

  12. Eligibility for Renal Denervation: Anatomical Classification and Results in Essential Resistant Hypertension

    International Nuclear Information System (INIS)

    Okada, Takuya; Pellerin, Olivier; Savard, Sébastien; Curis, Emmanuel; Monge, Matthieu; Frank, Michael; Bobrie, Guillaume; Yamaguchi, Masato; Sugimoto, Koji; Plouin, Pierre-François; Azizi, Michel; Sapoval, Marc

    2015-01-01

    PurposeTo classify the renal artery (RA) anatomy based on specific requirements for endovascular renal artery denervation (RDN) in patients with drug-resistant hypertension (RH).Materials and MethodsThe RA anatomy of 122 consecutive RH patients was evaluated by computed tomography angiography and classified as two types: A (main RA ≥20 mm in length and ≥4.0 mm in diameter) or B (main RA <20 mm in length or main RA <4.0 mm in diameter). The A type included three subtypes: A1 (without accessory RAs), A2 (with accessory RAs <3.0 mm in diameter), and A3 (with accessory RAs ≥3.0 mm in diameter]. A1 and A2 types were eligible for RDN with the Simplicity Flex catheter. Type B included twi subtypes based on the main RA length and diameter. Patients were accordingly classified into three eligibility categories: complete (CE; both RAs were eligible), partial (PE; one eligible RA), and noneligibility (NE; no eligible RA).ResultsBilateral A1 type was the most prevalent and was observed in 48.4 % of the patients followed by the A1/A2 type (18 %). CE, PE, and NE were observed in 69.7, 22.9, and 7.4 % of patients, respectively. The prevalence of accessory RAs was 41 %.ConclusionsOf RH patients, 30.3 % were not eligible for bilateral RDN with the current Simplicity Flex catheter. This classification provides the basis for standardized reporting to allow for pooling of results of larger patient cohorts in the future

  13. Renal denervation for refractory hypertension. Technical aspects, complications and radiation exposure

    Energy Technology Data Exchange (ETDEWEB)

    Scheurig-Muenkler, C.; Kroencke, T.J.; Powerski, M.J. [Charite Universitatesmedizin, Berlin (Germany). Radiologie; Weiss, W.; Toelle, M.; Giet, M. van der; Zidek, W. [Charite Universitatesmedizin, Berlin (Germany). Nephrologie; Foert, E. [DRK Klinikum Berlin Mitte, Berlin (Germany). Radiologie

    2013-06-15

    Purpose: To analyze procedural details, complications and radiation exposure in renal denervation (RDN) using the Medtronic Symplicity {sup registered} device in the treatment of refractory hypertension. Materials and Methods: Fifty three consecutive patients underwent RDN. The number of ablations per artery, peri-procedural complications, procedure time (PT), fluoroscopy time (FT), dose-area product (DAP) and procedure-related complications were documented. Additionally, the radiation dose was compared between obese (body mass index {>=} 30 kg/m{sup 2}) and non-obese patients. Results: Bilateral RDN was performed in 50/53 (94 %) cases and with a minimum of 4 ablations per artery in 33/50 (66 %), the mean count being 5.4 (range R: 2 - 13) on the right and 4.3 (R: 1 - 10) on the left. The FT and DAP decreased significantly over the first 12 procedures, reaching a steady state with a median FT of 11.2 min (R: 7.5 - 27) and a median DAP of 4796 cGy x cm{sup 2} (R: 1076 - 21 371), resulting in an effective dose of 15.7 mSv. The median PT was 57 min (R: 40 - 70). Obese patients had a 3.3-fold higher radiation dose (p < 0.001). We observed one severe spasm and one imminent respiratory depression, both resolved without sequelae. Conclusion: For an experienced interventionalist, RDN has a short learning curve with a low risk profile. The radiation dose does not exceed that of other renal artery interventions, but is explicitly higher in obese patients, who account for a large portion of patients with refractory hypertension. (orig.)

  14. Eligibility for Renal Denervation: Anatomical Classification and Results in Essential Resistant Hypertension

    Energy Technology Data Exchange (ETDEWEB)

    Okada, Takuya, E-mail: okabone@gmail.com; Pellerin, Olivier [Georges Pompidou European Hospital, Department of Cardiovascular and Interventional Radiology, Assistance Publique des Hôpitaux de Paris (France); Savard, Sébastien [Georges Pompidou European Hospital, Department of Hypertension, Assistance Publique des Hôpitaux de Paris (France); Curis, Emmanuel; Monge, Matthieu [INSERM, Clinical Investigation Center 9201 (France); Frank, Michael; Bobrie, Guillaume [Georges Pompidou European Hospital, Department of Hypertension, Assistance Publique des Hôpitaux de Paris (France); Yamaguchi, Masato; Sugimoto, Koji [Kobe University Hospital, Department of Radiology and Center for Endovascular Therapy (Japan); Plouin, Pierre-François; Azizi, Michel [Georges Pompidou European Hospital, Department of Hypertension, Assistance Publique des Hôpitaux de Paris (France); Sapoval, Marc [Georges Pompidou European Hospital, Department of Cardiovascular and Interventional Radiology, Assistance Publique des Hôpitaux de Paris (France)

    2015-02-15

    PurposeTo classify the renal artery (RA) anatomy based on specific requirements for endovascular renal artery denervation (RDN) in patients with drug-resistant hypertension (RH).Materials and MethodsThe RA anatomy of 122 consecutive RH patients was evaluated by computed tomography angiography and classified as two types: A (main RA ≥20 mm in length and ≥4.0 mm in diameter) or B (main RA <20 mm in length or main RA <4.0 mm in diameter). The A type included three subtypes: A1 (without accessory RAs), A2 (with accessory RAs <3.0 mm in diameter), and A3 (with accessory RAs ≥3.0 mm in diameter]. A1 and A2 types were eligible for RDN with the Simplicity Flex catheter. Type B included twi subtypes based on the main RA length and diameter. Patients were accordingly classified into three eligibility categories: complete (CE; both RAs were eligible), partial (PE; one eligible RA), and noneligibility (NE; no eligible RA).ResultsBilateral A1 type was the most prevalent and was observed in 48.4 % of the patients followed by the A1/A2 type (18 %). CE, PE, and NE were observed in 69.7, 22.9, and 7.4 % of patients, respectively. The prevalence of accessory RAs was 41 %.ConclusionsOf RH patients, 30.3 % were not eligible for bilateral RDN with the current Simplicity Flex catheter. This classification provides the basis for standardized reporting to allow for pooling of results of larger patient cohorts in the future.

  15. Renal Denervation vs. Spironolactone in Resistant Hypertension: Effects on Circadian Patterns and Blood Pressure Variability.

    Science.gov (United States)

    de la Sierra, Alejandro; Pareja, Julia; Armario, Pedro; Barrera, Ángela; Yun, Sergi; Vázquez, Susana; Sans, Laia; Pascual, Julio; Oliveras, Anna

    2017-01-01

    Sympathetic renal denervation (SRD) has been proposed as a therapeutic alternative for patients with resistant hypertension not controlled on pharmacological therapy. Two studies have suggested an effect of SRD in reducing short-term blood pressure variability (BPV). However, this has not been addressed in a randomized comparative trial. We aimed to compare the effects of spironolactone and SRD on circadian BP and BPV. This is a post-hoc analysis of a randomized trial in 24 true resistant hypertensive patients (15 men, 9 women; mean age 64 years) comparing 50mg of spironolactone (n = 13) vs. SRD (n = 11) on 24-hour BP. We report here the comparative effects on daytime (8 am-10 pm) and nighttime (0 am-6 am) BP, night-to-day ratios and BP and heart rate variabilities (SD and coefficient of variation of 24-hour, day and night, as well as weighted SD and average real variability (ARV)). Spironolactone was more effective than SRD in reducing daytime systolic (P = 0.006), daytime diastolic (P = 0.006), and nighttime systolic (P = 0.050) BP. No differences were observed in the night-to-day ratios. In contrast, SRD-reduced diastolic BPV (24 hours, daytime, nighttime, weighted, and ARV; all P < 0.05) with respect to spironolactone, without significant differences in systolic BPV. Spironolactone is more effective than SRD in reducing ambulatory BP. However, BPV is significantly more reduced with SRD. This effect could be important in terms of potential prevention beyond BP reduction and deserves further investigation. © American Journal of Hypertension, Ltd 2016. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  16. Impact of Lesion Placement on Efficacy and Safety of Catheter-Based Radiofrequency Renal Denervation.

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    Mahfoud, Felix; Tunev, Stefan; Ewen, Sebastian; Cremers, Bodo; Ruwart, Jennifer; Schulz-Jander, Daniel; Linz, Dominik; Davies, Justin; Kandzari, David E; Whitbourn, Robert; Böhm, Michael; Melder, Robert J

    2015-10-20

    Insufficient procedural efficacy has been proposed to explain nonresponse to renal denervation (RDN). The aim of this study was to examine the impact of different patterns of lesion placements on the efficacy and consistency of catheter-based radiofrequency RDN in pigs. The impact of increasing number of lesions versus location of RDN was investigated in a porcine model (Group 1; n = 51). The effect of treating the main artery, the branches, and the 2 combined was compared in Group 2 (n = 48). The durability of response and safety of combined treatment of the main artery plus branches was examined in Group 3 (n = 16). Renal norepinephrine (NE) tissue content and renal cortical axon density were assessed. Increasing the number of RF lesions (4, 8, and 12) in the main renal artery was not sufficient to yield a clear dose-response relationship on NE content and axon density. In contrast, targeted treatment of the renal artery branches or distal segment of the main renal artery resulted in markedly less variability of response and significantly greater reduction of both NE and axon density than conventional treatment of only the main renal artery. Combination treatment (main artery plus branches) produced the greatest change in renal NE and axon density with the least heterogeneity. The changes were durable through 28 days post-treatment. These data provide the rationale for investigation of an optimized approach for RDN in future clinical studies. This may have profound implications for the clinical application of RDN, as this approach may not only achieve greater reductions in sympathetic activity but also reduce treatment effect variability. Copyright © 2015 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

  17. Endovascular radiofrequency renal denervation in treating refractory arterial hypertension: a preliminary experience.

    Science.gov (United States)

    Simonetti, G; Spinelli, A; Gandini, R; Da Ros, V; Gaspari, E; Coco, I; De Francesco, M; Santucci, D; Di Daniele, N; Lauro, R

    2012-04-01

    This study was done to investigate the efficacy and safety of percutaneous renal denervation with the Symplicity catheter for reducing blood pressure in patients with essential hypertension resistant to medical therapy (systolic blood pressure >160 mmHg despite the use of three or more antihypertensive drugs, including a diuretic). In September 2010, five patients affected by essential hypertension resistant to medical therapy were treated. All patients were studied by computed tomography angiography (CTA) of the renal arteries before the procedure and underwent follow-up at 30 and 60 days with colour Doppler ultrasound (CDUS) with evaluation of resistive index, glomerular filtration rate (GFR), 24-h blood pressure and serum catecholamine concentration. Student's t test was used to assess the effectiveness of the procedure in lowering blood pressure. In treated patients, mean blood pressure at baseline was 171/100 mmHg [standard deviation (SD) ± 8/10]; mean GFR was 91.6 ml/min/1.73 m(2) (SD ± 15). Blood pressure after the procedure was reduced by -18/-5 and -13/-10 mmHg at 30 and 60 days, respectively, with a mean medication reduction of 3.6. No complications occurred during the intra- or periprocedural period or during short-term follow-up. The Symplicity system proved to be efficacious and without serious adverse events in reducing blood pressure and antihypertensive medication use in patients affected by essential hypertension resistant to medical therapy. Although encouraging, our data are preliminary and need to be validated by larger prospective randomised studies.

  18. Neurotrophic Factor-Secreting Autologous Muscle Stem Cell Therapy for the Treatment of Laryngeal Denervation Injury

    Science.gov (United States)

    Halum, Stacey L.; McRae, Bryan; Bijangi-Vishehsaraei, Khadijeh; Hiatt, Kelly

    2012-01-01

    Objectives To determine if the spontaneous reinnervation that characteristically ensues after recurrent laryngeal nerve (RLN) injury could be selectively promoted and directed to certain laryngeal muscles with the use of neurotrophic factor (NF)-secreting muscle stem cell (MSC) vectors while antagonistic reinnervation is inhibited with vincristine (VNC). Study Design Basic science investigations involving primary cell cultures, gene cloning/transfer, and animal experiments. Methods (i.) MSC survival assays were used to test multiple individual NFs in vitro. (ii.) Motoneuron outgrowth assays assessed the trophic effects of identified NF on cranial nerve X-derived (CNX) motoneurons in vitro. (iii.) Therapeutic NF was cloned into a lentiviral vector, and MSCs were tranduced to secrete NF. 60 rats underwent left RLN transection injury, and at 3 weeks received injections of either MSCs (n=24), MSCs secreting NF (n=24), or saline (n=12) into the left thyroarytenoid muscle complex (TA); half of the animals in the MSC groups simultaneously received left posterior cricoarytenoid (PCA) injections of vincristine (VNC) while half the animals received saline. Results (i.) Ciliary-derived neurotrophic factor (CNTF) had the greatest survival-promoting effect on MSCs in culture. (ii.) Addition of CNTF (50 ng/mL) to CN X motoneuron cultures resulted in enhanced neurite outgrowth and branching. (iii.) In the animal model, the injected MSCs fused with the denervated myofibers, immunohistochemistry demonstrated enhanced reinnervation based on motor endplate to nerve contact, and RT-PCR confirmed stable CNTF expression at longest follow-up (4 months) in the CNTF-secreting MSC treated groups. Conclusions MSC therapy may have a future role in selectively promoting and directing laryngeal reinnervation after RLN injury. Level of evidence: NA PMID:22965802

  19. Perivascular radiofrequency renal denervation lowers blood pressure and ameliorates cardiorenal fibrosis in spontaneously hypertensive rats

    Science.gov (United States)

    Zhang, Yan; Su, Linan; Zhang, Yunrong; Wang, Qiang; Yang, Dachun; Li, De; Yang, Yongjian; Ma, Shuangtao

    2017-01-01

    Background Catheter-based renal denervation (RDN) is a promising approach to treat hypertension, but innervation patterns limit the response to endovascular RDN and the post-procedural renal artery narrowing or stenosis questions the endovascular ablation strategy. This study was performed to investigate the anti-hypertensive and target organ protective effects of perivascular RDN in spontaneously hypertensive rats (SHR). Methods SHR and normotensive Wistar-Kyoto (WKY) rats were divided into sham group (n = 10), radiofrequency ablation group (n = 20) in which rats received bilateral perivascular ablation with radiofrequency energy (2 watts), and chemical (10% phenol in 95% ethanol) ablation group (n = 12). The tail-cuff blood pressure was measured before the ablation and on day 14 and day 28 after the procedure. The plasma levels of creatinine, urea nitrogen, and catecholamines, urinary excretion of electrolytes and protein, and myocardial and glomerular fibrosis were analyzed and compared among the groups on day 28 after the procedure. Results We identified that 2-watt is the optimal radiofrequency power for perivascular RDN in rats. Perivascular radiofrequency and chemical ablation achieved roughly comparable blood pressure reduction in SHR but not in WKY on day 14 and day 28 following the procedure. Radiofrequency-mediated ablation substantially destroyed the renal nerves surrounding the renal arteries of both SHR and WKY without damaging the renal arteries and diminished the expression of tyrosine hydroxylase, the enzyme marker for postganglionic sympathetic nerves. Additionally, perivascular radiofrequency ablation also decreased the plasma catecholamines of SHR. Interestingly, both radiofrequency and chemical ablation decreased the myocardial and glomerular fibrosis of SHR, while neither increased the plasma creatinine and blood urea nitrogen nor affected the urinary excretion of electrolytes and protein when compared to sham group. Conclusions Radiofrequency

  20. Changes in neurochemicals within the ventrolateral medullary respiratory column in awake goats after carotid body denervation

    Science.gov (United States)

    Miller, Justin Robert; Neumueller, Suzanne; Muere, Clarissa; Olesiak, Samantha; Pan, Lawrence; Hodges, Matthew R.

    2013-01-01

    A current and major unanswered question is why the highly sensitive central CO2/H+ chemoreceptors do not prevent hypoventilation-induced hypercapnia following carotid body denervation (CBD). Because perturbations involving the carotid bodies affect central neuromodulator and/or neurotransmitter levels within the respiratory network, we tested the hypothesis that after CBD there is an increase in inhibitory and/or a decrease in excitatory neurochemicals within the ventrolateral medullary column (VMC) in awake goats. Microtubules for chronic use were implanted bilaterally in the VMC within or near the pre-Bötzinger Complex (preBötC) through which mock cerebrospinal fluid (mCSF) was dialyzed. Effluent mCSF was collected and analyzed for neurochemical content. The goats hypoventilated (peak +22.3 ± 3.4 mmHg PaCO2) and exhibited a reduced CO2 chemoreflex (nadir, 34.8 ± 7.4% of control ΔV̇E/ΔPaCO2) after CBD with significant but limited recovery over 30 days post-CBD. After CBD, GABA and glycine were above pre-CBD levels (266 ± 29% and 189 ± 25% of pre-CBD; P 0.05) different from control after CBD. Analyses of brainstem tissues collected 30 days after CBD exhibited 1) a midline raphe-specific reduction (P < 0.05) in the percentage of tryptophan hydroxylase–expressing neurons, and 2) a reduction (P < 0.05) in serotonin transporter density in five medullary respiratory nuclei. We conclude that after CBD, an increase in inhibitory neurotransmitters and a decrease in excitatory neuromodulation within the VMC/preBötC likely contribute to the hypoventilation and attenuated ventilatory CO2 chemoreflex. PMID:23869058

  1. Denervation of pulmonary artery during mitral valve surgery in patients with high pulmonary hypertension

    Directory of Open Access Journals (Sweden)

    А. В. Богачев-Прокофьев

    2016-01-01

    Full Text Available Objective. Pulmonary hypertension impairs the mitral valve and often leads to more severe symptoms of heart failure, low exercise tolerance and thus higher rates of morbidity and mortality. The purpose of this study is to evaluate the safety and efficacy of simultaneous radiofrequency ablation of ganglionated plexi of the pulmonary artery in patients with high pulmonary hypertension during mitral valve surgery.Methods. The inclusion criteria were based on patients’ echocardiography/right heart catheterization data. The main criteria were mean pulmonary artery pressure ≥40 mm Hg at rest and a positive reactive test with nitric oxide inhalation. From January 2014 to May 2015, 14 patients underwent radiofrequency denervation of the pulmonary artery in addition to planned mitral valve surgery. Mean patient age was 53.4±7.8 years, with 57.1% of patients being females.Results. Mean cardiopulmonary bypass time was 116±12 minutes, mean cross-clamp time was 95±13 minutes, and mean ablation time amounted to 9.5±3.1 minutes. Pulmonary artery pressure decreased significantly from a mean of 56.5±9.8 mmHg to 32.0±7.3 mmHg immediately after the operation (p<0.001, and to 28.4±5.2 mmHg and 29.7±4.4 mmHg on the first and third days at ICU respectively. Mean ICU stay was 3.1±1.2 days. There were neither early deaths nor specific complications.Conclusions. Simultaneous radiofrequency ablation of pulmonary artery ganglionated plexi when performing mitral valve surgery in patients with pulmonary hypertension is a safe and effective procedure. Further research and long-term follow-up would help to determine whether a decrease in the mean pressure of the pulmonary artery can be interpreted as a clinical advantage.

  2. An improved strategy for evaluating the extent of chronic arterial baroreceptor denervation in conscious rats

    Directory of Open Access Journals (Sweden)

    M. Rodríguez-Martínez

    2010-11-01

    Full Text Available There is no index or criterion of aortic barodenervation, nor can we differentiate among rats that have suffered chronic sham, aortic or sino-aortic denervation. The objective of this study was to develop a procedure to generate at least one quantitative, reproducible and validated index that precisely evaluates the extent of chronic arterial barodenervation performed in conscious rats. Data from 79 conscious male Wistar rats of about 65-70 days of age with diverse extents of chronic arterial barodenervation and used in previous experiments were reanalyzed. The mean arterial pressure (MAP and the heart rate (HR of all rats were measured systematically before (over 1 h and after three consecutive iv bolus injections of phenylephrine (PHE and sodium nitroprusside (SNP. Four expressions of the effectiveness of barodenervation (MAP lability, PHE ratio, SNP ratio, and SNP-PHE slope were assessed with linear fixed models, three-level average variance, average separation among levels, outlier box plot analysis, and overlapping graphic analysis. The analysis indicated that a neither MAP lability nor SNP-PHE slope was affected by the level of chronic sodium intake; b even though the Box-Cox transformations of both MAP lability [transformed lability index (TLI] and SNP-PHE slope [transformed general sensitivity index (TGSI, {((3-(ΔHRSNP-ΔHRPHE/ΔMAPSNP-ΔMAPPHE-0.4-1/-0.04597}] could be two promising indexes, TGSI proved to be the best index; c TLI and TGSI were not freely interchangeable indexes for this purpose. TGSI ranges that permit differentiation between sham (10.09 to 11.46, aortic (8.40 to 9.94 and sino-aortic (7.68 to 8.24 barodenervated conscious rats were defined.

  3. Cardiac impairment evaluated by transesophageal echocardiography and invasive measurements in rats undergoing sinoaortic denervation.

    Directory of Open Access Journals (Sweden)

    Raquel A Sirvente

    Full Text Available BACKGROUND: Sympathetic hyperactivity may be related to left ventricular (LV dysfunction and baro- and chemoreflex impairment in hypertension. However, cardiac function, regarding the association of hypertension and baroreflex dysfunction, has not been previously evaluated by transesophageal echocardiography (TEE using intracardiac echocardiographic catheter. METHODS AND RESULTS: We evaluated exercise tests, baroreflex sensitivity and cardiovascular autonomic control, cardiac function, and biventricular invasive pressures in rats 10 weeks after sinoaortic denervation (SAD. The rats (n = 32 were divided into 4 groups: 16 Wistar (W with (n = 8 or without SAD (n = 8 and 16 spontaneously hypertensive rats (SHR with (n = 8 or without SAD (SHRSAD (n = 8. Blood pressure (BP and heart rate (HR did not change between the groups with or without SAD; however, compared to W, SHR groups had higher BP levels and BP variability was increased. Exercise testing showed that SHR had better functional capacity compared to SAD and SHRSAD. Echocardiography showed left ventricular (LV concentric hypertrophy; segmental systolic and diastolic biventricular dysfunction; indirect signals of pulmonary arterial hypertension, mostly evident in SHRSAD. The end-diastolic right ventricular (RV pressure increased in all groups compared to W, and the end-diastolic LV pressure increased in SHR and SHRSAD groups compared to W, and in SHRSAD compared to SAD. CONCLUSIONS: Our results suggest that baroreflex dysfunction impairs cardiac function, and increases pulmonary artery pressure, supporting a role for baroreflex dysfunction in the pathogenesis of hypertensive cardiac disease. Moreover, TEE is a useful and feasible noninvasive technique that allows the assessment of cardiac function, particularly RV indices in this model of cardiac disease.

  4. Renal Denervation Findings on Cardiac and Renal Fibrosis in Rats with Isoproterenol Induced Cardiomyopathy

    Science.gov (United States)

    Liu, Qian; Zhang, Qi; Wang, Kai; Wang, Shengchan; Lu, Dasheng; Li, Zhenzhen; Geng, Jie; Fang, Ping; Wang, Ying; Shan, Qijun

    2015-12-01

    Cardio-renal fibrosis plays key roles in heart failure and chronic kidney disease. We sought to determine the effects of renal denervation (RDN) on cardiac and renal fibrosis in rats with isoproterenol induced cardiomyopathy. Sixty male Sprague Dawley rats were randomly assigned to Control (n = 10) and isoproterenol (ISO)-induced cardiomyopathy group (n = 50). At week 5, 31 survival ISO-induced cardiomyopathy rats were randomized to RDN (n = 15) and Sham group (n = 16). Compared with Control group, ejection fraction was decreased, diastolic interventricular septal thickness and left atrial dimension were increased in ISO-induced cardiomyopathy group at 5 week. After 10 weeks, cardio-renal pathophysiologic results demonstrated that the collagen volume fraction of left atrio-ventricular and kidney tissues reduced significantly in RDN group compared with Sham group. Moreover the pro-fibrosis factors (TGF-β1, MMP2 and Collagen I), inflammatory cytokines (CRP and TNF-α), and collagen synthesis biomarkers (PICP, PINP and PIIINP) concentration significantly decreased in RDN group. Compared with Sham group, RDN group showed that release of noradrenaline and aldosterone were reduced, angiotensin-converting enzyme (ACE)/angiotensin II (Ang II)/angiotensin II type-1 receptor (AT1R) axis was downregulated. Meanwhile, angiotensin-converting enzyme 2 (ACE2)/angiotensin-1-7 (Ang-(1-7))/mas receptor (Mas-R) axis was upregulated. RDN inhibits cardio-renal fibrogenesis through multiple pathways, including reducing SNS over-activity, rebalancing RAAS axis.

  5. Mid-Term Vascular Safety of Renal Denervation Assessed by Follow-up MR Imaging

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    Schmid, Axel, E-mail: axel.schmid@uk-erlangen.de; Schmieder, Raphael; Lell, Michael; Janka, Rolf [Friedrich-Alexander University Erlangen-Nuremberg, Department of Radiology (Germany); Veelken, Roland; Schmieder, Roland E. [Friedrich-Alexander University Erlangen-Nuremberg, Department of Nephrology and Hypertension (Germany); Uder, Michael [Friedrich-Alexander University Erlangen-Nuremberg, Department of Radiology (Germany); Ott, Christian [Friedrich-Alexander University Erlangen-Nuremberg, Department of Nephrology and Hypertension (Germany)

    2016-03-15

    Background/AimsRenal denervation (RDN) emerged as a treatment option for reducing blood pressure (BP) in patients with treatment-resistant hypertension (TRH). However, concerns have been raised regarding the incidence of late renal artery stenosis or thromboembolism after RDN. The goal of the current study was, therefore, to conduct a prospective clinical trial on the mid-term vascular integrity of the renal arteries and the perfusion of the renal parenchyma assessed by magnetic resonance imaging (MRI) in the follow-up after catheter-based RDN.MethodsIn our single-centre investigator initiated study, 51 patients with true TRH underwent catheter-based RDN using the Symplicity Flex{sup TM} catheter (Medtronic Inc., Palo Alto, CA). Follow-up MRI was performed at a median of 11 months (interquartile range 6–18 months) after RDN on a 1.5T MR unit. High-resolution MR angiography (MRA) and MRI results were compared to the baseline digital angiography of renal arteries obtained at time of RDN. In case of uncertainties (N = 2) catheter angiography was repeated.ResultsBoth office and 24-h ambulatory BP were significantly reduced 6 and 12 months after RDN. Renal function remained unchanged 6 and 12 months after RDN. In all patients, MRA excluded new or progression of pre-existing low grade renal artery stenosis as well as focal aneurysms at the sites of radiofrequency ablation. In none of the patients new segmental perfusion deficits in either kidney were detected on MRI.ConclusionsNo vascular or parenchymal complications after radiofrequency-based RDN were detected in 51 patients followed up by MRI.

  6. Optimum and stepped care standardised antihypertensive treatment with or without renal denervation for resistant hypertension (DENERHTN): a multicentre, open-label, randomised controlled trial.

    Science.gov (United States)

    Azizi, Michel; Sapoval, Marc; Gosse, Philippe; Monge, Matthieu; Bobrie, Guillaume; Delsart, Pascal; Midulla, Marco; Mounier-Véhier, Claire; Courand, Pierre-Yves; Lantelme, Pierre; Denolle, Thierry; Dourmap-Collas, Caroline; Trillaud, Hervé; Pereira, Helena; Plouin, Pierre-François; Chatellier, Gilles

    2015-05-16

    Conflicting blood pressure-lowering effects of catheter-based renal artery denervation have been reported in patients with resistant hypertension. We compared the ambulatory blood pressure-lowering efficacy and safety of radiofrequency-based renal denervation added to a standardised stepped-care antihypertensive treatment (SSAHT) with the same SSAHT alone in patients with resistant hypertension. The Renal Denervation for Hypertension (DENERHTN) trial was a prospective, open-label randomised controlled trial with blinded endpoint evaluation in patients with resistant hypertension, done in 15 French tertiary care centres specialised in hypertension management. Eligible patients aged 18-75 years received indapamide 1·5 mg, ramipril 10 mg (or irbesartan 300 mg), and amlodipine 10 mg daily for 4 weeks to confirm treatment resistance by ambulatory blood pressure monitoring before randomisation. Patients were then randomly assigned (1:1) to receive either renal denervation plus an SSAHT regimen (renal denervation group) or the same SSAHT alone (control group). The randomisation sequence was generated by computer, and stratified by centres. For SSAHT, after randomisation, spironolactone 25 mg per day, bisoprolol 10 mg per day, prazosin 5 mg per day, and rilmenidine 1 mg per day were sequentially added from months two to five in both groups if home blood pressure was more than or equal to 135/85 mm Hg. The primary endpoint was the mean change in daytime systolic blood pressure from baseline to 6 months as assessed by ambulatory blood pressure monitoring. The primary endpoint was analysed blindly. The safety outcomes were the incidence of acute adverse events of the renal denervation procedure and the change in estimated glomerular filtration rate from baseline to 6 months. This trial is registered with ClinicalTrials.gov, number NCT01570777. Between May 22, 2012, and Oct 14, 2013, 1416 patients were screened for eligibility, 106 of those were randomly assigned to treatment

  7. Results of a randomized controlled pilot trial of intravascular renal denervation for management of treatment-resistant hypertension.

    Science.gov (United States)

    Jacobs, Lotte; Persu, Alexandre; Huang, Qi-Fang; Lengelé, Jean-Philippe; Thijs, Lutgarde; Hammer, Frank; Yang, Wen-Yi; Zhang, Zhen-Yu; Renkin, Jean; Sinnaeve, Peter; Wei, Fang-Fei; Pasquet, Agnès; Fadl Elmula, Fadl Elmula M; Carlier, Marc; Elvan, Arif; Wunder, Cora; Kjeldsen, Sverre E; Toennes, Stefan W; Janssens, Stefan; Verhamme, Peter; Staessen, Jan A

    2017-12-01

    Previous trials of catheter-based renal-artery denervation (RDN) as treatment modality in resistant hypertension (rHT) generated unconvincing results. In the Investigator-Steered Project on Intravascular Denervation for Management of Treatment-Resistant Hypertension (INSPiRED; NCT01505010), we optimized selection and management of rHT patients. With ethical clearance to randomize 18 patients, three Belgian hypertension centers screened 29 rHT patients on treatment with ≥3 drugs, of whom 17 after optimization of treatment (age efficacy endpoint, and 2.5 mL/min/1.73 m 2 (+1.5 vs. -1.1 mL/min/1.73 m 2 ; P = .86) for eGFR, the primary safety endpoint. At 6 month, ECG voltages and the number of prescribed drugs (P ≤ .036) were lower in RDN patients, but quality of life and adherence, captured by questionnaire and urine analysis were similar in both groups. Changes in BP and adherence were unrelated. No major complications occurred. The INSPiRED pilot suggests that RDN with the EnligHTN ™ system is effective and safe and generated insights useful for the design of future RDN trials.

  8. Denervation of nerve terminals in renal arteries: one-year follow-up of interventional treatment of arterial hypertension.

    Science.gov (United States)

    Bartuś, Krzysztof; Sadowski, Jerzy; Kapelak, Bogusław; Litwinowicz, Radosław; Zajdel, Wojciech; Godlewski, Jacek; Bartuś, Magdalena; Zmudka, Krzysztof; Chrapusta, Anna; Konstanty-Kalandyk, Janusz; Węgrzyn, Piotr; Sobotka, Paul A

    2014-01-01

    Arterial hypertension is the most common cardiovascular system disease, affecting nearly one billion people worldwide. Despite the widespread use of antihypertensive medications, in some groups of patients an optimal blood pressure (BP) cannot be achieved. To assess BP reduction in patients with resistant hypertension after a catheter-based renal sympathetic denervation procedure and to report vascular and kidney safety in one-year follow-up. Twenty eight patients with diagnosed resistant hypertension (median age 52.02 years, range 42-72) underwent percutaneous catheter-based renal denervation of nerve terminals in renal arteries. Arterial angiography and procedure of ablation was performed by Symplicity catheters and generator provided by Ardian (currently Medtronic Inc., USA). Mean BP value before ablation was [mm Hg]: systolic 176.6, diastolic 100.28 and pulse pressure 73.4. After the procedure, reductions in the value of BP were reported [mm Hg]: systolic 154.8/152.54; diastolic 90.2/89.8, pulse pressure 64.66/62.73, respectively in nine-month and one-year follow-up. All results were statistically significant. No complications during one year observation were observed. Percutaneous renal artery ablation procedure effectively reduces systolic BP, diastolic BP, and pulse pressure. No vascular or renal complications in any of the patients were observed. The results of a Polish research group showed no significant differences compared to the results obtained in the international studies Symplicity I and Symplicity II.

  9. 3D Modelling and monitoring of denervated muscle under Functional Electrical Stimulation treatment and associated bone structural changes

    Directory of Open Access Journals (Sweden)

    Paolo Gargiulo

    2011-03-01

    Full Text Available A novel clinical rehabilitation method for patients who have permanent and non recoverable muscle denervation in the legs was developed in the frame of the European Project RISE. The technique is based on FES and the project results shows, in these severely disabled patients, restoration of muscle tissue and function. This study propose novel methods based on image processing technique and medical modelling to monitor growth in denervated muscle treated with FES. Geometrical and structural changes in muscle and bone are studied and modelled. Secondary effects on the bone mineral density produced by the stimulation treatment and due the elicited muscle contraction are also investigated. The restoration process in DDM is an important object of discussion since there isn’t yet a complete understanding of the mechanisms regulating growth in denervated muscle. This study approaches the problem from a macroscopic point of view, developing 3-dimensional models of the whole stimulated muscles and following changes in volume, geometry and density very accurately. The method is based on the acquisition of high resolution Spiral CT scans from patients who have long-term flaccid paraplegia and the use of special image processing tools allowing tissue discriminations and muscle segmentation. Three patients were measured at different points of time during 4 years of electrical stimulation treatment. In this study is quantitatively demonstrated the influences of FES treatment on the different quadriceps bellies. The rectus femoris muscle is positioned in the middle of the quadriceps and responds (in general better to stimulation. In a patient with abundant adipose tissue surrounding the quadriceps, rectus femoris almost doubled the volume during the FES treatment while in the other bellies the changes measured were minimal. The analysis of the density shows clearly a restoration of the muscular structure in the growing muscle. The remarkable increase of

  10. Myostatin propeptide gene delivery by gene gun ameliorates muscle atrophy in a rat model of botulinum toxin-induced nerve denervation.

