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

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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.

[Jejunal myenteric denervation induced by benzalkonium chloride].

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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.

Renal denervation: unde venis et quo vadis?

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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

Chemical renal denervation in the rat.

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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.

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...

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....

Chemical Renal Denervation in the Rat

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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.

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

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.

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

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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.

RENAL DENERVATION IN RESISTANT ARTERIAL HYPERTENSION

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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.

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.

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.

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

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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.

Renal denervation: a new therapeutic approach for resistant hypertension.

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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.

Renal denervation: What happened, and why?

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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.

Renal sympathetic denervation in hypertension.

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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.

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.

Renal Sympathetic Denervation: Hibernation or Resurrection?

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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.

Functional Echomyography of the human denervated muscle: first results

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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

Symplicity multi-electrode radiofrequency renal denervation system feasibility study.

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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.

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

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.

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

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...

Autonomic cardiac innervation

Science.gov (United States)

Hasan, Wohaib

2013-01-01

Autonomic cardiac neurons have a common origin in the neural crest but undergo distinct developmental differentiation as they mature toward their adult phenotype. Progenitor cells respond to repulsive cues during migration, followed by differentiation cues from paracrine sources that promote neurochemistry and differentiation. When autonomic axons start to innervate cardiac tissue, neurotrophic factors from vascular tissue are essential for maintenance of neurons before they reach their targets, upon which target-derived trophic factors take over final maturation, synaptic strength and postnatal survival. Although target-derived neurotrophins have a central role to play in development, alternative sources of neurotrophins may also modulate innervation. Both developing and adult sympathetic neurons express proNGF, and adult parasympathetic cardiac ganglion neurons also synthesize and release NGF. The physiological function of these “non-classical” cardiac sources of neurotrophins remains to be determined, especially in relation to autocrine/paracrine sustenance during development.   Cardiac autonomic nerves are closely spatially associated in cardiac plexuses, ganglia and pacemaker regions and so are sensitive to release of neurotransmitter, neuropeptides and trophic factors from adjacent nerves. As such, in many cardiac pathologies, it is an imbalance within the two arms of the autonomic system that is critical for disease progression. Although this crosstalk between sympathetic and parasympathetic nerves has been well established for adult nerves, it is unclear whether a degree of paracrine regulation occurs across the autonomic limbs during development. Aberrant nerve remodeling is a common occurrence in many adult cardiovascular pathologies, and the mechanisms regulating outgrowth or denervation are disparate. However, autonomic neurons display considerable plasticity in this regard with neurotrophins and inflammatory cytokines having a central regulatory

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.

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.

[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.

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.

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.

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.

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.

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

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

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

[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.

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.

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

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

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.

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

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.

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

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.

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...

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

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

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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.

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

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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.

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.

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

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.)

[Renal denervation as treatment option for hypertension].

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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.

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

International Nuclear Information System (INIS)

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.)

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

Energy Technology Data Exchange (ETDEWEB)

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.)

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

Science.gov (United States)

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.

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.

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

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

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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.

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.

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.

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

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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.

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

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.

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.

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

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.

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.

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.)

Endocrine cells in the denervated intestine

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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

Renal Denervation: Intractable Hypertension and Beyond

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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

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

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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.

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

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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.

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

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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.

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

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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

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

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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...

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

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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.

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.

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

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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.

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

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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.

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

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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.

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

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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.

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

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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.

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

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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

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.)

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

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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.

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

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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.

A controlled trial of renal denervation for resistant hypertension.

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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.).

Increased phencyclidine-induced hyperactivity following cortical cholinergic denervation.

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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.

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

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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.

PET imaging of the autonomic nervous system

International Nuclear Information System (INIS)

THACKERAY, James T.; BENGEL, Frank M.

2016-01-01

The autonomic nervous system is the primary extrinsic control of heart rate and contractility, and is subject to adaptive and maladaptive changes in cardiovascular disease. Consequently, noninvasive assessment of neuronal activity and function is an attractive target for molecular imaging. A myriad of targeted radiotracers have been developed over the last 25 years for imaging various components of the sympathetic and parasympathetic signal cascades. While routine clinical use remains somewhat limited, a number of larger scale studies in recent years have supplied momentum to molecular imaging of autonomic signaling. Specifically, the findings of the ADMIRE HF trial directly led to United States Food and Drug Administration approval of 123I-metaiodobenzylguanidine (MIBG) for Single Photon Emission Computed Tomography (SPECT) assessment of sympathetic neuronal innervation, and comparable results have been reported using the analogous PET agent 11C-meta-hydroxyephedrine (HED). Due to the inherent capacity for dynamic quantification and higher spatial resolution, regional analysis may be better served by PET. In addition, preliminary clinical and extensive preclinical experience has provided a broad foundation of cardiovascular applications for PET imaging of the autonomic nervous system. Recent years have witnessed the growth of novel quantification techniques, expansion of multiple tracer studies, and improved understanding of the uptake of different radiotracers, such that the transitional biology of dysfunctional subcellular catecholamine handling can be distinguished from complete denervation. As a result, sympathetic neuronal molecular imaging is poised to play a role in individualized patient care, by stratifying cardiovascular risk, visualizing underlying biology, and guiding and monitoring therapy.

The biophysics of renal sympathetic denervation using radiofrequency energy.

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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.

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.

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

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.)

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.)

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

Directory of Open Access Journals (Sweden)

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.

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

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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.

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

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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.)

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.)

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

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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.

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

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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.)

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

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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

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

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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.

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.

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.

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.

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

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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.

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

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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

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

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

Directory of Open Access Journals (Sweden)

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.

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

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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.

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.

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

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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.

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

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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

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.

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

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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.

Anatomical and procedural determinants of catheter-based renal denervation

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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

Rat whisker movement after facial nerve lesion: evidence for autonomic contraction of skeletal muscle.

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Heaton, James T; Sheu, Shu Hsien; Hohman, Marc H; Knox, Christopher J; Weinberg, Julie S; Kleiss, Ingrid J; Hadlock, Tessa A

2014-04-18

Vibrissal whisking is often employed to track facial nerve regeneration in rats; however, we have observed similar degrees of whisking recovery after facial nerve transection with or without repair. We hypothesized that the source of non-facial nerve-mediated whisker movement after chronic denervation was from autonomic, cholinergic axons traveling within the infraorbital branch of the trigeminal nerve (ION). Rats underwent unilateral facial nerve transection with repair (N=7) or resection without repair (N=11). Post-operative whisking amplitude was measured weekly across 10weeks, and during intraoperative stimulation of the ION and facial nerves at ⩾18weeks. Whisking was also measured after subsequent ION transection (N=6) or pharmacologic blocking of the autonomic ganglia using hexamethonium (N=3), and after snout cooling intended to elicit a vasodilation reflex (N=3). Whisking recovered more quickly and with greater amplitude in rats that underwent facial nerve repair compared to resection (Pfacial-nerve-mediated whisking was elicited by electrical stimulation of the ION, temporarily diminished following hexamethonium injection, abolished by transection of the ION, and rapidly and significantly (Pfacial nerve resection. This study provides the first behavioral and anatomical evidence of spontaneous autonomic innervation of skeletal muscle after motor nerve lesion, which not only has implications for interpreting facial nerve reinnervation results, but also calls into question whether autonomic-mediated innervation of striated muscle occurs naturally in other forms of neuropathy. Copyright © 2014 IBRO. Published by Elsevier Ltd. All rights reserved.

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

Electromyographic permutation entropy quantifies diaphragmatic denervation and reinnervation.

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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.

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.

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

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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

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

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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

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

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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.

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

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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.

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.

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

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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

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

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

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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

Renal denervation for the management of resistant hypertension

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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

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

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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.

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

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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

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

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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

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

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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.

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

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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.

Cardiac troponin T and fast skeletal muscle denervation in ageing.

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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

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

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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.

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

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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.

Effects of renal denervation on end organ damage in hypertensive patients

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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

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

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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.

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

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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.

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.

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

Renal denervation in moderate treatment-resistant hypertension.

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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.

Electrically induced release of acetylcholine from denervated Schwann cells.

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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.

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

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

Renal sympathetic denervation for resistant hypertension.

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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.

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

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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

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

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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)

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

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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.

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

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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.

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

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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

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

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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.

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

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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

Integrative Blood Pressure Response to Upright Tilt Post Renal Denervation

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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

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

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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.

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

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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.

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

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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

Renal denervation by intravascular ultrasound: Preliminary in vivo study

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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.

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

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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.

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

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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.

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

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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

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

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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.

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

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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

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

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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

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

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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.

Renal Denervation Attenuates Progression of Atherosclerosis in Apolipoprotein E–Deficient Mice Independent of Blood Pressure Lowering

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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

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

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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

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

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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.

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

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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

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

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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.

Renal denervation for the management of resistant hypertension

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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

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.

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.

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.

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

Science.gov (United States)

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

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.

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.