    Science.gov (United States)

    Tsai, Sen-Wei; Tung, Yu-Tang; Chen, Hsiao-Ling; Yang, Shang-Hsun; Liu, Chia-Yi; Lu, Michelle; Pai, Hui-Jing; Lin, Chi-Chen; Chen, Chuan-Mu

    2016-02-01

    Muscle atrophy is a common symptom after nerve denervation. Myostatin propeptide, a precursor of myostatin, has been documented to improve muscle growth. However, the mechanism underlying the muscle atrophy attenuation effects of myostatin propeptide in muscles and the changes in gene expression are not well established. We investigated the possible underlying mechanisms associated with myostatin propeptide gene delivery by gene gun in a rat denervation muscle atrophy model, and evaluated gene expression patterns. In a rat botulinum toxin-induced nerve denervation muscle atrophy model, we evaluated the effects of wild-type (MSPP) and mutant-type (MSPPD75A) of myostatin propeptide gene delivery, and observed changes in gene activation associated with the neuromuscular junction, muscle and nerve. Muscle mass and muscle fiber size was moderately increased in myostatin propeptide treated muscles (pmyostatin propeptide gene delivery, especially the mutant-type of MSPPD75A, attenuates muscle atrophy through myogenic regulatory factors and acetylcholine receptor regulation. Our data concluded that myostatin propeptide gene therapy may be a promising treatment for nerve denervation induced muscle atrophy. Copyright © 2016 Elsevier Inc. All rights reserved.

  11. Musculoskeletal growth in the upper arm in infants after obstetric brachial plexus lesions partial denervation and its relation with residual muscle function

    NARCIS (Netherlands)

    Ruoff, J.M.; van der Sluijs, J.A.; van Ouwerkerk, W.J.R.; Jaspers, R.T.

    2012-01-01

    Aim Denervation after obstetric brachial plexus lesion (OBPL) is associated with reduced musculoskeletal growth in the upper arm. The aim of this study was to investigate whether reduced growth of upper arm flexor and extensor muscles is related to active elbow function and humeral length. Method In

  12. Executive summary of the joint position paper on renal denervation of the Cardiovascular and Interventional Radiological Society of Europe and the European Society of Hypertension

    NARCIS (Netherlands)

    Moss, Jonathan G.; Belli, Anna-Maria; Coca, Antonio; Lee, Michael; Mancia, Giuseppe; Peregrin, Jan H.; Redon, Josep; Reekers, Jim A.; Tsioufis, Costas; Vorwerk, Dierk; Schmieder, Roland E.

    2016-01-01

    Renal denervation (RDN) was reported as a novel exciting treatment for resistant hypertension in 2009. An initial randomized trial supported its efficacy and the technique gained rapid acceptance across the globe. However, a subsequent large blinded, sham arm randomized trial conducted in the USA

  13. Skin denervation does not alter cortical potentials to surface concentric electrode stimulation: A comparison with laser evoked potentials and contact heat evoked potentials.

    Science.gov (United States)

    La Cesa, S; Di Stefano, G; Leone, C; Pepe, A; Galosi, E; Alu, F; Fasolino, A; Cruccu, G; Valeriani, M; Truini, A

    2018-01-01

    In the neurophysiological assessment of patients with neuropathic pain, laser evoked potentials (LEPs), contact heat evoked potentials (CHEPs) and the evoked potentials by the intraepidermal electrical stimulation via concentric needle electrode are widely agreed as nociceptive specific responses; conversely, the nociceptive specificity of evoked potentials by surface concentric electrode (SE-PREPs) is still debated. In this neurophysiological study we aimed at verifying the nociceptive specificity of SE-PREPs. We recorded LEPs, CHEPs and SE-PREPs in eleven healthy participants, before and after epidermal denervation produced by prolonged capsaicin application. We also used skin biopsy to verify the capsaicin-induced nociceptive nerve fibre loss in the epidermis. We found that whereas LEPs and CHEPs were suppressed after capsaicin-induced epidermal denervation, the surface concentric electrode stimulation of the same denervated skin area yielded unchanged SE-PREPs. The suppression of LEPs and CHEPs after nociceptive nerve fibre loss in the epidermis indicates that these techniques are selectively mediated by nociceptive system. Conversely, the lack of SE-PREP changes suggests that SE-PREPs do not provide selective information on nociceptive system function. Capsaicin-induced epidermal denervation abolishes laser evoked potentials (LEPs) and contact heat evoked potentials (CHEPs), but leaves unaffected pain-related evoked potentials by surface concentric electrode (SE-PREPs). These findings suggest that unlike LEPs and CHEPs, SE-PREPs are not selectively mediated by nociceptive system. © 2017 European Pain Federation - EFIC®.

  14. Effects of sympathetic denervation or chronic reserpine on potassium (42K) and chloride (36Cl) efflux from guinea-pig vas deferens

    International Nuclear Information System (INIS)

    Urquilla, P.R.; Jones, A.W.; Fleming, W.W.

    1980-01-01

    Potassium ( 42 K) or chloride ( 36 Cl) efflux curves were determined in guinea-pig vas deferens from control, reserpine-treated animals (1 mg/kg/day i.p. for 5 days), and from animals whose vas deferens had been sympathetically denervated 1 week before. Steady-state 42 K turnover in control tissues was 0.0052+-0.0002 min -1 ; neither reserpine treatment nor sympathetic denervation changed this parameter significantly. Control 36 Cl turnover was 0.058+-0.002 min -1 and it was unaffected by either procedure. Methoxamine (3x10 -6 to 10 -4 M) induced dose-related increases in the fractional exchange of 42 K and 36 Cl. These were of greater magnitude after sympathetic denervation or reserpine treatment. Furtrethonium also produced dose-dependent increases in 42 K efflux; its dose-response curve was shifted 2.6-fold to the left of the control curve by reserpine treatment. These results indicate that interruption of adrenergic transmission to the guinea-pig vas deferens is associated with increased changes in membrane permeability to Cl and possibly K in response to drug activation of α-adrenergic and cholinegic receptors. It is suggested that the supersensitivity phenomenon observed in the guinea-pig vas deferens after reserpine or sympathetic denervation is, in part, related to improved transduction of drug-receptor interaction into ionic permeability changes. (Auth.)

  15. Chronic Kidney Pain in Autosomal Dominant Polycystic Kidney Disease : A Case Report of Successful Treatment by Catheter-Based Renal Denervation

    NARCIS (Netherlands)

    Casteleijn, Niek F.; de Jager, Rosa L.; Neeleman, M. Peer; Blankestijn, Peter J.; Gansevoort, Ron T.

    Chronic pain is a common concern in patients with autosomal dominant polycystic kidney disease (ADPKD). We report what to our knowledge is the first catheter-based renal denervation procedure in a patient with ADPKD resulting in successful management of chronic pain. The patient was a 43-year-old

  16. Renal denervation for mild-moderate treatment-resistant hypertension : A timely intervention?

    Science.gov (United States)

    Chen, S; Kiuchi, M G; Schmidt, B; Hoye, N A; Acou, W-J; Liu, S; Chun, K R J; Pürerfellner, H

    2017-12-18

    Renal denervation (RDN) has been proposed as a novel antihypertensive intervention for treating resistant hypertension. It remains to be investigated which patient groups can potentially benefit from RDN. The present study aimed to evaluate the efficacy and safety of RDN in patients with mild-moderate resistant hypertension, i. e., systolic office blood pressure (BP) of 140-160 mm Hg despite treatment with three antihypertensive drugs including one diuretic, or mean systolic BP by ambulatory BP monitoring (ABPM) of 135-150 mm Hg. We evaluated data from four relevant clinical studies, all conducted in Europe, comprising 185 eligible patients. The patients' age was 62.1 ± 10.3 years and 73% were male (RDN group n = 149, control group n = 36). A self-control comparison showed that RDN led to significantly reduced ABPM at the 6‑month follow-up (systolic ABPM: 147.3 ± 13.4 mm Hg vs. 136.9 ± 15.5 mm Hg; diastolic ABPM: 81.1 ± 9.6 mm Hg vs. 76.2 ± 9.7 mm Hg; p ABPM as compared with that in the control group (∆systolic-ABPM: -10.4 ± 9.4 vs. -3.5 ± 9.6 mm Hg, p ABPM: -5 ± 5.8 vs. -2.1 ± 5.5 mm Hg; p = 0.005, respectively). The decrease of office BP in the RDN group was also statistically significant. RDN led to a reduced number of antihypertensive medications. No severe adverse events were found during follow-up. Regression analysis showed that the available baseline characteristics did not correlate with the ABPM improvement after RDN. RDN appears to be a safe and effective intervention for patients with mild-moderate resistant hypertension; however, randomized studies are warranted.

  17. Renal denervation in patients with resistant hypertension: six-month results.

    Science.gov (United States)

    Dores, Hélder; de Sousa Almeida, Manuel; de Araújo Gonçalves, Pedro; Branco, Patrícia; Gaspar, Augusta; Sousa, Henrique; Canha Gomes, Angela; Andrade, Maria João; Carvalho, Maria Salomé; Campante Teles, Rui; Raposo, Luís; Mesquita Gabriel, Henrique; Pereira Machado, Francisco; Mendes, Miguel

    2014-04-01

    Increased activation of the sympathetic nervous system plays a central role in the pathophysiology of hypertension (HTN). Catheter-based renal denervation (RDN) was recently developed for the treatment of resistant HTN. To assess the safety and efficacy of RDN for blood pressure (BP) reduction at six months in patients with resistant HTN. In this prospective registry of patients with essential resistant HTN who underwent RDN between July 2011 and May 2013, the efficacy of RDN was defined as ≥ 10 mm Hg reduction in office systolic blood pressure (SBP) six months after the intervention. In a resistant HTN outpatient clinic, 177 consecutive patients were evaluated, of whom 34 underwent RDN (age 62.7 ± 7.6 years; 50.0% male). There were no vascular complications, either at the access site or in the renal arteries. Of the 22 patients with complete six-month follow-up, the response rate was 81.8% (n=18). The mean office SBP reduction was 22 mm Hg (174 ± 23 vs. 152 ± 22 mm Hg; p<0.001) and 9 mm Hg in diastolic BP (89 ± 16 vs. 80 ± 11 mm Hg; p=0.006). The number of antihypertensive drugs (5.5 ± 1.0 vs. 4.6 ± 1.1; p=0.010) and pharmacological classes (5.4 ± 0.7 vs. 4.6 ± 1.1; p=0.009) also decreased significantly. Of the 24-hour ambulatory BP monitoring and echocardiographic parameters analyzed, there were significant reductions in diastolic load (45 ± 29 vs. 27 ± 26%; p=0.049) and in left ventricular mass index (174 ± 56 vs. 158 ± 60 g/m(2); p=0.014). In this cohort of patients with resistant HTN, RDN was safe and effective, with a significant BP reduction at six-month follow-up. Copyright © 2013 Sociedade Portuguesa de Cardiologia. Published by Elsevier España. All rights reserved.

  18. Effects of renal sympathetic denervation on 24-hour blood pressure variability

    Directory of Open Access Journals (Sweden)

    Christine Stefanie Zuern

    2012-05-01

    Full Text Available Background: In patients with arterial hypertension, increased blood pressure (BP variability contributes to end organ damage independently from mean levels of arterial BP. Increased BP variability has been linked to alterations in autonomic function including sympathetic overdrive. We hypothesized that catheter-based renal sympathetic denervation (RDN confers beneficial effects on BPV. Methods and Results: Eleven consecutive patients with therapy-refractory arterial hypertension (age 68.9±7.0 years; baseline systolic BP 189±23mmHg despite medication with 5.6±2.1 antihypertensive drugs underwent bilateral RDN. Twenty-four hour ambulatory blood pressure monitoring (ABPM was performed before RDN and six months thereafter. BPV was primarily assessed by means of standard deviation of 24-hour systolic arterial blood pressures (SDsys. Secondary measures of BPV were maximum systolic blood pressure (MAXsys and maximum difference between two consecutive readings of systolic BP (deltamaxsys over 24 hours. Six months after RDN, SDsys, MAXsys and deltamaxsys were significantly reduced from 16.9±4.6mmHg to 13.5±2.5mmHg (p=0.003, from 190±22mmHg to 172±20mmHg (p<0.001 and from 40±15mmHg to 28±7mmHg (p=0.006, respectively, without changes in concomitant antihypertensive therapy. Reductions of SDsys, MAXsys and deltamaxsys were observed in 10/11 (90.9%, 11/11 (100% and 9/11 (81.8% patients, respectively. Although we noted a significant reduction of systolic office blood pressure by 30.4±27.7mmHg (p=0.007, there was only a trend in reduction of average systolic BP assessed from ABPM (149±19mmHg to 142±18mmHg; p=0.086.Conclusions: In patients with therapy-refractory arterial hypertension, RDN leads to significant reductions of BP variability. Effects of RDN on BPV over 24 hours were more pronounced than on average levels of BP.

  19. The Effect of Renal Denervation on Plasma Adipokine Profile in Patients with Treatment Resistant Hypertension

    Directory of Open Access Journals (Sweden)

    Nina Eikelis

    2017-05-01

    Full Text Available Background: We previously demonstrated the effectiveness of renal denervation (RDN to lower blood pressure (BP at least partially via the reduction of sympathetic stimulation to the kidney. A number of adipocyte-derived factors are implicated in BP control in obesity.Aim: The aim of this study was to examine whether RDN may have salutary effects on the adipokine profile in patients with resistant hypertension (RH.Methods: Fifty seven patients with RH undergoing RDN program have been included in this study (65% males, age 60.8 ± 1.5 years, BMI 32.6 ± 0.7 kg/m2, mean ± SEM. Throughout the study, the patients were on an average of 4.5 ± 2.7 antihypertensive drugs. Automated seated office BP measurements and plasma concentrations of leptin, insulin, non-esterified fatty acids (NEFA, adiponectin and resistin were assessed at baseline and the 3 months after RDN.Results: There was a significant reduction in mean office systolic (168.75 ± 2.57 vs. 155.23 ± 3.17 mmHg, p < 0.001 and diastolic (90.68 ± 2.31 vs. 83.74 ± 2.36 mmHg, p < 0.001 BP 3 months after RDN. Body weight, plasma leptin and resistin levels and heart rate remained unchanged. Fasting insulin concentration significantly increased 3 months after the procedure (20.05 ± 1.46 vs. 29.70 ± 2.51 uU/ml, p = 0.002. There was a significant drop in circulating NEFA at follow up (1.01 ± 0.07 vs. 0.47 ± 0.04 mEq/l, p < 0.001. Adiponectin concentration was significantly higher after RDN (5,654 ± 800 vs. 6,644 ± 967 ng/ml, p = 0.024.Conclusions: This is the first study to demonstrate that RDN is associated with potentially beneficial effects on aspects of the adipokine profile. Increased adiponectin and reduced NEFA production may contribute to BP reduction via an effect on metabolic pathways.Clinical Trial Registration Number: NCT00483808, NCT00888433.

  20. Safety and performance of the second generation EnligHTN™ Renal Denervation System in patients with drug-resistant, uncontrolled hypertension.

    Science.gov (United States)

    Worthley, Stephen G; Wilkins, Gerard T; Webster, Mark W; Montarello, Joseph K; Delacroix, Sinny; Whitbourn, Robert J; Warren, Roderic J

    2017-07-01

    Catheter-based renal denervation for the treatment of drug-resistant hypertension has been intensively investigated in recent years. To date, only limited data have been published using multi-electrode radiofrequency ablation systems that can deliver lesions with a pre-determined pattern. This study was designed to evaluate the safety and performance of the second generation EnligHTN™ Renal Denervation System. This first-in-human, prospective, multi-center, non-randomized study included 39 patients (62% male, mean age 63 years, and mean baseline office blood pressure 174/93 mmHg) with drug-resistant hypertension. The primary safety and performance objectives were to characterize, from baseline to 6 months post procedure, the rate of serious procedural and device related adverse events, as adjudicated by an independent Clinical Events Committee, and the reduction of office systolic blood pressure. Renal artery denervation, using the second generation EnligHTN multi-electrode system significantly reduced office blood pressure from baseline to 1, 3, 6, 12, 18 and 24 months by 19/7, 26/9, 25/7, 23/7, 25/8 and 27/9 mmHg, respectively (p ≤ 0.0005). No serious device or procedure related adverse events affecting the renal arteries or renal function occurred through 24 months of follow-up. Renal sympathetic denervation using the second generation EnligHTN Renal Denervation System resulted in safe, rapid, and significant mean office blood pressure reduction that was sustained through 24 months. Future studies will need to address the utility of this system against an appropriate sham based comparator. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

  1. Irisin is a pro-myogenic factor that induces skeletal muscle hypertrophy and rescues denervation-induced atrophy.

    Science.gov (United States)

    Reza, Musarrat Maisha; Subramaniyam, Nathiya; Sim, Chu Ming; Ge, Xiaojia; Sathiakumar, Durgalakshmi; McFarlane, Craig; Sharma, Mridula; Kambadur, Ravi

    2017-10-24

    Exercise induces expression of the myokine irisin, which is known to promote browning of white adipose tissue and has been shown to mediate beneficial effects following exercise. Here we show that irisin induces expression of a number of pro-myogenic and exercise response genes in myotubes. Irisin increases myogenic differentiation and myoblast fusion via activation of IL6 signaling. Injection of irisin in mice induces significant hypertrophy and enhances grip strength of uninjured muscle. Following skeletal muscle injury, irisin injection improves regeneration and induces hypertrophy. The effects of irisin on hypertrophy are due to activation of satellite cells and enhanced protein synthesis. In addition, irisin injection rescues loss of skeletal muscle mass following denervation by enhancing satellite cell activation and reducing protein degradation. These data suggest that irisin functions as a pro-myogenic factor in mice.

  2. Thoracoscopic Left Cardiac Sympathetic Denervation for a Patient with Catecholaminergic Polymorphic Ventricular Tachycardia and Recurrent Implantable Cardioverter-Defibrillator Shocks

    Directory of Open Access Journals (Sweden)

    Woo-Sik Yu

    2015-06-01

    Full Text Available A patient presented with loss of consciousness and conversion. During an exercise test, catecholaminergic polymorphic ventricular tachycardia (CPVT resulted in cardiac arrest. He started taking medication (a beta-blocker and flecainide and an implantable cardioverter defibrillator (ICD was inserted, but the ventricular tachycardia did not resolve. Left cardiac sympathetic denervation (LCSD was then performed under general anesthesia, and the patient was discharged on the second postoperative day without complications. One month after the operation, no shock had been administered by the ICD, and an exercise stress test did not induce ventricular tachycardia. Although beta- blockers are the gold standard of therapy in patients with CPVT, thoracoscopic LCSD is safe and can be an effective alternative treatment option for patients with intractable CPVT.

  3. The SPYRAL HTN Global Clinical Trial Program: Rationale and design for studies of renal denervation in the absence (SPYRAL HTN OFF-MED) and presence (SPYRAL HTN ON-MED) of antihypertensive medications.

    Science.gov (United States)

    Kandzari, David E; Kario, Kazuomi; Mahfoud, Felix; Cohen, Sidney A; Pilcher, Garrett; Pocock, Stuart; Townsend, Raymond; Weber, Michael A; Böhm, Michael

    2016-01-01

    Renal sympathetic activation plays a key role in the pathogenesis of hypertension, as demonstrated by high renal norepinephrine spillover into plasma of patients with essential hypertension. Renal denervation has demonstrated a significant reduction in blood pressure in unblinded studies of hypertensive patients. The SYMPLICITY HTN-3 trial, the first prospective, masked, randomized study of renal denervation versus sham control, failed its primary efficacy end point and raised important questions around potentially confounding factors, such as drug changes and adherence, study population, and procedural methods. The SPYRAL HTN Global Clinical Trial Program is designed to address limitations associated with predicate studies and provide insight into the impact of pharmacotherapy on renal denervation efficacy. The 2 initial trials of the program focus on the effect of renal denervation using the Symplicity Spyral multielectrode renal denervation catheter in hypertensive patients in the absence (SPYRAL HTN OFF-MED) and presence (SPYRAL HTN ON-MED) of antihypertensive medications. The SPYRAL HTN ON-MED study requires patients to be treated with a consistent triple therapy antihypertensive regimen, whereas the SPYRAL HTN OFF-MED study includes a 3- to 4-week drug washout period followed by a 3-month efficacy and safety end point in the absence of antihypertensive medications. The studies will randomize patients with combined systolic-diastolic hypertension to renal denervation or sham procedure. Both studies allow renal denervation treatments in renal artery branches and accessories. These studies will inform the design of the second pivotal phase of the program, which will more definitively analyze the antihypertensive effect of renal denervation. Copyright © 2015 Elsevier Inc. All rights reserved.

  4. Potential lifetime cost-effectiveness of catheter-based renal sympathetic denervation in patients with resistant hypertension.

    Science.gov (United States)

    Dorenkamp, Marc; Bonaventura, Klaus; Leber, Alexander W; Boldt, Julia; Sohns, Christian; Boldt, Leif-Hendrik; Haverkamp, Wilhelm; Frei, Ulrich; Roser, Mattias

    2013-02-01

    Recent studies have demonstrated the safety and efficacy of catheter-based renal sympathetic denervation (RDN) for the treatment of resistant hypertension. We aimed to determine the cost-effectiveness of this approach separately for men and women of different ages. A Markov state-transition model accounting for costs, life-years, quality-adjusted life-years (QALYs), and incremental cost-effectiveness was developed to compare RDN with best medical therapy (BMT) in patients with resistant hypertension. The model ran from age 30 to 100 years or death, with a cycle length of 1 year. The efficacy of RDN was modelled as a reduction in the risk of hypertension-related disease events and death. Analyses were conducted from a payer's perspective. Costs and QALYs were discounted at 3% annually. Both deterministic and probabilistic sensitivity analyses were performed. When compared with BMT, RDN gained 0.98 QALYs in men and 0.88 QALYs in women 60 years of age at an additional cost of €2589 and €2044, respectively. As the incremental cost-effectiveness ratios increased with patient age, RDN consistently yielded more QALYs at lower costs in lower age groups. Considering a willingness-to-pay threshold of €35 000/QALY, there was a 95% probability that RDN would remain cost-effective up to an age of 78 and 76 years in men and women, respectively. Cost-effectiveness was influenced mostly by the magnitude of effect of RDN on systolic blood pressure, the rate of RDN non-responders, and the procedure costs of RDN. Renal sympathetic denervation is a cost-effective intervention for patients with resistant hypertension. Earlier treatment produces better cost-effectiveness ratios.

  5. Boosted Regeneration and Reduced Denervated Muscle Atrophy by NeuroHeal in a Pre-clinical Model of Lumbar Root Avulsion with Delayed Reimplantation.

    Science.gov (United States)

    Romeo-Guitart, David; Forés, Joaquim; Navarro, Xavier; Casas, Caty

    2017-09-20

    The "gold standard" treatment of patients with spinal root injuries consists of delayed surgical reconnection of nerves. The sooner, the better, but problems such as injury-induced motor neuronal death and muscle atrophy due to long-term denervation mean that normal movement is not restored. Herein we describe a preclinical model of root avulsion with delayed reimplantation of lumbar roots that was used to establish a new adjuvant pharmacological treatment. Chronic treatment (up to 6 months) with NeuroHeal, a new combination drug therapy identified using a systems biology approach, exerted long-lasting neuroprotection, reduced gliosis and matrix proteoglycan content, accelerated nerve regeneration by activating the AKT pathway, promoted the formation of functional neuromuscular junctions, and reduced denervation-induced muscular atrophy. Thus, NeuroHeal is a promising treatment for spinal nerve root injuries and axonal regeneration after trauma.

  6. Intrinsic denervation of the colon is associated with a decrease of some colonic preneoplastic markers in rats treated with a chemical carcinogen

    Directory of Open Access Journals (Sweden)

    M.V.O. Vespúcio

    2008-04-01

    Full Text Available Denervation of the colon is protective against the colon cancer; however, the mechanisms involved are unknown. We tested the hypothesis that the denervated colonic mucosa could be less responsive to the action of the chemical carcinogen dimethylhydrazine (DMH. Three groups of 32 male Wistar rats were treated as follows: group 1 (G1 had the colon denervated with 0.3 mL 1.5 mM benzyldimethyltetradecylammonium (benzalkonium chloride, BAC; G2 received a single ip injection of 125 mg/kg DMH; G3 was treated with BAC + the same dose and route of DMH. A control group (Sham, N = 32 did not receive any treatment. Each group was subdivided into four groups according to the sacrifice time (1, 2, 6, and 12 weeks after DMH. Crypt fission index, ß-catenin accumulated crypts, aberrant crypt foci, and cell proliferation were evaluated and analyzed by ANOVA and the Student t-test. G3 animals presented a small number of aberrant crypt foci and low crypt fission index compared to G2 animals after 2 and 12 weeks, respectively. From the second week on, the index of ß-catenin crypt in G3 animals increased slower than in G2 animals. From the 12th week on, G2 animals presented a significant increase in cell proliferation when compared to the other groups. Colonic denervation plays an anticarcinogenic role from early stages of colon cancer development. This finding can be of importance for the study of the role of the enteric nervous system in the carcinogenic process.

  7. Organ damage changes in patients with resistant hypertension randomized to renal denervation or spironolactone: The DENERVHTA (Denervación en Hipertensión Arterial) study.

    Science.gov (United States)

    Oliveras, Anna; Armario, Pedro; Sans, Laia; Clarà, Albert; Vázquez, Susana; Molina, Luis; Pareja, Júlia; de la Sierra, Alejandro; Pascual, Julio

    2018-01-01

    Renal denervation and spironolactone have both been proposed for the treatment of resistant hypertension, but their effects on preclinical target organ damage have not been compared. Twenty-four patients with 24-hour systolic blood pressure ≥140 mm Hg despite receiving three or more full-dose antihypertensive drugs, one a diuretic, were randomized to receive spironolactone or renal denervation. Changes in 24-hour blood pressure, urine albumin excretion, arterial stiffness, carotid intima-media thickness, and left ventricular mass index were evaluated at 6 months. Mean baseline-adjusted difference between the two groups (spironolactone vs renal denervation) at 6 months in 24-hour systolic blood pressure was -17.9 mm Hg (95% confidence interval [CI], -30.9 to -4.9; P = .01). Mean baseline-adjusted change in urine albumin excretion was -87.2 (95% CI, -164.5 to -9.9) and -23.8 (95% CI, -104.5 to 56.9), respectively (P = .028). Mean baseline-adjusted variation of 24-hour pulse pressure was -13.5 (95% CI, -18.8 to -8.2) and -2.1 (95% CI, -7.9 to 3.7), respectively (P = .006). The correlation of change in 24-hour systolic blood pressure with change in log-transformed urine albumin excretion was r = .713 (P < .001). At 6 months there was a reduction in albuminuria in patients with resistant hypertension treated with spironolactone as compared with renal denervation. ©2018 Wiley Periodicals, Inc.

  8. Twelve-month results of the rapid renal sympathetic denervation for resistant hypertension using the OneShotTM ablation system (RAPID) study.

    Science.gov (United States)

    Verheye, Stefan; Ormiston, John; Bergmann, Martin W; Sievert, Horst; Schwindt, Arne; Werner, Nikos; Vogel, Britta; Colombo, Antonio

    2015-02-01

    Renal denervation has emerged as a treatment option for patients with drug-resistant hypertension. This study was designed to assess the safety and effectiveness of the OneShotª Renal Denervation System. RAPID is a prospective, multicentre, single-arm study which enrolled 50 patients at 11 clinical sites in Europe and New Zealand. Eligible patients had an office systolic blood pressure (SBP) ≥160 mmHg and were on a stable regimen of ≥3 antihypertensive medications including a diuretic. The primary safety endpoints were acute procedural safety at discharge and chronic procedural safety at six months. The primary effectiveness endpoint was the rate of office SBP reduction ≥10 mmHg at six months compared to baseline. While not a predefined endpoint, change in 24-hour ambulatory BP was evaluated. The mean baseline office SBP and diastolic BP measurements were 181.6±20.8 and 95.5±15.5 mmHg, respectively. Patients were on a mean of 5.1 antihypertensive medications at baseline. The mean office BP decreased by -20/-8 mmHg (prenal artery injury or SAE/adverse device effects at six months. The results of the RAPID study demonstrate safe delivery of RF energy by the OneShot Renal Denervation System for renal sympathetic denervation and sustained efficacy, as evidenced by a significant reduction in office and 24-hour ABPM for six months, which was sustained up to 12 months. ClinicalTrials.gov Identifier: NCT01520506.

  9. Combined application of neutrophin-3 gene and neural stem cells is ameliorative to delay of denervated skeletal muscular atrophy after tibial nerve transection in rats.

    Science.gov (United States)

    Lin, Sen; Xu, Jianguang; Hu, Shaonan; Xu, Lei; Zhang, Changqing; Wang, Yang; Gu, Yudong

    2011-01-01

    Examination of the therapeutic efficacy of neural stem cells (NSCs) has recently become the focus of much investigation. In this study we present an insight of the effects of combined application with neurotrophin-3 (NT-3) and NSCs that derived from rat embryo spinal cord on delaying denervated skeletal muscular atrophy after tibial nerve was severed. NT-3 gene was amplified by PCR and subcloned into lentiviral vector pWPXL-MOD to construct a lentiviral expression vector pWPXL-MOD-NT-3. A positive clone expressing NT-3 (named NSCs-NT-3) was obtained and used for differentiation in vitro and transplantation. Sixty adult rats, whose tibial nerves were sectioned, were divided into two groups: one grafted with NSCs-NT-3 (experimental group, n = 30) and the other with NSCs transfected by pWPXL-MOD (control group, n = 30). The cell survival and differentiation, NT-3 gene expression, and effect of delaying denervated skeletal muscular atrophy were examined through immunohistostaining, RT-PCR, Western blot, electrophysiological analysis, and mean cross-sectional area (CSA) of gastrocnemius, respectively. The results show that the NT-3 gene, which is comprised of 777 bp, was cloned and significantly different expression were detected between NSCs and NSCs-NT-3 in vitro. Quantitative analysis of the choline acetyltransferase (ChAT) immunopositive cells revealed a significant increase in experimental group compared to the control group 4 weeks after implantation (p ChAT immunopositive cells were detected near the engrafted region only in experimental group. Furthermore, the effect in delaying denervated skeletal muscular atrophy is indicated in the EMG examination and mean CSA of gastrocnemius. These findings suggest that the neural stem cells expressing NT-3 endogenously would be a better graft candidate for the delay of denervated skeletal muscular atrophy.

  10. Dopamine denervation does not alter in vivo 3H-spiperone binding in rat striatum: implications for external imaging of dopamine receptors in Parkinson's disease

    International Nuclear Information System (INIS)

    Bennett, J.P. Jr.; Wooten, G.F.

    1986-01-01

    Striatal particulate preparations, both from rats with lesion-induced striatal dopamine (DA) loss and from some striatal dopamine (DA) loss and from some patients with Parkinson's disease, exhibit increased 3 H-neuroleptic binding, which is interpreted to be the mechanism of denervation-induced behavioral supersensitivity to dopaminergic compounds. After intravenous 3 H-spiperone ( 3 H-SP) administration to rats with unilateral nigral lesions, we found no differences in accumulation of total or particulate-bound 3 H-SP in dopamine-denervated compared with intact striata. 3 H-SP in vivo binds to less than 10% of striatal sites labeled by 3 H-SP incubated with striatal particulate preparations in vitro. Quantitative autoradiography of 3 H-SP binding to striatal sections in vitro also failed to reveal any effects of dopamine denervation. 3 H-SP bound to striatal sites in vivo dissociates more slowly than that bound to striatal particulate preparations labeled in vitro. Striatal binding properties of 3 H-SP administered in vivo are quite different from the same kinetic binding parameters estimated in vitro using crude membrane preparations of striatum. In addition, striatal binding of in vivo-administered 3H-SP is not affected by prior lesion of the substantia nigra, which results in profound ipsilateral striatal dopamine depletion. Thus, behavioral supersensitivity to dopaminergic compounds may not be associated with altered striatal binding properties for dopamine receptor ligands in vivo

  11. The role of sympathetic nervous system in the progression of chronic kidney disease in the era of catheter based sympathetic renal denervation.

    Science.gov (United States)

    Petras, Dimitrios; Koutroutsos, Konstantinos; Kordalis, Athanasios; Tsioufis, Costas; Stefanadis, Christodoulos

    2013-08-01

    The kidney has been shown to be critically involved as both trigger and target of sympathetic nervous system overactivity in both experimental and clinical studies. Renal injury and ischemia, activation of renin angiotensin system and dysfunction of nitric oxide system have been implicated in adrenergic activation from kidney. Conversely, several lines of evidence suggest that sympathetic overactivity, through functional and morphological alterations in renal physiology and structure, may contribute to kidney injury and chronic kidney disease progression. Pharmacologic modulation of sympathetic nervous system activity has been found to have a blood pressure independent renoprotective effect. The inadequate normalization of sympathoexcitation by pharmacologic treatment asks for novel treatment options. Catheter based renal denervation targets selectively both efferent and afferent renal nerves and functionally denervates the kidney providing blood pressure reduction in clinical trials and renoprotection in experimental models by ameliorating the effects of excessive renal sympathetic drive. This review will focus on the role of sympathetic overactivity in the pathogenesis of kidney injury and CKD progression and will speculate on the effect of renal denervation to these conditions.

  12. The role of subscapularis muscle denervation in the pathogenesis of shoulder internal rotation contracture after neonatal brachial plexus palsy: a study in a rat model.

    Science.gov (United States)

    Mascarenhas, Vasco V; Casaccia, Marcelo; Fernandez-Martin, Alejandra; Marotta, Mario; Fontecha, Cesar G; Haddad, Sleiman; Knörr, Jorge; Soldado, Francisco

    2014-12-01

    We assessed the role of subscapularis muscle denervation in the development of shoulder internal rotation contracture in neonatal brachial plexus injury. Seventeen newborn rats underwent selective denervation of the subscapular muscle. The rats were evaluated at weekly intervals to measure passive shoulder external rotation. After 4 weeks, the animals were euthanized. The subscapularis thickness was measured using 7.2T MRI axial images. The subscapularis muscle was then studied grossly, and its mass was registered. The fiber area and the area of fibrosis were measured using collagen-I inmunostained muscle sections. Significant progressive decrease in passive shoulder external rotation was noted with a mean loss of 58° at four weeks. A significant decrease in thickness and mass of the subscapularis muscles in the involved shoulders was also found with a mean loss of 69%. Subscapularis muscle fiber size decreased significantly, while the area of fibrosis remained unchanged. Our study shows that subscapularis denervation, per se, could explain shoulder contracture after neonatal brachial plexus injury, though its relevance compared to other pathogenic factors needs further investigation. © 2014 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.