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

Evaluation of cardiac autonomic nerves by iodine-123 metaiodobenzylguanidine scintigraphy and ambulatory electrocardiography in patients after arterial switch operations

Energy Technology Data Exchange (ETDEWEB)

Sakurai, Hajime; Maeda, Masanobu; Miyahara, Ken [Shakaihoken Chukyo Hospital, Nagoya (Japan)] [and others

2000-05-01

The autonomic cardiac nerves reach the heart after passing through the vicinity of the aortic root and the pulmonary trunk. The arterial switch operation (ASO) completely transects the ascending aorta and the pulmonary trunk. Therefore, this surgical procedure virtually denerves the heart. Cardiac sympathetic denervation and reinnervation were evaluated in patients after ASO using iodine-123 metaiodobenzylguanidine (MIBG) myocardial scintigraphy and parasympathetic denervation and reinnervation using ambulatory electrocardiography [Holter electrocardiogram (ECG)]. MIBG scintigraphy was performed in 14 patients who underwent ASO (ASO group) and 3 patients who underwent other open heart surgery (control group). All patients in the ASO group underwent the operation in the neonatal or infantile period. Planar and single photon emission computed tomography (SPECT) images of the myocardium were obtained. Defect score was determined by the SPECT images as a semi-quantitative index. The mean interval between ASO and MIBG scintigraphy was 25.6{+-}14.6 months. Holter ECG was also performed in 14 patients in the ASO group and 19 age-matched normal children. The Holter ECGs were plotted on a Lorenz plot. The H index, which is related to vagal tone for the cardiovascular system, was calculated from the R-R intervals. The mean interval between the ASO and Holter ECG was 8.3{+-}9.7 months. MIBG scintigraphy in the control group demonstrated an almost normal homogeneous tracer uptake, but showed extremely reduced tracer uptake and significantly higher defect score in the ASO group. The extent and degree of the reduction of MIBG uptake improved with time after the ASO. The heart-to-mediastinum MIBG count ratio tended to increase with time. The H index of the ASO group was lower than that of normal children (<12 months: Control group 0.0280{+-}0.0068 vs ASO group 0.0219{+-}0.0083), and gradually increased with time (1-3 years: 0.0470{+-}0.0157 vs 0.0314{+-}0.0124). (author)

Evaluation of cardiac autonomic nerves by iodine-123 metaiodobenzylguanidine scintigraphy and ambulatory electrocardiography in patients after arterial switch operations

International Nuclear Information System (INIS)

Sakurai, Hajime; Maeda, Masanobu; Miyahara, Ken

2000-01-01

The autonomic cardiac nerves reach the heart after passing through the vicinity of the aortic root and the pulmonary trunk. The arterial switch operation (ASO) completely transects the ascending aorta and the pulmonary trunk. Therefore, this surgical procedure virtually denerves the heart. Cardiac sympathetic denervation and reinnervation were evaluated in patients after ASO using iodine-123 metaiodobenzylguanidine (MIBG) myocardial scintigraphy and parasympathetic denervation and reinnervation using ambulatory electrocardiography [Holter electrocardiogram (ECG)]. MIBG scintigraphy was performed in 14 patients who underwent ASO (ASO group) and 3 patients who underwent other open heart surgery (control group). All patients in the ASO group underwent the operation in the neonatal or infantile period. Planar and single photon emission computed tomography (SPECT) images of the myocardium were obtained. Defect score was determined by the SPECT images as a semi-quantitative index. The mean interval between ASO and MIBG scintigraphy was 25.6±14.6 months. Holter ECG was also performed in 14 patients in the ASO group and 19 age-matched normal children. The Holter ECGs were plotted on a Lorenz plot. The H index, which is related to vagal tone for the cardiovascular system, was calculated from the R-R intervals. The mean interval between the ASO and Holter ECG was 8.3±9.7 months. MIBG scintigraphy in the control group demonstrated an almost normal homogeneous tracer uptake, but showed extremely reduced tracer uptake and significantly higher defect score in the ASO group. The extent and degree of the reduction of MIBG uptake improved with time after the ASO. The heart-to-mediastinum MIBG count ratio tended to increase with time. The H index of the ASO group was lower than that of normal children (<12 months: Control group 0.0280±0.0068 vs ASO group 0.0219±0.0083), and gradually increased with time (1-3 years: 0.0470±0.0157 vs 0.0314±0.0124). (author)

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.

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)

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

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.)

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.

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

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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.

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

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

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

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

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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

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

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

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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

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

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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.

Twelve-month results of the rapid renal sympathetic denervation for resistant hypertension using the OneShotTM ablation system (RAPID) study.

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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.

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

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.

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

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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

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

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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.

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

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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

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

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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®.

Nonuniform cardiac denervation observed by 11C-meta-hydroxyephedrine PET in 6-OHDA-treated monkeys.

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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.

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.

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

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

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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.

The role of sympathetic nervous system in the progression of chronic kidney disease in the era of catheter based sympathetic renal denervation.

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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.

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

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

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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.

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

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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.

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.

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

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

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.

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.

Autonomic headache with autonomic seizures: a case report.

Science.gov (United States)

Ozge, Aynur; Kaleagasi, Hakan; Yalçin Tasmertek, Fazilet

2006-10-01

The aim of the report is to present a case of an autonomic headache associated with autonomic seizures. A 19-year-old male who had had complex partial seizures for 15 years was admitted with autonomic complaints and left hemicranial headache, independent from seizures, that he had had for 2 years and were provoked by watching television. Brain magnetic resonance imaging showed right hippocampal sclerosis and electroencephalography revealed epileptic activity in right hemispheric areas. Treatment with valproic acid decreased the complaints. The headache did not fulfil the criteria for the diagnosis of trigeminal autonomic cephalalgias, and was different from epileptic headache, which was defined as a pressing type pain felt over the forehead for several minutes to a few hours. Although epileptic headache responds to anti-epileptics and the complaints of the present case decreased with antiepileptics, it has been suggested that the headache could be a non-trigeminal autonomic headache instead of an epileptic headache.

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

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.

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

Science.gov (United States)

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.

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.

[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.

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.)

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.)

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.

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

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

Science.gov (United States)

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.

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

Autonomic Neuropathy

Science.gov (United States)

... risk of autonomic neuropathy. Other diseases. Amyloidosis, porphyria, hypothyroidism and cancer (usually due to side effects from treatment) may also increase the risk of autonomic neuropathy. ...

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.

[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.

Genetic autonomic disorders.

Science.gov (United States)

Axelrod, Felicia B

2013-03-01

Genetic disorders affecting the autonomic nervous system can result in abnormal development of the nervous system or they can be caused by neurotransmitter imbalance, an ion-channel disturbance or by storage of deleterious material. The symptoms indicating autonomic dysfunction, however, will depend upon whether the genetic lesion has disrupted peripheral or central autonomic centers or both. Because the autonomic nervous system is pervasive and affects every organ system in the body, autonomic dysfunction will result in impaired homeostasis and symptoms will vary. The possibility of genetic confirmation by molecular testing for specific diagnosis is increasing but treatments tend to remain only supportive and directed toward particular symptoms. Copyright © 2013 Elsevier Inc. All rights reserved.

Patients With Fibromyalgia Have Significant Autonomic Symptoms But Modest Autonomic Dysfunction.

Science.gov (United States)

Vincent, Ann; Whipple, Mary O; Low, Phillip A; Joyner, Michael; Hoskin, Tanya L

2016-05-01

Research suggests that disordered autonomic function may be one contributor to deconditioning reported in fibromyalgia; however, no study to date has assessed these variables simultaneously with comprehensive measures. To characterize physical fitness and autonomic function with the use of clinically validated measures and subjective questionnaires between patients with fibromyalgia and healthy controls. Cross-sectional, observational, controlled study. Community sample of patients with fibromyalgia and healthy controls. Thirty patients with fibromyalgia and 30 pain and fatigue-free controls. Participants completed a battery of self-report questionnaires and physiological measures, including clinically validated measures of physical fitness and autonomic function. Six-Minute Walk Test total distance, maximal oxygen consumption as assessed by cardiopulmonary exercise testing, total steps using activity monitor, Composite Autonomic Scoring Scale as assessed by Autonomic Reflex Screen, total metabolic equivalents per week using the International Physical Activity Questionnaire, and self-reported autonomic symptoms via the 31-item Composite Autonomic Symptom Score questionnaire. Autonomic function, as assessed by self-report, was significantly different between patients and controls (P physical activity was not significantly different between patients and controls (P = .99), but levels of moderate and vigorous physical activity as measured by actigraphy were significantly lower in patients (P = .012 and P = .047, respectively). Exercise capacity (6-Minute Walk) was poorer in patients (P = .0006), but there was no significant difference in maximal volume of oxygen consumption (P = .07). Patients with fibromyalgia report more severe symptoms across all domains, including physical activity and autonomic symptoms, compared with controls, but the objective assessments only showed modest differences. Our results suggest that patients with widespread subjective impairment of

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

Renal denervation using catheter-based radiofrequency ablation with temperature control: renovascular safety profile and underlying mechanisms in a hypertensive canine model.

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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.

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

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.

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

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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.

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...

Semi-Autonomous Systems Laboratory

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Federal Laboratory Consortium — VisionThe Semi-Autonomous Systems Lab focuses on developing a comprehensive framework for semi-autonomous coordination of networked robotic systems. Semi-autonomous...

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

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.

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

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.

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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.

Blood Pressure Response to Main Renal Artery and Combined Main Renal Artery Plus Branch Renal Denervation in Patients With Resistant Hypertension.

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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.

A multinational clinical approach to assessing the effectiveness of catheter-based ultrasound renal denervation: The RADIANCE-HTN and REQUIRE clinical study designs.

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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

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

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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

Safety and efficacy of a multi-electrode renal sympathetic denervation system in resistant hypertension: the EnligHTN I trial.

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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.

[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.

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...

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

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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.

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

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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.

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.

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.

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.

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.

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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.

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

Testing for autonomic neuropathy

DEFF Research Database (Denmark)

Hilsted, J

1984-01-01

Autonomic neuropathy is a common complication in long-term diabetes, about 30% of the patients showing measurable signs of autonomic dysfunction after 10 years duration of disease. The diagnosis is often difficult to establish because clinical symptoms generally occur late in the course of the di......Autonomic neuropathy is a common complication in long-term diabetes, about 30% of the patients showing measurable signs of autonomic dysfunction after 10 years duration of disease. The diagnosis is often difficult to establish because clinical symptoms generally occur late in the course...

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

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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.

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

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....

Renal denervation for resistant hypertension using an irrigated radiofrequency balloon: 12-month results from the Renal Hypertension Ablation System (RHAS) trial.

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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.

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

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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

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

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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.

Autonomic components of Complex Regional Pain Syndrome (CRPS) are favourably affected by Electrical Twitch-Obtaining Intramuscular Stimulation (ETOIMS): effects on blood pressure and heart rate.

Science.gov (United States)

Chu, Jennifer; Bruyninckx, Frans; Neuhauser, Duncan V

2017-07-01

Favourable pain relief results on evoking autonomous twitches at myofascial trigger points with Electrical Twitch Obtaining Intramuscular Stimulation (ETOIMS). To document autonomic nervous system (ANS) dysfunction in Complex Regional Pain Syndrome (CRPS) from blood pressure (BP) and pulse/heart rate changes with ETOIMS. A patient with persistent pain regularly received serial ETOIMS sessions of 60, 90, 120 or ≥150 min over 24 months. Outcome measures include BP: systolic, diastolic, pulse pressure and pulse/heart rate, pre-session/immediate-post-session summed differences (SDPPP index), and pain reduction. His results were compared with that of two other patients and one normal control. Each individual represented the following maximal elicitable twitch forces (TWF) graded 1-5: maximum TWF2: control subject; maximum TWF3: CRPS patient with suspected ANS dysfunction; and maximum TWF4 and TWF5: two patients with respective slow-fatigue and fast-fatigue twitches who during ETOIMS had autonomous twitching at local and remote myotomes simultaneously from denervation supersensitivity. ETOIMS results between TWFs were compared using one-way analysis of variance test. The patients showed immediate significant pain reduction, BP and pulse/heart rate changes/reduction(s) except for diastolic BP in the TWF5 patient. TWF2 control subject had diastolic BP reduction with ETOIMS but not with rest. Linear regression showed TWF grade to be the most significant variable in pain reduction, more so than the number of treatments, session duration and treatment interval. TWF grade was the most important variable in significantly reducing outcome measures, especially pulse/heart rate. Unlike others, the TWF3 patient had distinctive reductions in SDPPP index. Measuring BP and pulse/heart rate is clinically practical for alerting ANS dysfunction maintained CRPS. SDPPP index (≥26) and pulse/heart rate (≥8) reductions with almost every ETOIMS treatment, plus inability to evoke

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

Overview of the Autonomic Nervous System

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... be reversible or progressive. Anatomy of the autonomic nervous system The autonomic nervous system is the part of ... organs they connect with. Function of the autonomic nervous system The autonomic nervous system controls internal body processes ...

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

Role of the autonomic nervous system in rat liver regeneration.

Science.gov (United States)

Xu, Cunshuan; Zhang, Xinsheng; Wang, Gaiping; Chang, Cuifang; Zhang, Lianxing; Cheng, Qiuyan; Lu, Ailing

2011-05-01

To study the regulatory role of autonomic nervous system in rat regenerating liver, surgical operations of rat partial hepatectomy (PH) and its operation control (OC), sympathectomy combining partial hepatectomy (SPH), vagotomy combining partial hepatectomy (VPH), and total liver denervation combining partial hepatectomy (TDPH) were performed, then expression profiles of regenerating livers at 2 h after operation were detected using Rat Genome 230 2.0 array. It was shown that the expressions of 97 genes in OC, 230 genes in PH, 253 genes in SPH, 187 genes in VPH, and 177 genes in TDPH were significantly changed in biology. The relevance analysis showed that in SPH, genes involved in stimulus response, immunity response, amino acids and K(+) transport, amino acid catabolism, cell adhesion, cell proliferation mediated by JAK-STAT, Ca(+), and platelet-derived growth factor receptor, cell growth and differentiation through JAK-STAT were up-regulated, while the genes involved in chromatin assembly and disassembly, and cell apoptosis mediated by MAPK were down-regulated. In VPH, the genes associated with chromosome modification-related transcription factor, oxygen transport, and cell apoptosis mediated by MAPK pathway were up-regulated, but the genes associated with amino acid catabolism, histone acetylation-related transcription factor, and cell differentiation mediated by Wnt pathway were down-regulated. In TDPH, the genes related to immunity response, growth and development of regenerating liver, cell growth by MAPK pathway were up-regulated. Our data suggested that splanchnic and vagal nerves could regulate the expressions of liver regeneration-related genes.

Catecholamines and diabetic autonomic neuropathy

DEFF Research Database (Denmark)

Hilsted, J

1995-01-01

In diabetic patients with autonomic neuropathy plasma noradrenaline concentration, used as an index of sympathetic nervous activity, is low. This decrease is, however, only found in patients with a long duration of diabetes with clinically severe autonomic neuropathy. This apparent insensitivity...... of plasma catecholamine measurements is not due to changes in the clearance of catecholamines in diabetic autonomic neuropathy. The physiological responses to infused adrenaline and to noradrenaline are enhanced, for noradrenaline mainly cardiovascular responses. Adrenoceptors (alpha and beta adrenoceptors......) are not altered in circulating blood cells in diabetic autonomic neuropathy. Thus, a generalized up-regulation of adrenoceptors does not occur in diabetic autonomic neuropathy....

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.

[Effects of low anterior resection on colonic motor activity and defecation. An experimental study].

Science.gov (United States)

Iikura, M

1995-06-01

The functional disorder of defecation after low anterior resection (LAR) was studied from the aspect of colonic motility in an experiment with dogs using a strain gage transducer, and the following results were obtained: 1) In early phase after LAR, the frequency of the colonic contractile waves increased at the proximal and distal sites of the anastomosis in both subgroups of dogs denervated and innervated of hypogastric and pelvic nerves. The increase was more remarkable at the distal site of the anastomosis. Also, the contractile waves were not propagated across the anastomosis. 2) After LAR, strong colonic contractions occurred during defecation only at the distal anastomosis. Various patterns of contraction time required for defecation were demonstrated as compared to a single pattern in control dogs. 3) The frequency of the occurrence of colonic contractile waves and the propagation of the contraction tended to be normalized with time after LAR both in denervated and innervated groups, though the recovery was faster in the latter subgroup. 4) The frequency of defecation increased after LAR both in denervated and innervated groups compared to be in the control dogs, though more remarkable in the denervated groups. Although tended to be gradually normalized with time after LAR, the colectomized dogs required a long time for normalization of the frequency of defecation. These results suggested the significant effect of reduction in reservoir space and disturbed continuity of intramural plexus caused by colectomy. Less severity, however, of functional disorder of defecation and earlier recovery from colonic motility disorder in the subgroup of the dogs innervated of autonomic nerves indicated usefulness of retaining autonomic nerves in colectomy.

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

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

A Secure, Scalable and Elastic Autonomic Computing Systems Paradigm: Supporting Dynamic Adaptation of Self-* Services from an Autonomic Cloud

Directory of Open Access Journals (Sweden)

Abdul Jaleel

2018-05-01

Full Text Available Autonomic computing embeds self-management features in software systems using external feedback control loops, i.e., autonomic managers. In existing models of autonomic computing, adaptive behaviors are defined at the design time, autonomic managers are statically configured, and the running system has a fixed set of self-* capabilities. An autonomic computing design should accommodate autonomic capability growth by allowing the dynamic configuration of self-* services, but this causes security and integrity issues. A secure, scalable and elastic autonomic computing system (SSE-ACS paradigm is proposed to address the runtime inclusion of autonomic managers, ensuring secure communication between autonomic managers and managed resources. Applying the SSE-ACS concept, a layered approach for the dynamic adaptation of self-* services is presented with an online ‘Autonomic_Cloud’ working as the middleware between Autonomic Managers (offering the self-* services and Autonomic Computing System (requiring the self-* services. A stock trading and forecasting system is used for simulation purposes. The security impact of the SSE-ACS paradigm is verified by testing possible attack cases over the autonomic computing system with single and multiple autonomic managers running on the same and different machines. The common vulnerability scoring system (CVSS metric shows a decrease in the vulnerability severity score from high (8.8 for existing ACS to low (3.9 for SSE-ACS. Autonomic managers are introduced into the system at runtime from the Autonomic_Cloud to test the scalability and elasticity. With elastic AMs, the system optimizes the Central Processing Unit (CPU share resulting in an improved execution time for business logic. For computing systems requiring the continuous support of self-management services, the proposed system achieves a significant improvement in security, scalability, elasticity, autonomic efficiency, and issue resolving time

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.

Autonomic computing enabled cooperative networked design

CERN Document Server

Wodczak, Michal

2014-01-01

This book introduces the concept of autonomic computing driven cooperative networked system design from an architectural perspective. As such it leverages and capitalises on the relevant advancements in both the realms of autonomic computing and networking by welding them closely together. In particular, a multi-faceted Autonomic Cooperative System Architectural Model is defined which incorporates the notion of Autonomic Cooperative Behaviour being orchestrated by the Autonomic Cooperative Networking Protocol of a cross-layer nature. The overall proposed solution not only advocates for the inc

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...

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

Science.gov (United States)

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.

Insights into the background of autonomic medicine.

Science.gov (United States)

Laranjo, Sérgio; Geraldes, Vera; Oliveira, Mário; Rocha, Isabel

2017-10-01

Knowledge of the physiology underlying the autonomic nervous system is pivotal for understanding autonomic dysfunction in clinical practice. Autonomic dysfunction may result from primary modifications of the autonomic nervous system or be secondary to a wide range of diseases that cause severe morbidity and mortality. Together with a detailed history and physical examination, laboratory assessment of autonomic function is essential for the analysis of various clinical conditions and the establishment of effective, personalized and precise therapeutic schemes. This review summarizes the main aspects of autonomic medicine that constitute the background of cardiovascular autonomic dysfunction. Copyright © 2017 Sociedade Portuguesa de Cardiologia. Publicado por Elsevier España, S.L.U. All rights reserved.

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.

Autonomic Nervous System Disorders

Science.gov (United States)

Your autonomic nervous system is the part of your nervous system that controls involuntary actions, such as the beating of your heart ... breathing and swallowing Erectile dysfunction in men Autonomic nervous system disorders can occur alone or as the result ...