  13. Renal denervation using catheter-based radiofrequency ablation with temperature control: renovascular safety profile and underlying mechanisms in a hypertensive canine model.

    Science.gov (United States)

    Li, Huijie; Yu, Hang; Zeng, Chunyu; Fang, Yuqiang; He, Duofen; Zhang, Xiaoqun; Wen, Chunlan; Yang, Chengming

    2015-01-01

    Renal denervation is a novel method for hypertension treatment. In this study, we aimed to investigate the safety and efficacy of radiofrequency ablation (RFA) at ablation temperatures of 45 °C or 50 °C and its possible mechanisms. A hypertensive canine model was established by abdominal aortic constriction in 20 healthy hybrid dogs. These dogs were then randomly assigned to the treatment and the control groups, with dogs in the treatment group further randomly assigned to receive RFA at ablation temperatures of 45 °C or 50 °C. In the treatment group, RFA was performed at 1 month after modeling; renal angiography was performed at 2 months after ablation. The arterial vessels of the dogs were examined histologically with hematoxylin and eosin staining. Changes in blood pressure in the foreleg and whole-body norepinephrine spillover rate were also assessed. No arterial stenosis, dissection, thrombosis or other abnormalities were detected in the treated vessels by renal angiography, yet histology results showed minimal to mild renal arterial injury. Renal denervation resulted in a marked decrease in the whole-body norepinephrine spillover rate (p 0.05). Renal denervation can be performed without acute major adverse events, using catheter-based RFA with temperature control. The procedure was feasible in reducing blood pressure by at least partially inhibiting sympathetic drive and systemic sympathetic outflow.

  14. Anatomical and procedural determinants of ambulatory blood pressure lowering following catheter-based renal denervation using radiofrequency.

    Science.gov (United States)

    Lauder, Lucas; Ewen, Sebastian; Tzafriri, Abraham R; Edelman, Elazer R; Cremers, Bodo; Kulenthiran, Saarraaken; Ukena, Christian; Linz, Dominik; Kindermann, Ingrid; Tsioufis, Costas; Scheller, Bruno; Böhm, Michael; Mahfoud, Felix

    2018-03-02

    Catheter-based renal sympathetic denervation (RDN) has been introduced to lower blood pressure (BP) and sympathetic activity in patients with uncontrolled hypertension with at best equivocal results. It has been postulated that anatomic and procedural elements introduce unaccounted variability and yet little is known of the impact of renal anatomy and procedural parameters on BP response to RDN. Anatomical parameters such as length and diameter were analyzed by quantitative vascular analysis and the prevalence of accessory renal arteries and renal artery disease were documented in 150 patients with resistant hypertension undergoing bilateral RDN using a mono-electrode radiofrequency catheter (Symplicity Flex, Medtronic). Accessory renal arteries and renal artery disease were present in 56 (37%) and 14 patients (9%), respectively. At 6-months, 24 h-ambulatory BP was reduced by 11/6 mm Hg (p renal arteries (p = 0.543) or renal artery disease (p = 0.598). Patients with at least one main renal artery diameter ≤ 4 mm had a more pronounced reduction of 24 h-ambulatory SBP compared to patients where both arteries were >4 mm (-19 vs. -10 mmHg; p = 0.038). Neither the length of the renal artery nor the number of RF ablations influenced 24 h-ambulatory BP reduction at 6 months. 24 h-ambulatory BP lowering was most pronounced in patients with smaller renal artery diameter but not related to renal artery length, accessory arteries or renal artery disease. Further, there was no dose-response relationship observed with increasing number of ablations. Because little is known of the impact of renal anatomy and procedural parameters on blood pressure (BP) response to renal denervation (RDN), anatomical and procedural data were analyzed in 150 patients undergoing bilateral RDN. BP lowering was most pronounced in patients with smaller renal artery diameter but not related to renal artery length, the presence of renal artery disease or accessory renal

  15. Favorable effects on arterial stiffness after renal sympathetic denervation for the treatment of resistant hypertension: a cardiovascular magnetic resonance study

    Directory of Open Access Journals (Sweden)

    Hammer TA

    2016-09-01

    Full Text Available Tommy Arild Hammer,1 Knut Asbjørn Rise Langlo,2 Pål Erik Goa,1,3 Fadl Elmula M Fadl Elmula,4,5 Pavel Hoffmann,6 Knut Haakon Stensaeth1,7 1Department of Radiology and Nuclear Medicine, 2Department of Nephrology, St Olav’s University Hospital, Trondheim, Norway; 3Department of Physics, Norwegian University of Science and Technology, Trondheim, Norway; 4Institute of Cardiovascular and Renal Research, Department of Cardiology, Oslo University Hospital, Oslo, Norway; 5Faculty of Clinical Medicine, University of Oslo, Oslo, Norway; 6Department of Cardiology, Oslo University Hospital, Oslo, Norway; 7Institute of Circulation and Medical Imaging, Norwegian University of Science and Technology, Trondheim, Norway Aims: Renal sympathetic denervation (RDN has recently been suggested to be a novel treatment strategy for patients with treatment-resistant hypertension. However, the latest randomized studies have provided conflicting results and the influence of RDN on arterial stiffness remains unclear. Therefore, this study aimed to detect the effects of RDN on arterial stiffness as measured with aortic pulse wave velocity (PWV and distensibility in addition to cardiac function and T1 mapping at baseline and at 6-month follow-up.Methods: RDN was performed in a total of 16 patients with treatment-resistant hypertension, and the procedures were conducted at two university hospitals using two different RDN devices. All patients and age-matched controls underwent a comprehensive clinical examination and cardiac magnetic resonance protocols both at baseline and at a 6-month follow-up.Results: In the treatment group, the systolic blood pressure (SBP was found to be decreased at the follow-up visit (office SBP; 173±24 compared to 164±25 mmHg [P= 0.033], the 24-hour ambulatory SBP had decreased (163±25 compared to 153±20 mmHg [P=0.057], the aortic PWV had decreased from 8.24±3.34 to 6.54±1.31 m/s (P=0.053, and the aortic distensibility had increased from 2

  16. Renal Denervation Attenuates Progression of Atherosclerosis in Apolipoprotein E–Deficient Mice Independent of Blood Pressure Lowering

    Science.gov (United States)

    Wang, Hui; Wang, Jintao; Guo, Chiao; Luo, Wei; Kleiman, Kyle; Eitzman, Daniel T.

    2016-01-01

    The renal autonomic nervous system may contribute to hypertension and vascular disease. Although the effects of renal artery denervation on blood pressure lowering are controversial, there may be other beneficial vascular effects independent of blood pressure lowering. Bilateral renal denervation (RDN) or sham operation (SO) was performed in 14-week-old male apolipoprotein E–deficient mice on a Western diet starting at 10 weeks of age. Efficacy of RDN was confirmed by reduction of renal norepinephrine levels (SO: 3.8±0.1 versus RDN: 1.7±0.3 ng/mL; P<0.01) at 6 weeks after procedure. Compared with SO, RDN had no effect on blood pressure (SO: 101.0±2.4 versus RDN: 97.5±1.6 mm Hg; P=0.25), total cholesterol (SO: 536.7±28.5 versus RDN: 535.7±62.9 mg/dL; P=0.99), or triglycerides (SO: 83.7±3.5 versus RDN: 86.9±10.2 mg/dL; P=0.78). Quantification of atherosclerosis at 20 weeks of age demonstrated reduced atherosclerosis in mice receiving RDN compared with SO (arterial tree oil-red-O surface staining RDN: 4.2±0.5% versus SO: 6.3±0.7%; P<0.05). Reduced atherosclerosis was associated with increased smooth muscle cell content in atherosclerotic plaques (RDN: 13.3±2.1 versus SO: 8.1±0.6%; P<0.05). Serum levels of aldosterone, monocyte chemoattractant protein-1, and 8-isoprostane were lower in mice that received RDN compared with sham-operated mice (aldosterone; RDN: 206.8±33.2 versus SO: 405.5±59.4 pg/mL, P<0.05; monocyte chemoattractant protein-1; RDN: 51.7±7.9 versus SO: 91.71±4.6 pg/mL, P<0.05; 8-isoprostane; RDN: 331.9±38.2 versus SO: 468.5±42.0 pg/mL, P<0.05). RDN reduces progression of atherosclerosis in apolipoprotein E–deficient mice. These changes are associated with reduced aldosterone levels, monocyte chemoattractant protein-1, and markers of oxidative stress. PMID:25646301

  17. Clinical Outcome Following Radiofrequency Denervation for Refractory Sacroiliac Joint Dysfunction Using the Simplicity III Probe: A 12-Month Retrospective Evaluation.

    Science.gov (United States)

    Hegarty, Dominic

    2016-01-01

    Sacroiliac joint syndrome (SIJ) is diagnosed in 10% to 25% of cases of lower back pain. The response to traditional radiofrequency (RF) denervation of the SIJ has being inconsistent. The Simplicity III RF probe (Neruotherm. Inc.) offers a novel treatment option. To evaluate the long-term clinical outcome (12 months) refractory SIJ syndrome in terms of pain intensity and functional improvement. A 50% reduction in intensity pain intensity (VAS) at 12 months was deemed clinically significant. A 12-month retrospective observational evaluation all of adults treated with RF for refractory SIJ. Chronic pain management center. The medical records of all adults treated with this technique was retrospectively reviewed. The primary outcome was pain intensity scores (VAS) over a 12 months period; Secondary outcomes included Roland-Morris Functional scores (RMF), Brief Pain Inventory (BPI), general health assessment (Sf12), and patient satisfaction scores (GPI), which were recorded pre and post denervation. Pain Intensity improved by 4.7 points compared to pre-treatment representing a 61% reduction in pain at 12 months (n=11, P < 0.001). Significant improvements in (a) RMF (P < 0.01, W2 = 0.63 (large effect size); (b) BPI (P < 0.001, W2 = 0.72 (strong effect size); and (c) Sf12 (P < 0.01) were noted. Overall patients were satisfied with the outcome (GPI = 77.7%). The retrospective in nature of the study and the small sample size are limitations. As it was our policy to monitor the progress of the individuals since the introduction of this technique a reliable method of recording the baseline and outcome variables at each point of contact was in place. Access to a complete set of variables in all individuals over a 12-month period was therefore possible, which we feel contributes to the quality of the dataset. By creating a consistent radiofrequency lesion between the sacral foramen and the SIJ will reliably capture the innervation to the SIJ with significant long-term clinical

  18. Magnitude of blood pressure reduction in the placebo arms of modern hypertension trials: implications for trials of renal denervation.

    Science.gov (United States)

    Patel, Hitesh C; Hayward, Carl; Ozdemir, Baris Ata; Rosen, Stuart D; Krum, Henry; Lyon, Alexander R; Francis, Darrel P; di Mario, Carlo

    2015-02-01

    Early phase studies of novel interventions for hypertension, such as renal sympathetic denervation, are sometimes single-armed (uncontrolled). We explored the wisdom of this by quantifying the blood pressure fall in the placebo arms of contemporary trials of hypertension. We searched Medline up to June 2014 and identified blinded, randomized trials of hypertension therapy in which the control arm received placebo medication or a sham (placebo) procedure. For nonresistant hypertension, we have identified all such trials of drugs licensed by the US Food and Drug Administration since 2000 (5 drugs). This US Food and Drug Administration-related restriction was not applied to resistant hypertension trials. This produced 7451 patients, who were allocated to a blinded control from 52 trials of nonresistant hypertension and 694 patients from 8 trials of resistant hypertension (3 drugs and 2 interventions). Systolic blood pressure fell by 5.92 mm Hg (95% confidence interval, 5.14-6.71; Pefficacy explorations of novel therapies for hypertension, once safety is established, should be performed with a randomized, appropriately controlled, and blinded design. © 2014 American Heart Association, Inc.

  19. On the appearance of acetylcholine receptors in denervated rat diaphragm, and its dependence on nerve stump length

    International Nuclear Information System (INIS)

    Uchitel, O.; Robbins, N.

    1978-01-01

    Acetylcholine (ACh) sensitivity and extrajunctional receptor distribution of the rat diaphragm were closely monitored during the early period following denervation. Both contracture in response to 10 μg/ml of ACh and extrajunctional binding of [ 125 I]alpha-bungarotoxin ([ 125 I]α-BTX) were first detectable 30 h after cutting the phrenic nerve in the thorax. If the nerve were cut more proximally, leaving a 3.5 cm distal nerve stump, the same level of ACh contracture and [ 125 I]α-BTX binding did not appear until 40 h after operation. This 10-h delay was far longer than the 3-h delay in transmission failure reportedly dependent on stump length. The earliest detectable extrajunctional [ 125 I]α-BTX binding appeared throughout the entire muscle fiber, and was not localized to the endplate region as would be expected if degeneration in the nerve terminal induced new receptors. However, later significant increases in [ 125 I]α-BTX binding at the endplate region could have resulted from such degeneration. All these results are consistent with neurotrophic regulation of muscle ACh receptors, working via a mechanism involving axonal transport. (Auth.)

  20. Denervation (ablation) of nerve terminalis in renal arteries: early results of interventional treatment of arterial hypertension in Poland.

    Science.gov (United States)

    Bartuś, Krzysztof; Sadowski, Jerzy; Kapelak, Bogusław; Zajdel, Wojciech; Godlewski, Jacek; Bartuś, Stanisław; Bochenek, Maciej; Bartuś, Magdalena; Żmudka, Krzysztof; Sobotka, Paul A

    2013-01-01

    Arterial hypertension is one of the main causes of cardiovascular disease morbidity and overall mortality. To report the single centre experiences with changes in arterial blood pressure (BP) in patients after intra-arterial application of radiofrequency (RF) energy to cause renal sympathetic efferent and somatic afferent nerve and report vascular and kidney safety in a six month follow up. Twenty-eight patients, with hypertension despite medical therapy (median age 52.02 years, range 42-72 years) consented to therapeutic renal nerve ablation. SIMPLICITY RF catheters and generator provided by Ardian (currently Medtronic Inc., USA) were used to perform renal artery angiography and ablation. The mean BP at baseline, and after one month, three months and six months were measured [mm Hg]: systolic 176.6; 162.3 (p = 0.004); 150.6 (p arterial renal nerve denervation was not associated with either vascular or renal complications out to six months. Nerve ablation of renal arteries led to significant reduction of mean values of arterial systolic, diastolic BP and significant reduction of pulse pressure. The Polish experience is not significantly different compared to that reported in the Symplicity I and Symplicity II international cohorts. The long term durability of this therapy and its application to earlier stages of hypertension or other disease states will require further investigation.

  1. Controlled circumferential renal sympathetic denervation with preservation of the renal arterial wall using intraluminal ultrasound: a next-generation approach for treating sympathetic overactivity.

    Science.gov (United States)

    Sakakura, Kenichi; Roth, Austin; Ladich, Elena; Shen, Kai; Coleman, Leslie; Joner, Michael; Virmani, Renu

    2015-02-01

    The Paradise Ultrasound Renal Denervation System is a next-generation catheter-based device which was used to investigate whether the target ablation area can be controlled by changing ultrasound energy and duration to optimise nerve injury while preventing damage to the arterial wall. Five ultrasound doses were tested in a thermal gel model. Catheter-based ultrasound denervation was performed in 15 swine (29 renal arteries) to evaluate five different doses in vivo, and animals were euthanised at seven days for histopathologic assessment. In the gel model, the peak temperature was highest in the low power-long duration (LP-LD) dose, followed by the mid-low power-mid duration (MLP-MD) dose and the mid-high power-short duration (MHP-SD) dose, and lowest in the mid power-short duration (MP-SD) dose and the high power-ultra short duration (HP-USD) dose. In the animal study, total ablation area was significantly greater in the LP-LD group, followed by the MLP-MD group, and it was least in the HP-USD, MP-SD and MHP-SD groups (p=0.02). Maximum distance was significantly greater in the LP-LD group, followed by the MLP-MD group, the MHP-SD group, and the HP-USD group, and shortest in the MP-SD group (p=0.007). The short spare distance was not different among the five groups (p=0.38). Renal artery damage was minimal, while preserving significant nerve damage in all groups. The Paradise Ultrasound Renal Denervation System is a controllable system where total ablation area and depth of ablation can be optimised by changing ultrasound power and duration while sparing renal arterial tissue damage but allowing sufficient peri-arterial nerve damage.

  2. Renal denervation for resistant hypertension using an irrigated radiofrequency balloon: 12-month results from the Renal Hypertension Ablation System (RHAS) trial.

    Science.gov (United States)

    Ormiston, John A; Watson, Timothy; van Pelt, Niels; Stewart, Ralph; Stewart, James T; White, Jonathon M; Doughty, Robert N; Stewart, Fiona; Macdonald, Rhona; Webster, Mark W I

    2013-05-20

    Renal denervation using the point-by-point application of radiofrequency energy delivered by the first-generation Symplicity system is effective in lowering office blood pressure but may be time-consuming. The OneShot Renal Denervation System with a balloon-mounted spiral electrode potentially shortens and simplifies the procedure. This study is a hypothesis-generating first-in-human study to assess feasibility, and to provide preliminary efficacy and safety data. Eligible patients had a baseline office systolic blood pressure ≥160 mmHg (or ≥150 mmHg for diabetics) and were on two or more antihypertensive medications. Nine patients were enrolled. The primary endpoint, the insertion of the OneShot balloon into each renal artery and the delivery of radiofrequency energy, was achieved in 8/9 (89%) of patients. The one failure (the first patient) was due to generator high-impedance safety shut-off threshold set too low for humans. Adverse events were minor. No patient developed renal artery stenosis. Baseline BP was 185.67 ± 18.7 mmHg and the reductions at 1, 3, 6 and 12 months were 30.1 ± 13.6 (p=0.0004), 34.2 ± 20.2 (p=0.002), 33.6 ± 32.2 (p=0.021) and 30.6 ± 22.0 (p=0.019). The OneShot renal denervation system successfully delivered radiofrequency energy to the renal arteries in a short and straightforward procedure. Australian New Zealand Clinical Trials Registry - URL: anzctr.org.au. Trial identification: ACTRN12611000987965.

  3. Safety and efficacy of a multi-electrode renal sympathetic denervation system in resistant hypertension: the EnligHTN I trial.

    Science.gov (United States)

    Worthley, Stephen G; Tsioufis, Costas P; Worthley, Matthew I; Sinhal, Ajay; Chew, Derek P; Meredith, Ian T; Malaiapan, Yuvi; Papademetriou, Vasilios

    2013-07-01

    Catheter-based renal artery sympathetic denervation has emerged as a novel therapy for treatment of patients with drug-resistant hypertension. Initial studies were performed using a single electrode radiofrequency catheter, but recent advances in catheter design have allowed the development of multi-electrode systems that can deliver lesions with a pre-determined pattern. This study was designed to evaluate the safety and efficacy of the EnligHTN(™) multi-electrode system. We conducted the first-in-human, prospective, multi-centre, non-randomized study in 46 patients (67% male, mean age 60 years, and mean baseline office blood pressure 176/96 mmHg) with drug-resistant hypertension. The primary efficacy objective was change in office blood pressure from baseline to 6 months. Safety measures included all adverse events with a focus on the renal artery and other vascular complications and changes in renal function. Renal artery denervation, using the EnligHTN system significantly reduced the office blood pressure from baseline to 1, 3, and 6 months by -28/10, -27/10 and -26/10 mmHg, respectively (P renal artery injury or other serious vascular complications occurred. Small, non-clinically relevant, changes in average estimated glomerular filtration rate were reported from baseline (87 ± 19 mL/min/1.73 m2) to 6 months post-procedure (82 ± 20 mL/min/1.73 m2). Renal sympathetic denervation, using the EnligHTN multi-electrode catheter results in a rapid and significant office blood pressure reduction that was sustained through 6 months. The EnligHTN system delivers a promising therapy for the treatment of drug-resistant hypertension.

  4. Blood Pressure Response to Main Renal Artery and Combined Main Renal Artery Plus Branch Renal Denervation in Patients With Resistant Hypertension.

    Science.gov (United States)

    Fengler, Karl; Ewen, Sebastian; Höllriegel, Robert; Rommel, Karl-Philipp; Kulenthiran, Saaraaken; Lauder, Lucas; Cremers, Bodo; Schuler, Gerhard; Linke, Axel; Böhm, Michael; Mahfoud, Felix; Lurz, Philipp

    2017-08-10

    Single-electrode ablation of the main renal artery for renal sympathetic denervation showed mixed blood pressure (BP)-lowering effects. Further improvement of the technique seems crucial to optimize effectiveness of the procedure. Because sympathetic nerve fibers are closer to the lumen in the distal part of the renal artery, treatment of the distal main artery and its branches has been shown to reduce variability in treatment effects in preclinical studies and a recent randomized trial. Whether this optimized technique improves clinical outcomes remains uncertain. We report a 2-center experience of main renal artery and combined main renal artery plus branches renal denervation in patients with resistant hypertension using a multielectrode catheter. Twenty-five patients with therapy-resistant hypertension underwent renal sympathetic denervation with combined main renal artery and renal branch ablation and were compared to matched controls undergoing an ablation of the main renal artery only. BP change was assessed by ambulatory measurement at baseline and after 3 months. At baseline, BP was balanced between the groups. After 3 months, BP changed significantly in the combined ablation group (systolic/diastolic 24-hour mean and daytime mean BP -8.5±9.8/-7.0±10.7 and -9.4±9.8/-7.1±13.5 mm Hg, P renal artery and branches appears to improve BP-lowering efficacy and should be further investigated. © 2017 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.

  5. Is the failure of SYMPLICITY HTN-3 trial to meet its efficacy endpoint the "end of the road" for renal denervation?

    Science.gov (United States)

    Epstein, Murray; de Marchena, Eduardo

    2015-02-01

    Resistant hypertension is a common medical problem that is increasing with the advent of an increasingly older and heavier population. The etiology of resistant hypertension is almost always multifactorial, but the results of numerous studies indicate that renal sympathetic activation is a particularly common cause of resistance to antihypertensive treatment. Consistent with the belief in a pivotal role of renal sympathetic stimulation, there has been a growing interest in renal denervation (RDN) treatment strategies. The long-awaited results of SYMPLICITY HTN-3 study disclosed that the reduction in blood pressure by the SYMPLICITY device did not differ from that in the sham-procedure arm of the study. In the present article, we identify several factors that explain why the study failed to demonstrate any benefit from the intervention. The reasons are multifactorial and include inadequate screening at entry and frequent medication changes during the study. Additional problems include the lack of experience of many operators with the SYMPLICITY device and procedure variability, as attested to by a diminished number of ablation "quadrants." Also a factor was the inability of the first generation Medtronic device to allow four ablations to be performed simultaneously. We recommend that future RDN studies adhere to more rigorous screening procedures, and utilize newer multi-site denervation systems that facilitate four ablations simultaneously. Drug optimization should be achieved by monitoring adherence throughout the study. Nevertheless, we are optimistic about a future role of RDN. To optimize chances of success, increased efforts are necessary to identify the appropriate patients for RDN and investigators must use second and third generation denervation devices and techniques. Copyright © 2015 American Society of Hypertension. Published by Elsevier Inc. All rights reserved.

  6. Regional interaction between myocardial sympathetic denervation, contractile dysfunction, and fibrosis in heart failure with preserved ejection fraction: {sup 11}C-hydroxyephedrine PET study

    Energy Technology Data Exchange (ETDEWEB)

    Aikawa, Tadao; Naya, Masanao; Obara, Masahiko [Hokkaido University, Department of Cardiovascular Medicine, Faculty of Medicine and Graduate School of Medicine, Sapporo (Japan); Oyama-Manabe, Noriko [Hokkaido University Hospital, Department of Diagnostic and Interventional Radiology, Sapporo (Japan); Manabe, Osamu [Hokkaido University, Department of Nuclear Medicine, Faculty of Medicine and Graduate School of Medicine, Sapporo (Japan); Magota, Keiichi [Hokkaido University Hospital, Division of Medical Imaging and Technology, Sapporo (Japan); Ito, Yoichi M. [Hokkaido University, Department of Biostatistics, Faculty of Medicine and Graduate School of Medicine, Sapporo (Japan); Katoh, Chietsugu [Hokkaido University, Department of Biomedical Science and Engineering, Faculty of Health Sciences, Sapporo (Japan); Tamaki, Nagara [Kyoto Prefectural University of Medicine, Department of Radiology, Kyoto (Japan)

    2017-10-15

    This investigation aimed to identify significant predictors of regional sympathetic denervation quantified by {sup 11}C-hydroxyephedrine (HED) positron emission tomography (PET) in patients with heart failure with preserved left ventricular ejection fraction (HFpEF). Included in the study were 34 patients (age 63 ± 15 years, 23 men) with HFpEF (left ventricular ejection fraction ≥40%) and 11 age-matched volunteers without heart failure. Cardiac magnetic resonance imaging was performed to measure left ventricular size and function, and the extent of myocardial late gadolinium enhancement (LGE). {sup 11}C-HED PET was performed to quantify myocardial sympathetic innervation that was expressed as a {sup 11}C-HED retention index (RI, %/min). To identify predictors of regional {sup 11}C-HED RI in HFpEF patients, we propose a multivariate mixed-effects model for repeated measures over segments with an unstructured covariance matrix. Global {sup 11}C-HED RI was significantly lower and more heterogeneous in HFpEF patients than in volunteers (P < 0.01 for all). Regional {sup 11}C-HED RI was correlated positively with systolic wall thickening (r = 0.42, P < 0.001) and negatively with the extent of LGE (r = -0.43, P < 0.001). Segments in HFpEF patients with a large extent of LGE had the lowest regional {sup 11}C-HED RI among all segments (P < 0.001 in post hoc tests). Multivariate analysis demonstrated that systolic wall thickening and the extent of LGE were significant predictors of regional {sup 11}C-HED RI in HFpEF patients (both P ≤ 0.001). Regional sympathetic denervation was associated with contractile dysfunction and fibrotic burden in HFpEF patients, suggesting that regional sympathetic denervation may provide an integrated measure of myocardial damage in HFpEF. (orig.)

  7. 3D false color computed tomography for diagnosis and follow-up of permanent denervated human muscles submitted to home-based Functional Electrical Stimulation

    Directory of Open Access Journals (Sweden)

    Ugo Carraro

    2015-03-01

    Full Text Available This report outlines the use of a customized false-color 3D computed tomography (CT protocol for the imaging of the rectus femoris of spinal cord injury (SCI patients suffering from complete and permanent denervation, as characterized by complete Conus and Cauda Equina syndrome. This muscle imaging method elicits the progression of the syndrome from initial atrophy to eventual degeneration, as well as the extent to which patients' quadriceps could be recovered during four years of home-based functional electrical stimulation (h-b FES. Patients were pre-selected from several European hospitals and functionally tested by, and enrolled in the EU Commission Shared Cost Project RISE (Contract n. QLG5-CT-2001-02191 at the Department of Physical Medicine, Wilhelminenspital, Vienna, Austria. Denervated muscles were electrically stimulated using a custom-designed stimulator, large surface electrodes, and customized progressive stimulation settings. Spiral CT images and specialized computational tools were used to isolate the rectus femoris muscle and produce 3D and 2D reconstructions of the denervated muscles. The cross sections of the muscles were determined by 2D Color CT, while muscle volumes were reconstructed by 3D Color CT. Shape, volume, and density changes were measured over the entirety of each rectus femoris muscle. Changes in tissue composition within the muscle were visualized by associating different colors to specified Hounsfield unit (HU values for fat, (yellow: [-200; -10], loose connective tissue or atrophic muscle, (cyan: [-9; 40], and normal muscle, fascia and tendons included, (red: [41; 200]. The results from this analysis are presented as the average HU values within the rectus femoris muscle reconstruction, as well as the percentage of these tissues with respect to the total muscle volume. Results from this study demonstrate that h-b FES induces a compliance-dependent recovery of muscle volume and size of muscle fibers, as

  8. A multinational clinical approach to assessing the effectiveness of catheter-based ultrasound renal denervation: The RADIANCE-HTN and REQUIRE clinical study designs.

    Science.gov (United States)

    Mauri, Laura; Kario, Kazuomi; Basile, Jan; Daemen, Joost; Davies, Justin; Kirtane, Ajay J; Mahfoud, Felix; Schmieder, Roland E; Weber, Michael; Nanto, Shinsuke; Azizi, Michel

    2018-01-01

    Catheter-based renal denervation is a new approach to treat hypertension via modulation of the renal sympathetic nerves. Although nonrandomized and small, open-label randomized studies resulted in significant reductions in office blood pressure 6months after renal denervation with monopolar radiofrequency catheters, the first prospective, randomized, sham-controlled study (Symplicity HTN-3) failed to meet its blood pressure efficacy end point. New clinical trials with new catheters have since been designed to address the limitations of earlier studies. Accordingly, the RADIANCE-HTN and REQUIRE studies are multicenter, blinded, randomized, sham-controlled trials designed to assess the blood pressure-lowering efficacy of the ultrasound-based renal denervation system (Paradise) in patients with established hypertension either on or off antihypertensive medications, is designed to evaluate patients in 2 cohorts-SOLO and TRIO, in the United States and Europe. The SOLO cohort includes patients with essential hypertension, at low cardiovascular risk, and either controlled on 1 to 2 antihypertensive medications or uncontrolled on 0 to 2 antihypertensive medications. Patients undergo a 4-week medication washout period before randomization to renal denervation (treatment) or renal angiogram (sham). The TRIO cohort includes patients with hypertension resistant to at least 3 antihypertensive drugs including a diuretic. Patients will be stabilized on a single-pill, triple-antihypertensive-drug combination for 4weeks before randomization to treatment or sham. Reduction in daytime ambulatory systolic blood pressure (primary end point) will be assessed at 2months in both cohorts. A predefined medication escalation protocol, as needed for blood pressure control, is implemented between 2 and 6months in both cohorts by a study staff member blinded to the randomization process. At 6months, daytime ambulatory blood pressure and antihypertensive treatment score will be assessed. REQUIRE

  9. 3D False Color Computed Tomography for Diagnosis and Follow-Up of Permanent Denervated Human Muscles Submitted to Home-Based Functional Electrical Stimulation.

    Science.gov (United States)

    Carraro, Ugo; Edmunds, Kyle J; Gargiulo, Paolo

    2015-03-11

    This report outlines the use of a customized false-color 3D computed tomography (CT) protocol for the imaging of the rectus femoris of spinal cord injury (SCI) patients suffering from complete and permanent denervation, as characterized by complete Conus and Cauda Equina syndrome. This muscle imaging method elicits the progression of the syndrome from initial atrophy to eventual degeneration, as well as the extent to which patients' quadriceps could be recovered during four years of home-based functional electrical stimulation (h-b FES). Patients were pre-selected from several European hospitals and functionally tested by, and enrolled in the EU Commission Shared Cost Project RISE (Contract n. QLG5-CT-2001-02191) at the Department of Physical Medicine, Wilhelminenspital, Vienna, Austria. Denervated muscles were electrically stimulated using a custom-designed stimulator, large surface electrodes, and customized progressive stimulation settings. Spiral CT images and specialized computational tools were used to isolate the rectus femoris muscle and produce 3D and 2D reconstructions of the denervated muscles. The cross sections of the muscles were determined by 2D Color CT, while muscle volumes were reconstructed by 3D Color CT. Shape, volume, and density changes were measured over the entirety of each rectus femoris muscle. Changes in tissue composition within the muscle were visualized by associating different colors to specified Hounsfield unit (HU) values for fat, (yellow: [-200; -10]), loose connective tissue or atrophic muscle, (cyan: [-9; 40]), and normal muscle, fascia and tendons included, (red: [41; 200]). The results from this analysis are presented as the average HU values within the rectus femoris muscle reconstruction, as well as the percentage of these tissues with respect to the total muscle volume. Results from this study demonstrate that h-b FES induces a compliance-dependent recovery of muscle volume and size of muscle fibers, as evidenced by the

  10. Nonuniform cardiac denervation observed by 11C-meta-hydroxyephedrine PET in 6-OHDA-treated monkeys.

    Science.gov (United States)

    Joers, Valerie; Seneczko, Kailie; Goecks, Nichole C; Kamp, Timothy J; Hacker, Timothy A; Brunner, Kevin G; Engle, Jonathan W; Barnhart, Todd E; Nickles, R Jerome; Holden, James E; Emborg, Marina E

    2012-01-01

    Parkinson's disease presents nonmotor complications such as autonomic dysfunction that do not respond to traditional anti-parkinsonian therapies. The lack of established preclinical monkey models of Parkinson's disease with cardiac dysfunction hampers development and testing of new treatments to alleviate or prevent this feature. This study aimed to assess the feasibility of developing a model of cardiac dysautonomia in nonhuman primates and preclinical evaluations tools. Five rhesus monkeys received intravenous injections of 6-hydroxydopamine (total dose: 50 mg/kg). The animals were evaluated before and after with a battery of tests, including positron emission tomography with the norepinephrine analog (11)C-meta-hydroxyephedrine. Imaging 1 week after neurotoxin treatment revealed nearly complete loss of specific radioligand uptake. Partial progressive recovery of cardiac uptake found between 1 and 10 weeks remained stable between 10 and 14 weeks. In all five animals, examination of the pattern of uptake (using Logan plot analysis to create distribution volume maps) revealed a persistent region-specific significant loss in the inferior wall of the left ventricle at 10 (P<0.001) and 14 weeks (P<0.01) relative to the anterior wall. Blood levels of dopamine, norepinephrine (P<0.05), epinephrine, and 3,4-dihydroxyphenylacetic acid (P<0.01) were notably decreased after 6-hydroxydopamine at all time points. These results demonstrate that systemic injection of 6-hydroxydopamine in nonhuman primates creates a nonuniform but reproducible pattern of cardiac denervation as well as a persistent loss of circulating catecholamines, supporting the use of this method to further develop a monkey model of cardiac dysautonomia.

  11. Adjusted drug treatment is superior to renal sympathetic denervation in patients with true treatment-resistant hypertension.