Autonomous authority in relation to the staff regulations of autonomous parliaments

Directory of Open Access Journals (Sweden)

Rafael Cano Silva

2018-04-01

Full Text Available The statutes of Autonomous Parliaments are parliamentary administrative norms approved by each legislative chamber by virtue of their parliamentary autonomy. However, the parliamentary autonomy of each autonomous parliament does not have the same normative aspect for these purposes. It is studied in this article as despite having the Constitution as a common element, it is essential the special attribution that each autonomous chamber has and that the jurisprudence, both of the Constitutional Court, and that of the Supreme Court, has put in value, question that is included in the section related to the jurisprudence. In conclusion, the bureaucratic organization, in what refers to personal media, may be substantially different in each one of the legislative assemblies, as analyzed in the conclusions of this study.

Formal Verification of Autonomous Vehicle Platooning

OpenAIRE

Kamali, Maryam; Dennis, Louise A.; McAree, Owen; Fisher, Michael; Veres, Sandor M.

2016-01-01

The coordination of multiple autonomous vehicles into convoys or platoons is expected on our highways in the near future. However, before such platoons can be deployed, the new autonomous behaviors of the vehicles in these platoons must be certified. An appropriate representation for vehicle platooning is as a multi-agent system in which each agent captures the "autonomous decisions" carried out by each vehicle. In order to ensure that these autonomous decision-making agents in vehicle platoo...

Autonomous Landing on Moving Platforms

KAUST Repository

Mendoza Chavez, Gilberto

2016-08-01

This thesis investigates autonomous landing of a micro air vehicle (MAV) on a nonstationary ground platform. Unmanned aerial vehicles (UAVs) and micro air vehicles (MAVs) are becoming every day more ubiquitous. Nonetheless, many applications still require specialized human pilots or supervisors. Current research is focusing on augmenting the scope of tasks that these vehicles are able to accomplish autonomously. Precise autonomous landing on moving platforms is essential for self-deployment and recovery of MAVs, but it remains a challenging task for both autonomous and piloted vehicles. Model Predictive Control (MPC) is a widely used and effective scheme to control constrained systems. One of its variants, output-feedback tube-based MPC, ensures robust stability for systems with bounded disturbances under system state reconstruction. This thesis proposes a MAV control strategy based on this variant of MPC to perform rapid and precise autonomous landing on moving targets whose nominal (uncommitted) trajectory and velocity are slowly varying. The proposed approach is demonstrated on an experimental setup.

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

Autonomic Neuropathy in Diabetes Mellitus

OpenAIRE

Verrotti, Alberto; Prezioso, Giovanni; Scattoni, Raffaella; Chiarelli, Francesco

2014-01-01

Diabetic autonomic neuropathy (DAN) is a serious and common complication of diabetes, often overlooked and misdiagnosed. It is a systemic-wide disorder that may be asymptomatic in the early stages. The most studied and clinically important form of DAN is cardiovascular autonomic neuropathy defined as the impairment of autonomic control of the cardiovascular system in patients with diabetes after exclusion of other causes. The reported prevalence of DAN varies widely depending on inconsistent ...

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

Directory of Open Access Journals (Sweden)

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.

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

Science.gov (United States)

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

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.

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.

Discerning non-autonomous dynamics

Energy Technology Data Exchange (ETDEWEB)

Clemson, Philip T.; Stefanovska, Aneta, E-mail: aneta@lancaster.ac.uk

2014-09-30

Structure and function go hand in hand. However, while a complex structure can be relatively safely broken down into the minutest parts, and technology is now delving into nanoscales, the function of complex systems requires a completely different approach. Here the complexity clearly arises from nonlinear interactions, which prevents us from obtaining a realistic description of a system by dissecting it into its structural component parts. At best, the result of such investigations does not substantially add to our understanding or at worst it can even be misleading. Not surprisingly, the dynamics of complex systems, facilitated by increasing computational efficiency, is now readily tackled in the case of measured time series. Moreover, time series can now be collected in practically every branch of science and in any structural scale—from protein dynamics in a living cell to data collected in astrophysics or even via social networks. In searching for deterministic patterns in such data we are limited by the fact that no complex system in the real world is autonomous. Hence, as an alternative to the stochastic approach that is predominantly applied to data from inherently non-autonomous complex systems, theory and methods specifically tailored to non-autonomous systems are needed. Indeed, in the last decade we have faced a huge advance in mathematical methods, including the introduction of pullback attractors, as well as time series methods that cope with the most important characteristic of non-autonomous systems—their time-dependent behaviour. Here we review current methods for the analysis of non-autonomous dynamics including those for extracting properties of interactions and the direction of couplings. We illustrate each method by applying it to three sets of systems typical for chaotic, stochastic and non-autonomous behaviour. For the chaotic class we select the Lorenz system, for the stochastic the noise-forced Duffing system and for the non-autonomous

Discerning non-autonomous dynamics

International Nuclear Information System (INIS)

Clemson, Philip T.; Stefanovska, Aneta

2014-01-01

Structure and function go hand in hand. However, while a complex structure can be relatively safely broken down into the minutest parts, and technology is now delving into nanoscales, the function of complex systems requires a completely different approach. Here the complexity clearly arises from nonlinear interactions, which prevents us from obtaining a realistic description of a system by dissecting it into its structural component parts. At best, the result of such investigations does not substantially add to our understanding or at worst it can even be misleading. Not surprisingly, the dynamics of complex systems, facilitated by increasing computational efficiency, is now readily tackled in the case of measured time series. Moreover, time series can now be collected in practically every branch of science and in any structural scale—from protein dynamics in a living cell to data collected in astrophysics or even via social networks. In searching for deterministic patterns in such data we are limited by the fact that no complex system in the real world is autonomous. Hence, as an alternative to the stochastic approach that is predominantly applied to data from inherently non-autonomous complex systems, theory and methods specifically tailored to non-autonomous systems are needed. Indeed, in the last decade we have faced a huge advance in mathematical methods, including the introduction of pullback attractors, as well as time series methods that cope with the most important characteristic of non-autonomous systems—their time-dependent behaviour. Here we review current methods for the analysis of non-autonomous dynamics including those for extracting properties of interactions and the direction of couplings. We illustrate each method by applying it to three sets of systems typical for chaotic, stochastic and non-autonomous behaviour. For the chaotic class we select the Lorenz system, for the stochastic the noise-forced Duffing system and for the non-autonomous

Structural Discrimination and Autonomous Vehicles

DEFF Research Database (Denmark)

Liu, Hin-Yan

2016-01-01

This paper examines the potential for structural discrimination to be woven into the fabric of autonomous vehicle developments, which remain underexplored and undiscussed. The prospect for structural discrimination arises as a result of the coordinated modes of autonomous vehicle behaviour...... individual identity, and potentially relative worth, to autonomous vehicles engaging in a crash damage calculus. At the risk of introducing these ideas into the development of autonomous vehicles, this paper hopes to spark a debate to foreclose these eventualities....... that is prescribed by its code. This leads to the potential for individuated outcomes to be networked and thereby multiplied consistently to any number of vehicles implementing such a code. The aggregated effects of such algorithmic policy preferences will thus cumulate in the reallocation of benefits and burdens...

Decentralized Control of Autonomous Vehicles

Science.gov (United States)

2003-01-01

Autonomous Vehicles by John S. Baras, Xiaobo Tan, Pedram Hovareshti CSHCN TR 2003-8 (ISR TR 2003-14) Report Documentation Page Form ApprovedOMB No. 0704...AND SUBTITLE Decentralized Control of Autonomous Vehicles 5a. CONTRACT NUMBER 5b. GRANT NUMBER 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S) 5d. PROJECT...Standard Form 298 (Rev. 8-98) Prescribed by ANSI Std Z39-18 Decentralized Control of Autonomous Vehicles ∗ John S. Baras, Xiaobo Tan, and Pedram

Public Health, Ethics, and Autonomous Vehicles.

Science.gov (United States)

Fleetwood, Janet

2017-04-01

With the potential to save nearly 30 000 lives per year in the United States, autonomous vehicles portend the most significant advance in auto safety history by shifting the focus from minimization of postcrash injury to collision prevention. I have delineated the important public health implications of autonomous vehicles and provided a brief analysis of a critically important ethical issue inherent in autonomous vehicle design. The broad expertise, ethical principles, and values of public health should be brought to bear on a wide range of issues pertaining to autonomous vehicles.

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

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.

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.)

Behavioural domain knowledge transfer for autonomous agents

CSIR Research Space (South Africa)

Rosman, Benjamin S

2014-11-01

Full Text Available , and Behavior Transfer in Autonomous Robots, AAAI 2014 Fall Symposium Series, 13-15 November 2014 Behavioural Domain Knowledge Transfer for Autonomous Agents Benjamin Rosman Mobile Intelligent Autonomous Systems Modelling and Digital Science Council...

Current challenges in autonomous vehicle development

Science.gov (United States)

Connelly, J.; Hong, W. S.; Mahoney, R. B., Jr.; Sparrow, D. A.

2006-05-01

The field of autonomous vehicles is a rapidly growing one, with significant interest from both government and industry sectors. Autonomous vehicles represent the intersection of artificial intelligence (AI) and robotics, combining decision-making with real-time control. Autonomous vehicles are desired for use in search and rescue, urban reconnaissance, mine detonation, supply convoys, and more. The general adage is to use robots for anything dull, dirty, dangerous or dumb. While a great deal of research has been done on autonomous systems, there are only a handful of fielded examples incorporating machine autonomy beyond the level of teleoperation, especially in outdoor/complex environments. In an attempt to assess and understand the current state of the art in autonomous vehicle development, a few areas where unsolved problems remain became clear. This paper outlines those areas and provides suggestions for the focus of science and technology research. The first step in evaluating the current state of autonomous vehicle development was to develop a definition of autonomy. A number of autonomy level classification systems were reviewed. The resulting working definitions and classification schemes used by the authors are summarized in the opening sections of the paper. The remainder of the report discusses current approaches and challenges in decision-making and real-time control for autonomous vehicles. Suggested research focus areas for near-, mid-, and long-term development are also presented.

Compact autonomous navigation system (CANS)

Science.gov (United States)

Hao, Y. C.; Ying, L.; Xiong, K.; Cheng, H. Y.; Qiao, G. D.

2017-11-01

Autonomous navigation of Satellite and constellation has series of benefits, such as to reduce operation cost and ground station workload, to avoid the event of crises of war and natural disaster, to increase spacecraft autonomy, and so on. Autonomous navigation satellite is independent of ground station support. Many systems are developed for autonomous navigation of satellite in the past 20 years. Along them American MANS (Microcosm Autonomous Navigation System) [1] of Microcosm Inc. and ERADS [2] [3] (Earth Reference Attitude Determination System) of Honeywell Inc. are well known. The systems anticipate a series of good features of autonomous navigation and aim low cost, integrated structure, low power consumption and compact layout. The ERADS is an integrated small 3-axis attitude sensor system with low cost and small volume. It has the Earth center measurement accuracy higher than the common IR sensor because the detected ultraviolet radiation zone of the atmosphere has a brightness gradient larger than that of the IR zone. But the ERADS is still a complex system because it has to eliminate many problems such as making of the sapphire sphere lens, birefringence effect of sapphire, high precision image transfer optical fiber flattener, ultraviolet intensifier noise, and so on. The marginal sphere FOV of the sphere lens of the ERADS is used to star imaging that may be bring some disadvantages., i.e. , the image energy and attitude measurements accuracy may be reduced due to the tilt image acceptance end of the fiber flattener in the FOV. Besides Japan, Germany and Russia developed visible earth sensor for GEO [4] [5]. Do we have a way to develop a cheaper/easier and more accurate autonomous navigation system that can be used to all LEO spacecraft, especially, to LEO small and micro satellites? To return this problem we provide a new type of the system—CANS (Compact Autonomous Navigation System) [6].

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

Science.gov (United States)

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.

The Renal Nerves in Chronic Heart Failure: Afferent and Efferent Mechanisms

Directory of Open Access Journals (Sweden)

Alicia Marie Schiller

2015-08-01

Full Text Available The function of the renal nerves has been an area of scientific and medical interest for many years. The recent advent of a minimally invasive catheter-based method of renal denervation has renewed excitement in understanding the afferent and efferent actions of the renal nerves in multiple diseases. While hypertension has been the focus of much this work, less attention has been given to the role of the renal nerves in the development of chronic heart failure (CHF. Recent studies from our laboratory and those of others implicate an essential role for the renal nerves in the development and progression of CHF. Using a rabbit tachycardia model of CHF and surgical unilateral renal denervation, we provide evidence for both renal efferent and afferent mechanisms in the pathogenesis of CHF. Renal denervation prevented the decrease in renal blood flow observed in CHF while also preventing increases in Angiotensin-II receptor protein in the microvasculature of the renal cortex. Renal denervation in CHF also reduced physiological markers of autonomic dysfunction including an improvement in arterial baroreflex function, heart rate variability, and decreased resting cardiac sympathetic tone. Taken together, the renal sympathetic nerves are necessary in the pathogenesis of CHF via both efferent and afferent

Human Supervision of Multiple Autonomous Vehicles

Science.gov (United States)

2013-03-22

AFRL-RH-WP-TR-2013-0143 HUMAN SUPERVISION OF MULTIPLE AUTONOMOUS VEHICLES Heath A. Ruff Ball...REPORT TYPE Interim 3. DATES COVERED (From – To) 09-16-08 – 03-22-13 4. TITLE AND SUBTITLE HUMAN SUPERVISION OF MULTIPLE AUTONOMOUS VEHICLES 5a...Supervision of Multiple Autonomous Vehicles To support the vision of a system that enables a single operator to control multiple next-generation

A Priori User Acceptance and the Perceived Driving Pleasure in Semi-autonomous and Autonomous Vehicles

DEFF Research Database (Denmark)

Bjørner, Thomas

The aim of this minor pilot study is, from a sociological user perspective, to explore a priori user acceptance and the perceived driving pleasure in semi- autonomous and autonomous vehicles. The methods used were 13 in-depth interviews while having participants watch video examples within four...... different scenarios. After each scenario, two different numerical rating scales were used. There was a tendency toward positive attitudes regarding semi- autonomous driving systems, especially the use of a parking assistant and while driving in city traffic congestion. However, there were also major...

Intelligent autonomous systems 12. Vol. 2. Proceedings

Energy Technology Data Exchange (ETDEWEB)

Lee, Sukhan [Sungkyunkwan Univ., Gyeonggi-Do (Korea, Republic of). College of Information and Communication Engineering; Yoon, Kwang-Joon [Konkuk Univ., Seoul (Korea, Republic of); Cho, Hyungsuck [Daegu Gyeongbuk Institute of Science and Technology, Daegu (Korea, Republic of); Lee, Jangmyung (eds.) [Pusan National Univ. (Korea, Republic of). Dept. of Electronics Engineering

2013-02-01

Recent research in Intelligent and Autonomous Systems. Volume 2 of the proceedings of the 12th International Conference IAS-12, held June 26-29, 2012, jeju Island, Korea. Written by leading experts in the field. Intelligent autonomous systems are emerged as a key enabler for the creation of a new paradigm of services to humankind, as seen by the recent advancement of autonomous cars licensed for driving in our streets, of unmanned aerial and underwater vehicles carrying out hazardous tasks on-site, and of space robots engaged in scientific as well as operational missions, to list only a few. This book aims at serving the researchers and practitioners in related fields with a timely dissemination of the recent progress on intelligent autonomous systems, based on a collection of papers presented at the 12th International Conference on Intelligent Autonomous Systems, held in Jeju, Korea, June 26-29, 2012. With the theme of ''Intelligence and Autonomy for the Service to Humankind, the conference has covered such diverse areas as autonomous ground, aerial, and underwater vehicles, intelligent transportation systems, personal/domestic service robots, professional service robots for surgery/rehabilitation, rescue/security and space applications, and intelligent autonomous systems for manufacturing and healthcare. This volume 2 includes contributions devoted to Service Robotics and Human-Robot Interaction and Autonomous Multi-Agent Systems and Life Engineering.

Autonomous Star Tracker Algorithms

DEFF Research Database (Denmark)

Betto, Maurizio; Jørgensen, John Leif; Kilsgaard, Søren

1998-01-01

Proposal, in response to an ESA R.f.P., to design algorithms for autonomous star tracker operations.The proposal also included the development of a star tracker breadboard to test the algorithms performances.......Proposal, in response to an ESA R.f.P., to design algorithms for autonomous star tracker operations.The proposal also included the development of a star tracker breadboard to test the algorithms performances....

Renal denervation therapy for hypertension: Current and future perspectives

Directory of Open Access Journals (Sweden)

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.

Effect of Sleep/Wake Cycle on Autonomic Regulation

International Nuclear Information System (INIS)

Jabeen, S.

2015-01-01

Objective: To evaluate the association between irregular sleep/wake cycle in shift workers and autonomic regulation. Study Design: Cross-sectional, analytical study. Place and Duration of Study: Dow University Hospital, Karachi, from August to November 2013. Methodology: All health care providers working in rotating shifts making a total (n=104) were included. Instrument was an integrated questionnaire applied to assess autonomic regulation, taken from Kroz et al. on scoring criteria, ranging from 18 - 54, where higher rating signifies strong autonomic regulation, indicating a stable Autonomic Nervous System (ANS) and vice versa. Participants were interviewed and their response was recorded by the investigator. Influence of sleep misalignment was measured quantitatively to extract index of autonomic activity. Results: There was a reduced trend in autonomic strength amongst shift workers. The mean score obtained on the Autonomic Scale was 37.8 ± 5.9. Conclusion: Circadian misalignment has an injurious influence on ANS which might be valuable in controlling autonomic dysfunction that leads to fatal triggers in rotating shift workers. (author)

Physics Simulation Software for Autonomous Propellant Loading and Gas House Autonomous System Monitoring

Science.gov (United States)

Regalado Reyes, Bjorn Constant

2015-01-01

1. Kennedy Space Center (KSC) is developing a mobile launching system with autonomous propellant loading capabilities for liquid-fueled rockets. An autonomous system will be responsible for monitoring and controlling the storage, loading and transferring of cryogenic propellants. The Physics Simulation Software will reproduce the sensor data seen during the delivery of cryogenic fluids including valve positions, pressures, temperatures and flow rates. The simulator will provide insight into the functionality of the propellant systems and demonstrate the effects of potential faults. This will provide verification of the communications protocols and the autonomous system control. 2. The High Pressure Gas Facility (HPGF) stores and distributes hydrogen, nitrogen, helium and high pressure air. The hydrogen and nitrogen are stored in cryogenic liquid state. The cryogenic fluids pose several hazards to operators and the storage and transfer equipment. Constant monitoring of pressures, temperatures and flow rates are required in order to maintain the safety of personnel and equipment during the handling and storage of these commodities. The Gas House Autonomous System Monitoring software will be responsible for constantly observing and recording sensor data, identifying and predicting faults and relaying hazard and operational information to the operators.

Mining in the Future: Autonomous Robotics for Safer Mines

CSIR Research Space (South Africa)

Shahdi, A

2012-10-01

Full Text Available ? Require less support infrastructure ? Advanced sensors ? CSIR 2012 Slide 4 Degree of Autonomy ? Teleoperation ? Semi-autonomous ? Autonomous ? CSIR 2012 Slide 5 Mobile Intelligent Autonomous Systems Group ? The Mobile Intelligent Autonomous...

From cooperative to autonomous vehicles

NARCIS (Netherlands)

van der Sande, T.P.J.; Nijmeijer, H.; Fossen, T.I.; Pettersen, K.Y.; Nijmeijer, H.