    Science.gov (United States)

    Fadl Elmula, Fadl Elmula M; Hoffmann, Pavel; Larstorp, Anne C; Fossum, Eigil; Brekke, Magne; Kjeldsen, Sverre E; Gjønnæss, Eyvind; Hjørnholm, Ulla; Kjaer, Vibeke N; Rostrup, Morten; Os, Ingrid; Stenehjem, Aud; Høieggen, Aud

    2014-05-01

    We aimed to investigate for the first time the blood pressure (BP)-lowering effect of renal sympathetic denervation (RDN) versus clinically adjusted drug treatment in true treatment-resistant hypertension (TRH) after excluding patients with confounding poor drug adherence. Patients with apparent TRH (n=65) were referred for RDN, and those with secondary and spurious hypertension (n=26) were excluded. TRH was defined as office systolic BP (SBP) >140 mm Hg, despite maximally tolerated doses of ≥3 antihypertensive drugs including a diuretic. In addition, ambulatory daytime SBP >135 mm Hg after witnessed intake of antihypertensive drugs was required, after which 20 patients had normalized BP and were excluded. Patients with true TRH were randomized and underwent RDN (n=9) performed with Symplicity Catheter System versus clinically adjusted drug treatment (n=10). The study was stopped early for ethical reasons because RDN had uncertain BP-lowering effect. Office SBP and diastolic BP in the drug-adjusted group changed from 160±14/88±13 mm Hg (±SD) at baseline to 132±10/77±8 mm Hg at 6 months (P<0.0005 and P=0.02, SBP and diastolic BP, respectively) and in the RDN group from 156±13/91±15 to 148±7/89±8 mm Hg (P=0.42 and P=0.48, SBP and diastolic BP, respectively). SBP and diastolic BP were significantly lower in the drug-adjusted group at 6 months (P=0.002 and P=0.004, respectively), and absolute changes in SBP were larger in the drug-adjusted group (P=0.008). Ambulatory BPs changed in parallel to office BPs. Our data suggest that adjusted drug treatment has superior BP lowering effects compared with RDN in patients with true TRH. Clinical Trial Registration- URL: http://www.clinicaltrials.gov. Unique identifier: NCT01673516.

  12. The effect of renal denervation on kidney oxygenation as determined by BOLD MRI in patients with hypertension

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    Vink, E.E.; Boer, A.; Blankestijn, P.J. [University Medical Center Utrecht, Department of Nephrology, P.O. Box 85500, GA, Utrecht (Netherlands); Verloop, W.L.; Voskuil, M. [University Medical Center Utrecht, Department of Cardiology, Utrecht (Netherlands); Spiering, W.; Leiner, T. [University Medical Center Utrecht, Department of Vascular Medicine, Utrecht (Netherlands); Vonken, E.; Hoogduin, J.M. [University Medical Center Utrecht, Department of Radiology, Utrecht (Netherlands); Bots, M.L. [University Medical Center Utrecht, Julius Center for Health Sciences and Primary Care, Utrecht (Netherlands)

    2015-07-15

    Renal denervation (RDN) is a promising therapy for resistant hypertension. RDN is assumed to decrease sympathetic activity. Consequently, RDN can potentially increase renal oxygenation. Blood oxygen level-dependent MRI (BOLD-MRI) provides a non-invasive tool to determine renal oxygenation in humans. The aim of the current study was to investigate the effect of RDN on renal oxygenation as determined by BOLD-MRI. Patients with resistant hypertension or the inability to follow a stable drug regimen due to unacceptable side effects were included. BOLD-MRI was performed before and 12 months after RDN. Twenty-seven patients were imaged on 3 T and 19 on 1.5 T clinical MRI systems. Fifty-four patients were included, 46 patients (23 men, mean age 57 years) completed the study. Mean 24-h BP changed from 163(±20)/98(±14) mmHg to 154(±22)/92(±13) mmHg (p = 0.001 and p < 0.001). eGFR did not change after RDN [77(±18) vs. 79(±20) mL/min/1.73 m{sup 2}; p = 0.13]. RDN did not affect renal oxygenation [1.5 T: cortical R2*: 12.5(±0.9) vs. 12.5(±0.9), p = 0.94; medullary R2*: 19.6(±1.7) vs. 19.3(1.4), p = 0.40; 3 T: cortical R2*: 18.1(±0.8) vs. 17.8(±1.2), p = 0.47; medullary R2*: 27.4(±1.9) vs. 26.7(±1.8), p = 0.19]. The current study shows that RDN does not lead to changes in renal oxygenation 1 year after RDN as determined by BOLD-MRI. (orig.)

  13. Circumferential targeted renal sympathetic nerve denervation with preservation of the renal arterial wall using intra-luminal ultrasound

    Science.gov (United States)

    Roth, Austin; Coleman, Leslie; Sakakura, Kenichi; Ladich, Elena; Virmani, Renu

    2015-03-01

    An intra-luminal ultrasound catheter system (ReCor Medical's Paradise System) has been developed to provide circumferential denervation of the renal sympathetic nerves, while preserving the renal arterial intimal and medial layers, in order to treat hypertension. The Paradise System features a cylindrical non-focused ultrasound transducer centered within a balloon that circulates cooling fluid and that outputs a uniform circumferential energy pattern designed to ablate tissues located 1-6 mm from the arterial wall and protect tissues within 1 mm. RF power and cooling flow rate are controlled by the Paradise Generator which can energize transducers in the 8.5-9.5 MHz frequency range. Computer simulations and tissue-mimicking phantom models were used to develop the proper power, cooling flow rate and sonication duration settings to provide consistent tissue ablation for renal arteries ranging from 5-8 mm in diameter. The modulation of these three parameters allows for control over the near-field (border of lesion closest to arterial wall) and far-field (border of lesion farthest from arterial wall, consisting of the adventitial and peri-adventitial spaces) depths of the tissue lesion formed by the absorption of ultrasonic energy and conduction of heat. Porcine studies have confirmed the safety (protected intimal and medial layers) and effectiveness (ablation of 1-6 mm region) of the system and provided near-field and far-field depth data to correlate with bench and computer simulation models. The safety and effectiveness of the Paradise System, developed through computer model, bench and in vivo studies, has been demonstrated in human clinical studies.

  14. Role of Adding Spironolactone and Renal Denervation in True Resistant Hypertension: One-Year Outcomes of Randomized PRAGUE-15 Study.

    Science.gov (United States)

    Rosa, Ján; Widimský, Petr; Waldauf, Petr; Lambert, Lukáš; Zelinka, Tomáš; Táborský, Miloš; Branny, Marian; Toušek, Petr; Petrák, Ondřej; Čurila, Karol; Bednář, František; Holaj, Robert; Štrauch, Branislav; Václavík, Jan; Nykl, Igor; Krátká, Zuzana; Kociánová, Eva; Jiravský, Otakar; Rappová, Gabriela; Indra, Tomáš; Widimský, Jiří

    2016-02-01

    This randomized, multicenter study compared the relative efficacy of renal denervation (RDN) versus pharmacotherapy alone in patients with true resistant hypertension and assessed the effect of spironolactone addition. We present here the 12-month data. A total of 106 patients with true resistant hypertension were enrolled in this study: 52 patients were randomized to RDN and 54 patients to the spironolactone addition, with baseline systolic blood pressure of 159±17 and 155±17 mm Hg and average number of drugs 5.1 and 5.4, respectively. Twelve-month results are available in 101 patients. The intention-to-treat analysis found a comparable mean 24-hour systolic blood pressure decline of 6.4 mm Hg, P=0.001 in RDN versus 8.2 mm Hg, P=0.002 in the pharmacotherapy group. Per-protocol analysis revealed a significant difference of 24-hour systolic blood pressure decline between complete RDN (6.3 mm Hg, P=0.004) and the subgroup where spironolactone was added, and this continued within the 12 months (15 mm Hg, P= 0.003). Renal artery computed tomography angiograms before and after 1 year post-RDN did not reveal any relevant changes. This study shows that over a period of 12 months, RDN is safe, with no serious side effects and no major changes in the renal arteries. RDN in the settings of true resistant hypertension with confirmed compliance is not superior to intensified pharmacological treatment. Spironolactone addition (if tolerated) seems to be more effective in blood pressure reduction. © 2015 American Heart Association, Inc.

  15. Account for Clinical Heterogeneity in Assessment of Catheter-based Renal Denervation among Resistant Hypertension Patients: Subgroup Meta-analysis.

    Science.gov (United States)

    Chen, Xiao-Han; Kim, Sehee; Zeng, Xiao-Xi; Chen, Zhi-Bing; Cui, Tian-Lei; Hu, Zhang-Xue; Li, Yi; Fu, Ping

    2017-07-05

    Catheter-based renal denervation (RDN) is a novel treatment for resistant hypertension (RH). A recent meta-analysis reported that RDN did not significantly reduce blood pressure (BP) based on the pooled effects with mild to severe heterogeneity. The aim of the present study was to identify and reduce clinical sources of heterogeneity and reassess the safety and efficacy of RDN within the identified homogeneous subpopulations. This was a meta-analysis of 9 randomized clinical trials (RCTs) among patients with RH up to June 2016. Sensitivity analyses and subgroup analyses were extensively conducted by baseline systolic blood pressure (SBP) level, antihypertensive medication change rates, and coronary heart disease (CHD). In all patients with RH, no statistical differences were found in mortality, severe cardiovascular events rate, and changes in 24-h SBP and office SBP at 6 and 12 months. However, subgroup analyses showed significant differences between the RDN and control groups. In the subpopulations with baseline 24-h SBP ≥155 mmHg (1 mmHg = 0.133 kPa) and the infrequently changed medication, the use of RDN resulted in a significant reduction in 24-h SBP level at 6 months (P = 0.100 and P= 0.009, respectively). Subgrouping RCTs with a higher prevalent CHD in control showed that the control treatment was significantly better than RDN in office SBP reduction at 6 months (P < 0.001). In all patients with RH, the catheter-based RDN is not more effective in lowering ambulatory or office BP than an optimized antihypertensive drug treatment at 6 and 12 months. However, among RH patients with higher baseline SBP, RDN might be more effective in reducing SBP.

  16. Renal denervation for improving outcomes of catheter ablation in patients with atrial fibrillation and hypertension: early experience.

    Science.gov (United States)

    Pokushalov, Evgeny; Romanov, Alexander; Katritsis, Demosthenes G; Artyomenko, Sergey; Bayramova, Sevda; Losik, Denis; Baranova, Vera; Karaskov, Alexander; Steinberg, Jonathan S

    2014-07-01

    The potential role of renal denervation (RD) in patients with AF and less severe hypertension is unknown. The purpose of this study was to assess the potential role of RD as an adjunct to pulmonary vein isolation (PVI) in patients with atrial fibrillation (AF) and moderate resistant or severe resistant hypertension. The data for this study were obtained from 2 different prospective randomized studies, analyzed by meta-analysis. Patients with paroxysmal AF or persistent AF and moderate resistant hypertension (office blood pressure BP ≥140/90 mm Hg and hypertension (≥160/100 mm Hg; second study; n = 38) were randomized to PVI or PVI with RD. At 12 months, 26 of the 41 PVI with RD patients (63%) were AF-free vs 16 of the 39 patients (41%) in the PVI-only group (P = .014). In patients with severe hypertension, 11 of the 18 PVI with RD patients (61%) vs 5 of the 18 PVI-only patients (28%) were AF-free (P = .03). For moderate hypertension, the differences were less dramatic: 11 of 21 (52%) vs 15 of 23 (65%) when RD added (P = .19). The superior efficacy of adding RD was most apparent in persistent AF and severe hypertension (hazard ratio 0.25, confidence interval 0.09-0.72, P = .01). Duration of the procedure and fluoroscopy were nonsignificantly longer in the RD group. RD may improve the results of PVI in patients with persistent AF and/or severe resistant hypertension. Copyright © 2014 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.

  17. Effects of catheter-based renal denervation on cardiac sympathetic activity and innervation in patients with resistant hypertension.

    Science.gov (United States)

    Donazzan, Luca; Mahfoud, Felix; Ewen, Sebastian; Ukena, Christian; Cremers, Bodo; Kirsch, Carl-Martin; Hellwig, Dirk; Eweiwi, Tareq; Ezziddin, Samer; Esler, Murray; Böhm, Michael

    2016-04-01

    To investigate, whether renal denervation (RDN) has a direct effect on cardiac sympathetic activity and innervation density. RDN demonstrated its efficacy not only in reducing blood pressure (BP) in certain patients, but also in decreasing cardiac hypertrophy and arrhythmias. These pleiotropic effects occur partly independent from the observed BP reduction. Eleven patients with resistant hypertension (mean office systolic BP 180 ± 18 mmHg, mean antihypertensive medications 6.0 ± 1.5) underwent I-123-mIBG scintigraphy to exclude pheochromocytoma. We measured cardiac sympathetic innervation and activity before and 9 months after RDN. Cardiac sympathetic innervation was assessed by heart to mediastinum ratio (H/M) and sympathetic activity by wash out ratio (WOR). Effects on office BP, 24 h ambulatory BP monitoring, were documented. Office systolic BP and mean ambulatory systolic BP were significantly reduced from 180 to 141 mmHg (p = 0.006) and from 149 to 129 mmHg (p = 0.014), respectively. Cardiac innervation remained unchanged before and after RDN (H/M 2.5 ± 0.5 versus 2.6 ± 0.4, p = 0.285). Cardiac sympathetic activity was significantly reduced by 67 % (WOR decreased from 24.1 ± 12.7 to 7.9 ± 25.3 %, p = 0.047). Both, responders and non-responders experienced a reduction of cardiac sympathetic activity. RDN significantly reduced cardiac sympathetic activity thereby demonstrating a direct effect on the heart. These changes occurred independently from BP effects and provide a pathophysiological basis for studies, investigating the potential effect of RDN on arrhythmias and heart failure.

  18. Renal denervation in comparison with intensified pharmacotherapy in true resistant hypertension: 2-year outcomes of randomized PRAGUE-15 study.

    Science.gov (United States)

    Rosa, Ján; Widimský, Petr; Waldauf, Petr; Zelinka, Tomáš; Petrák, Ondřej; Táborský, Miloš; Branny, Marian; Toušek, Petr; Čurila, Karol; Lambert, Lukáš; Bednář, František; Holaj, Robert; Štrauch, Branislav; Václavík, Jan; Kociánová, Eva; Nykl, Igor; Jiravský, Otakar; Rappová, Gabriela; Indra, Tomáš; Krátká, Zuzana; Widimský, Jiří

    2017-05-01

    The randomized, multicentre study compared the efficacy of renal denervation (RDN) versus spironolactone addition in patients with true resistant hypertension. We present the 24-month data. A total of 106 patients with true resistant hypertension were enrolled in this study: 52 patients were randomized to RDN and 54 patients to the spironolactone addition, with baseline SBP of 159 ± 17 and 155 ± 17 mmHg and average number of drugs 5.1 and 5.4, respectively. Two-year data are available in 86 patients. Spironolactone addition, as crossover after 1 year, was performed in 23 patients after RDN, and spironolactone addition followed by RDN was performed in five patients. Similar and comparable reduction of 24-h SBP after RDN or spironolactone addition after randomization was observed, 9.1 mmHg (P = 0.001) and 10.9 mmHg (P = 0.001), respectively. Similar decrease of office blood pressure (BP) was observed, 17.7 mmHg (P efficacy of spironolactone addition in 24-h SBP and office SBP reduction than RDN (3.7 mmHg, P = 0.27 and 4.6 mmHg, P = 0.28 in favour of spironolactone addition, respectively). Meanwhile, the number of antihypertensive drugs was significantly increased after spironolactone addition (+0.7, P = 0.001). In the settings of true resistant hypertension, spironolactone addition (if tolerated) seems to be of better efficacy than RDN in BP reduction over a period of 24 months. However, by contrast to the 12-month results, BP changes were not significantly greater.

  19. The morphological substrate for Renal Denervation: Nerve distribution patterns and parasympathetic nerves. A post-mortem histological study.

    Science.gov (United States)

    van Amsterdam, Wouter A C; Blankestijn, Peter J; Goldschmeding, Roel; Bleys, Ronald L A W

    2016-03-01

    Renal Denervation as a possible treatment for hypertension has been studied extensively, but knowledge on the distribution of nerves surrounding the renal artery is still incomplete. While sympathetic and sensory nerves have been demonstrated, there is no mention of the presence of parasympathetic nerve fibers. To provide a description of the distribution patterns of the renal nerves in man, and, in addition, provide a detailed representation of the relative contribution of the sympathetic, parasympathetic and afferent divisions of the autonomic nervous system. Renal arteries of human cadavers were each divided into four longitudinal segments and immunohistochemically stained with specific markers for afferent, parasympathetic and sympathetic nerves. Nerve fibers were semi-automatically quantified by computerized image analysis, and expressed as cross-sectional area relative to the distance to the lumen. A total of 3372 nerve segments were identified in 8 arteries of 7 cadavers. Sympathetic, parasympathetic and afferent nerves contributed for 73.5% (95% CI: 65.4-81.5%), 17.9% (10.7-25.1%) and 8.7% (5.0-12.3%) of the total cross-sectional nerve area, respectively. Nerves are closer to the lumen in more distal segments and larger bundles that presumably innervate the kidney lie at 1-3.5mm distance from the lumen. The tissue-penetration depth of the ablation required to destroy 50% of the nerve fibers is 2.37 mm in the proximal segment and 1.78 mm in the most distal segments. Sympathetic, parasympathetic and afferent nerves exist in the vicinity of the renal artery. The results warrant further investigation of the role of the parasympathetic nervous system on renal physiology, and may contribute to refinement of the procedure by focusing the ablation on the most distal segment. Copyright © 2015 Elsevier GmbH. All rights reserved.

  20. Nonuniform cardiac denervation observed by 11C-meta-hydroxyephedrine PET in 6-OHDA-treated monkeys.

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    Valerie Joers

    Full Text Available Parkinson's disease presents nonmotor complications such as autonomic dysfunction that do not respond to traditional anti-parkinsonian therapies. The lack of established preclinical monkey models of Parkinson's disease with cardiac dysfunction hampers development and testing of new treatments to alleviate or prevent this feature. This study aimed to assess the feasibility of developing a model of cardiac dysautonomia in nonhuman primates and preclinical evaluations tools. Five rhesus monkeys received intravenous injections of 6-hydroxydopamine (total dose: 50 mg/kg. The animals were evaluated before and after with a battery of tests, including positron emission tomography with the norepinephrine analog (11C-meta-hydroxyephedrine. Imaging 1 week after neurotoxin treatment revealed nearly complete loss of specific radioligand uptake. Partial progressive recovery of cardiac uptake found between 1 and 10 weeks remained stable between 10 and 14 weeks. In all five animals, examination of the pattern of uptake (using Logan plot analysis to create distribution volume maps revealed a persistent region-specific significant loss in the inferior wall of the left ventricle at 10 (P<0.001 and 14 weeks (P<0.01 relative to the anterior wall. Blood levels of dopamine, norepinephrine (P<0.05, epinephrine, and 3,4-dihydroxyphenylacetic acid (P<0.01 were notably decreased after 6-hydroxydopamine at all time points. These results demonstrate that systemic injection of 6-hydroxydopamine in nonhuman primates creates a nonuniform but reproducible pattern of cardiac denervation as well as a persistent loss of circulating catecholamines, supporting the use of this method to further develop a monkey model of cardiac dysautonomia.

  1. Effects of percutaneous renal sympathetic denervation on cardiac function and exercise tolerance in patients with chronic heart failure.

    Science.gov (United States)

    Gao, Jun-Qing; Xie, Yun; Yang, Wei; Zheng, Jian-Pu; Liu, Zong-Jun

    2017-01-01

    Sympathetic hyperactivity, a vital factor in the genesis and development of heart failure (HF), has been reported to be effectively reduced by percutaneous renal denervation (RDN), which may play an important role in HF treatment. To determine the effects of percutaneous RDN on cardiac function in patients with chronic HF (CHF). Fourteen patients (mean age 69.6 years; ejection fraction [EF] <45%) with CHF received bilateral RDN. Adverse cardiac events, blood pressure (BP), and biochemical parameters were assessed before and six months after percutaneous operation. Patients also underwent echocardiographic assessment of cardiac function and 6-min walk test before and at six months after percutaneous operation. The distance achieved by the 14 patients in the 6-min walk test increased significantly from 152.9±38.0 m before RDN to 334.3±94.4 m at six months after RDN (p<0.001), while EF increased from 36.0±4.1% to 43.8±7.9% (p=0.003) on echocardiography. No RDN-related complications were observed during the follow-up period. In 6-month follow-up, systolic BP decreased from 138.6±22.1 mmHg to 123.2±10.5 mmHg (p=0.026) and diastolic BP from 81.1±11.3 mmHg to 72.9±7.5 mmHg (p=0.032). Creatinine levels did not change significantly (1.3±0.65 mg/dl to 1.2±0.5 mg/dl, p=0.8856). RDN is potentially an effective technique for the treatment of severe HF that can significantly increase EF and improve exercise tolerance. Copyright © 2016 Sociedade Portuguesa de Cardiologia. Publicado por Elsevier España, S.L.U. All rights reserved.

  2. Renal denervation improves cardiac function in rats with chronic heart failure: Effects on expression of β-adrenoceptors

    Science.gov (United States)

    Zheng, Hong; Liu, Xuefei; Sharma, Neeru M.

    2016-01-01

    Chronic activation of the sympathetic drive contributes to cardiac remodeling and dysfunction during chronic heart failure (HF). The present study was undertaken to assess whether renal denervation (RDN) would abrogate the sympathoexcitation in HF and ameliorate the adrenergic dysfunction and cardiac damage. Ligation of the left coronary artery was used to induce HF in Sprague-Dawley rats. Four weeks after surgery, RDN was performed, 1 wk before the final measurements. At the end of the protocol, cardiac function was assessed by measuring ventricular hemodynamics. Rats with HF had an average infarct area >30% of the left ventricle and left ventricular end-diastolic pressure (LVEDP) >20 mmHg. β1- and β2-adrenoceptor proteins in the left ventricle were reduced by 37 and 49%, respectively, in the rats with HF. RDN lowered elevated levels of urinary excretion of norepinephrine and brain natriuretic peptide levels in the hearts of rats with HF. RDN also decreased LVEDP to 10 mmHg and improved basal dP/dt to within the normal range in rats with HF. RDN blunted loss of β1-adrenoceptor (by 47%) and β2-adrenoceptor (by 100%) protein expression and improved isoproterenol (0.5 μg/kg)-induced increase in +dP/dt (by 71%) and −dP/dt (by 62%) in rats with HF. RDN also attenuated the increase in collagen 1 expression in the left ventricles of rats with HF. These findings demonstrate that RDN initiated in chronic HF condition improves cardiac function mediated by adrenergic agonist and blunts β-adrenoceptor expression loss, providing mechanistic insights for RDN-induced improvements in cardiac function in the HF condition. PMID:27288440

  3. CT-guided injection of botulinic toxin for percutaneous therapy of piriformis muscle syndrome with preliminary MRI results about denervative process

    Energy Technology Data Exchange (ETDEWEB)

    Fanucci, E.; Masala, S.; Sodani, G.; Varrucciu, V.; Romagnoli, A.; Squillaci, E.; Simonetti, G. [Dept. of Radiology, Univ. of Rome (Italy)

    2001-12-01

    Piriformis muscle syndrome (PMS) is a cause of sciatica, leg or buttock pain and disability. The pain is usually increased by muscular contraction, palpation or prolonged sitting. The aim of our paper was to evaluate the feasibility of CT-guided percutaneous botulinic toxin (BTX) injection for the purpose of PMS treatment. Thirty patients suffering from PMS, suspected with clinical and electrophysiological criteria, after imaging examinations excluding other causes of sciatic pain, resulted positive at the lidocaine test and were treated by intramuscular injection of BTX type A under CT guidance. The follow-up (12 months) was performed with clinical examination in all cases and with MR 3 months after the procedure in 9 patients to evaluate the denervative process entity of the treated muscle. In 26 cases relief of symptoms was obtained after 5-7 days. In 4 patients an insufficient relief of pain justified a second percutaneous treatment which was clinically successful. No complications or side effects were recorded after BTX injection. The MR examination showed a signal intensity change of the treated muscle in 7 patients due to the denervative process of PM, whereas in the remaining 2 cases only an atrophy of the treated muscle was detected. Larger series are necessary to confirm these MRI preliminary results. The CT-guided BTX injection in the PMS is an emergent and feasible technique that obtains an excellent local therapeutic effect without risk of imprecise inoculation. (orig.)

  4. [Renal denervation for the treatment of resistant hypertension: definition, patient selection and description of the procedure. 2012 Position paper of the Italian Society of Hypertension].

    Science.gov (United States)

    Volpe, Massimo; Agabiti-Rosei, Enrico; Ambrosioni, Ettore; Cottone, Santina; Cuspidi, Cesare; Borghi, Claudio; De Luca, Nicola; Fallo, Francesco; Ferri, Claudio; Mancia, Giuseppe; Morganti, Alberto; Muiesan, Maria Lorenza; Sarzani, Riccardo; Sechi, Leonardo; Tocci, Giuliano; Virdis, Agostino

    2012-12-01

    Hypertension is responsible for a relevant burden of cardiovascular morbidity and mortality worldwide. Although several appropriate and integrated pharmacological strategies are available, blood pressure control still remains largely unsatisfactory. Failure to achieve effective blood pressure control in treated hypertensive patients may have a substantial impact on overall cardiovascular risk, since it significantly increases the risk of both macrovascular and microvascular complications. Hypertension is arbitrarily defined as "resistant" or "refractory" when recommended blood pressure goals (clinic blood pressure hypertension has recently become available. Renal sympathetic denervation is a minimally invasive procedure performed via femoral access that uses radiofrequency catheter ablation to disable renal sympathetic afferent and efferent nerves. It results in isolation of renal parenchymal and juxtaglomerular cells from the abnormal enhancement of renal adrenergic nerve activity. The present position paper of the Italian Society of Hypertension provides a diagnostic and therapeutic approach to the early identification and effective clinical management of patients with resistant hypertension, who may be candidates for renal denervation. These indications may have important implications not only from a clinical viewpoint but also from an economic perspective. The accurate identification of patients with resistant hypertension and the appropriate selection of patients eligible for this procedure may help improve blood pressure control and reduce the risk of cardiovascular and cerebrovascular complications in these patients.

  5. Randomized comparison of renal denervation versus intensified pharmacotherapy including spironolactone in true-resistant hypertension: six-month results from the Prague-15 study.

    Science.gov (United States)

    Rosa, Ján; Widimský, Petr; Toušek, Petr; Petrák, Ondřej; Čurila, Karol; Waldauf, Petr; Bednář, František; Zelinka, Tomáš; Holaj, Robert; Štrauch, Branislav; Šomlóová, Zuzana; Táborský, Miloš; Václavík, Jan; Kociánová, Eva; Branny, Marian; Nykl, Igor; Jiravský, Otakar; Widimský, Jiří

    2015-02-01

    This prospective, randomized, open-label multicenter trial evaluated the efficacy of catheter-based renal denervation (Symplicity, Medtronic) versus intensified pharmacological treatment including spironolactone (if tolerated) in patients with true-resistant hypertension. This was confirmed by 24-hour ambulatory blood pressure monitoring after excluding secondary hypertension and confirmation of adherence to therapy by measurement of plasma antihypertensive drug levels before enrollment. One-hundred six patients were randomized to renal denervation (n=52), or intensified pharmacological treatment (n=54) with baseline systolic blood pressure of 159±17 and 155±17 mm Hg and average number of drugs 5.1 and 5.4, respectively. A significant reduction in 24-hour average systolic blood pressure after 6 months (-8.6 [95% cofidence interval: -11.8, -5.3] mm Hg; Pblood pressure (-12.4 [95% cofidence interval: -17.0, -7.8] mm Hg; Pblood pressure comparable with intensified pharmacotherapy. © 2014 American Heart Association, Inc.

  6. Renal sympathetic denervation using an externally irrigated radiofrequency ablation catheter for treatment of resistant hypertension - Acute safety and short term efficacy.

    Science.gov (United States)

    Yalagudri, Sachin; Raju, Narayana; Das, Bharati; Daware, Ashwin; Maiya, Shreesha; Jothiraj, Kannan; Ravikishore, A G

    2015-01-01

    This study was conducted to assess the acute safety and short term efficacy of renal sympathetic denervation (RSDN) using solid tip radiofrequency ablation (RFA) catheter and saline irrigation through the renal guiding catheter to achieve effective denervation. RSDN using a specialized solid-tip RFA catheter has recently been demonstrated to safely reduce systemic blood pressure in patients with refractory hypertension, the limitation being inadequate power delivery in renal arteries. So, we used solid-tip RFA catheter along with saline irrigation for RSDN. Nine patients with resistant hypertension underwent CT and conventional renal angiography, followed by bilateral or unilateral RSDN using 5F RFA catheter with saline irrigation through renal guiding catheter. Repeat renal angiography was performed at the end of the procedure. In all patients, pre- and post-procedure serum creatinine was measured. Over 1-month period: 1) the systolic/diastolic blood pressure decreased by -57 ± 20/-25 ± 7.5 mm Hg; 2) all patients experienced a decrease in systolic blood pressure of at least -36 mm Hg (range 36-98 mm Hg); 3) there was no evidence of renal artery injury immediate post-procedure. There was no significant change in serum creatinine level. This data shows the acute procedural safety and short term efficacy of RSDN using modified externally irrigated solid tip RFA catheter. Copyright © 2015 Cardiological Society of India. Published by Elsevier B.V. All rights reserved.

  7. Renal denervation with a percutaneous bipolar radiofrequency balloon catheter in patients with resistant hypertension: 6-month results from the REDUCE-HTN clinical study.

    Science.gov (United States)

    Sievert, Horst; Schofer, Joachim; Ormiston, John; Hoppe, Uta C; Meredith, Ian T; Walters, Darren L; Azizi, Michel; Diaz-Cartelle, Juan; Cohen-Mazor, Meital

    2015-02-01

    To evaluate the safety and efficacy of the balloon-based bipolar Vessix Renal Denervation System in treating patients with resistant hypertension. In this prospective, multicentre, single-arm study, 146 patients (age 58.6±10.5 years; 61% men) with office systolic blood pressure (BP) ≥160 mmHg despite ≥3 antihypertensive medications at maximally tolerated doses were treated with the Vessix System. Efficacy endpoints were reductions in office and 24-hour ambulatory systolic and diastolic BPs at six months. Acute and long-term safety, with a focus on the renal artery and estimated glomerular filtration rate (eGFR), were assessed. Baseline office and ambulatory BPs were 182.4±18.4/100.2±14.0 mmHg and 153.0±15.1/87.5±13.2 mmHg, respectively. No acute renal artery injury requiring intervention or serious periprocedural cardiovascular events occurred. At six months, office BP was reduced by 24.7±22.1/10.3±12.7 mmHg (prenal artery stenosis which required stenting. Mean eGFR remained stable. Renal artery denervation with the Vessix System reduced both office and ambulatory BP at six months in patients with resistant hypertension. Renal artery safety and renal function results are favourable.

  8. Catheter-based renal denervation in patients with uncontrolled hypertension in the absence of antihypertensive medications (SPYRAL HTN-OFF MED): a randomised, sham-controlled, proof-of-concept trial.

    Science.gov (United States)

    Townsend, Raymond R; Mahfoud, Felix; Kandzari, David E; Kario, Kazuomi; Pocock, Stuart; Weber, Michael A; Ewen, Sebastian; Tsioufis, Konstantinos; Tousoulis, Dimitrios; Sharp, Andrew S P; Watkinson, Anthony F; Schmieder, Roland E; Schmid, Axel; Choi, James W; East, Cara; Walton, Anthony; Hopper, Ingrid; Cohen, Debbie L; Wilensky, Robert; Lee, David P; Ma, Adrian; Devireddy, Chandan M; Lea, Janice P; Lurz, Philipp C; Fengler, Karl; Davies, Justin; Chapman, Neil; Cohen, Sidney A; DeBruin, Vanessa; Fahy, Martin; Jones, Denise E; Rothman, Martin; Böhm, Michael

    2017-11-11

    Previous randomised renal denervation studies did not show consistent efficacy in reducing blood pressure. The objective of our study was to evaluate the effect of renal denervation on blood pressure in the absence of antihypertensive medications. SPYRAL HTN-OFF MED was a multicentre, international, single-blind, randomised, sham-controlled, proof-of-concept trial. Patients were enrolled at 21 centres in the USA, Europe, Japan, and Australia. Eligible patients were drug-naive or discontinued their antihypertensive medications. Patients with an office systolic blood pressure (SBP) of 150 mm Hg or greater and less than 180 mm Hg, office diastolic blood pressure (DBP) of 90 mm Hg or greater, and a mean 24-h ambulatory SBP of 140 mm Hg or greater and less than 170 mm Hg at second screening underwent renal angiography and were randomly assigned to renal denervation or sham control. Patients, caregivers, and those assessing blood pressure were blinded to randomisation assignments. The primary endpoint, change in 24-h blood pressure at 3 months, was compared between groups. Drug surveillance was done to ensure patient compliance with absence of antihypertensive medication. The primary analysis was done in the intention-to-treat population. Safety events were assessed at 3 months. This study is registered with ClinicalTrials.gov, number NCT02439749. Between June 25, 2015, and Jan 30, 2017, 353 patients were screened. 80 patients were randomly assigned to renal denervation (n=38) or sham control (n=42) and followed up for 3 months. Office and 24-h ambulatory blood pressure decreased significantly from baseline to 3 months in the renal denervation group: 24-h SBP -5·5 mm Hg (95% CI -9·1 to -2·0; p=0·0031), 24-h DBP -4·8 mm Hg (-7·0 to -2·6; prenal denervation for 3-month change in both office and 24-h blood pressure from baseline: 24-h SBP -5·0 mm Hg (95% CI -9·9 to -0·2; p=0·0414), 24-h DBP -4·4 mm Hg (-7·2 to -1·6; p=0·0024), office SBP -7·7 mm Hg (-14·0

  9. [The study of chronic partial denervation and quality of life in patients with motor neuron disease treated with semax].