2017-01-01

What defines an autonomous vehicle? In this chapter the authors will try to answer this question and formulate the limitations of driver assistance systems as well as for—conditionally—autonomous vehicles . First a short summary of the levels of automation as provided by the society of automotive

Autonomous Learner Model Resource Book

Science.gov (United States)

Betts, George T.; Carey, Robin J.; Kapushion, Blanche M.

2016-01-01

"Autonomous Learner Model Resource Book" includes activities and strategies to support the development of autonomous learners. More than 40 activities are included, all geared to the emotional, social, cognitive, and physical development of students. Teachers may use these activities and strategies with the entire class, small groups, or…

Cybersecurity for aerospace autonomous systems

Science.gov (United States)

Straub, Jeremy

2015-05-01

High profile breaches have occurred across numerous information systems. One area where attacks are particularly problematic is autonomous control systems. This paper considers the aerospace information system, focusing on elements that interact with autonomous control systems (e.g., onboard UAVs). It discusses the trust placed in the autonomous systems and supporting systems (e.g., navigational aids) and how this trust can be validated. Approaches to remotely detect the UAV compromise, without relying on the onboard software (on a potentially compromised system) as part of the process are discussed. How different levels of autonomy (task-based, goal-based, mission-based) impact this remote characterization is considered.

The Human Element and Autonomous Ships

Directory of Open Access Journals (Sweden)

Sauli Ahvenjärvi

2016-09-01

Full Text Available The autonomous ship technology has become a “hot” topic in the discussion about more efficient, environmentally friendly and safer sea transportation solutions. The time is becoming mature for the introduction of commercially sensible solutions for unmanned and fully autonomous cargo and passenger ships. Safety will be the most interesting and important aspect in this development. The utilization of the autonomous ship technology will have many effects on the safety, both positive and negative. It has been announced that the goal is to make the safety of an unmanned ship better that the safety of a manned ship. However, it must be understood that the human element will still be present when fully unmanned ships are being used. The shore-based control of a ship contains new safety aspects and an interesting question will be the interaction of manned and unmanned ships in the same traffic area. The autonomous ship technology should therefore be taken into account on the training of seafarers. Also it should not be forgotten that every single control algorithm and rule of the internal decision making logic of the autonomously navigating ship has been designed and coded by a human software engineer. Thus the human element is present also in this point of the lifetime navigation system of the autonomous ship.

Morphologic Changes in Autonomic Nerves in Diabetic Autonomic Neuropathy

Directory of Open Access Journals (Sweden)

Heung Yong Jin

2015-12-01

Full Text Available Diabetic neuropathy is one of the major complications of diabetes, and it increases morbidity and mortality in patients with both type 1 diabetes mellitus (T1DM and type 2 diabetes mellitus (T2DM. Because the autonomic nervous system, for example, parasympathetic axons, has a diffuse and wide distribution, we do not know the morphological changes that occur in autonomic neural control and their exact mechanisms in diabetic patients with diabetic autonomic neuropathy (DAN. Although the prevalence of sympathetic and parasympathetic neuropathy is similar in T1DM versus T2DM patients, sympathetic nerve function correlates with parasympathetic neuropathy only in T1DM patients. The explanation for these discrepancies might be that parasympathetic nerve function was more severely affected among T2DM patients. As parasympathetic nerve damage seems to be more advanced than sympathetic nerve damage, it might be that parasympathetic neuropathy precedes sympathetic neuropathy in T2DM, which was Ewing's concept. This could be explained by the intrinsic morphologic difference. Therefore, the morphological changes in the sympathetic and parasympathetic nerves of involved organs in T1DM and T2DM patients who have DAN should be evaluated. In this review, evaluation methods for morphological changes in the epidermal nerves of skin, and the intrinsic nerves of the stomach will be discussed.

Connected and autonomous vehicles 2040 vision.

Science.gov (United States)

2014-07-01

The Pennsylvania Department of Transportation (PennDOT) commissioned a one-year project, Connected and Autonomous : Vehicles 2040 Vision, with researchers at Carnegie Mellon University (CMU) to assess the implications of connected and : autonomous ve...

Autonomous Operations System: Development and Application

Science.gov (United States)

Toro Medina, Jaime A.; Wilkins, Kim N.; Walker, Mark; Stahl, Gerald M.

2016-01-01

Autonomous control systems provides the ability of self-governance beyond the conventional control system. As the complexity of mechanical and electrical systems increases, there develops a natural drive for developing robust control systems to manage complicated operations. By closing the bridge between conventional automated systems to knowledge based self-awareness systems, nominal control of operations can evolve into relying on safe critical mitigation processes to support any off-nominal behavior. Current research and development efforts lead by the Autonomous Propellant Loading (APL) group at NASA Kennedy Space Center aims to improve cryogenic propellant transfer operations by developing an automated control and health monitoring system. As an integrated systems, the center aims to produce an Autonomous Operations System (AOS) capable of integrating health management operations with automated control to produce a fully autonomous system.

ROV90 - A prototype autonomous inspection vehicle

Energy Technology Data Exchange (ETDEWEB)

Roedseth, Oe.J.; Hallset, J.O.

1991-04-01

Simple autonomous inspection vehicles are suitable for operations where the cost, danger to humans, or area of operation prohibits the use of conventional underwater technology. Autonomous vehicles are, however, in their infancy and few such vehicles are available. There are still some problems to be overcome before this technology becomes useful in commercial applications. We have built ROV90 to investigate these problems. It is a test bed for experimenting with the different parts of an autonomous underwater vehicle. ROV90 will be able to autonomously follow prominent features in the real world, man made or natural. Examples are pipelines or walls in tunnels. ROV90 is tethered, but we are planning to use experience and results from ROV90 to develop av ''real'' autonomous underwater vehicle (AUV) called PISCIS. 11 refs., 8 figs.

Autonomous Cryogenic Load Operations: KSC Autonomous Test Engineer

Science.gov (United States)

Shrading, Nicholas J.

2012-01-01

The KSC Autonomous Test Engineer (KATE) program has a long history at KSC. Now a part of the Autonomous Cryogenic Load Operations (ACLO) mission, this software system has been sporadically developed over the past 20+ years. Originally designed to provide health and status monitoring for a simple water-based fluid system, it was proven to be a capable autonomous test engineer for determining sources of failure in. the system, As part.of a new goal to provide this same anomaly-detection capability for a complicated cryogenic fluid system, software engineers, physicists, interns and KATE experts are working to upgrade the software capabilities and graphical user interface. Much progress was made during this effort to improve KATE. A display ofthe entire cryogenic system's graph, with nodes for components and edges for their connections, was added to the KATE software. A searching functionality was added to the new graph display, so that users could easily center their screen on specific components. The GUI was also modified so that it displayed information relevant to the new project goals. In addition, work began on adding new pneumatic and electronic subsystems into the KATE knowledgebase, so that it could provide health and status monitoring for those systems. Finally, many fixes for bugs, memory leaks, and memory errors were implemented and the system was moved into a state in which it could be presented to stakeholders. Overall, the KATE system was improved and necessary additional features were added so that a presentation of the program and its functionality in the next few months would be a success.

Autonomous power networks based power system

International Nuclear Information System (INIS)

Jokic, A.; Van den Bosch, P.P.J.

2006-01-01

This paper presented the concept of autonomous networks to cope with this increased complexity in power systems while enhancing market-based operation. The operation of future power systems will be more challenging and demanding than present systems because of increased uncertainties, less inertia in the system, replacement of centralized coordinating activities by decentralized parties and the reliance on dynamic markets for both power balancing and system reliability. An autonomous network includes the aggregation of networked producers and consumers in a relatively small area with respect to the overall system. The operation of an autonomous network is coordinated and controlled with one central unit acting as an interface between internal producers/consumers and the rest of the power system. In this study, the power balance problem and system reliability through provision of ancillary services was formulated as an optimization problem for the overall autonomous networks based power system. This paper described the simulation of an optimal autonomous network dispatching in day ahead markets, based on predicted spot prices for real power, and two ancillary services. It was concluded that large changes occur in a power systems structure and operation, most of them adding to the uncertainty and complexity of the system. The introduced concept of an autonomous power network-based power system was shown to be a realistic and consistent approach to formulate and operate a market-based dispatch of both power and ancillary services. 9 refs., 4 figs

Advancing Autonomous Operations for Deep Space Vehicles

Science.gov (United States)

Haddock, Angie T.; Stetson, Howard K.

2014-01-01

Starting in Jan 2012, the Advanced Exploration Systems (AES) Autonomous Mission Operations (AMO) Project began to investigate the ability to create and execute "single button" crew initiated autonomous activities [1]. NASA Marshall Space Flight Center (MSFC) designed and built a fluid transfer hardware test-bed to use as a sub-system target for the investigations of intelligent procedures that would command and control a fluid transfer test-bed, would perform self-monitoring during fluid transfers, detect anomalies and faults, isolate the fault and recover the procedures function that was being executed, all without operator intervention. In addition to the development of intelligent procedures, the team is also exploring various methods for autonomous activity execution where a planned timeline of activities are executed autonomously and also the initial analysis of crew procedure development. This paper will detail the development of intelligent procedures for the NASA MSFC Autonomous Fluid Transfer System (AFTS) as well as the autonomous plan execution capabilities being investigated. Manned deep space missions, with extreme communication delays with Earth based assets, presents significant challenges for what the on-board procedure content will encompass as well as the planned execution of the procedures.

Autonomous Science Analysis with the New Millennium Program-Autonomous Sciencecraft Experiment

Science.gov (United States)

Doggett, T.; Davies, A. G.; Castano, R. A.; Baker, V. R.; Dohm, J. M.; Greeley, R.; Williams, K. K.; Chien, S.; Sherwood, R.