    Science.gov (United States)

    Serdiuk, A V; Levitskiĭ, G N; Miasoedov, N F; Skvortsova, V I

    2007-01-01

    The study of chronic partial denervation (CPD) and quality of life was carried out in 27 patients with definite, probable and possible diagnosis of motor neuron disease (MND) treated with semax (1% solution). The needle electromyography (EMG) was performed thrice with short-term 2 month interval (60 days before enrollment and on day 1 and day 48 of the study) in three muscles on bulbar, cervical and lumbosacral levels on the less affected side. According to Revised El-Escorial Criteria (1998) the needle EMG for diagnostic purposes was also performed in two muscles on the cervical and lumbosacral levels on the more affected side along with stimulation electroneuronmyography of motor and sensory fibers of the peripheral nerves of neck, upper and lower extremities. The open-label clinical trial of Semax (1% solution) was conducted in sequential groups of patients. The drug was administered intranasally in two 10-day-long courses with 2-weeks break in daily dose of 12 mg. Sixty days before enrollment, and on days 1, 10, 24, 34 and 48, patients were assessed by the Norris ALS, the ALS Functioning Rating Scale and the ALSAQ-40 quality of life in the ALS scale. It was shown that CPD on the early as well as on the late stages was characterized by forward-backward, but not unidirectional course, that did not allow to recommend the follow-up needle EMG with short-term interval for evaluation of drug efficacy monitoring. Early CPD stages were characterized by forward-backwards fluctuations reflecting the compensatory reinnervation process (a phenomenon of exchange of muscle fibers, more rational in view of reinnervation, between adjacent motor units) whereas on the late CPD stages these forward-backwards CPD fluctuations reflected the processes of progressive deterioration of muscle fibers and secondary demyelination of large motor axons. Semax (1% solution) does not influence either the course of CPD or the dynamics of clinical estimates, in particular the terms of ensuing

  10. Spironolactone versus sympathetic renal denervation to treat true resistant hypertension: results from the DENERVHTA study – a randomized controlled trial

    Science.gov (United States)

    Oliveras, Anna; Armario, Pedro; Clarà, Albert; Sans-Atxer, Laia; Vázquez, Susana; Pascual, Julio; De la Sierra, Alejandro

    2016-01-01

    Objective: Both renal denervation (RDN) and spironolactone have been proposed for the treatment of resistant hypertension. However, they have not been compared in a randomized clinical trial. We aimed to compare the efficacy of spironolactone versus RDN in patients with resistant hypertension. Methods: A total of 24 patients with office SBP at least 150 mmHg and 24-h SBP at least 140 mmHg despite receiving at least three full-dose antihypertensive drugs, one a diuretic, but without aldosterone antagonists, were randomized to receive RDN or spironolactone (50 mg) as add-on therapy. Primary endpoint was change in 24-h SBP at 6 months. Comparisons between treatment groups were performed using generalized linear models adjusted by age, sex, and baseline values. Results: Spironolactone was more effective than RDN in reducing 24-h SBP and 24-h DBP: mean baseline-adjusted differences between the two groups were −17.9 mmHg (95%CI −30.9 to −4.9); P = 0.010 and −6.6 mmHg (95%CI −12.9 to −0.3); P = 0.041, for 24-h SBP and 24-h DBP, respectively. As regards changes in office blood pressure, mean baseline-adjusted differences between the two groups were −12.1 mmHg (95%CI −29.1 to 5.1); P = 0.158 and of −5.3 mmHg (95%CI −16.3 to 5.8); P = 0.332, for office SBP and office DBP, respectively. Otherwise, the decrease of estimated glomerular filtration rate was greater in the spironolactone group; mean baseline-adjusted difference between the two groups was −10.7 ml/min per 1.73 m2 (95%CI −20.1 to −1.4); P = 0.027. Conclusion: We conclude that spironolactone is more effective than RDN to reduce 24-h SBP and 24-h DBP in patients with resistant hypertension. Therefore, spironolactone should be the fourth antihypertensive drug to prescribe if deemed well tolerated’ in all patients with resistant hypertension before considering RDN. PMID:27327441

  11. Spironolactone versus sympathetic renal denervation to treat true resistant hypertension: results from the DENERVHTA study - a randomized controlled trial.

    Science.gov (United States)

    Oliveras, Anna; Armario, Pedro; Clarà, Albert; Sans-Atxer, Laia; Vázquez, Susana; Pascual, Julio; De la Sierra, Alejandro

    2016-09-01

    Both renal denervation (RDN) and spironolactone have been proposed for the treatment of resistant hypertension. However, they have not been compared in a randomized clinical trial. We aimed to compare the efficacy of spironolactone versus RDN in patients with resistant hypertension. A total of 24 patients with office SBP at least 150 mmHg and 24-h SBP at least 140 mmHg despite receiving at least three full-dose antihypertensive drugs, one a diuretic, but without aldosterone antagonists, were randomized to receive RDN or spironolactone (50 mg) as add-on therapy. Primary endpoint was change in 24-h SBP at 6 months. Comparisons between treatment groups were performed using generalized linear models adjusted by age, sex, and baseline values. Spironolactone was more effective than RDN in reducing 24-h SBP and 24-h DBP: mean baseline-adjusted differences between the two groups were -17.9 mmHg (95%CI -30.9 to -4.9); P = 0.010 and -6.6 mmHg (95%CI -12.9 to -0.3); P = 0.041, for 24-h SBP and 24-h DBP, respectively. As regards changes in office blood pressure, mean baseline-adjusted differences between the two groups were -12.1 mmHg (95%CI -29.1 to 5.1); P = 0.158 and of -5.3 mmHg (95%CI -16.3 to 5.8); P = 0.332, for office SBP and office DBP, respectively. Otherwise, the decrease of estimated glomerular filtration rate was greater in the spironolactone group; mean baseline-adjusted difference between the two groups was -10.7 ml/min per 1.73 m (95%CI -20.1 to -1.4); P = 0.027. We conclude that spironolactone is more effective than RDN to reduce 24-h SBP and 24-h DBP in patients with resistant hypertension. Therefore, spironolactone should be the fourth antihypertensive drug to prescribe if deemed well tolerated' in all patients with resistant hypertension before considering RDN.

  12. {sup 123}I-Labelled metaiodobenzylguanidine for the evaluation of cardiac sympathetic denervation in early stage amyloidosis

    Energy Technology Data Exchange (ETDEWEB)

    Noordzij, Walter; Glaudemans, Andor W.J.M.; Rheenen, Ronald W.J. van; Dierckx, Rudi A.J.O.; Slart, Riemer H.J.A. [University of Groningen, Department of Nuclear Medicine and Molecular Imaging, University Medical Center Groningen, PO Box 30.001, Groningen (Netherlands); Hazenberg, Bouke P.C. [University of Groningen, Department of Rheumatology and Clinical Immunology, University Medical Center Groningen, Groningen (Netherlands); Tio, Rene A. [University of Groningen, Department of Cardiology, University Medical Center Groningen, Groningen (Netherlands)

    2012-10-15

    Cardiac amyloidosis is a rare disorder, but it may lead to potentially life-threatening restrictive cardiomyopathy. Cardiac manifestations frequently occur in primary amyloidosis (AL) and familial amyloidosis (ATTR), but are uncommon in secondary amyloidosis (AA). Echocardiography is the method of choice for assessing cardiac amyloidosis. Amyloid deposits impair the function of sympathetic nerve endings. Disturbance of myocardial sympathetic innervations may play an important role in the remodelling process. {sup 123}I-MIBG can detect these innervation changes. Patients with biopsy-proven amyloidosis underwent general work-up, echocardiography and {sup 123}I-MIBG scintigraphy. Left ventricular internal dimensions and wall thickness were measured, and highly refractile cardiac echoes (sparkling) were analysed. Early (15 min) and late (4 h) heart-to-mediastinum ratio (HMR) and wash-out rate were determined after administration of MIBG. Included in the study were 61 patients (30 women and 31 men; mean age 62 years; 39 AL, 11 AA, 11 ATTR). Echocardiographic parameters were not significantly different between the groups. Sparkling was present in 72 % of ATTR patients, in 54 % of AL patients and in 45 % of AA patients. Mean late HMR in all patients was 2.3 {+-} 0.75, and the mean wash-out rate was 8.6 {+-} 14 % (the latter not significantly different between the patient groups). Late HMR was significantly lower in patients with echocardiographic signs of amyloidosis than in patients without (2.0 {+-} 0.70 versus 2.8 {+-} 0.58, p < 0.001). Wash-out rates were significantly higher in these patients (-3.3 {+-} 9.9 % vs. 17 {+-} 10 %, p < 0.001). In ATTR patients without echocardiographic signs of amyloidosis, HMR was lower than in patients with the other types (2.0 {+-} 0.59 vs. 2.9 {+-} 0.50, p = 0.007). MIBG HMR is lower and wash-out rate is higher in patients with echocardiographic signs of amyloidosis. Also, {sup 123}I-MIBG scintigraphy can detect cardiac denervation in

  13. Enhancement of the intrinsic defecation reflex by mosapride, a 5-HT4 agonist, in chronically lumbosacral denervated guinea pigs.

    Science.gov (United States)

    Kojima, Yu; Fujii, Hisao; Katsui, Renta; Nakajima, Yoshiyuki; Takaki, Miyako

    2006-10-01

    The defecation reflex is composed of rectal distension-evoked rectal (R-R) reflex contractions and synchronous internal anal sphincter (R-IAS) reflex relaxations in guinea pigs. These R-R and R-IAS reflexes are controlled via extrinsic sacral excitatory nerve pathway (pelvic nerves), lumbar inhibitory nerve pathways (colonic nerves) and by intrinsic cholinergic excitatory and nitrergic inhibitory nerve pathways. The effect of mosapride (a prokinetic benzamide) on the intrinsic reflexes, mediated via enteric 5-HT(4) receptors, was evaluated by measuring the mechanical activity of the rectum and IAS in anesthetized guinea pigs using an intrinsic R-R and R-IAS reflex model resulting from chronic (two to nine days) lumbosacral denervation (PITH). In this model, the myenteric plexus remains undamaged and the distribution of myenteric and intramuscular interstitial cells of Cajal is unchanged. Although R-R and R-IAS reflex patterns markedly changed, the reflex indices (reflex pressure or force curve-time integral) of both the R-R contractions and the synchronous R-IAS relaxations were unchanged. The frequency of the spontaneous R and IAS motility was also unchanged. Mosapride (0.1-1.0 mg/kg) dose-dependently increased both intrinsic R-R (maximum: 1.82) and R-IAS reflex indices (maximum: 2.76) from that of the control (1.0) 6-9 days following chronic PITH. The dose-response curve was similar to that in the intact guinea pig, and had shifted to the left from that in the guinea pig after acute PITH. A specific 5-HT(4) receptor antagonist, GR 113808 (1.0 mg/kg), decreased both reflex indices by approximately 50% and antagonized the effect of mosapride 1.0 mg/kg. This was quite different from the result in the intact guinea pig where GR 113808 (1.0 mg/kg) did not affect either of the reflex indices. The present results indicate that mosapride enhanced the intrinsic R-R and R-IAS reflexes and functionally compensated for the deprivation of extrinsic innervation. The actions of

  14. Impaired social interaction and enhanced sensitivity to phencyclidine-induced deficits in novel object recognition in rats with cortical cholinergic denervation.

    Science.gov (United States)

    Savage, S; Kehr, J; Olson, L; Mattsson, A

    2011-11-10

    Dysregulated cholinergic neurotransmission has been implicated in the pathophysiology of schizophrenia, particularly negative symptoms and cognitive deficits. The aim of the present study was to evaluate the role of neocortical cholinergic innervation and of the N-methyl-d-aspartate (NMDA) receptor antagonist phencyclidine (PCP) on social interaction and novel object recognition (NOR), a declarative memory task. The cholinergic corticopetal projection was lesioned by local infusion of the immunotoxin 192 IgG-saporin into nucleus basalis magnocellularis of adult male Lister hooded rats. Behavior was assessed 2.5 weeks later in a social interaction paradigm followed by the NOR task. We found that selective cholinergic denervation of neocortex led to a significant reduction in duration of social interaction, specifically active social interaction. Acute administration of PCP (1.0 mg/kg, s.c.) caused a marked decrease of active social interaction, such that there was no longer a difference between intact and denervated animals. Neither cholinergic denervation alone, nor PCP (1.0 mg/kg, s.c.) alone blocked the ability of rats to recognize a novel object. However, when animals lacking cortical cholinergic innervation were challenged by PCP, they were no longer able to recognize a novel object. This study indicates that rats lacking cholinergic innervation of neocortex have impaired social interaction and specifically that the duration of active contact is shortened. Animals with severe cortical cholinergic hypofunction maintain the ability to perform in a declarative memory test, although the task is carried out less intensively. However, a provocation of psychosis-like behavior by a dose of PCP that does not by itself impair performance in normal animals, will abolish the ability to recognize novel objects in animals lacking cortical cholinergic innervation. The present findings support a possible role for cortical cholinergic hypofunction in the negative and cognitive

  15. Use of iodine-123 metaiodobenzylguanidine scintigraphy to assess cardiac sympathetic denervation and the impact of hypertension in patients with non-insulin-dependent diabetes mellitus

    Energy Technology Data Exchange (ETDEWEB)

    Tamura, Koji; Nakatani, Yuko; Onishi, Satoshi [Dept. of Internal Medicine, Keihanna Hospital, Hirakata City, Osaka (Japan); Utsunomiya, Keita; Saika, Yoshinori [Dept. of Radiology, Keihanna Hospital, Hirakata City (Japan); Iwasaka, Toshiji [Cardiovascular Center, Kansai Medical University, Osaka (Japan)

    1999-10-01

    The objectives of this clinical study using iodine-123 metaiodobenzylguanidine (MIBG) scintigraphy were (a) to evaluate cardiac sympathetic denervation in non-insulin-dependent diabetes mellitus (NIDDM) patients with and without hypertension and (b) to investigate the relation between cardiac sympathetic denervation and prognosis in NIDDM patients. We compared clinical characteristics and MIBG data [heart to mediastinum (H/M) ratio and % washout rate (WR)] in a control group and NIDDM patients with and without hypertension. MIBG scintigraphy was performed in 11 controls and 82 NIDDM patients without overt cardiovascular disease except for hypertension (systolic blood pressure {>=}140 and/or diastolic blood pressure {>=}90 mmHg). After MIBG examination, blood pressure was measured regularly in all NIDDM patients. There were significant differences between 65 normotensive and 17 hypertensive NIDDM patients with respect to age (55{+-}11 vs 63{+-}12 years, respectively, P<0.05), prevalence of diabetic retinopathy (12% vs 35%, respectively, P<0.05) and systolic blood pressure (120{+-}12 vs 145{+-}16 mmHg, respectively, P<0.001). The H/M ratio in hypertensive NIDDM patients was significantly lower than in the control group (1.81{+-}0.29 vs 2.27{+-}0.20, respectively, P<0.01). During the follow-up period (18{+-} 12 months), 17 NIDDM patients newly developed hypertension after MIBG examination. There were no significant differences in their clinical characteristics compared with persistently normotensive or hypertensive NIDDM patients. %WR in patients with new onset hypertension was significantly higher than in the control group (30.88%{+-}16.87% vs 12.89%{+-}11.94%, respectively, P<0.05). Moreover, in these patients %WR correlated with duration from the date of MIBG scintigraphy to the onset of hypertension (r=-0.512, P<0.05). Five NIDDM patients died during the follow-up period (four newly hypertensive patients and one normotensive patient). There were significant

  16. How to perform a cost-effectiveness analysis with surrogate endpoint: renal denervation in patients with resistant hypertension (DENERHTN) trial as an example.

    Science.gov (United States)

    Bulsei, Julie; Darlington, Meryl; Durand-Zaleski, Isabelle; Azizi, Michel

    2018-04-01

    Whilst much uncertainty exists as to the efficacy of renal denervation (RDN), the positive results of the DENERHTN study in France confirmed the interest of an economic evaluation in order to assess efficiency of RDN and inform local decision makers about the costs and benefits of this intervention. The uncertainty surrounding both the outcomes and the costs can be described using health economic methods such as the non-parametric bootstrap. Internationally, numerous health economic studies using a cost-effectiveness model to assess the impact of RDN in terms of cost and effectiveness compared to antihypertensive medical treatment have been conducted. The DENERHTN cost-effectiveness study was the first health economic evaluation specifically designed to assess the cost-effectiveness of RDN using individual data. Using the DENERHTN results as an example, we provide here a summary of the principle methods used to perform a cost-effectiveness analysis.

  17. Executive summary of the joint position paper on renal denervation of the Cardiovascular and Interventional Radiological Society of Europe and the European Society of Hypertension.

    Science.gov (United States)

    Moss, Jonathan G; Belli, Anna-Maria; Coca, Antonio; Lee, Michael; Mancia, Giuseppe; Peregrin, Jan H; Redon, Josep; Reekers, Jim A; Tsioufis, Costas; Vorwerk, Dierk; Schmieder, Roland E

    2016-12-01

    Renal denervation (RDN) was reported as a novel exciting treatment for resistant hypertension in 2009. An initial randomized trial supported its efficacy and the technique gained rapid acceptance across the globe. However, a subsequent large blinded, sham arm randomized trial conducted in the USA (to gain Food and Drug Administration approval) failed to achieve its primary efficacy end point in reducing office blood pressure at 6 months. Published in 2014 this trial received both widespread praise and criticism. RDN has effectively stopped out with clinical trials pending further evidence. This joint consensus document representing the European Society of Hypertension and the Cardiovascular and Radiological Society of Europe attempts to distill the current evidence and provide future direction and guidance.

  18. Blood Pressure Regulation by the Rostral Ventrolateral Medulla in Conscious Rats: Effects of Hypoxia, Hypercapnia, Baroreceptor Denervation, and Anesthesia

    Science.gov (United States)

    Wenker, Ian C.; Abe, Chikara; Viar, Kenneth E.; Stornetta, Daniel S.

    2017-01-01

    Current understanding of the contribution of C1 neurons to blood pressure (BP) regulation derives predominantly from experiments performed in anesthetized animals or reduced ex vivo preparations. Here, we use ArchaerhodopsinT3.0 (ArchT) loss-of-function optogenetics to explore BP regulation by C1 neurons in intact, unanesthetized rats. Using a lentivirus that expresses ArchT under the Phox2b-activated promoter PRSx8 (PRSx8-ArchT), ∼65% of transduced neurons were C1 (balance retrotrapezoid nucleus, RTN). Other rats received CaMKII-ArchT3.0 AAV2 (CaMKII-ArchT), which transduced C1 neurons and larger numbers of unidentified glutamatergic and GABAergic cells. Under anesthesia, ArchT photoactivation reduced sympathetic nerve activity and BP and silenced/strongly inhibited most (7/12) putative C1 neurons. In unanesthetized PRSx8-ArchT-treated rats breathing room air, bilateral ArchT photoactivation caused a very small BP reduction that was only slightly larger under hypercapnia (6% FiCO2), but was greatly enhanced during hypoxia (10 and 12% FiO2), after sino-aortic denervation, or during isoflurane anesthesia. The degree of hypotension correlated with percentage of ArchT-transduced C1 neurons. ArchT photoactivation produced similar BP changes in CaMKII-ArchT-treated rats. Photoactivation in PRSX8-ArchT rats reduced breathing frequency (FR), whereas FR increased in CaMKII-ArchT rats. We conclude that the BP drop elicited by ArchT activation resulted from C1 neuron inhibition and was unrelated to breathing changes. C1 neurons have low activity under normoxia, but their activation is important to BP stability during hypoxia or anesthesia and contributes greatly to the hypertension caused by baroreceptor deafferentation. Finally, C1 neurons are marginally activated by hypercapnia and the large breathing stimulation caused by this stimulus has very little impact on resting BP. SIGNIFICANCE STATEMENT C1 neurons are glutamatergic/peptidergic/catecholaminergic neurons located

  19. Sympathetic Response and Outcomes Following Renal Denervation in Patients With Chronic Heart Failure: 12-Month Outcomes From the Symplicity HF Feasibility Study.

    Science.gov (United States)

    Hopper, Ingrid; Gronda, Edoardo; Hoppe, Uta C; Rundqvist, Bengt; Marwick, Thomas H; Shetty, Sharad; Hayward, Christopher; Lambert, Thomas; Hering, Dagmara; Esler, Murray; Schlaich, Markus; Walton, Antony; Airoldi, Flavio; Brandt, Mathias C; Cohen, Sidney A; Reiters, Pascalle; Krum, Henry

    2017-09-01

    Heart failure (HF) is associated with chronic sympathetic activation. Renal denervation (RDN) aims to reduce sympathetic activity by ablating the renal sympathetic nerves. We investigated the effect of RDN in patients with chronic HF and concurrent renal dysfunction in a prospective, multicenter, single-arm feasibility study. Thirty-nine patients with chronic systolic HF (left ventricular ejection fraction [LVEF] renal impairment (estimated glomerular filtration rate [eGFR; assessed with the use of the Modification of Diet in Renal Disease equation] renal artery occlusion that was possibly related to the denervation procedure. Statistically significant reductions in N-terminal pro-B-type natriuretic peptide (NT-proBNP; 1530 ± 1228 vs 1428 ± 1844 ng/mL; P = .006) and 120-minute glucose tolerance test (11.2 ± 5.1 vs 9.9 ± 3.6; P = .026) were seen at 12 months, but there was no significant change in LVEF (28 ± 9% vs 29 ± 11%; P= .536), 6-minute walk test (384 ± 96 vs 391 ± 97 m; P= .584), or eGFR (52.6 ± 15.3 vs 52.3 ± 18.5 mL • min -1  • 1.73 m -2 ; P= .700). RDN was associated with reductions in NT-proBNP and 120-minute glucose tolerance test in HF patients 12 months after RDN treatment. There was no deterioration in other indices of cardiac and renal function in this small feasibility study. Copyright © 2017 Elsevier Inc. All rights reserved.

  20. Use of iodine-123 metaiodobenzylguanidine scintigraphy to assess cardiac sympathetic denervation and the impact of hypertension in patients with non-insulin-dependent diabetes mellitus

    International Nuclear Information System (INIS)

    Tamura, Koji; Nakatani, Yuko; Onishi, Satoshi; Utsunomiya, Keita; Saika, Yoshinori; Iwasaka, Toshiji

    1999-01-01

    The objectives of this clinical study using iodine-123 metaiodobenzylguanidine (MIBG) scintigraphy were (a) to evaluate cardiac sympathetic denervation in non-insulin-dependent diabetes mellitus (NIDDM) patients with and without hypertension and (b) to investigate the relation between cardiac sympathetic denervation and prognosis in NIDDM patients. We compared clinical characteristics and MIBG data [heart to mediastinum (H/M) ratio and % washout rate (WR)] in a control group and NIDDM patients with and without hypertension. MIBG scintigraphy was performed in 11 controls and 82 NIDDM patients without overt cardiovascular disease except for hypertension (systolic blood pressure ≥140 and/or diastolic blood pressure ≥90 mmHg). After MIBG examination, blood pressure was measured regularly in all NIDDM patients. There were significant differences between 65 normotensive and 17 hypertensive NIDDM patients with respect to age (55±11 vs 63±12 years, respectively, P<0.05), prevalence of diabetic retinopathy (12% vs 35%, respectively, P<0.05) and systolic blood pressure (120±12 vs 145±16 mmHg, respectively, P<0.001). The H/M ratio in hypertensive NIDDM patients was significantly lower than in the control group (1.81±0.29 vs 2.27±0.20, respectively, P<0.01). During the follow-up period (18± 12 months), 17 NIDDM patients newly developed hypertension after MIBG examination. There were no significant differences in their clinical characteristics compared with persistently normotensive or hypertensive NIDDM patients. %WR in patients with new onset hypertension was significantly higher than in the control group (30.88%±16.87% vs 12.89%±11.94%, respectively, P<0.05). Moreover, in these patients %WR correlated with duration from the date of MIBG scintigraphy to the onset of hypertension (r=-0.512, P<0.05). Five NIDDM patients died during the follow-up period (four newly hypertensive patients and one normotensive patient). There were significant statistical differences

  1. Renal denervation in treatment-resistant essential hypertension. A randomized, SHAM-controlled, double-blinded 24-h blood pressure-based trial.

    Science.gov (United States)

    Mathiassen, Ole N; Vase, Henrik; Bech, Jesper N; Christensen, Kent L; Buus, Niels H; Schroeder, Anne P; Lederballe, Ole; Rickers, Hans; Kampmann, Ulla; Poulsen, Per L; Hansen, Klavs W; Btker, Hans E; Peters, Christian D; Engholm, Morten; Bertelsen, Jannik B; Lassen, Jens F; Langfeldt, Sten; Andersen, Gratien; Pedersen, Erling B; Kaltoft, Anne

    2016-08-01

    Renal denervation (RDN), treating resistant hypertension, has, in open trial design, been shown to lower blood pressure (BP) dramatically, but this was primarily with respect to office BP. We conducted a SHAM-controlled, double-blind, randomized, single-center trial to establish efficacy data based on 24-h ambulatory BP measurements (ABPM). Inclusion criteria were daytime systolic ABPM at least 145 mmHg following 1 month of stable medication and 2 weeks of compliance registration. All RDN procedures were carried out by an experienced operator using the unipolar Medtronic Flex catheter (Medtronic, Santa Rosa, California, USA). We randomized 69 patients with treatment-resistant hypertension to RDN (n = 36) or SHAM (n = 33). Groups were well balanced at baseline. Mean baseline daytime systolic ABPM was 159 ± 12 mmHg (RDN) and 159 ± 14 mmHg (SHAM). Groups had similar reductions in daytime systolic ABPM compared with baseline at 3 months [-6.2 ± 18.8 mmHg (RDN) vs. -6.0 ± 13.5 mmHg (SHAM)] and at 6 months [-6.1 ± 18.9 mmHg (RDN) vs. -4.3 ± 15.1 mmHg (SHAM)]. Mean usage of antihypertensive medication (daily defined doses) at 3 months was equal [6.8 ± 2.7 (RDN) vs. 7.0 ± 2.5 (SHAM)].RDN performed at a single center and by a high-volume operator reduced ABPM to the same level as SHAM treatment and thus confirms the result of the HTN3 trial. Further, clinical use of RDN for treatment of resistant hypertension should await positive results from double-blinded, SHAM-controlled trials with multipolar ablation catheters or novel denervation techniques.

  2. Effects of renal denervation with a standard irrigated cardiac ablation catheter on blood pressure and renal function in patients with chronic kidney disease and resistant hypertension.

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    Kiuchi, Márcio Galindo; Maia, George Luiz Marques; de Queiroz Carreira, Maria Angela Magalhães; Kiuchi, Tetsuaki; Chen, Shaojie; Andrea, Bruno Rustum; Graciano, Miguel Luis; Lugon, Jocemir Ronaldo

    2013-07-01

    Evaluation of the safety and efficacy of renal denervation with a standard irrigated cardiac ablation catheter (SICAC) in chronic kidney disease (CKD) patients with refractory hypertension. Twenty-four patients were included and treated with a SICAC. Denervation was performed by a single operator following the standard technique. Patients included with CKD were on stages 2 (n = 16), 3 (n = 4), and 4 (n = 4). Data were obtained at baseline and monthly until 180th day of follow-up. Baseline values of blood pressure (mean ± SD) were 186 ± 19 mmHg/108 ± 13 mmHg in the office, and 151 ± 18 mmHg/92 ± 11 mmHg by 24 h ambulatory blood pressure monitoring (ABPM). Office blood pressure values at 180th day after the procedure were 135 ± 13 mmHg/88 ± 7 mmHg (P < 0.0001, for both comparisons). The mean ABPM decreased to 132 ± 15 mmHg/85 ± 11 mmHg at the 180th day after the procedure (P < 0.0001 for systolic and P = 0.0015 for diastolic). Estimated glomerular filtration (mean ± SD) increased from baseline (64.4 ± 23.9 mL/min/1.73 m(2)) to the 180th day (85.4 ± 34.9 mL/min/1.73 m(2), P < 0.0001) of follow-up. The median urine albumin:creatinine ratio decreased from baseline (48.5, IQR: 35.8-157.2 mg/g) to the 180th day after ablation (ACR = 15.7, IQR: 10.3-34.2 mg/g, P = 0.0017). No major complications were seen. The procedure using SICAC seemed to be feasible, effective, and safe resulting in a better control of BP, a short-term increase in estimated glomerular filtration rate, and reduced albuminuria. Although encouraging, our data are preliminary and need to be validated in the long term.

  3. Accurate Depth of Radiofrequency-Induced Lesions in Renal Sympathetic Denervation Based on a Fine Histological Sectioning Approach in a Porcine Model.

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    Sakaoka, Atsushi; Terao, Hisako; Nakamura, Shintaro; Hagiwara, Hitomi; Furukawa, Toshihito; Matsumura, Kiyoshi; Sakakura, Kenichi

    2018-02-01

    Ablation lesion depth caused by radiofrequency-based renal denervation (RDN) was limited to radiofrequency-RDN cannot ablate a substantial percentage of renal sympathetic nerves. We aimed to define the true lesion depth achieved with radiofrequency-RDN using a fine sectioning method and to investigate biophysical parameters that could predict lesion depth. Radiofrequency was delivered to 87 sites in 14 renal arteries from 9 farm pigs at various ablation settings: 2, 4, 6, and 9 W for 60 seconds and 6 W for 120 seconds. Electric impedance and electrode temperature were recorded during ablation. At 7 days, 2470 histological sections were obtained from the treated arteries. Maximum lesion depth increased at 2 to 6 W, peaking at 6.53 (95% confidence interval, 4.27-8.78) mm under the 6 W/60 s condition. It was not augmented by greater power (9 W) or longer duration (120 seconds). There were statistically significant tendencies at 6 and 9 W, with higher injury scores in the media, nerves, arterioles, and fat. Maximum lesion depth was positively correlated with impedance reduction and peak electrode temperature (Pearson correlation coefficients were 0.59 and 0.53, respectively). Lesion depth was 6.5 mm for radiofrequency-RDN at 6 W/60 s. The impedance reduction and peak electrode temperature during ablation were closely associated with lesion depth. Hence, these biophysical parameters could provide prompt feedback during radiofrequency-RDN procedures in the clinical setting. © 2018 The Authors.

  4. FIRST SOUND EVIDENCE OF MUSCLE REGENERATION IN RECOVERY OF FUNCTION OF HUMAN PERMANENT DENERVATED MUSCLES BY A LONG-LASTING FUNCTIONAL ELECTRICAL STIMULATION (FES TRAINING: BIOPSY FINDINGS

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    Helmut Kern

    2004-12-01

    Full Text Available Contrary to general believe, in one case of 18month cauda equina lesion four-month electrical stimulation of thigh muscles (impulse energy 1.92 Joule increased stimulation frequency from 2 to 20 Hz, i. e., up to tetanic contractions. After 2 years of treatment, CT-cross sectional area of quadriceps improved 58.3% (right and 44.4% (left with increased muscle density. Mean myofiber size was 37.2 ± 24.8 µm (right and 40.5 ±  24.9 µm (left. Improvement of stimulated knee torque, from zero to 12.0 Nm and 10.5 Nm, respectively, enabled to stand up trials. Surviving myofibers undergo re-growth (they show the chess board appearance of normal muscle, and dying myofibers continuously regenerate (up to 3% are embryonic myosin positive 3-year post-FES. Regeneration events are essential components of the FES rehabilitation protocol due to superior excitability of regenerated myofibers in comparison to long-term denervated, degenerated myofibers, which were almost not excitable before FES training.

  5. [Comparison of efficacy between continuous positive airway pressure and renal artery sympathetic denervation by radiofrequency ablation in obstructive sleep apnea syndrome patients with hypertension].

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    Zhao, Meng-meng; Tan, Xue-xue; Ding, Ning; Zhang, Xi-long

    2013-04-23

    To compare the efficacy of renal arterial sympathetic denervation (RSD) and continuous positive airway pressure (CPAP) in patients with coexisting moderate-to-severe obstructive sleep apnea syndrome (OSAS) and hypertension. Retrospective analysis was conducted for patients with coexisting moderate to severe OSAS and hypertension for the efficacy of RSD (RSD group, n = 15) and CPAP (CPAP group, n = 16). Comparison was made for polysomnographic parameters and 24 hours ambulatory blood pressure (Bp) between two groups. There was no significant difference in age, gender, body mass index, nocturnal apnea hypopnea index (AHI), mean and minimal pulse oxygen saturation (mean SpO2 and mini SpO2) between two groups. Compared with those at pre-treatment, the following changes were observed at Day 30 post-treatment: in RSD group, the nocturnal AHI and T90 statistically decreased (27 ± 14 vs 32 ± 12, 8.7% ± 7.8% vs 13.8% ± 13.1%, all P 0.05); in CPAP group during treatment, nocturnal AHI and the ratio of duration SpO2 hypertension, both RSD and CPAP may improve sleep respiratory parameters and blood pressure to varying degrees. There is a more significant improvement of nocturnal AHI and SpO2 in CPAP group and more lower MSBp in RSD group.

  6. Catheter-based renal denervation for resistant hypertension: 12-month results of the EnligHTN I first-in-human study using a multielectrode ablation system.

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    Papademetriou, Vasilios; Tsioufis, Costas P; Sinhal, Ajay; Chew, Derek P; Meredith, Ian T; Malaiapan, Yuvi; Worthley, Matthew I; Worthley, Stephen G

    2014-09-01

    Renal denervation has emerged as a novel approach for the treatment of patients with drug-resistant hypertension. To date, only limited data have been published using multielectrode radiofrequency ablation systems. In this article, we present the 12-month data of EnligHTN I, a first-in-human study using a multielectrode ablation catheter. EnligHTN I enrolled 46 patients (average age, 60±10 years; on average 4.7±1.0 medications) with drug-resistant hypertension. Eligible patients were on ≥3 antihypertensive medications and had a systolic blood pressure (BP) ≥160 mm Hg (≥150 mm Hg for diabetics). Bilateral renal artery ablation was performed using a percutaneous femoral approach and standardized techniques. The average baseline office BP was 176/96 mm Hg, average 24-hour ambulatory BP was 150/83 mm Hg, and average home BP was 158/90 mm Hg. The average reductions (mm Hg) at 1, 3, 6, and 12 months were as follows: office: -28/-10, -27/-10, -26/-10, and -27/-11 mm Hg (Prenal function and no new serious or life-threatening adverse events. One patient with baseline nonocclusive renal artery stenosis progressed to 75% diameter stenosis, requiring renal artery stenting. The 12-month data continue to demonstrate safety and efficacy of the EnligHTN ablation system in patients with drug-resistant hypertension. Home BP measurements parallel measurements obtained with 24-hour ambulatory monitoring. © 2014 American Heart Association, Inc.

  7. Experimental american trypanomiasis in rats: sympathetic denervation, parasitism and inflammatory process Desnervação simpática, parasitismo e processo inflamatório durante a doença de Chagas experimental, em ratos

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    Conceição R. S. Machado

    1989-12-01

    Full Text Available Tissue parasitism, inflammatory process (histologic methods and sympathetic denervation (glyoxylic acid-induced histofluorescence for demonstration of catecholamines were studied in the heart (atrium and verntricle and the submandibular gland of rats infected with the Y strain of Trypanosoma cruzi. In the heart paralleling intense parasitism and inflammatory process, the sympathetic denervation started at day 6 of infection and at the end of the acute phase (day 20 practically no varicose nerve terminals were found in both myocardium and vessels. In the submandibular gland, in spite of the rarity of anastigote pseudocysts and the scarcity of inflammatory foci, slight to moderate (days 13-15 of infection or moderate to severe denervation (day 20 was found. At day 120 of infection both organs exhibited normal pattern of sympathetic innervation and only the heart showed some inflammatory foci and rare psudocysts (ventricle. Our data suggest the involvement of circulating factors in the sympathetic denervation phenomena but indicate that local inflammatory process is, at least, an aggravating factor.Parasitismo tecidual, processo inflamatório (métodos histológicos e desnervação simpática (histofluorescência induzida por ácido glioxílico para demosntração de catecolaminas foram estudados no coração (átrio e ventrículo e na glândula submandibular de ratos infectados com cepa Y de Trypanosoma cruzi. No coração, em paralelo com intenso parasitismo e processo inglamatório, a desnervação simpática iniciuo-se no 6º dia de infecção e ao fim da fase aguda (20º dia praticamente nenhuma terminação nervosa varicosa foi encontrada tanto no miocárdio como em vasos. Na glândula submandibular, apesar da raridade de ninhos de amastigotas e da escassez de focos inflamatórios, encontram-se discreta e moderada 13º-15º dia de infeccção ou moderada a severa (20º dia desnervação. Aos 120 dias de infecção, ambos os órgãos exibiram

  8. [Influence of Sympathetic Denervation of the Renal Artery on the Level of Arterial Blood Pressure, Cerebral Blood Flow and Cognitive Function In Patients With Resistant Arterial Hypertension].

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    Efimova, Y N; Lichikaki, A V; Lishmanov, B Y

    2017-07-01

    To study the effect of radiofrequency ablation of renal arteries on regional cerebral blood flow and cognitive function in patients with resistant arterial hypertension (AH). Transcatheter renal denervation (TRD) was performed in 17 patients with resistant AH. Examination before and after TRD included SPECT with mTc-HMPAO, 24-hours blood pressure (BP) monitoring, and comprehensive neuropsychological testing. Fifteen patients without angiographic signs of carotid atherosclerosis, coronary artery disease and AH, neurological and psychiatric disorders were investigated as control group. Compared with control group patients with AH had decreases of regional cerebral blood flow (rCBF) in right (by 13.5%, p=0.00002) and left (by 15.5%, p=0.0006) inferior frontal lobes, in right temporal brain region (by 11.5%, p=0.008); in right and left occipital lobes (by 8.2%, p=0.04). In 6 months after TRD we observed significant improvement of cognitive function, parameters of 24-hour BP monitoring, and rCBF. We also noted definite close interdependence between changes of rCBF, indices of 24-hours BP monitoring, and dynamics of cognitive function. Improvement of long-term verbal memory correlated with increases of rCBF in left superior frontal and right occipital regions while dynamics of mentation and attention correlated positively with augmentation of rCBF in right posterior parietal region. Changes of perfusion in inferior parts of left frontal lobe and in right occipital region correlated with dynamics of index of diurnal diastolic hypertension time (R2=0.64, p=0.001, and R2=0.60, p=0.03, respectively). Our results suggest, that in patients with resistant AH positive effect of TRD on levels of 24-hour mean BP as well as on indices of BP load leads to in augmentation of rCBF and improvement of cognitive function.

  9. Comparison of branch and distally focused main renal artery denervation using two different radio-frequency systems in a porcine model.

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    Mahfoud, Felix; Pipenhagen, Catherine A; Boyce Moon, L; Ewen, Sebastian; Kulenthiran, Saarraaken; Fish, Jeffrey M; Jensen, James A; Virmani, Renu; Joner, Michael; Yahagi, Kazuyuki; Tsioufis, Costas; Böhm, Michael

    2017-08-15

    Anatomic placement of lesions may impact efficacy of radio-frequency (RF) catheter renal denervation (RDN). However, it is unclear if it is necessary to perform treatments post bifurcation with systems that may provide deeper penetration to achieve successful RDN. Sixteen domestic swine (n=16) were randomly assigned to 4 groups: 1) 8 lesions created in the branch arteries using the Spyral catheter (SP8); 2) 8 lesions created in the branch arteries plus 4 lesions created in the main artery using the SP catheter (SP12); 3) 8 lesions created in the main artery using the EnligHTN catheter with the distal position as close as possible to the bifurcation (EN8); and 4) 12 lesions created in the main artery using the EN catheter with the distal position as close as possible to the bifurcation (EN12). Each arm showed statistically significant changes in kidney norepinephrine (NE, ng/g) between treated kidneys vs. untreated contralateral control. There were no statistically significant differences in tissue NE% reductions across each arm based on catheter, anatomic location, & number of lesions (p=0.563): EN8 -74±34%, EN12 -95±3%, SP8 -76±16%, SP12 -82±17% (p=0.496). A total of 46 lesions were measured for lesion depth: EN main (3.3±2.8mm) vs. SP branch (2.0±1.0mm, p=0.039), SP main (2.9±1.6mm) vs. SP branch (p=0.052), and EN main vs. SP main (p=0.337). Distally-focused main renal artery treatment using the EN system appears to be equally efficacious in reducing tissue NE levels compared with SP treatment in the branches plus main renal arteries, advocating for device-specific procedure execution. Copyright © 2017 Elsevier B.V. All rights reserved.

  10. Effects of catheter-based renal denervation on heart failure with reduced ejection fraction: a systematic review and meta-analysis.

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    Fukuta, Hidekatsu; Goto, Toshihiko; Wakami, Kazuaki; Ohte, Nobuyuki

    2017-11-01

    Despite the recent advances in the management of heart failure, the mortality of heart failure patients remains high. It is of urgent need to develop new therapy for heart failure. Heart failure is characterized by increased sympathetic activity, and chronic sympathetic activation is involved in the maintenance of the pathological state. Catheter-based renal denervation (RDN) has emerged as an invasive but safe approach that can reduce sympathetic activation. Studies have reported inconsistent results regarding the effect of RDN in heart failure patients due to limited power with small sample sizes. We aimed to conduct a meta-analysis of the effect of RDN on heart failure patients with reduced left ventricular (LV) ejection fraction (EF). An electronic search for studies examining the effect of RDN on LV function in heart failure patients with reduced EF was conducted. Two controlled (80 patients) and 2 uncontrolled studies (21 patients) were included in this meta-analysis. In the pooled analysis, 6 months after RDN, there was a greater increase in EF (weighted mean difference [95% CI] = 8.63 [6.02, 11.24] %) and a greater decrease in LV end-diastolic diameter (-0.58 [-0.83, -0.34] cm) in RDN group than in control group. No serious adverse events such as acute renal artery stenosis and dissection occurred. Our meta-analysis of feasibility studies suggests that RDN may improve LV function in heart failure patients with reduced EF, providing the rationale to conduct next phase trials to confirm the observed potential benefits of RDN.

  11. Prospective double-blind preoperative pain clinic screening before microsurgical denervation of the spermatic cord in patients with testicular pain syndrome.

    Science.gov (United States)

    Oomen, Robert J A; Witjens, Annemijke C; van Wijck, Albert J M; Grobbee, Diederik E; Lock, Tycho M T W

    2014-09-01

    Testicular pain syndrome (TPS), defined as an intermittent or constant pain in one or both testicles for at least 3 months, resulting in significant reduction of daily activities, is common. Microsurgical denervation of the spermatic cord (MDSC) has been suggested as an effective treatment option. The study population comprised 180 TPS patients admitted to our outpatient urology clinic between 1999 and 2011. On 3 different occasions, patients were offered a double-blind, placebo-controlled temporary blockade of the spermatic cord. A single blockade consisted of 10 mL 2% lidocaine, 10 mL 0.25% bupivacaine, or 10 mL 0.9% sodium chloride. If the results of these blockades were positive, MDSC was offered. All MDSCs were performed by a single urologist (M.T.W.T.L.) using an inguinal approach. Pain reduction was determined at prospective follow-up. This study evaluated 180 patients. Most patients (61.1%) had undergone a scrotal or inguinal procedure. Patients had complaints during sexual activities (51.7%), sitting (37.5%), and/or cycling (36.7%); 189 randomized blockades were offered to all patients. There was a positive response in 37% and a negative response in 51%. MDSC was performed on 58 testicular units, including 3 patients with a negative outcome of the blockades. At mean follow-up of 42.8 months, 86.2% had a ≥ 50% reduction of pain and 51.7% were completely pain free. MDSC is a valuable treatment option for TPS patients because in this study 86.2% experienced a ≥ 50% reduction of pain. To prevent superfluous diagnostics and treatment, it is mandatory to follow a systematic protocol in the treatment of TPS. Copyright © 2014 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.

  12. The effect of two different renal denervation strategies on blood pressure in resistant hypertension: Comparison of full-length versus proximal renal artery ablation.

    Science.gov (United States)

    Chen, Weijie; Ling, Zhiyu; Du, Huaan; Song, Wenxin; Xu, Yanping; Liu, Zengzhang; Su, Li; Xiao, Peilin; Yuan, Yuelong; Lu, Jiayi; Zhang, Jianhong; Li, Zhifeng; Shao, Jiang; Zhong, Bin; Zhou, Bei; Woo, Kamsang; Yin, Yuehui

    2016-11-01

    Renal denervation (RDN) is used to manage blood pressure (BP) in patients with resistant hypertension (rHT), but effectiveness is still a concern, and key arterial portion for successful RDN is not clear. The aim of this study was to investigate the efficacy and safety of proximal versus full-length renal artery ablation in patients with resistant hypertension (rHT). Forty-seven patients with rHT were randomly assigned to receive full-length ablation (n = 23) or proximal ablation (n = 24) of the renal arteries. All lesions were treated with radiofrequency energy via a saline-irrigated catheter. Office BP was measured during 12 months of follow-up and ambulatory BP at baseline and 6 months (n = 15 in each group). Compared with full-length ablation, proximal ablation reduced the number of ablation points in both the right (6.1 ± 0.7 vs. 3.3 ± 0.6, P renal arteries (6.2 ± 0.7 vs. 3.3 ± 0.8, P  0.5). Similar office BPs was reduced by -39.4 ± 11.5/-20.9 ± 7.1 mm Hg at 6 months and -38.2 ± 10.3/-21.5 ± 5.8 mm Hg at 12 months in the full-length group (P efficacy and safety profile compared with full-length RDN, and propose the proximal artery as the key portion for RDN. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  13. Rationale and design of the Investigator-Steered Project on Intravascular Renal Denervation for Management of Drug-Resistant Hypertension (INSPiRED) trial.

    Science.gov (United States)

    Jin, Yu; Jacobs, Lotte; Baelen, Marie; Thijs, Lutgarde; Renkin, Jean; Hammer, Frank; Kefer, Joelle; Petit, Thibault; Verhamme, Peter; Janssens, Stefan; Sinnaeve, Peter; Lengelé, Jean-Philippe; Persu, Alexandre; Staessen, Jan A

    2014-06-01

    The SYMPLICITY studies showed that renal denervation (RDN) is feasible as novel treatment for resistant hypertension. However, RDN is a costly and invasive procedure, the long-term efficacy and safety of which has not yet been proven. Therefore, we designed the INSPiRED trial to compare the blood pressure lowering efficacy and safety of RDN vs usual medical therapy. INSPiRED is a randomized controlled trial enrolling 240 treatment-resistant hypertensive patients at 16 expert hypertension centres in Belgium. Eligible patients, aged 20-69 years old, have a 24-h ambulatory blood pressure of 130 mmHg systolic or 80 mmHg diastolic or more, while taking at least three antihypertensive drugs. They are randomized to RDN (EnligHTN(TM), SJM system) plus usual care (intervention group) or usual care alone (control group) in a ratio of 1:1. The primary endpoints for efficacy and safety, measured after 6 months, are the baseline-adjusted between-group differences in 24h systolic blood pressure and in glomerular filtration rate as estimated by the Chronic Kidney Disease Epidemiology Collaboration equation. Follow-up will continue up to 36 months after randomization. INSPiRED is powered to demonstrate a 10-mmHg difference in systolic blood pressure between randomized groups with a two-sided p-value of 0.01 and 90% power. It will generate long-term efficacy and safety data, identify the subset of treatment-resistant hypertensive patients responsive to RDN, provide information on cost-effectiveness, and by doing so INSPiRED will inform guideline committees and health policy makers. ClinicalTrials.gov Identifier: NCT 01505010.

  14. Efficacy and safety of renal denervation for Chinese patients with resistant hypertension using a microirrigated catheter: study design and protocol for a prospective multicentre randomised controlled trial.

    Science.gov (United States)

    Liu, Zongjun; Shen, Li; Huang, Weijian; Zhao, Xianxian; Fang, Weiyi; Wang, Changqian; Yin, Zhaofang; Wang, Jianan; Fu, Guosheng; Liu, Xuebo; Jiang, Jianjun; Zhang, Zhihui; Li, Jingbo; Lu, Yingmin; Ge, Junbo

    2017-09-01

    Available data show that approximately 8%-18% of patients with primary hypertension will develop resistant hypertension. In recent years, catheter-based renal denervation (RDN) has emerged as a potential treatment option for resistant hypertension. A number of observational studies and randomised controlled trials among non-Chinese patients have demonstrated its potential safety and efficacy. This is a multicentre, randomised, open-label, parallel-group, active controlled trial that will investigate the efficacy and safety of a 5F saline-irrigated radiofrequency ablation (RFA) used for RDN in the treatment of Chinese patients with resistant hypertension. A total of 254 patients who have failed pharmacological therapy will be enrolled. Eligible subjects will be randomised in a 1:1 ratio to undergo RDN using the RFA plus antihypertensive medication or to receive treatment with antihypertensive medication alone. The primary outcome measure is the change in 24 hours average ambulatory systolic blood pressure from baseline to 3 months, comparing the RDN-plus-medication group with the medication-alone group. Important secondary endpoints include the change in office blood pressure from baseline to 6 months after randomisation. Safety endpoints such as changes in renal function will also be evaluated. The full analysis set, according to the intent-to-treat principle, will be established as the primary analysis population. All participants will provide informed consent; the study protocol has been approved by the Independent Ethics Committee for each site. This study is designed to investigate the efficacy and safety of RDN using a 5F saline microirrigated RFA. Findings will be shared with participating hospitals, policymakers and the academic community to promote the clinical management of resistant hypertension in China. ClinicalTrials.gov ID: NCT02900729; pre-results. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017

  15. First-in-Man Experience with a Novel Catheter-Based Renal Denervation System of Ultrasonic Ablation in Patients with Resistant Hypertension.

    Science.gov (United States)

    Chernin, Gil; Szwarcfiter, Iris; Scheinert, Dierk; Blessing, Erwin; Diehm, Nicolas; Dens, Jo; Walton, Antony; Verheye, Stefan; Shetty, Sharad; Jonas, Michael

    2018-06-16

    To report results of renal denervation (RDN) with the first catheter-based, non-balloon occlusion ultrasonic system in patients with resistant hypertension. In a multicenter, single-arm trial, 39 patients with resistant hypertension (defined as uncontrolled hypertension while taking ≥ 3 antihypertensive medications) were treated. The cohort consisted of 4 groups: severe resistant hypertension (office systolic blood pressure [OSBP] ≥ 160 mm Hg) treated with a unidirectional catheter (group 1; n = 14); severe resistant hypertension treated with a multidirectional catheter (group 2; n = 18); moderate resistant hypertension (OSBP 140-159 mm Hg) treated with a multidirectional catheter (group 3; n = 5); and recurrent severe resistant hypertension, after an initial response to RF RDN (group 4; n = 2). Blood pressure monitoring was performed for 6 months. Severe adverse events were not noted immediately after the procedure or during follow-up. Treatment time was longer with unidirectional than with multidirectional catheters (36.7 min ± 9.6 vs 11.9 min ± 5.8; P < .001). Mean reductions in office blood pressure (systolic/diastolic) at 1, 3, and 6 months were -26.1/-9.6 mm Hg, -28.0/-9.9 mm Hg, and -30.6/-14.1 mm Hg (P < .01 for all). Per-group analysis showed significant OSBP reduction for groups 1 and 2. Patients with isolated systolic hypertension had a significantly smaller reduction in OSBP after 6 months compared with patients with combined systolic/diastolic hypertension (-16.2 mm Hg ± 18.5 vs -9.9 mm Hg ± 33.4; P < .005). Use of the RDN system was feasible and safe in this phase I study. Significant blood pressure reductions were observed over 6 months, although less in patients with isolated systolic hypertension. Copyright © 2018 SIR. All rights reserved.

  16. Enteric Neuronal Damage, Intramuscular Denervation and Smooth Muscle Phenotype Changes as Mechanisms of Chagasic Megacolon: Evidence from a Long-Term Murine Model of Trypanosoma cruzi Infection.

    Directory of Open Access Journals (Sweden)

    Camila França Campos

    hypothesize that the long-term inflammatory process mediates neuronal damage and intramuscular and intramural denervation, leading to phenotypic changes in smooth muscle cells associated with fibrosis. These long-term structural changes may represent the basic mechanism for the formation of the Chagasic megacolon.

  17. Effects of renal denervation on cardiac oxidative stress and local activity of the sympathetic nervous system and renin-angiotensin system in acute myocardial infracted dogs.

    Science.gov (United States)

    Feng, Qiaoli; Lu, Chengzhi; Wang, Li; Song, Lijun; Li, Chao; Uppada, Ravi Chandra

    2017-02-17

    This study sought to evaluate the therapeutic effects of renal denervation (RDN) on acute myocardial infarction (MI) in canines and explore its possible mechanisms of action. Eighteen healthy mongrel dogs were randomly assigned to either the control group, the MI group or the MI + RDN group. To assess cardiac function, left ventricular ejection fraction (LVEF), left ventricular end-diastolic dimension (LVEDD), left ventricular end-systolic dimension (LVESD) and fraction shortening (FS) were recorded. Additionally, haemodynamic parameters such as left ventricular systolic pressure (LVSP), left ventricular end-diastolic pressure (LVEDP) and heart rate (HR) were measured. Cardiac oxidative stress levels were evaluated based on the expression of p47 phox mRNA, malondialdehyde (MDA), anti-superoxide anion free radical (ASAFR) and activity of superoxide dismutase (SOD). To measure the local activity of the sympathetic nervous system (SNS) and renin-angiotensin system (RAS), the levels of tyrosine hydroxylase (TH), angiotensin II (AngII), angiotensin-converting enzyme 2 (ACE2), angiotensin (1-7) [Ang(1-7)] and Mas receptor (MasR) in myocardial tissues were recorded. The expression of TH in renal tissue and serum creatinine were used to assess the effectiveness of the RDN procedure and renal function, respectively. We found that MI deteriorated heart function and activated cardiac oxidative stress and the local neurohumoral system, while RDN partially reversed these changes. Compared with the control group, parameters including LVEDD, LVESD, LVEDP and the levels of ASAFR, MDA, p47 phox ,ACE2, Ang(1-7), MasR, AngII and TH-positive nerves were increased (all P < 0.05) in myocardial infracted dogs; meanwhile, LVEF, FS, LVSP and SOD expression were decreased (all P < 0.05). However, after RDN therapy, these changes were significantly improved (P < 0.05), except that there were no significant differences observed in FS or LVSP between the two groups (P = 0

  18. The Prevalence of Japanese Outpatients with Hypertension Who Meet the Definition of Treatment Resistant Hypertension and Are Eligible for Enrolment in Clinical Trials of Endovascular Ultrasound Renal Denervation.

    Science.gov (United States)

    Okamura, Keisuke; Shirai, Kazuyuki; Okuda, Tetsu; Urata, Hidenori

    2018-01-01

    Objective A clinical trial (REQUIRE) was started to investigate the use of an ultrasound renal denervation system in the treatment of resistant hypertension (RHT). We analyzed the prevalence of patients who were eligible for inclusion in this cross-sectional study at the time of screening. Methods Nine-hundred ninety-nine consecutive hypertension (HT) patients who were treated in our hospital as outpatients were classified into the following categories: patients treated with at least 3 types of antihypertensive drugs including diuretic agents who were eligible for enrolment in SYMPLICITY HTN-Japan (SH-J) with an office systolic blood pressure (SBP) of ≥160 mmHg, who were ≤80 years of age, and an estimated glomerular filtration rate (eGFR) of ≥45 mL/min/1.73 m 2 (RHT-S); and patients who were treated similar medications and who were eligible for enrolment in REQUIRE, with an SBP of ≥150 mmHg, ≤75 years of age, and an eGFR of ≥40 mL/min/1.73 m 2 (RHT-R). We investigated the proportion of patients in each category. We also investigated HT patients (1,423 cases) who were enrolled in the Chikushi Anti-Hypertension Trial (CHAT), a research network that includes general practitioners. Results Eleven patients (1.1%) with RHT-S and 18 patients (1.8%) with RHT-R were identified. After the exclusion of patients with secondary HT and a diastolic blood pressure (DBP) of <90 mmHg (applied in REQUIRE), 5 patients (0.5%) with RHT-S and 4 patients (0.4%) with RHT-R remained. In the analysis of the CHAT study, only 2 (0.1%) patients with RHT-R remained. Conclusion The number of eligible patients in the REQUIRE trial was decreased, largely due to the strict age restriction and the new DBP limitation. The prevalence of eligible patients in REQUIRE was estimated to be approximately 0.5 to 0.8 times that in SH-J. Since patient enrollment will be difficult, drastic measures may be required to recruit eligible patients.

  19. Desnervação capsular percutânea ou aberta no tratamento da dor na displasia coxofemoral canina Percutaneous versus open hip denervation in the treatment of canine pain hip dysplasia

    Directory of Open Access Journals (Sweden)

    Gisele Francine da Silva

    2012-04-01

    Full Text Available A desnervação capsular (DC se baseia na desperiostização da borda acetabular e tem sido utilizada como uma das técnicas de alívio da dor articular em cães displásicos. Compararam-se as técnicas de DC percutânea e aberta, aplicadas em 25 cães, que apresentaram diagnóstico clínico e radiográfico de displasia coxofemoral, totalizando 31 cirurgias. Os efeitos das técnicas foram comparados, em período de 180 dias, por meio de avaliação subjetiva de claudicação e dor, perimetria da coxa, graus máximos de flexão e extensão da articulação coxofemoral e amplitude de movimento articular. Os graus de claudicação e dor apresentaram decréscimo significativo ao longo do período avaliado em ambos os grupos, sem apresentarem diferenças quando comparados entre si. Com relação à perimetria da coxa, flexão, extensão e amplitude de movimento articular, foi observado o aumento dos valores numéricos destas variáveis ao longo do estudo. Baseado nos achados, concluiu-se que a abordagem percutânea ou aberta na DC produz similitude nas variáveis avaliadas, e ambas trazem bons resultados.Joint capsule denervation is based on removal of sensitive fibers from the acetabular edge and has been used as one of the techniques to joint pain relief in the canine dysplastic hip. This study compared the techniques of percutaneous and open hip denervation in 25 dogs that showed clinical and radiographic signs of hip dysplasia, totaling 31 surgeries. The effects of the techniques were evaluated and compared in a period of 180 days following surgery, including subjective evaluation of lameness and pain, thigh girth, maximum degree of hip flexion and extension and range of motion (ROM. Degree of lameness and pain significantly decreased during the study period for both groups, and no difference could be observed between groups. Thigh girth, degree of flexion, extension and ROM presented an increase in the numerical values throughout the study

  20. Ação do citrato de sildenafil sobre a função uretral de ratas com desnervação vesical Effect of sildenafil citrate in the urethral function in rats with denervated bladder

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    Haylton Jorge Suaid

    2003-01-01

    urethane at a dosage of 1.25mg/kg. All animals underwent cystostomy with a catheter P50 connected by a Y to an infusion pump and to a polygraph Narco-Biosystem. The cystometry was performed trice in each animal: right after the cystostomy, after surgical of bladder denervation and 1h after gastric infusion of 1mg/kg of sildenafil citrate. Maximum (MaP and minimum (MiP vesical pressure were compared in the following moments: I - before bladder denervation, II - after bladder denervation and III - after bladder denervation and sildenafil administration. Wilcoxon test was used for a level of significance of 5%. RESULTS: Mean values of MaP were: I - 86.6±10.1, II - 42.6±15.0 and III - 30.8±12.4. The corresponding values of MiP were: : I - 72.1±18.9, II - 31.1±9.8 and III - 14.5±9.5. The comparison between MaP and MiP in each moment showed difference only in moment III (p0.05 in IIxIII. For MiP the p values were <0.004 in IxII, <0.002 in IxIII and <0.01 in IIxIII. CONCLUSION: 1 Bladder denervation reduces maximum and minimum urethral pressure; 2 Sildenafil citrate reduces the minimum urethral pressure widening the interval between the peak and bottom pressures; and, 3 Sildenafil citrate does not interfere on the peak urethral pressure after bladder denervation.

  1. Effects of low-level laser therapy after nerve reconstruction in rat denervated soleus muscle adaptation Efeitos do laser de baixa potência após reconstrução nervosa na adaptação do músculo sóleo de rato

    OpenAIRE

    Marcela A Silva-Couto; Davilene Gigo-Benato; Carla R. Tim; Nivaldo A. Parizotto; Tania F. Salvini; Thiago L. Russo

    2012-01-01

    BACKGROUND: Peripheral nerve injury (PNI) rehabilitation remains a challenge for physical therapists because PNI effects are very disabling. Low-level laser therapy (LLLT) has been described as a physical resource that is able to influence enzymes called metallopeptidases (MMPs) associated with extracellular matrix (ECM) turnover, thus accelerating neuromuscular recovery after nerve crush injuries. However, the effects of LLLT in the treatment of severe nerve injuries and denervated slow-twit...

  2. Effects of electrical stimulation and stretching on the adaptation of denervated skeletal muscle: implications for physical therapy Efeitos da eletroestimulação e do alongamento muscular sobre a adaptação do músculo desnervado: implicações para a fisioterapia

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    Tania F. Salvini

    2012-06-01

    Full Text Available BACKGROUND: This review will describe the main cellular mechanisms involved in the reduction and increase of myoproteins synthesis commonly associated with muscle atrophy and hypertrophy, respectively. OBJECTIVE: We analyzed the effects of electrical stimulation (ES and stretching exercise on the molecular pathways involved in muscle atrophy and hypertrophy. We also described the main effects and limits of these resources in the skeletal muscle, particularly on the denervated muscle. DISCUSSION: Recently, our studies showed that the ES applied in a similar manner as performed in clinical practice is able to attenuate the increase of genes expression involved in muscle atrophy. However, ES was not effective to prevent the loss of muscle mass caused by denervation. Regarding to stretching exercises, their mechanisms of action on the denervated muscle are not fully understood and studies on this area are scarce. Studies from our laboratory have found that stretching exercise increased the extracellular matrix remodeling and decreased genes expression related to atrophy in denervated muscle. Nevertheless, it was not enough to prevent muscle atrophy after denervation. CONCLUSIONS: In spite of the use of stretching exercise and ES in clinical practice in order to minimize the atrophy of denervated muscle, there is still lack of scientific evidence to justify the effectiveness of these resources to prevent muscle atrophy in denervated muscle.CONTEXTUALIZAÇÃO: Esta revisão abordará os principais mecanismos celulares envolvidos na redução e aumento da síntese de mioproteínas comumente associadas às situações de atrofia e hipertrofia muscular, respectivamente. OBJETIVO: Analisaremos os efeitos da estimulação elétrica (EE e do exercício de alongamento sobre as vias moleculares envolvidas na atrofia e hipertrofia muscular. Serão descritos os principais efeitos e os limites desses recursos no músculo esquelético, particularmente sobre o m

  3. Catheter-based renal denervation for resistant hypertension: Twenty-four month results of the EnligHTN I first-in-human study using a multi-electrode ablation system.

    Science.gov (United States)

    Tsioufis, Costas P; Papademetriou, Vasilios; Dimitriadis, Kyriakos S; Kasiakogias, Alexandros; Tsiachris, Dimitrios; Worthley, Matthew I; Sinhal, Ajay R; Chew, Derek P; Meredith, Ian T; Malaiapan, Yuvi; Thomopoulos, Costas; Kallikazaros, Ioannis; Tousoulis, Dimitrios; Worthley, Stephen G

    2015-12-15

    Long term safety and efficacy data of multi-electrode ablation system for renal denervation (RDN) in patients with drug resistant hypertension (dRHT) are limited. We studied 46 patients (age: 60 ± 10 years, 4.7 ± 1.0 antihypertensive drugs) with drug resistant hypertension (dRHT). Reduction in office BP at 24 months from baseline was -29/-13 mmHg, while the reduction in 24-hour ambulatory BP and in home BP at 24 months were -13/-7 mmHg and -11/-6 mmHg respectively (p<0.05 for all). A correlation analysis revealed that baseline office and ambulatory BP were related to the extent of office and ambulatory BP drop. Apart from higher body mass index (33.3 ± 4.7 vs 29.5 ± 6.2 kg/m(2), p<0.05), there were no differences in patients that were RDN responders defined as ≥10 mmHg decrease (74%, n=34) compared to non-responders. Stepwise logistic regression analysis revealed no prognosticators of RDN response (p=NS for all). At 24 months there were no new serious device or procedure related adverse events. The EnligHTN I study shows that the multi-electrode ablation system provides a safe method of RDN in dRHT accompanied by a clinically relevant and sustained BP reduction. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  4. 4A.10: PREFERENTIAL REDUCTION IN MORNING/NOCTURNAL HYPERTENSION BY RENAL DENERVATION FOR DRUG- RESISTANT HYPERTENSION: A NEW ABPM ANALYSIS OF SYMPLICITY HTN-3 AND HTN-JAPAN.

    Science.gov (United States)

    Kario, K; Bakris, G L; Bhatt, D

    2015-06-01

    To study the impact of catheter-based renal artery denervation (RDN) on change in morning and night systolic BP (SBP) defined by ambulatory BP measurements (ABPM) 6 months post-randomization. SYMPLICITY HTN-3 and SYMPLICITY HTN-Japan are prospective, randomized, controlled trials of RDN for treatment of resistant hypertension. However, SYMPLICITY HTN-3 included a blinded, sham control and HTN-Japan control patients were not blinded and continued medical management alone. Patients in both trials were on a stable antihypertensive regimen of at least 3 drugs including a diuretic before randomization. Average morning SBP (7 am to 9 am), maximum morning SBP (between 6 am and 10 am), average nocturnal SBP (1 am to 6 am), average peak nocturnal SBP (average of 3 highest SBPs between 1 am and 6 am) and average daytime SBP were calculated using pooled patient-level ABPM data. Six-month change in SBP parameters were compared between RDN and control patients. A total of 386 patients (364 from HTN-3 and 22 from Japan) received RDN and 190 patients were in the control group (171 from HTN-3 and 19 from Japan). The average morning SBP was reduced -8.0 ± 22.3 mmHg in the RDN group which was significantly more than the change in the control group (-3.5 ± 22.2 mmHg, p = 0.023). The maximum morning SBP change was -8.6 ± 22.3 mmHg for RDN patients and -4.8 ± 23.8mmHg for controls (p = 0.072). Furthermore, the change in average nocturnal and average peak nocturnal SBP was significantly greater in the RDN patients compared with the control patients; -6.3 ± 18.1 vs -1.7 ± 19.2 mmHg, p = 0.008 for average nocturnal SBP and -6.7 ± 20.0 vs -1.3 ± 20.5 mmHg, p = 0.004 for average peak nocturnal SBP. Average daytime SBP change was not significantly between the RDN and control groups (-7.1 ± 16.0 vs -5.7 ± 18.0 mmHg, p = 0.349). This analysis demonstrated that RDN significantly reduced morning and nighttime SBP compared with

  5. Towards personalized antihypertensive therapy: innovate or denervate?

    NARCIS (Netherlands)

    Eeftinck Schattenkerk, D.W.