2002-12-01

The NASA New Millennium Program (NMP) is a testbed for new, high-risk technologies, including new software and hardware. The Autonomous Sciencecraft Experiment (ASE) will fly on the Air Force Research Laboratory TechSat-21 mission in 2006 is such a NMP mission, and is managed by the Jet Propulsion Laboratory, California Institute of Technology. TechSat-21 consists of three satellites, each equipped with X-band Synthetic Aperture Radar (SAR) that will occupy a 13-day repeat track Earth orbit. The main science objectives of ASE are to demonstrate that process-related change detection and feature identification can be conducted autonomously during space flight, leading to autonomous onboard retargeting of the spacecraft. This mission will observe transient geological and environmental processes using SAR. Examples of geologic processes that may be observed and investigated include active volcanism, the movement of sand dunes and transient features in desert environments, water flooding, and the formation and break-up of lake ice. Science software onboard the spacecraft will allow autonomous processing and formation of SAR images and extraction of scientific information. The subsequent analyses, performed on images formed onboard from the SAR data, will include feature identification using scalable feature "templates" for each target, change detection through comparison of current and archived images, and science discovery, a search for other features of interest in each image. This approach results in obtaining the same science return for a reduced amount of resource use (such as downlink) when compared to that from a mission operating without ASE technology. Redundant data is discarded. The science-driven goals of ASE will evolve during the ASE mission through onboard replanning software that can re-task satellite operations. If necessary, as a result of a discovery made autonomously by onboard science processing, existing observation sequences will be pre-empted to

Autonomous search

CERN Document Server

Hamadi, Youssef; Saubion, Frédéric

2012-01-01

Autonomous combinatorial search (AS) represents a new field in combinatorial problem solving. Its major standpoint and originality is that it considers that problem solvers must be capable of self-improvement operations. This is the first book dedicated to AS.

Perception, Planning, Control, and Coordination for Autonomous Vehicles

Directory of Open Access Journals (Sweden)

Scott Drew Pendleton

2017-02-01

Full Text Available Autonomous vehicles are expected to play a key role in the future of urban transportation systems, as they offer potential for additional safety, increased productivity, greater accessibility, better road efficiency, and positive impact on the environment. Research in autonomous systems has seen dramatic advances in recent years, due to the increases in available computing power and reduced cost in sensing and computing technologies, resulting in maturing technological readiness level of fully autonomous vehicles. The objective of this paper is to provide a general overview of the recent developments in the realm of autonomous vehicle software systems. Fundamental components of autonomous vehicle software are reviewed, and recent developments in each area are discussed.

Energy homeostasis, autonomic activity and obesity

NARCIS (Netherlands)

Scheurink, AJW; Balkan, B; Nyakas, C; vanDijk, G; Steffens, AB; Bohus, B

1995-01-01

Obesity is often accompanied by alterations in both sympathetic and parasympathetic autonomic functions. The present paper summarizes the results of a number of studies designed to investigate autonomic functioning in normal, genetically, and experimentally obese rats, Particular emphasis is given

The renal nerves in chronic heart failure: efferent and afferent mechanisms

Science.gov (United States)

Schiller, Alicia M.; Pellegrino, Peter R.; Zucker, Irving H.

2015-01-01

The function of the renal nerves has been an area of scientific and medical interest for many years. The recent advent of a minimally invasive catheter-based method of renal denervation has renewed excitement in understanding the afferent and efferent actions of the renal nerves in multiple diseases. While hypertension has been the focus of much this work, less attention has been given to the role of the renal nerves in the development of chronic heart failure (CHF). Recent studies from our laboratory and those of others implicate an essential role for the renal nerves in the development and progression of CHF. Using a rabbit tachycardia model of CHF and surgical unilateral renal denervation, we provide evidence for both renal efferent and afferent mechanisms in the pathogenesis of CHF. Renal denervation prevented the decrease in renal blood flow observed in CHF while also preventing increases in Angiotensin-II receptor protein in the microvasculature of the renal cortex. Renal denervation in CHF also reduced physiological markers of autonomic dysfunction including an improvement in arterial baroreflex function, heart rate variability, and decreased resting cardiac sympathetic tone. Taken together, the renal sympathetic nerves are necessary in the pathogenesis of CHF via both efferent and afferent mechanisms. Additional investigation is warranted to fully understand the role of these nerves and their role as a therapeutic target in CHF. PMID:26300788

Role of the autonomic nervous system and baroreflex in stress-evoked cardiovascular responses in rats.

Science.gov (United States)

Dos Reis, Daniel Gustavo; Fortaleza, Eduardo Albino Trindade; Tavares, Rodrigo Fiacadori; Corrêa, Fernando Morgan Aguiar

2014-07-01

Restraint stress (RS) is an experimental model to study stress-related cardiovascular responses, characterized by sustained pressor and tachycardiac responses. We used pharmacologic and surgical procedures to investigate the role played by sympathetic nervous system (SNS) and parasympathetic nervous system (PSNS) in the mediation of stress-evoked cardiovascular responses. Ganglionic blockade with pentolinium significantly reduced RS-evoked pressor and tachycardiac responses. Intravenous treatment with homatropine methyl bromide did not affect the pressor response but increased tachycardia. Pretreatment with prazosin reduced the pressor and increased the tachycardiac response. Pretreatment with atenolol did not affect the pressor response but reduced tachycardia. The combined treatment with atenolol and prazosin reduced both pressor and tachycardiac responses. Adrenal demedullation reduced the pressor response without affecting tachycardia. Sinoaortic denervation increased pressor and tachycardiac responses. The results indicate that: (1) the RS-evoked cardiovascular response is mediated by the autonomic nervous system without an important involvement of humoral factors; (2) hypertension results primarily from sympathovascular and sympathoadrenal activation, without a significant involvement of the cardiac sympathetic component (CSNS); (3) the abrupt initial peak in the hypertensive response to restraint is sympathovascular-mediated, whereas the less intense but sustained hypertensive response observed throughout the remaining restraint session is mainly mediated by sympathoadrenal activation and epinephrine release; (4) tachycardia results from CSNS activation, and not from PSNS inhibition; (5) RS evokes simultaneous CSNS and PSNS activation, and heart rate changes are a vector of both influences; (6) the baroreflex is functional during restraint, and modulates both the vascular and cardiac responses to restraint.

Research Institute for Autonomous Precision Guided Systems

National Research Council Canada - National Science Library

Rogacki, John R

2007-01-01

... vehicles, cooperative flight of autonomous aerial vehicles using GPS and vision information, cooperative and sharing of information in search missions involving multiple autonomous agents, multi-scale...

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

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

Directory of Open Access Journals (Sweden)

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

Selective plasticity of primary afferent innervation to the dorsal horn and autonomic nuclei following lumbosacral ventral root avulsion and reimplantation in long term studies.

Science.gov (United States)

Wu, Lisa; Wu, Jun; Chang, Huiyi H; Havton, Leif A

2012-02-01

Previous studies involving injuries to the nerves of the cauda equina and the conus medullaris have shown that lumbosacral ventral root avulsion in rat models results in denervation and dysfunction of the lower urinary tract, retrograde and progressive cell death of the axotomized motor and parasympathetic neurons, as well as the emergence of neuropathic pain. Root reimplantation has also been shown to ameliorate several of these responses, but experiments thus far have been limited to studying the effects of lesion and reimplantation local to the lumbosacral region. Here, we have expanded the region of investigation after lumbosacral ventral root avulsion and reimplantation to include the thoracolumbar sympathetic region of the spinal cord. Using a retrograde tracer injected into the major pelvic ganglion, we were able to define the levels of the spinal cord that contain sympathetic preganglionic neurons innervating the lower urinary tract. We have conducted studies on the effects of the lumbosacral ventral root avulsion and reimplantation models on the afferent innervation of the dorsal horn and autonomic nuclei at both thoracolumbar and lumbosacral levels through immunohistochemistry for the markers calcitonin gene-related peptide (CGRP) and vesicular glutamate transporter 1 (VGLUT1). Surprisingly, our experiments reveal a selective and significant decrease of CGRP-positive innervation in the dorsal horn at thoracolumbar levels that is partially restored with root reimplantation. However, no similar changes were detected at the lumbosacral levels despite the injury and repair targeting efferent neurons, and being performed at the lumbosacral levels. Despite the changes evident in the thoracolumbar dorsal horn, we find no changes in afferent innervation of the autonomic nuclei at either sympathetic or parasympathetic segmental levels by CGRP or VGLUT1. We conclude that even remote, efferent root injuries and repair procedures can have an effect on remote and non

Adaptive Control Allocation for Fault Tolerant Overactuated Autonomous Vehicles

Science.gov (United States)

2007-11-01

Tolerant Overactuated Autonomous Vehicles Casavola, A.; Garone, E. (2007) Adaptive Control Allocation for Fault Tolerant Overactuated Autonomous ...Adaptive Control Allocation for Fault Tolerant Overactuated Autonomous Vehicles 5a. CONTRACT NUMBER 5b. GRANT NUMBER 5c. PROGRAM ELEMENT NUMBER 6...Tolerant Overactuated Autonomous Vehicles 3.2 - 2 RTO-MP-AVT-145 UNCLASSIFIED/UNLIMITED Control allocation problem (CAP) - Given a virtual input v(t

Overfeeding, autonomic regulation and metabolic consequences.

NARCIS (Netherlands)

Scheurink, A.J.W.; Balkan, B; Strubbe, J.H.; van Dijk, G.; Steffens, A.B

The autonomic nervous system plays an important role in the regulation of body processes in health and disease. Overfeeding and obesity (a disproportional increase of the fat mass of the body) are often accompanied by alterations in both sympathetic and parasympathetic autonomic functions. The

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.

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.)

Autonomic dysfunction in different subtypes of multiple system atrophy.