    2017-01-01

    In this thesis we employed novel techniques to gain a better understanding of hypertensive disorders and improve antihypertensive treatment strategies. We discuss novel aspects in phenotyping and treatment modalities. Assessment of central hemodynamics may improve hypertensive phenotyping beyond

  6. Efeito da denervação cardíaca ventral na incidência de fibrilação atrial após revascularização cirúrgica do miocárdio Effect of ventral cardiac denervation in the incidence of atrial fibrilation after coronary artery bypass graft surgery

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    João Roberto Breda

    2008-06-01

    Full Text Available OBJETIVO: Verificar o efeito da denervação cardíaca ventral na incidência de fibrilação atrial no pós-operatório de revascularização cirúrgica do miocárdio. MÉTODOS: Entre setembro e novembro de 2005, 50 pacientes consecutivos da mesma instituição foram alocados neste estudo prospectivo e randomizado. Foram selecionados pacientes portadores de insuficiência coronariana com indicação de revascularização cirúrgica do miocárdio, sem história ou diagnóstico prévio de arritmia atrial. Os critérios de exclusão foram: idade acima de 75 anos, história prévia de arritmia atrial e operações cardíacas associadas. A denervação era realizada antes do início da circulação extracorpórea pela remoção do tecido gorduroso ao redor da veia cava superior, aorta e artéria pulmonar. Os grupos foram comparados de acordo com as características clínicas, demográficas e variáveis operatórias. RESULTADOS: Não houve mortalidade hospitalar em ambos os grupos. O tempo médio adicional para realização da denervação foi de 7,64 + 2,33 minutos e não houve complicações associadas ao procedimento. Cinco pacientes apresentaram fibrilação atrial no pós-operatório, sendo dois (8% no grupo controle e três (12% no grupo denervação. O risco dos pacientes do grupo denervação apresentarem fibrilação atrial foi 22% maior do que no grupo controle (intervalo de confiança, 0,56-2,66, porém, este resultado não foi estatisticamente significativo (p=0,64. CONCLUSÕES: A denervação cardíaca ventral, apesar de rápida execução e de baixo risco, não apresentou efeito na redução da incidência de fibrilação atrial no pós-operatório de revascularização cirúrgica do miocárdio.OBJECTIVE: To evaluate the effect of ventral cardiac denervation in the incidence of atrial fibrillation after coronary artery bypass surgery. METHODS: Between September and November, 50 patients without history or previous diagnosis of atrial

  7. Abordagem cirúrgica inédita para denervação acetabular em cães A new surgical approach to acetabular denervation in dogs

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    Cássio R.A. Ferrigno

    2007-02-01

    Full Text Available Este artigo tem por objetivo demonstrar nova abordagem cirúrgica para denervação seletiva das fibras sensitivas do periósteo acetabular, para tratamento da displasia coxo femoral em cães, conduzidas em 189 articulações. Para tanto, é descrita abordagem da região cranial e dorso-lateral do acetábulo de cães por incisão em forma de meia lua de aproximadamente de três centímetros de extensão, iniciando trocânter maior do fêmur e em direção ao corpo do ílio. Após rebatimento dorsal do músculo glúteo médio, secciona-se parcialmente a inserção do m. glúteo profundo para acesso às regiões citadas. Com auxílio de cureta foi removido, em todos os pacientes, periósteo na margem acetabular cranial e dorso lateral, até a exposição da cortical óssea. Em todos os animais foi possível a abordagem, tanto da face cranial como também acesso para a curetagem da face dorsal do acetábulo, com a técnica descrita, com incisão de pele de aproximadamente 3,2cm. A curetagem da porção cranial do acetábulo foi, em todos os casos realizados, sem visualização do osso, mas de fácil confecção e sem intercorrências de lesão de nervos ou músculos. Em todas as abordagens foi possível visualizar a cápsula articular da articulação coxo femoral, e em nenhum dos animais esta estrutura foi incisada por erro de técnica. Conclui-se que a abordagem cirúrgica descrita no presente trabalho é factível para este tipo de procedimento cirúrgico em cães, promovendo acesso adequado, com mínima invasão e sem complicações de qualquer natureza.The purpose of this study is to demonstrate a new surgical approach for the selective denervation of the sensitive fibers of the acetabular periosteum, for the treatment of hip dysplasia in dogs, conducted in 189 joints.The surgical approach of the cranial and dorso-lateral regions of the acetabular joint in dogs, by moon-shaped incision of approximately 3cm in extension, starting from the

  8. Effects of low-level laser therapy after nerve reconstruction in rat denervated soleus muscle adaptation Efeitos do laser de baixa potência após reconstrução nervosa na adaptação do músculo sóleo de rato

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    Marcela A Silva-Couto

    2012-08-01

    Full Text Available BACKGROUND: Peripheral nerve injury (PNI rehabilitation remains a challenge for physical therapists because PNI effects are very disabling. Low-level laser therapy (LLLT has been described as a physical resource that is able to influence enzymes called metallopeptidases (MMPs associated with extracellular matrix (ECM turnover, thus accelerating neuromuscular recovery after nerve crush injuries. However, the effects of LLLT in the treatment of severe nerve injuries and denervated slow-twitch muscles are still inconclusive. OBJECTIVES: The aim of this study was to evaluate the effects of different wavelengths and energy densities of LLLT irradiation, applied to a severe nerve injury after reconstruction, on denervated slow-twitch skeletal muscle adaptation. METHOD: Rats were submitted to a neurotmesis of the sciatic nerve followed by end-to-end neurorrhaphy. They received transcutaneous LLLT irradiation at the lesion site. The LLLT parameters were: wavelengths - 660 or 780 nm; energy densities - 10, 60 or 120 J/cm²; power - 40 mW; spot - 4 mm². Sciatic functional index (SFI, histological, morphometric, and zymographic analyses were performed. One-way ANOVA followed by Tukey's test was used (pCONTEXTUALIZAÇÃO: A reabilitaçao das lesões nervosas periféricas (LNP ainda é um desafio para a fisioterapia. A terapia com o laser de baixa potência (LBP é descrita como um recurso físico capaz de interagir com enzimas relacionadas à alteração da matrix extracelular. Denominadas metalopeptidases (MMPs, essas enzimas atuam durante a recuperação neuromuscular após LNP. No entanto, os efeitos da LBP no tratamento de músculos desnervados de contração lenta após LNP graves ainda são inconclusivos. OBJETIVO: Avaliar os efeitos de diferentes comprimentos de onda e densidades de energia de irradiação de LBP, aplicado sobre o local do nervo após LNP grave e reconstrução. MÉTODO: Ratos foram submetidos a neurotmese do nervo isquiático e

  9. Left cardiac sympathetic denervation for catecholaminergic polymorphic ventricular tachycardia

    NARCIS (Netherlands)

    Wilde, Arthur A. M.; Bhuiyan, Zahurul A.; Crotti, Lia; Facchini, Mario; de Ferrari, Gaetano M.; Paul, Thomas; Ferrandi, Chiara; Koolbergen, Dave R.; Odero, Attilio; Schwartz, Peter J.

    2008-01-01

    Catecholaminergic polymorphic ventricular tachycardia is a potentially lethal disease characterized by adrenergically mediated ventricular arrhythmias manifested especially in children and teenagers. Beta-blockers are the cornerstone of therapy, but some patients do not have a complete response to

  10. Renal denervation therapy for hypertension: pathways for moving development forward.

    Science.gov (United States)

    White, William B; Galis, Zorina S; Henegar, Jeffrey; Kandzari, David E; Victor, Ronald; Sica, Domenic; Townsend, Raymond R; Turner, J Rick; Virmani, Renu; Mauri, Laura

    2015-05-01

    This scientific statement provides a summary of presentations and discussions at a cardiovascular Think Tank co-sponsored by the American Society of Hypertension (ASH), the United States Food and Drug Administration (FDA), and the National Heart, Lung, and Blood Institute (NHLBI) held in North Bethesda, Maryland, on June 26, 2014. Studies of device therapies for the treatment of hypertension are requested by regulators to evaluate their safety and efficacy during their development programs. Think Tank participants thought that important considerations in undertaking such studies were: (1) Preclinical assessment: how likely it is that both efficacy and safety data indicating benefit in humans will be obtained, and/or whether a plausible mechanism of action for efficacy can be identified; (2) Early human trial(s): the ability to determine that the device has an acceptable benefit-to-risk balance for its use in the intended patient population and without the influence of drug therapy during a short-term follow-up period; and (3) Pivotal Phase III trial(s): the ability to prove the effectiveness of the device in a broad population in which the trial can be made as non-confounded as possible while still allowing for the determination for benefits when added to antihypertensive therapies. Copyright © 2015 American Society of Hypertension. All rights reserved.

  11. Adrenergic receptors are a fallible index of adrenergic denervation hypersensitivity

    DEFF Research Database (Denmark)

    Dejgaard, Anders; Liggett, S B; Christensen, N J

    1991-01-01

    In view of evidence that neither interindividual nor induced intra-individual variations of adrenergic receptor status are related to metabolic or haemodynamic sensitivity to adrenaline in vivo, we took an alternative approach to assessment of the relevance of adrenergic receptor measurement...... densities (and binding affinities), measured with 3H-labelled yohimbine, and adrenaline-induced suppression of cyclic AMP contents did not differ among the three groups. Thus, in contrast to idiopathic autonomic failure, there is no generalized increase in adrenergic receptors in autonomic failure due...

  12. Partial Denervation of Subbasal Axons Persists Following Debridement Wounds to the Mouse Cornea

    Science.gov (United States)

    Pajoohesh-Ganji, Ahdeah; Pal-Ghosh, Sonali; Tadvalkar, Gauri; Kyne, Briana M.; Saban, Daniel R.; Stepp, Mary Ann

    2015-01-01

    Although sensory reinnervation occurs after injury in the PNS, poor reinnervation in the elderly and those with diabetes often leads to pathology. Here we quantify subbasal axon density in the central and peripheral mouse cornea over time after three different types of injury. The mouse cornea is highly innervated with a dense array of subbasal nerves that form a spiral called the vortex at the corneal center or apex; these nerves are readily detected within flat mounted corneas. After anesthesia, corneal epithelial cells were removed using either a dulled blade or a rotating burr within an area demarcated centrally with a 1.5 mm trephine. A third wound type, superficial trephination, involved demarcating the area with the 1.5 mm trephine but not removing cells. By 7d after superficial trephination, subbasal axon density returns to control levels; by 28d the vortex reforms. Although axon density is similar to control 14d after dulled blade and rotating burr wounding, defects in axon morphology at the corneal apex remain. After 14d, axons retract from the center leaving the subbasal axon density reduced by 37.2% and 36.8% at 28d after dulled blade and rotating burr wounding, respectively, compared to control. Assessment of inflammation using flow cytometry shows that persistent inflammation is not a factor in the incomplete reinnervation. Expression of mRNAs encoding 22 regeneration associated genes (RAGs) involved in axon targeting assessed by QPCR reveals that netrin-1 and ephrin signaling are altered after wounding. Subpopulations of corneal epithelial basal cells at the corneal apex stop expressing ki67 as early as 7d after injury and by 14d and 28d after wounding, many of these basal cells undergo apoptosis and die. While subbasal axons are restored to their normal density and morphology after superficial trephination, subbasal axon recovery is partial after debridement wounds. The increase in corneal epithelial basal cell apoptosis at the apex observed at 14d after corneal debridement may destabilize newly reinnervated subbasal axons and lead to their retraction towards the periphery. PMID:26280222

  13. Partial denervation of sub-basal axons persists following debridement wounds to the mouse cornea.

    Science.gov (United States)

    Pajoohesh-Ganji, Ahdeah; Pal-Ghosh, Sonali; Tadvalkar, Gauri; Kyne, Briana M; Saban, Daniel R; Stepp, Mary Ann

    2015-11-01

    Although sensory reinnervation occurs after injury in the peripheral nervous system, poor reinnervation in the elderly and those with diabetes often leads to pathology. Here we quantify sub-basal axon density in the central and peripheral mouse cornea over time after three different types of injury. The mouse cornea is highly innervated with a dense array of sub-basal nerves that form a spiral called the vortex at the corneal center or apex; these nerves are readily detected within flat mounted corneas. After anesthesia, corneal epithelial cells were removed using either a dulled blade or a rotating burr within an area demarcated centrally with a 1.5 mm trephine. A third wound type, superficial trephination, involved demarcating the area with the 1.5 mm trephine but not removing cells. By 7 days after superficial trephination, sub-basal axon density returns to control levels; by 28 days the vortex reforms. Although axon density is similar to control 14 days after dulled blade and rotating burr wounding, defects in axon morphology at the corneal apex remain. After 14 days, axons retract from the center leaving the sub-basal axon density reduced by 37.2 and 36.8% at 28 days after dulled blade and rotating burr wounding, respectively, compared with control. Assessment of inflammation using flow cytometry shows that persistent inflammation is not a factor in the incomplete reinnervation. Expression of mRNAs encoding 22 regeneration-associated genes involved in axon targeting assessed by QPCR reveals that netrin-1 and ephrin signaling are altered after wounding. Subpopulations of corneal epithelial basal cells at the corneal apex stop expressing ki67 as early as 7 days after injury and by 14 and 28 days after wounding, many of these basal cells undergo apoptosis and die. Although sub-basal axons are restored to their normal density and morphology after superficial trephination, sub-basal axon recovery is partial after debridement wounds. The increase in corneal epithelial basal cell apoptosis at the apex observed at 14 days after corneal debridement may destabilize newly reinnervated sub-basal axons and lead to their retraction toward the periphery.

  14. Macrophage populations and cardiac sympathetic denervation during L-NAME-induced hypertension in rats

    DEFF Research Database (Denmark)

    Neves, S R S; Machado, C R S; Pinto, A M T

    2006-01-01

    The rat model of hypertension induced by prolonged treatment with Nomega-nitro-L-arginine methyl ester (L-NAME) has been extensively used. However, the effects on cardiac autonomic innervation are unknown. Here, the cardiac sympathetic innervation is analyzed in parallel with myocardial lesions a...

  15. INFLUENCE OF PERI-ARTERIAL HEPATIC DENERVATION ON THE GLYCEMIC RESPONSE TO EXERCISE IN RATS

    NARCIS (Netherlands)

    LINDFELDT, J; BALKAN, B; VANDIJK, G; SCHEURINK, A; AHREN, B; STEFFENS, AB

    Exercise is known to increase hepatic glucose production. Previous studies have suggested that the sympathetic nerves only marginally contribute to this process. This study examined whether increased catecholamine response or increased adrenoceptor sensitivity might have affected previous results

  16. Contribution of denervated muscle to contractures after neonatal brachial plexus injury: not just muscle fibrosis.

    Science.gov (United States)

    Nikolaou, Sia; Liangjun, Hu; Tuttle, Lori J; Weekley, Holly; Christopher, Wylie; Lieber, Richard L; Cornwall, Roger

    2014-03-01

    We investigated the contribution of muscle fibrosis to elbow flexion contractures in a murine model of neonatal brachial plexus injury (NBPI). Four weeks after NBPI, biceps and brachialis fibrosis were assessed histologically and compared with the timing of contracture development and the relative contribution of each muscle to contractures. Modulus of elasticity and hydroxyproline (collagen) content were measured and correlated with contracture severity. The effect of halofuginone antifibrotic therapy on fibrosis and contractures was investigated. Elbow contractures preceded muscle fibrosis development. The brachialis was less fibrotic than the biceps, yet contributed more to contractures. Modulus and hydroxyproline content increased in both elbow flexors, but neither correlated with contracture severity. Halofuginone reduced biceps fibrosis but did not reduce contracture severity. Contractures after NBPI cannot be explained solely by muscle fibrosis, arguing for investigation of alternate pathophysiologic targets for contracture prevention and treatment. Copyright © 2013 Wiley Periodicals, Inc.

  17. The fate of neurotization techniques on reinnervation after denervation of the gastrocnemius muscle: an experimental study.

    Science.gov (United States)

    Askar, I; Sabuncuoglu, B T; Yormuk, E; Saray, A

    2001-07-01

    In nerve injuries, if it is not possible to reinnervate muscle by using neurorrhaphy and nerve grafting technique, reinnervation should be provided by the use of neuroization-directly implanting motor nerve into muscle. A comparative study of three techniques of neurotization is presented in rabbits. In this experimental study, a total of 40 white New Zealand rabbits were used and divided into four groups, each including 10 rabbits. In the first group (control--Group 1), only surgical exposure of the gastrocnemius muscle, main muscle nerve (tibial nerve), and peroneal nerve was done, without any injury to the nerves. In the second group (direct neurotization group--Group 2), the tibial nerve was transected, and the peroneal nerve, which had already been divided into fascicles, was implanted into the lateral head of the gastrocnemius muscle aneural zone. In the third group (dual neurotization group--Group 3), the tibial nerve which had been transected and re-anastomosed, and the peroneal nerve were implanted into the lateral head of the gastrocnemius muscle. In the last experimental group (hyperneurotization group--Group 4), fascicles of the peroneal nerve were implanted into the lateral head of the gastrocnemius, preserving the tibial nerve. Six months later, changes in the histologic pattern and the functional recovery of the gastrocnemius muscle were investigated. It was found that functional recovery was achieved in all neurotization groups. Groups with the tibial nerve transected had less muscular weights than those of groups with the tibial nerve intact. EMG recordings showed that polyphasic and late potentials were frequently seen in groups with the tibial nerve transected. Degeneration and regeneration of myofibrils was observed in such groups as well. New motor end-plates, including vesicles, were formed in a scattered manner in all neurotization groups. As a result, the authors conclude that direct and dual neurotization techniques are useful in peripheral nerve injuries, if it is not possible to reinnervate muscle by using neurorraphy and nerve grafting, and that there is no suggested superiority among these techniques.

  18. International expert consensus statement: Percutaneous transluminal renal denervation for the treatment of resistant hypertension.

    Science.gov (United States)

    Schlaich, Markus P; Schmieder, Roland E; Bakris, George; Blankestijn, Peter J; Böhm, Michael; Campese, Vito M; Francis, Darrel P; Grassi, Guido; Hering, Dagmara; Katholi, Richard; Kjeldsen, Sverre; Krum, Henry; Mahfoud, Felix; Mancia, Giuseppe; Messerli, Franz H; Narkiewicz, Krzysztof; Parati, Gianfranco; Rocha-Singh, Krishna J; Ruilope, Luis M; Rump, Lars C; Sica, Domenic A; Sobotka, Paul A; Tsioufis, Costas; Vonend, Oliver; Weber, Michael A; Williams, Bryan; Zeller, Thomas; Esler, Murray D

    2013-12-03

    Catheter-based radiofrequency ablation technology to disrupt both efferent and afferent renal nerves has recently been introduced to clinical medicine after the demonstration of significant systolic and diastolic blood pressure reductions. Clinical trial data available thus far have been obtained primarily in patients with resistant hypertension, defined as standardized systolic clinic blood pressure ≥ 160 mm Hg (or ≥ 150 mm Hg in patients with type 2 diabetes) despite appropriate pharmacologic treatment with at least 3 antihypertensive drugs, including a diuretic agent. Accordingly, these criteria and blood pressure thresholds should be borne in mind when selecting patients for renal nerve ablation. Secondary forms of hypertension and pseudoresistance, such as nonadherence to medication, intolerance of medication, and white coat hypertension, should have been ruled out, and 24-h ambulatory blood pressure monitoring is mandatory in this context. Because there are theoretical concerns with regard to renal safety, selected patients should have preserved renal function, with an estimated glomerular filtration rate ≥ 45 ml/min/1.73 m(2). Optimal periprocedural management of volume status and medication regimens at specialized and experienced centers equipped with adequate infrastructure to cope with potential procedural complications will minimize potential patient risks. Long-term safety and efficacy data are limited to 3 years of follow-up in small patient cohorts, so efforts to monitor treated patients are crucial to define the long-term performance of the procedure. Although renal nerve ablation could have beneficial effects in other conditions characterized by elevated renal sympathetic nerve activity, its potential use for such indications should currently be limited to formal research studies of its safety and efficacy. Copyright © 2013 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

  19. Renal sympathetic denervation in uncontrolled arterial hypertension after successful repair for aortic coarctation.

    Science.gov (United States)

    Lurz, Philipp; Okon, Thomas; Riede, Thomas; Wagner, Robert; Schuler, Gerhard; Daehnert, Ingo; Desch, Steffen

    2016-01-01

    Uncontrolled arterial hypertension is a frequent problem after successful repair of CoA and has been attributed to increased central sympathetic drive as well as a blunted baroreceptor reflex. RSD is a promising therapy to reduce central sympathetic drive and improve baroreflex sensitivity. 8 patients (age: 27±6 years) with previous surgical and/or percutaneous repair of CoA, absence of any relevant restenosis (invasive gradient across the site of previous treatment 3±4 mmHg) and resistant arterial hypertension (daytime SBP≥140 mmHg on 24 hour ambulatory blood pressure measurements [ABPM] in spite of the concurrent use of 3 antihypertensive agents of different classes or intolerance to BP medications) were included. Bilateral RSD was performed using the Symplicity Flex™ catheter (Medtronic, MN, USA). RSD was successful in all patients with no procedural complications and no evidence for renal artery stenosis 6 months post procedure. From baseline to 6 month follow-up, RSD was followed by a significant reduction in average daytime systolic BP (150.4±7.8 to 143.1±8.0 mmHg; p=0.0117) as well as systolic BP throughout 24 h (146.8±7.3 vs. 140.5±7.8, p=0.04). The BP reductions observed in these patients justify engaging in a larger clinical trial on the efficacy of RSD in this specific type of secondary hypertension and bares the hope that RSD might extend the currently very limited armory against arterial hypertension in young adults with previous repair of CoA. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  20. Renal denervation to improve catheter ablation outcomes in patients with arterial hypertension and atrial fibrillation

    Directory of Open Access Journals (Sweden)

    Д. А. Заманов

    2016-01-01

    Full Text Available Objective. The aim of this study was to assess the impact of RD in conjunction with pulmonary vein isolation (PVI on patients with atrial fibrillation (AF and moderate resistant or severe resistant hypertension.Methods. The data for this study were obtained from two different prospective randomized trials and evaluated by means of meta-analysis. Patients with paroxysmal or persistent AF and moderate resistant hypertension (BP ≥140/90 mm Hg and <160/100 mm Hg; n = 60 or resistant hypertension (≥160/100 mm Hg; second study; n = 50 were randomized to PVI or PVI with RD groups and followed up during 18 months. Results. Each group had 55 patients. At 18-months, 35 (63.6% of the 55 PVI with RD group patients were AF-free vs 22 (40% of the 55 patients in the PVI-only group (p = 0.013; log-rank test. In patients with severe hypertension, 16 (64% of the 25 PVI with RD group patients vs 6 (24% of the 25 PVI-only group patients were AF-free (p = 0.004; log-rank test. For moderate hypertension, the differences were less dramatic: 16 (53.3% of 30 vs 19 (63.3% of 30 when RD was added (p = 0.43. Superior efficacy of adding RD was most apparent in persistent AF and resistant hypertension (probability risk 0.24 95%, confidence interval 0.08–0.69, p = 0.012. Conclusion. RD improves the outcomes of PVI, especially in patients with persistent AF and resistant hypertension.

  1. An Update on Renal Artery Denervation and Its Clinical Impact on Hypertensive Disease

    OpenAIRE

    Bhat, Aditya; Kuang, Ye Min; Gan, Gary C. H.; Burgess, David; Denniss, Alan Robert

    2015-01-01

    Hypertension is a globally prevalent condition, with a heavy clinical and economic burden. It is the predominant risk factor for premature cardiovascular and cerebrovascular disease, and is associated with a variety of clinical disorders including stroke, congestive cardiac failure, ischaemic heart disease, chronic renal failure, and peripheral arterial disease. A significant subset of hypertensive patients have resistant hypertensive disease. In this group of patients, catheter-based renal a...

  2. Proximal Neuropathy and Associated Skeletal Muscle Changes Resembling Denervation Atrophy in Hindlimbs of Chronic Hypoglycaemic Rats

    DEFF Research Database (Denmark)

    Jensen, Vivi F.H.; Molck, Anne Marie; Soeborg, Henrik

    2017-01-01

    Peripheral neuropathy is one of the most common complications of diabetic hyperglycaemia. Insulin-induced hypoglycaemia (IIH) might potentially exacerbate or contribute to neuropathy as hypoglycaemia also causes peripheral neuropathy. In rats, IIH induces neuropathy associated with skeletal muscle......, and severity of the myofibre atrophy correlated with severity of axonal degeneration in sciatic nerve. Both neuropathy and myopathy were still present after four weeks of recovery, although the neuropathy was less severe. In conclusion, the results suggest that peripheral neuropathy induced by IIH progresses...... changes. Aims of this study were to investigate the progression and sequence of histopathologic changes caused by chronic IIH in rat peripheral nerves and skeletal muscle, and whether such changes were reversible. Chronic IIH was induced by infusion of human insulin, followed by an infusion-free recovery...

  3. Proximal Neuropathy and Associated Skeletal Muscle Changes Resembling Denervation Atrophy in Hindlimbs of Chronic Hypoglycaemic Rats

    DEFF Research Database (Denmark)

    Jensen, Vivi F.H.; Molck, Anne Marie; Soeborg, Henrik

    2018-01-01

    Peripheral neuropathy is one of the most common complications of diabetic hyperglycaemia. Insulin-induced hypoglycaemia (IIH) might potentially exacerbate or contribute to neuropathy as hypoglycaemia also causes peripheral neuropathy. In rats, IIH induces neuropathy associated with skeletal muscle......, and severity of the myofibre atrophy correlated with severity of axonal degeneration in sciatic nerve. Both neuropathy and myopathy were still present after four weeks of recovery, although the neuropathy was less severe. In conclusion, the results suggest that peripheral neuropathy induced by IIH progresses...... changes. Aims of this study were to investigate the progression and sequence of histopathologic changes caused by chronic IIH in rat peripheral nerves and skeletal muscle, and whether such changes were reversible. Chronic IIH was induced by infusion of human insulin, followed by an infusion-free recovery...

  4. Hemodynamic and ADH responses to central blood volume shifts in cardiac-denervated humans

    Science.gov (United States)

    Convertino, V. A.; Thompson, C. A.; Benjamin, B. A.; Keil, L. C.; Savin, W. M.; Gordon, E. P.; Haskell, W. L.; Schroeder, J. S.; Sandler, H.

    1990-01-01

    Hemodynamic responses and antidiuretic hormone (ADH) were measured during body position changes designed to induce blood volume shifts in ten cardiac transplant recipients to assess the contribution of cardiac and vascular volume receptors in the control of ADH secretion. Each subject underwent 15 min of a control period in the seated posture, then assumed a lying posture for 30 min at 6 deg head down tilt (HDT) followed by 20 min of seated recovery. Venous blood samples and cardiac dimensions (echocardiography) were taken at 0 and 15 min before HDT, 5, 15, and 30 min of HDT, and 5, 15, and 30 min of seated recovery. Blood samples were analyzed for hematocrit, plasma osmolality, plasma renin activity (PRA), and ADH. Resting plasma volume (PV) was measured by Evans blue dye and percent changes in PV during posture changes were calculated from changes in hematocrit. Heart rate (HR) and blood pressure (BP) were recorded every 2 min. Results indicate that cardiac volume receptors are not the only mechanism for the control of ADH release during acute blood volume shifts in man.

  5. Axonal sprouting regulates myelin basic protein gene expression in denervated mouse hippocampus

    DEFF Research Database (Denmark)

    Jensen, M B; Poulsen, F R; Finsen, B

    2000-01-01

    to 35 days after transection of the entorhino-hippocampal perforant path axonal projection. In situ hybridization analysis showed that anterograde axonal and terminal degeneration lead to upregulated oligodendrocyte MBP mRNA expression starting between day 2 and day 4, in (1) the deep part of stratum...... axonal and terminal degeneration, myelin degenerative changes, microglial activation and axotomi-induced axonal sprouting. Oligodendrocyte MBP mRNA expression reached maximum in both these areas at day 7. MBP gene transcription remained constant in stratum radiatum, stratum pyramidale and stratum oriens...... of CA1, areas that were unaffected by perforant path transection. These results provide strong evidence that oligodendrocyte MBP gene expression can be regulated by axonal sprouting independently of microglial activation in the injured adult CNS....

  6. Direct Posterior Bipolar Cervical Facet Radiofrequency Rhizotomy: A Simpler and Safer Approach to Denervate the Facet Capsule.

    Science.gov (United States)

    Palea, Ovidiu; Andar, Haroon M; Lugo, Ramon; Granville, Michelle; Jacobson, Robert E

    2018-03-14

    Radiofrequency cervical rhizotomy has been shown to be effective for the relief of chronic neck pain, whether it be due to soft tissue injury, cervical spondylosis, or post-cervical spine surgery. The target and technique have traditionally been taught using an oblique approach to the anterior lateral capsule of the cervical facet joint. The goal is to position the electrode at the proximal location of the recurrent branch after it leaves the exiting nerve root and loops back to the cervical facet joint. The standard oblique approach to the recurrent nerve requires the testing of both motor and sensory components to verify the correct position and ensure safety so as to not damage the slightly more anterior nerve root. Bilateral lesions require the repositioning of the patient's neck. Poorly positioned electrodes can also pass anteriorly and contact the nerve root or vertebral artery. The direct posterior approach presented allows electrode positioning over a broader expanse of the facet joint without risk to the nerve root or vertebral artery. Over a four-year period, direct posterior radiofrequency ablation was performed under fluoroscopic guidance at multiple levels without neuro-stimulation testing with zero procedural neurologic events even as high as the C2 spinal segment. The direct posterior approach allows either unipolar or bipolar lesioning at multiple levels. Making a radiofrequency lesion along the larger posterior area of the facet capsule is as effective as the traditional target point closer to the nerve root but technically easier, allowing bilateral access and safety. The article will review the anatomy and innervation of the cervical facet joint and capsule, showing the diffuse nerve supply extending into the capsule of the facet joint that is more extensive than the recurrent medial sensory branches that have been the focus of radiofrequency lesioning.

  7. Association between left ventricular regional sympathetic denervation and mechanical dyssynchrony in phase analysis: a cardiac CZT study

    Energy Technology Data Exchange (ETDEWEB)

    Gimelli, Alessia; Genovesi, Dario; Giorgetti, Assuero; Kusch, Annette [Fondazione Toscana Gabriele Monasterio, Pisa (Italy); Liga, Riccardo [Scuola Superiore Sant' Anna, Pisa (Italy); Marzullo, Paolo [Fondazione Toscana Gabriele Monasterio, Pisa (Italy); CNR, Institute of Clinical Physiology, Pisa (Italy)

    2014-05-15

    To evaluate the relationships among myocardial sympathetic innervation, perfusion and mechanical synchronicity assessed with cardiac cadmium-zinc-telluride (CZT) scintigraphy. A group of 29 patients underwent an evaluation of myocardial perfusion with {sup 99m}Tc-tetrofosmin CZT scintigraphy and adrenergic innervation with {sup 123}I-metaiodobenzylguanidine (MIBG) CZT scintigraphy. The summed rest score (SRS), motion score (SMS) and thickening score (STS), as well as the summed {sup 123}I-MIBG defect score (SS-MIBG), were determined. Regional tracer uptake for both {sup 99m}Tc-tetrofosmin and {sup 123}I-MIBG was also calculated. Finally, the presence of significant myocardial mechanical dyssynchrony was evaluated in phase analysis on gated CZT images and the region of latest mechanical activation identified. Significant mechanical dyssynchrony was present in 17 patients (59 %) and associated with higher SRS (P = 0.030), SMS (P < 0.001), STS (P = 0.003) and early SS-MIBG (P = 0.037) as well as greater impairments in left ventricular ejection fraction (P < 0.001) and end-diastolic volume (P < 0.001). In multivariate analysis a higher end-diastolic volume remained the only predictor of mechanical dyssynchrony (P = 0.047). Interestingly, while in the whole population regional myocardial perfusion and adrenergic activity were strongly correlated (R = 0.68), in patients with mechanical dyssynchrony the region of latest mechanical activation was predicted only by greater impairment in regional {sup 123}I-MIBG uptake (P = 0.012) that overwhelmed the effect of depressed regional perfusion. Left ventricular mechanical dyssynchrony is associated with greater depression in contractile function and greater impairments in regional myocardial perfusion and sympathetic activity. In patients with dyssynchrony, the region of latest mechanical activation is characterized by a significantly altered adrenergic tone. (orig.)

  8. A report of 3 soldiers returned to full duty after lumbar radiofrequency facet denervation in a theater of war.

    Science.gov (United States)

    Dragovich, Anthony; Trainer, Robert J

    2011-04-01

    To provide the advanced interventional procedure of zygapophysial joint neurotomy to soldiers meeting the diagnostic criteria in a combat environment and thus reduce medical evacuations of soldiers from a theater of war. Retrospective chart review was performed on three consecutive soldiers who received neuroablation of the lumbar ZP joint. Patients received single MBB with 1 cc of 1% lidocaine at the b/l L3-L5 levels considered diagnostic if >50% analgesia was achieved concordant with duration of anesthetic.   All procedures were co-performed by the two authors at the Ibn Sina hospital in Baghdad, Iraq over a 3-month period. Three consecutive patients with >50% pain relief from diagnostic medial branch blocks were treated with radiofrequency ablation of the bilateral L3-L4 medial branch nerves and L5 posterior primary ramus. Sensory test stimulation at 50 Hz and motor stimulation at 2 Hz were performed at each level. The nerves were then lesioned at 80° Centigrade for 90 seconds after injection of lidocaine and methylprednisolone. Procedure was considered successful if patients were able to wear body armour without significant discomfort (at least 1 hour/day). Medical evacuation from Iraq was prevented and all soldiers returned to rigorous combat duties including the wearing of body armour daily. We believe to be the first to report on the use of RF nerve ablation in a war time setting and with this functional outcome. Wiley Periodicals, Inc.

  9. Association between left ventricular regional sympathetic denervation and mechanical dyssynchrony in phase analysis: a cardiac CZT study

    International Nuclear Information System (INIS)

    Gimelli, Alessia; Genovesi, Dario; Giorgetti, Assuero; Kusch, Annette; Liga, Riccardo; Marzullo, Paolo

    2014-01-01

    To evaluate the relationships among myocardial sympathetic innervation, perfusion and mechanical synchronicity assessed with cardiac cadmium-zinc-telluride (CZT) scintigraphy. A group of 29 patients underwent an evaluation of myocardial perfusion with 99m Tc-tetrofosmin CZT scintigraphy and adrenergic innervation with 123 I-metaiodobenzylguanidine (MIBG) CZT scintigraphy. The summed rest score (SRS), motion score (SMS) and thickening score (STS), as well as the summed 123 I-MIBG defect score (SS-MIBG), were determined. Regional tracer uptake for both 99m Tc-tetrofosmin and 123 I-MIBG was also calculated. Finally, the presence of significant myocardial mechanical dyssynchrony was evaluated in phase analysis on gated CZT images and the region of latest mechanical activation identified. Significant mechanical dyssynchrony was present in 17 patients (59 %) and associated with higher SRS (P = 0.030), SMS (P 123 I-MIBG uptake (P = 0.012) that overwhelmed the effect of depressed regional perfusion. Left ventricular mechanical dyssynchrony is associated with greater depression in contractile function and greater impairments in regional myocardial perfusion and sympathetic activity. In patients with dyssynchrony, the region of latest mechanical activation is characterized by a significantly altered adrenergic tone. (orig.)

  10. Denervation and high-fat diet reduce insulin signaling in T-tubules in skeletal muscle of living mice

    DEFF Research Database (Denmark)

    Lauritzen, Hans P M; Ploug, Thorkil; Ai, Hua

    2008-01-01

    OBJECTIVE: Insulin stimulates muscle glucose transport by translocation of GLUT4 to sarcolemma and T-tubules. Despite muscle glucose uptake playing a major role in insulin resistance and type 2 diabetes, the temporal and spatial changes in insulin signaling and GLUT4 translocation during these co...

  11. Anterograde transneuronal viral tract tracing reveals central sensory circuits from brown fat and sensory denervation alters its thermogenic responses.

    Science.gov (United States)

    Vaughan, Cheryl H; Bartness, Timothy J

    2012-05-01

    Brown adipose tissue (BAT) thermogenic activity and growth are controlled by its sympathetic nervous system (SNS) innervation, but nerve fibers containing sensory-associated neuropeptides [substance P, calcitonin gene-related peptide (CGRP)] also suggest sensory innervation. The central nervous system (CNS) projections of BAT afferents are unknown. Therefore, we used the H129 strain of the herpes simplex virus-1 (HSV-1), an anterograde transneuronal viral tract tracer used to delineate sensory nerve circuits, to define these projections. HSV-1 was injected into interscapular BAT (IBAT) of Siberian hamsters and HSV-1 immunoreactivity (ir) was assessed 24, 48, 72, 96, and 114 h postinjection. The 96- and 114-h groups had the most HSV-1-ir neurons with marked infections in the hypothalamic paraventricular nucleus, periaqueductal gray, olivary areas, parabrachial nuclei, raphe nuclei, and reticular areas. These sites also are involved in sympathetic outflow to BAT suggesting possible BAT sensory-SNS thermogenesis feedback circuits. We tested the functional contribution of IBAT sensory innervation on thermogenic responses to an acute (24 h) cold exposure test by injecting the specific sensory nerve toxin capsaicin directly into IBAT pads and then measuring core (T(c)) and IBAT (T(IBAT)) temperature responses. CGRP content was significantly decreased in capsaicin-treated IBAT demonstrating successful sensory nerve destruction. T(IBAT) and T(c) were significantly decreased in capsaicin-treated hamsters compared with the saline controls at 2 h of cold exposure. Thus the central sensory circuits from IBAT have been delineated for the first time, and impairment of sensory feedback from BAT appears necessary for the appropriate, initial thermogenic response to acute cold exposure.

  12. Superficial or deep implantation of motor nerve after denervation: an experimental study--superficial or deep implantation of motor nerve.

    Science.gov (United States)

    Askar, Ibrahím; Sabuncuoglu, Bízden Tavíl

    2002-01-01

    Neurorraphy, conventional nerve grafting technique, and artificial nerve conduits are not enough for repair in severe injuries of peripheral nerves, especially when there is separation of motor nerve from muscle tissue. In these nerve injuries, reinnervation is indicated for neurotization. The distal end of a peripheral nerve is divided into fascicles and implanted into the aneural zone of target muscle tissue. It is not known how deeply fascicles should be implanted into muscle tissue. A comparative study of superficial and deep implantation of separated motor nerve into muscle tissue is presented in the gastrocnemius muscle of rabbits. In this experimental study, 30 white New Zealand rabbits were used and divided into 3 groups of 10 rabbits each. In the first group (controls, group I), only surgical exposure of the gastrocnemius muscle and motor nerve (tibial nerve) was done without any injury to nerves. In the superficial implantation group (group II), tibial nerves were separated and divided into their own fascicles. These fascicles were implanted superficially into the lateral head of gastrocnemius muscle-aneural zone. In the deep implantation group (group III), the tibial nerves were separated and divided into their own fascicles. These fascicles were implanted around the center of the muscle mass, into the lateral head of the gastrocnemius muscle-aneural zone. Six months later, histopathological changes and functional recovery of the gastrocnemius muscle were investigated. Both experimental groups had less muscular weight than in the control group. It was found that functional recovery was achieved in both experimental groups, and was better in the superficial implantation group than the deep implantation group. EMG recordings revealed that polyphasic and late potentials were frequently seen in both experimental groups. Degeneration and regeneration of myofibrils were observed in both experimental groups. New motor end-plates were formed in a scattered manner in both experimental groups. However, they were more dense in the superficial implantation group than the deep implantation group. It was concluded that superficial implantation has a more powerful contractile capacity than that of deep implantation. We believe that this might arise from the high activity of glycolytic enzymes in peripheral muscle fibers of gastrocnemius muscle, decrease in insufficient intramuscular guidance apparatus, and intramuscular microneuroma formation at the insufficient neuromuscular junction since the motor nerve had less route to muscle fibers. Copyright 2002 Wiley-Liss, Inc.

  13. Account for Clinical Heterogeneity in Assessment of Catheter-based Renal Denervation among Resistant Hypertension Patients: Subgroup Meta-analysis

    Directory of Open Access Journals (Sweden)

    Xiao-Han Chen

    2017-01-01

    Conclusions: In all patients with RH, the catheter-based RDN is not more effective in lowering ambulatory or office BP than an optimized antihypertensive drug treatment at 6 and 12 months. However, among RH patients with higher baseline SBP, RDN might be more effective in reducing SBP.

  14. Denervation of the Lacrimal Gland Leads to Corneal Hypoalgesia in a Novel Rat Model of Aqueous Dry Eye Disease.

    Science.gov (United States)

    Aicher, Sue A; Hermes, Sam M; Hegarty, Deborah M

    2015-10-01

    Some dry eye disease (DED) patients have sensitized responses to corneal stimulation, while others experience hypoalgesia. Many patients have normal tear production, suggesting that reduced tears are not always the cause of DED sensory dysfunction. In this study, we show that disruption of lacrimal innervation can produce hypoalgesia without changing basal tear production. Injection of a saporin toxin conjugate into the extraorbital lacrimal gland of male Sprague-Dawley rats was used to disrupt cholinergic innervation to the gland. Tear production was assessed by phenol thread test. Corneal sensory responses to noxious stimuli were assessed using eye wipe behavior. Saporin DED animals were compared to animals treated with atropine to produce aqueous DED. Cholinergic innervation and acetylcholine content of the lacrimal gland were significantly reduced in saporin DED animals, yet basal tear production was normal. Saporin DED animals demonstrated normal eye wipe responses to corneal application of capsaicin, but showed hypoalgesia to corneal menthol. Corneal nerve fiber density was normal in saporin DED animals. Atropine-treated animals had reduced tear production but normal responses to ocular stimuli. Because only menthol responses were impaired, cold-sensitive corneal afferents appear to be selectively altered in our saporin DED model. Hypoalgesia is not due to reduced tear production, since we did not observe hypoalgesia in an atropine DED model. Corneal fiber density is unaltered in saporin DED animals, suggesting that molecular mechanisms of nociceptive signaling may be impaired. The saporin DED model will be useful for exploring the mechanism underlying corneal hypoalgesia.

  15. Relationship between left ventricular diastolic function and myocardial sympathetic denervation measured by {sup 123}I-meta-iodobenzylguanidine imaging in Anderson-Fabry disease

    Energy Technology Data Exchange (ETDEWEB)

    Spinelli, Letizia; Giudice, Caterina Anna; Imbriaco, Massimo; Trimarco, Bruno; Cuocolo, Alberto [University Federico II, Department of Advanced Biomedical Sciences, Naples (Italy); Pellegrino, Teresa [Institute of Biostructure and Bioimaging, National Council of Research, Naples (Italy); Pisani, Antonio; Riccio, Eleonora [University Federico II, Department of Public Health, Naples (Italy); Salvatore, Marco [IRCCS SDN, Naples (Italy)

    2016-04-15

    Whether cardiac sympathetic nervous function abnormalities may be present in patients with Anderson-Fabry disease (AFD) remains unexplored. We investigated the relationship between left ventricular (LV) function and cardiac sympathetic nervous function in patients with AFD. Twenty-five patients (12 men, mean age 43 ± 13 years) with genetically proved AFD and preserved LV ejection fraction and ten age and gender-matched control subjects underwent speckle tracking echocardiography and {sup 123}I-meta-iodobenzylguanidine (MIBG) imaging from which early and late heart to mediastinum (H/M) ratios and myocardial washout rate values were calculated. In AFD patients, a significant correlation between late H/M ratio and LV mass index (r = -61, p = 0.001), left atrial volume (r = -0.72, p < 0.001), systolic pulmonary artery pressure (r = -0.75, p < 0.001), and early diastolic untwisting rate (r = -0.66, p < 0.001) was found. Ten AFD patients exhibited a late H/M ratio below two fold standard deviation of control subjects (≤1.75). Patients showing late H/M ratio ≤ 1.75 had significantly higher LV mass index, relative wall thickness, left atrial volume and systolic pulmonary artery pressure, lower systolic longitudinal strain and an early diastolic untwisting rate compared to patients with late H/M ratio > 1.75. At multivariable linear regression analysis, early diastolic untwisting rate was the only independent predictor of late H/M ratio ≤ 1.75 (odds ratio 1.15, 95 % confidence interval 1.07-1.31, p < 0.05). The present findings provide the first demonstration of a cardiac sympathetic derangement in AFD patients with preserved LV ejection fraction, which is mostly related to LV diastolic dysfunction. (orig.)

  16. LHRH incorporation in normal and denervated pineal gland, and in pineal gland of rats with constant estrous-anovulatory syndrome: a preliminary study

    International Nuclear Information System (INIS)

    Trentini, G.P.; DeGaetani, C.F.; DiGregorio, C.; Botticelli, C.S.

    1980-01-01

    Pineal gland and superior sympathetic cervical ganglia accumulated intravenously injected 3 H-LHRH in an amount significantly higher than anterior and posterior hypothalamus, cerebral cortex and pituitary gland, the latter a specific target for LHRH. The prior administration of unlabelled LHRH significantly decreased the 3 H-LHRH incorporation only in pineal and pituitary gland. Autoradiography showed that the radiolabel was localized at the level of the pinealocytes, with a seemingly, prevalent distribution of grains on the cellular contours. Pineal incorporation of LHRH was not significantly modified by either acute or chronic bilateral cervical ganglionectomy, although acute ganglioectomy resulted in a slight decrease in LHRH accumulation by pineal gland. Constant estrous anovulatory syndromes induced by either frontal hypothalamic deafferentation, or continuous illumination or neonatal androgenization did not appear to modify the LHRH incorporation in either pineal gland or cervical ganglia. Basing on these results, the pineal gland is supposed to be a target organ for LHRH. (author)

  17. Bilateral LMAN lesions cancel differences in HVC neuronal recruitment induced by unilateral syringeal denervation. Lateral magnocellular nucleus of the anterior neostriatum.

    Science.gov (United States)

    Wilbrecht, L; Petersen, T; Nottebohm, F

    2002-12-01

    Twenty-six-day-old male zebra finches received (1) unilateral section of their tracheosyringeal nerve, (2) bilateral lesions of the lateral magnocellular nucleus of the anterior neostriatum (LMAN), and (3) both operations. All birds were kept with an adult, singing male as a tutor until day 65. Tracheo-syringeal nerve-cut birds were able to imitate this model, but LMAN-lesioned birds were not. Bromodeoxyuridine, a marker of cell division, was injected intramuscularly during post-hatching days 61-65 and all birds were killed at 91 days of age. The number of bromodeoxyuridine+ neurons in the high vocal center of the tracheosyringeal-cut birds was twice as high in the intact as in the nerve cut side. This asymmetry disappeared when nerve section was combined with bilateral LMAN lesions. The latter operation, by itself, had no effect on new neuron counts. We suggest that the single nerve cut produced a hemispheric asymmetry in learning, reflected in new neuron recruitment, which disappeared when LMAN lesions blocked learning.

  18. BNN-20, a synthetic microneurotrophin, strongly protects dopaminergic neurons in the "weaver" mouse, a genetic model of dopamine-denervation, acting through the TrkB neurotrophin receptor.

    Science.gov (United States)

    Botsakis, Konstantinos; Mourtzi, Theodora; Panagiotakopoulou, Vasiliki; Vreka, Malamati; Stathopoulos, Georgios T; Pediaditakis, Iosif; Charalampopoulos, Ioannis; Gravanis, Achilleas; Delis, Foteini; Antoniou, Katerina; Zisimopoulos, Dimitrios; Georgiou, Christos D; Panagopoulos, Nikolaos T; Matsokis, Nikolaos; Angelatou, Fevronia

    2017-07-15

    Neurotrophic factors are among the most promising treatments aiming at slowing or stopping and even reversing Parkinson's disease (PD). However, in most cases, they cannot readily cross the human blood-brain-barrier (BBB). Herein, we propose as a therapeutic for PD the small molecule 17-beta-spiro-[5-androsten-17,2'-oxiran]-3beta-ol (BNN-20), a synthetic analogue of DHEA, which crosses the BBB and is deprived of endocrine side-effects. Using the "weaver" mouse, a genetic model of PD, which exhibits progressive dopaminergic neurodegeneration in the Substantia Nigra (SN), we have shown that long-term administration (P1-P21) of BNN-20 almost fully protected the dopaminergic neurons and their terminals, via i) a strong anti-apoptotic effect, probably mediated through the Tropomyosin receptor kinase B (TrkB) neurotrophin receptor's PI3K-Akt-NF-κB signaling pathway, ii) by exerting an efficient antioxidant effect, iii) by inducing significant anti-inflammatory activity and iv) by restoring Brain-Derived Neurotrophic Factor (BDNF) levels. By intercrossing "weaver" with NGL mice (dual GFP/luciferase-NF-κΒ reporter mice, NF-κΒ.GFP.Luc), we obtained Weaver/NGL mice that express the NF-κB reporter in all somatic cells. Acute BNN-20 administration to Weaver/NGL mice induced a strong NF-κB-dependent transcriptional response in the brain as detected by bioluminescence imaging, which was abolished by co-administration of the TrkB inhibitor ANA-12. This indicates that BNN-20 exerts its beneficial action (at least in part) through the TrkB-PI3K-Akt-NF-κB signaling pathway. These results could be of clinical relevance, as they suggest BNN-20 as an important neuroprotective agent acting through the TrkB neurotrophin receptor pathway, mimicking the action of the endogenous neurotrophin BDNF. Thus BNN-20 could be proposed for treatment of PD. Copyright © 2017. Published by Elsevier Ltd.

  19. Microglial reactivity correlates to the density and the myelination of the anterogradely degenerating axons and terminals following perforant path denervation of the mouse fascia dentata

    DEFF Research Database (Denmark)

    Jensen, M B; Hegelund, I V; Rom Poulsen, Frantz

    1999-01-01

    Transection of the entorhino-dentate perforant path is a well known model for lesion-induced axonal sprouting and glial reactions in the rat. In this study, we have characterized the microglial reaction in the dentate molecular layer of the SJL/J and C57Bl/6 mouse. The morphological transformatio...... in the individual cases. The finding of a potentiated or accelerated microglial activation in the medial as compared to the lateral perforant path zone suggests different kinetics of microglial activation in areas with degenerating myelinated and unmyelinated fibers....

  20. Beta-amyloid-induced cholinergic denervation correlates with enhanced nitric oxide synthase activity in rat cerebral cortex: Reversal by NMDA receptor blockade : Reversal by NMDA receptor blockade

    NARCIS (Netherlands)

    O’Mahony, S.; Harkany, T.; Ábrahám, I.; Jong, G.I. de; Varga, J.L.; Zarándi, M.; Penke, B.; Nyakas, C.; Luiten, P.G.M.; Leonard, B.E.

    1998-01-01

    Ample experimental evidence indicates that acute beta-amyloid infusion into the nucleus basalis of rats elicits abrupt degeneration of the magnocellular cholinergic neurons projecting to the cerebral cortex, In fact, involvement of a permanent Ca2+ overload, partially via N-methyl-D-aspartate (NMDA)

  1. Comparison of ST-depression in stress ECG with stress induced ischemia and denervation of myocardium measured by scintigraphic methods in patients after myocardial infarction

    OpenAIRE

    Kilgert, Katharina

    2005-01-01

    Die vorliegende Arbeit überprüft unter Berücksichtigung des Innervationsstatus des Herzens Belastungsuntersuchungen mit EKG und Szintigraphie auf ihre Übereinstimmung in der nichtinvasiven Postinfarktdiagnostik. Diese bestand in 57,4% der untersuchten Fälle. Ein möglicher Einfluss des Innervationsstatus des Herzens auf die Untersuchungsergebnisse konnte nicht bestätigt werden. Aufgrund nicht sicher einschätzbarer morphologischer Veränderungen nach einem Infarkt verlieren die hier behandelten ...

  2. Baroreflex failure: a neglected type of secondary hypertension

    NARCIS (Netherlands)

    Timmers, H. J. L. M.; Wieling, W.; Karemaker, J. M.; Lenders, J. W. M.

    2004-01-01

    The arterial baroreflex buffers abrupt transients of blood pressure and prevents pressure from rising or falling excessively. In experimental animals, baroreceptor denervation results in temporary or permanent increases in blood pressure level and variability, depending on the extent of denervation.

  3. Baroreflex failure: a neglected type of secondary hypertension.

    NARCIS (Netherlands)

    Timmers, H.J.L.M.; Wieling, W.; Karemaker, J.M.; Lenders, J.W.M.

    2004-01-01

    The arterial baroreflex buffers abrupt transients of blood pressure and prevents pressure from rising or falling excessively. In experimental animals, baroreceptor denervation results in temporary or permanent increases in blood pressure level and variability, depending on the extent of denervation.

  4. The Physiology of Neural Injury and Regeneration: The Role of Neurotrophic Factors

    Science.gov (United States)

    Gordon, Tessa

    2010-01-01

    Injured nerves regenerate slowly and often over long distances. Prolonged periods for regenerating nerves to make functional connections with denervated targets prolong the period of isolation of the neurons from the target (chronic axotomy) and of the denervation of Schwann cells in the distal nerve pathways (chronic denervation). In an animal…

  5. Drug Resistant Hypertension - No SIMPLE Way Out

    Directory of Open Access Journals (Sweden)

    Janusz Skrzypecki

    2015-02-01

    Full Text Available Hypertension poses growing challenge for health policy-makers and doctors worldwide. Recently published results of Symplicity-III trial (HTN-3, the first blinded, randomized, multicenter study on the efficacy of renal denervation for the treatment of resistant hypertension did not show a significant reduction of BP in patients with resistant hypertension 6 months after renal-artery denervation, as compared with controls. In this paper we review clinical and experimental studies on renal denervation. In order to identify causes of inconsistent results in renal denervation studies we look at basic science support for renal denervation and at designs of clinical trials.

  6. Renal nerves and nNOS

    DEFF Research Database (Denmark)

    Kompanowska-Jezierska, Elzbieta; Wolff, Helle; Kuczeriszka, Marta

    2008-01-01

    ). This was tested by NaLoad after chronic renal denervation with and without inhibition of nNOS by S-methyl-thiocitrulline (SMTC). In addition, the acute effects of renal denervation on MABP and sodium balance were assessed. Rats were investigated in the conscious, catheterized state, in metabolic cages...... of acutely and chronically denervated rats were less than control (15% and 9%, respectively, P reduced by renal denervation (14.5 +/- 0.2 vs. 19.3 +/- 1.3 mIU/l, P reduced...... PRC (P sodium excretion six-fold, irrespective of renal denervation and SMTC. The metabolic data demonstrated that renal denervation lowered sodium balance during the first days after denervation (P

  7. Efeito dos aminoácidos de cadeia ramificada no músculo imobilizado e no músculo desnervado = Effect of branched - chain amino acids on immobilized skeletal muscle and denervated muscle

    Directory of Open Access Journals (Sweden)

    Pezolato, Vitor Alexandre

    2014-01-01

    Full Text Available Objetivo: Este trabalho teve como objetivo avaliar histologicamente o músculo sóleo imobilizado e desnervado de ratos suplementados com aminoácidos de cadeia ramificada. Materiais e Métodos: Para a realização da pesquisa foram utilizados 30 ratos navergicus albinus machos, variedade Wistar, com 3 a 4 meses de vida, divididos em 6 grupos (n=5 e denominados: controle (C, desnervado 7 dias (D, imobilizado 7 dias (I, suplementado com aminoácidos de cadeia ramificada 7 dias (BCAA, desnervado suplementado com aminoácidos de cadeia ramificada (D+BCAA e imobilizado suplementado com aminoácidos de cadeia ramificada (I+BCAA. Os animais desnervados passaram pelo seccionamento do nervo ciático (1 cm. O s animais dos grupos imobilizados receberam uma órtese de resina acrílica acoplada na pata posterior promovendo a imobilização. Após a fase experimental os animais foram eutanasiados e os músculos foram analisados histologicamente. O teste de Shapiro - Wilk avaliou a normalidade dos dados, seguido da análise de variância e, posteriormente, Tukey - Kramer com nível de significância menor de 5%. Resultados: A suplementação aumentou a área de secçã o transversa da fibra muscular em 74,94% no grupo I+BCAA e 90,37% no grupo D+BCAA em relação aos grupos I e D, respectivamente. Houve aumento de 97,21% na densidade de área de tecido conjuntivo no grupo BCAA em relação ao grupo C, porém a suplementação pro moveu redução de 34,44% no grupo D+BCAA em relação ao grupo D, no entanto, não houve diferença significativa entre os grupos I+BCAA e I. Conclusão: Observa-se que a utilização dos aminoácidos de cadeia ramificada pode diminuir a atrofia provocada pelo desuso muscular, tanto na condição de desnervação quanto na condição de imobilização

  8. Device-based approaches for renal nerve ablation for hypertension and beyond.

    Science.gov (United States)

    Thorp, Alicia A; Schlaich, Markus P

    2015-01-01

    Animal and human studies have demonstrated that chronic activation of renal sympathetic nerves is critical in the pathogenesis and perpetuation of treatment-resistant hypertension. Bilateral renal denervation has emerged as a safe and effective, non-pharmacological treatment for resistant hypertension that involves the selective ablation of efferent and afferent renal nerves to lower blood pressure. However, the most recent and largest randomized controlled trial failed to confirm the primacy of renal denervation over a sham procedure, prompting widespread re-evaluation of the therapy's efficacy. Disrupting renal afferent sympathetic signaling to the hypothalamus with renal denervation lowers central sympathetic tone, which has the potential to confer additional clinical benefits beyond blood pressure control. Specifically, there has been substantial interest in the use of renal denervation as either a primary or adjunct therapy in pathological conditions characterized by central sympathetic overactivity such as renal disease, heart failure and metabolic-associated disorders. Recent findings from pre-clinical and proof-of-concept studies appear promising with renal denervation shown to confer cardiovascular and metabolic benefits, largely independent of changes in blood pressure. This review explores the pathological rationale for targeting sympathetic renal nerves for blood pressure control. Latest developments in renal nerve ablation modalities designed to improve procedural success are discussed along with prospective findings on the efficacy of renal denervation to lower blood pressure in treatment-resistant hypertensive patients. Preliminary evidence in support of renal denervation as a possible therapeutic option in disease states characterized by central sympathetic overactivity is also presented.

  9. Odor identification deficits identify Parkinson’s disease patients with poor cognitive performance

    DEFF Research Database (Denmark)

    Damholdt, Malene Flensborg; Borghammer, Per; Larsen, Lars

    2011-01-01

    Olfactory dysfunction is a prodromal and prevalent nonmotor symptom of Parkinson's disease. Unlike olfactory dysfunction in Alzheimer's disease, it is believed to be unrelated to cognitive impairment. However, recent research has implicated cholinergic denervation in Parkinson's disease hyposmia ...

  10. CONTRIBUTION OF LIVER NERVES, GLUCAGON, AND ADRENALINE TO THE GLYCEMIC RESPONSE TO EXERCISE IN RATS

    NARCIS (Netherlands)

    VAN DIJK, G; BALKAN, B; LINDFELDT, J; BOUWS, G; SCHEURINK, AJW; AHREN, B; STEFFENS, AB

    The contribution of hepatic sympathetic innervation, glucagon and adrenaline to the glycaemic response to exercise was investigated in rats. Hepatically denervated (LDX) or sham operated (SHAM) rats with permanent catheters were therefore submitted to swimming with or without infusion of

  11. SAJS SAJS

    African Journals Online (AJOL)

    Trauma. SAJS. 48. Achalasia of the cardia is the most common primary motil- ity disorder of ... However, the cumulative risk of subsequent intervention for achalasia at ... a primary denervation disorder but rather by neoplasm or postoperative ...

  12. Botulinum toxin injection causes hyper-reflexia and increased muscle stiffness of the triceps surae muscle in the rat

    OpenAIRE

    Pingel, Jessica; Wienecke, Jacob; Lorentzen, Jakob; Nielsen, Jens Bo

    2016-01-01

    This study demonstrates, for the first time, adaptive plastic changes in the stretch reflex circuitry following denervation induced by botulinum toxin injection. The study also demonstrates alterations of the elastic properties of the muscles following botulinum injection.

  13. Contribution of liver nerves, glucagon, and adrenaline to the glycaemic response to exercise in rats

    NARCIS (Netherlands)

    van Dijk, Gertjan; Balkan, B.; Lindfeldt, J.; Bouws, G.; Scheurink, A.J.W.; Ahrén, B.; Steffens, A.B.

    1994-01-01

    The contribution of hepatic sympathetic innervation, glucagon and adrenaline to the glycaemic response to exercise was investigated in rats. Hepatically denervated (LDX) or sham operated (SHAM) rats with permanent catheters were therefore submitted to swimming with or without infusion of

  14. Role of liver nerves and adrenal medulla in glucose turnover of running rats

    DEFF Research Database (Denmark)

    Sonne, B; Mikines, K J; Richter, Erik

    1985-01-01

    Sympathetic control of glucose turnover was studied in rats running 35 min at 21 m X min-1 on the level. The rats were surgically liver denervated, adrenodemedullated, or sham operated. Glucose turnover was measured by primed constant infusion of [3-3H]glucose. At rest, the three groups had...... identical turnover rates and concentrations of glucose in plasma. During running, glucose production always rose rapidly to steady levels. The increase was not influenced by liver denervation but was halved by adrenodemedullation. Similarly, hepatic glycogen depletion was identical in denervated and control...... rats but reduced after adrenodemedullation. Early in exercise, glucose uptake rose identically in all groups and, in adrenodemedullated rats, matched glucose production. Accordingly, plasma glucose concentration increased in liver-denervated and control rats but was constant in adrenodemedullated rats...

  15. Análise do exercício físico e eletroestimulção do músculo tibial cranial após neurorrafia término-lateral do nervo fibular em ratos

    OpenAIRE

    Rosa, Vívian Cristina [UNESP

    2015-01-01

    Lesions of peripheral nerves can be extremely disabling. In this context, microsurgery has presented a major role in the treatment of patients. However, even with all technical refinement achieved by microsurgery, full motor recovery has not been ensured yet. This can be explained by muscle degeneration, atrophy and functional losses generated by denervation. In the clinical setting, some physiotherapy resources have been suggested in order to minimize losses due to denervation. Among these r...

  16. Drug Resistant Hypertension - No SIMPLE Way Out

    OpenAIRE

    Janusz Skrzypecki; Marcin Ufnal

    2015-01-01

    Hypertension poses growing challenge for health policy-makers and doctors worldwide. Recently published results of Symplicity-III trial (HTN-3), the first blinded, randomized, multicenter study on the efficacy of renal denervation for the treatment of resistant hypertension did not show a significant reduction of BP in patients with resistant hypertension 6 months after renal-artery denervation, as compared with controls. In this paper we review clinical and experimental studies on renal dene...

  17. Role of the renin-angiotensin system in cardiac hypertrophy induced in rats by hyperthyroidism

    OpenAIRE

    KOBORI, HIROYUKI; ICHIHARA, ATSUHIRO; SUZUKI, HIROMICHI; TAKENAKA, TSUNEO; MIYASHITA, YUTAKA; HAYASHI, MATSUHIKO; SARUTA, TAKAO

    1997-01-01

    This study was conducted to examine whether the renin-angiotensin system contributes to hyperthyroidism-induced cardiac hypertrophy without involving the sympathetic nervous system. Sprague-Dawley rats were divided into control-innervated, control-denervated, hyperthyroid-innervated, and hyperthyroid-denervated groups using intraperitoneal injections of thyroxine and 6-hydroxydopamine. After 8 wk, the heart-to-body weight ratio increased in hyperthyroid groups (63%), and this increase was onl...

  18. Soy Glycinin Contains a Functional Inhibitory Sequence against Muscle-Atrophy-Associated Ubiquitin Ligase Cbl-b

    Directory of Open Access Journals (Sweden)

    Tomoki Abe

    2013-01-01

    Full Text Available Background. Unloading stress induces skeletal muscle atrophy. We have reported that Cbl-b ubiquitin ligase is a master regulator of unloading-associated muscle atrophy. The present study was designed to elucidate whether dietary soy glycinin protein prevents denervation-mediated muscle atrophy, based on the presence of inhibitory peptides against Cbl-b ubiquitin ligase in soy glycinin protein. Methods. Mice were fed either 20% casein diet, 20% soy protein isolate diet, 10% glycinin diet containing 10% casein, or 20% glycinin diet. One week later, the right sciatic nerve was cut. The wet weight, cross sectional area (CSA, IGF-1 signaling, and atrogene expression in hindlimb muscles were examined at 1, 3, 3.5, or 4 days after denervation. Results. 20% soy glycinin diet significantly prevented denervation-induced decreases in muscle wet weight and myofiber CSA. Furthermore, dietary soy protein inhibited denervation-induced ubiquitination and degradation of IRS-1 in tibialis anterior muscle. Dietary soy glycinin partially suppressed the denervation-mediated expression of atrogenes, such as MAFbx/atrogin-1 and MuRF-1, through the protection of IGF-1 signaling estimated by phosphorylation of Akt-1. Conclusions. Soy glycinin contains a functional inhibitory sequence against muscle-atrophy-associated ubiquitin ligase Cbl-b. Dietary soy glycinin protein significantly prevented muscle atrophy after denervation in mice.

  19. Role of Renal Nerves in the Treatment of Renovascular Hypertensive Rats with L-Arginine

    Directory of Open Access Journals (Sweden)

    Sonia Alves Gouvea

    2014-01-01

    Full Text Available The purpose was to determine the role of renal nerves in mediating the effects of antihypertensive treatment with L-arginine in a renovascular hypertension model. The 2K1C (two-kidney one-clip model hypertensive rats were submitted to bilateral surgical-pharmacological renal denervation. The animals were subdivided into six experimental groups: normotensive control rats (SHAM, 2K1C rats, 2K1C rats treated with L-arginine (2K1C + L-arg, denervated normotensive (DN rats, denervated 2K1C (2K1C + DN rats, and denervated 2K1C + L-arg (2K1C + DN + L-arg rats. Arterial blood pressure, water intake, urine volume, and sodium excretion were measured. The 2K1C rats exhibited an increase in the mean arterial pressure (MAP (from 106 ± 3 to 183 ± 5.8 mmHg, P<0.01, whereas L-arg treatment induced a reduction in the MAP (143 ± 3.4 mmHg without lowering it to the control level. Renal nerve denervation reduced the MAP to normotensive levels in 2K1C rats with or without chronic L-arg treatment. L-arg and denervation induced increases in water intake and urine volume, and L-arg caused a significant natriuretic effect. Our results suggest that renal sympathetic activity participates in the genesis and the maintenance of the hypertension and also demonstrate that treatment with L-arg alone is incapable of normalizing the MAP and that the effect of such treatment is not additive with the effect of kidney denervation.

  20. Neural regulation of the kidney function in rats with cisplatin induced renal failure

    Science.gov (United States)

    Goulding, Niamh E.; Johns, Edward J.

    2015-01-01

    Aim: Chronic kidney disease (CKD) is often associated with a disturbed cardiovascular homeostasis. This investigation explored the role of the renal innervation in mediating deranged baroreflex control of renal sympathetic nerve activity (RSNA) and renal excretory function in cisplatin-induced renal failure. Methods: Rats were either intact or bilaterally renally denervated 4 days prior to receiving cisplatin (5 mg/kg i.p.) and entered a chronic metabolic study for 8 days. At day 8, other groups of rats were prepared for acute measurement of RSNA or renal function with either intact or denervated kidneys. Results: Following the cisplatin challenge, creatinine clearance was 50% lower while fractional sodium excretion and renal cortical and medullary TGF-β1 concentrations were 3–4 fold higher in both intact and renally denervated rats compared to control rats. In cisplatin-treated rats, the maximal gain of the high-pressure baroreflex curve was only 20% that of control rats, but following renal denervation not different from that of renally denervated control rats. Volume expansion reduced RSNA by 50% in control and in cisplatin-treated rats but only following bilateral renal denervation. The volume expansion mediated natriuresis/diuresis was absent in the cisplatin-treated rats but was normalized following renal denervation. Conclusions: Cisplatin-induced renal injury impaired renal function and caused a sympatho-excitation with blunting of high and low pressure baroreflex regulation of RSNA, which was dependent on the renal innervation. It is suggested that in man with CKD there is a dysregulation of the neural control of the kidney mediated by its sensory innervation. PMID:26175693

  1. Device-based approaches for renal nerve ablation for hypertension and beyond

    Directory of Open Access Journals (Sweden)

    Alicia Ann Thorp

    2015-07-01

    Full Text Available Animal and human studies have demonstrated that chronic activation of renal sympathetic nerves is critical in the pathogenesis and perpetuation of treatment-resistant hypertension. Bilateral renal denervation has emerged as a safe and effective, non-pharmacological treatment for resistant hypertension that involves the selective ablation of efferent and afferent renal nerves to lower blood pressure. However, the most recent and largest randomized controlled trial failed to confirm the primacy of renal denervation over a sham procedure, prompting widespread re-evaluation of the therapy’s efficacy. Disrupting renal afferent sympathetic signalling to the hypothalamus with renal denervation lowers central sympathetic tone, which has the potential to confer additional clinical benefits beyond blood pressure control. Specifically, there has been substantial interest in the use of renal denervation as either a primary or adjunct therapy in pathological conditions characterized by central sympathetic over-activity such as renal disease, heart failure and metabolic-associated disorders. Recent findings from pre-clinical and proof-of–concept studies appear promising with renal denervation shown to confer cardiovascular and metabolic benefits, largely independent of changes in blood pressure. This review explores the pathological rationale for targeting sympathetic renal nerves for blood pressure control. Latest developments in renal nerve ablation modalities designed to improve procedural success are discussed along with prospective findings on the efficacy of renal denervation to lower blood pressure in treatment-resistant hypertensive patients. Preliminary evidence in support of renal denervation as a possible therapeutic option in disease states characterized by central sympathetic over-activity is also presented.

  2. Device-based approaches for renal nerve ablation for hypertension and beyond

    Science.gov (United States)

    Thorp, Alicia A.; Schlaich, Markus P.

    2015-01-01

    Animal and human studies have demonstrated that chronic activation of renal sympathetic nerves is critical in the pathogenesis and perpetuation of treatment-resistant hypertension. Bilateral renal denervation has emerged as a safe and effective, non-pharmacological treatment for resistant hypertension that involves the selective ablation of efferent and afferent renal nerves to lower blood pressure. However, the most recent and largest randomized controlled trial failed to confirm the primacy of renal denervation over a sham procedure, prompting widespread re-evaluation of the therapy's efficacy. Disrupting renal afferent sympathetic signaling to the hypothalamus with renal denervation lowers central sympathetic tone, which has the potential to confer additional clinical benefits beyond blood pressure control. Specifically, there has been substantial interest in the use of renal denervation as either a primary or adjunct therapy in pathological conditions characterized by central sympathetic overactivity such as renal disease, heart failure and metabolic-associated disorders. Recent findings from pre-clinical and proof-of-concept studies appear promising with renal denervation shown to confer cardiovascular and metabolic benefits, largely independent of changes in blood pressure. This review explores the pathological rationale for targeting sympathetic renal nerves for blood pressure control. Latest developments in renal nerve ablation modalities designed to improve procedural success are discussed along with prospective findings on the efficacy of renal denervation to lower blood pressure in treatment-resistant hypertensive patients. Preliminary evidence in support of renal denervation as a possible therapeutic option in disease states characterized by central sympathetic overactivity is also presented. PMID:26217232

  3. Influence of the neural microenvironment on prostate cancer.

    Science.gov (United States)

    Coarfa, Christian; Florentin, Diego; Putluri, NagiReddy; Ding, Yi; Au, Jason; He, Dandan; Ragheb, Ahmed; Frolov, Anna; Michailidis, George; Lee, MinJae; Kadmon, Dov; Miles, Brian; Smith, Christopher; Ittmann, Michael; Rowley, David; Sreekumar, Arun; Creighton, Chad J; Ayala, Gustavo

    2018-02-01

    Nerves are key factors in prostate cancer (PCa), but the functional role of innervation in prostate cancer is poorly understood. PCa induced neurogenesis and perineural invasion (PNI), are associated with aggressive disease. We denervated rodent prostates chemically and physically, before orthotopically implanting cancer cells. We also performed a human neoadjuvant clinical trial using botulinum toxin type A (Botox) and saline in the same patient, before prostatectomy. Bilateral denervation resulted in reduced tumor incidence and size in mice. Botox treatment in humans resulted in increased apoptosis of cancer cells in the Botox treated side. A similar denervation gene array profile was identified in tumors a