Science.gov (United States)

Schmidt, Claudia; Herting, Birgit; Prieur, Silke; Junghanns, Susann; Schweitzer, Katherine; Globas, Christoph; Schöls, Ludger; Reichmann, Heinz; Berg, Daniela; Ziemssen, Tjalf

2008-09-15

Multiple system atrophy (MSA) can clinically be divided into the cerebellar (MSA-C) and the parkinsonian (MSA-P) variant. However, till now, it is unknown whether autonomic dysfunction in these two entities differs regarding severity and profile. We compared the pattern of autonomic dysfunction in 12 patients with MSA-C and 26 with MSA-P in comparison with 27 age- and sex-matched healthy controls using a standard battery of autonomic function tests and a structured anamnesis of the autonomic nervous system. MSA-P patients complained significantly more often about the symptoms of autonomic dysfunctions than MSA-C patients, especially regarding vasomotor, secretomotor, and gastrointestinal subsystems. However, regarding cardiovascular, sudomotor pupil, urogenital, and sleep subsystems, there were no significant quantitative or qualitative differences as analyzed by autonomic anamnesis and testing. Our results suggest that there are only minor differences in the pattern of autonomic dysfunction between the two clinical MSA phenotypes. (c) 2007 Movement Disorder Society.

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.

The Bering Autonomous Target Detection

DEFF Research Database (Denmark)

Jørgensen, John Leif; Denver, Troelz; Betto, Maurizio

2003-01-01

An autonomous asteroid target detection and tracking method has been developed. The method features near omnidirectionality and focus on high speed operations and completeness of search of the near space rather than the traditional faint object search methods, employed presently at the larger...... telescopes. The method has proven robust in operation and is well suited for use onboard spacecraft. As development target for the method and the associated instrumentation the asteroid research mission Bering has been used. Onboard a spacecraft, the autonomous detection is centered around the fully...... autonomous star tracker the Advanced Stellar Compass (ASC). One feature of this instrument is that potential targets are registered directly in terms of date, right ascension, declination, and intensity, which greatly facilitates both tracking search and registering. Results from ground and inflight tests...

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.

Autonomic Dysfunction in Patients with Mild to Moderate Alzheimer's Disease

DEFF Research Database (Denmark)

Jensen-Dahm, Christina; Waldemar, Gunhild; Staehelin Jensen, Troels

2015-01-01

BACKGROUND: Autonomic function has received little attention in Alzheimer's disease (AD). AD pathology has an impact on brain regions which are important for central autonomic control, but it is unclear if AD is associated with disturbance of autonomic function. OBJECTIVE: To investigate autonomic...

Functional Imaging of Autonomic Regulation: Methods and Key Findings

Directory of Open Access Journals (Sweden)

Paul M Macey

2016-01-01

Full Text Available Central nervous system processing of autonomic function involves a network of regions throughout the brain which can be visualized and measured with neuroimaging techniques, notably functional magnetic resonance imaging (fMRI. The development of fMRI procedures has both confirmed and extended earlier findings from animal models, and human stroke and lesion studies. Assessments with fMRI can elucidate interactions between different central sites in regulating normal autonomic patterning, and demonstrate how disturbed systems can interact to produce aberrant regulation during autonomic challenges. Understanding autonomic dysfunction in various illnesses reveals mechanisms that potentially lead to interventions in the impairments. The objectives here are to: 1 describe the fMRI neuroimaging methodology for assessment of autonomic neural control, 2 outline the widespread, lateralized distribution of function in autonomic sites in the normal brain which includes structures from the neocortex through the medulla and cerebellum, 3 illustrate the importance of the time course of neural changes when coordinating responses, and how those patterns are impacted in conditions of sleep-disordered breathing, and 4 highlight opportunities for future research studies with emerging methodologies. Methodological considerations specific to autonomic testing include timing of challenges relative to the underlying fMRI signal, spatial resolution sufficient to identify autonomic brainstem nuclei, blood pressure and blood oxygenation influences on the fMRI signal, and the sustained timing, often measured in minutes of challenge periods and recovery. Key findings include the lateralized nature of autonomic organization, which is reminiscent of asymmetric motor, sensory and language pathways. Testing brain function during autonomic challenges demonstrate closely-integrated timing of responses in connected brain areas during autonomic challenges, and the involvement with

Advanced Autonomous Systems for Space Operations

Science.gov (United States)

Gross, A. R.; Smith, B. D.; Muscettola, N.; Barrett, A.; Mjolssness, E.; Clancy, D. J.

2002-01-01

New missions of exploration and space operations will require unprecedented levels of autonomy to successfully accomplish their objectives. Inherently high levels of complexity, cost, and communication distances will preclude the degree of human involvement common to current and previous space flight missions. With exponentially increasing capabilities of computer hardware and software, including networks and communication systems, a new balance of work is being developed between humans and machines. This new balance holds the promise of not only meeting the greatly increased space exploration requirements, but simultaneously dramatically reducing the design, development, test, and operating costs. New information technologies, which take advantage of knowledge-based software, model-based reasoning, and high performance computer systems, will enable the development of a new generation of design and development tools, schedulers, and vehicle and system health management capabilities. Such tools will provide a degree of machine intelligence and associated autonomy that has previously been unavailable. These capabilities are critical to the future of advanced space operations, since the science and operational requirements specified by such missions, as well as the budgetary constraints will limit the current practice of monitoring and controlling missions by a standing army of ground-based controllers. System autonomy capabilities have made great strides in recent years, for both ground and space flight applications. Autonomous systems have flown on advanced spacecraft, providing new levels of spacecraft capability and mission safety. Such on-board systems operate by utilizing model-based reasoning that provides the capability to work from high-level mission goals, while deriving the detailed system commands internally, rather than having to have such commands transmitted from Earth. This enables missions of such complexity and communication` distances as are not

A Primer on Autonomous Aerial Vehicle Design.

Science.gov (United States)

Coppejans, Hugo H G; Myburgh, Herman C

2015-12-02

There is a large amount of research currently being done on autonomous micro-aerial vehicles (MAV), such as quadrotor helicopters or quadcopters. The ability to create a working autonomous MAV depends mainly on integrating a simultaneous localization and mapping (SLAM) solution with the rest of the system. This paper provides an introduction for creating an autonomous MAV for enclosed environments, aimed at students and professionals alike. The standard autonomous system and MAV automation are discussed, while we focus on the core concepts of SLAM systems and trajectory planning algorithms. The advantages and disadvantages of using remote processing are evaluated, and recommendations are made regarding the viability of on-board processing. Recommendations are made regarding best practices to serve as a guideline for aspirant MAV designers.

Cyber Security Considerations for Autonomous Tactical Wheeled Vehicles

Science.gov (United States)

2016-04-01

Update Will Enable Autonomous Driving. Retrieved August 6, 2015, from http://spectrum.ieee.org/: http://spectrum.ieee.org/ cars -that-think...Cyber Security Considerations for Autonomous Tactical Wheeled Vehicles 1 UNCLASSIFIED Cyber Security Considerations for... Autonomous Tactical Wheeled Vehicles Sebastian C Iovannitti 4/1/2016 Submitted to Lawrence Technological University College of Management in

Exact Solutions for Certain Nonlinear Autonomous Ordinary Differential Equations of the Second Order and Families of Two-Dimensional Autonomous Systems

Directory of Open Access Journals (Sweden)

M. P. Markakis

2010-01-01

Full Text Available Certain nonlinear autonomous ordinary differential equations of the second order are reduced to Abel equations of the first kind ((Ab-1 equations. Based on the results of a previous work, concerning a closed-form solution of a general (Ab-1 equation, and introducing an arbitrary function, exact one-parameter families of solutions are derived for the original autonomous equations, for the most of which only first integrals (in closed or parametric form have been obtained so far. Two-dimensional autonomous systems of differential equations of the first order, equivalent to the considered herein autonomous forms, are constructed and solved by means of the developed analysis.

May a unitary autonomic index help assess autonomic cardiac regulation in elite athletes? Preliminary observations on the national Italian Olympic committee team.

Science.gov (United States)

Sala, Roberto; Malacarne, Mara; Tosi, Fabio; Benzi, Manuela; Solaro, Nadia; Tamorri, Stefano; Spataro, Antonio; Pagani, Massimo; Lucini, Daniela

2017-12-01

Long term endurance training, as occurring in elite athletes, is associated to cardiac neural remodeling in favor of cardioprotective vagal mechanisms, resulting in resting bradycardia and augmented contribution of cardiac parasympathetic nerve activity. Autonomic assessment can be performed by way of heart rate variability. This technique however provides multiple indices, and there is not yet complete agreement on their specific significance. Purpose of the study was to assess whether a rank transformation and radar plot could provide a unitary autonomic index, capable to show a correlation between intensity of individual work and quality of autonomic regulation. We studied 711 (23.6±6.2 years) elite athletes that took part in the selection procedure for the 2016 Rio Olympic Games for the National Italian Olympic Committee (CONI). Indices from Heart Rate Variability HRV obtained at rest, during standing up and during recovery from an exercise test were used to compute a percent ranked unitary autonomic index for sport (ANSIs), taken as proxy of quality of autonomic regulation. Within the observed wide range of energy expenditure, the unitary autonomic index ANSIs appears significantly correlated to individual and discipline specific training workloads (r=0.25, P<0.001 and r=0.78, P<0.001, respectively), correcting for possible age and gender bias. ANSIs also positively correlates to lipid profile. Estimated intensity of physical activity correlates with quality of cardiac autonomic regulation, as expressed by a novel unitary index of cardiac autonomic regulation. ANSIs could provide a novel and convenient approach to individual autonomic evaluation in athletes.

PHM Enabled Autonomous Propellant Loading Operations

Science.gov (United States)

Walker, Mark; Figueroa, Fernando

2017-01-01

The utility of Prognostics and Health Management (PHM) software capability applied to Autonomous Operations (AO) remains an active research area within aerospace applications. The ability to gain insight into which assets and subsystems are functioning properly, along with the derivation of confident predictions concerning future ability, reliability, and availability, are important enablers for making sound mission planning decisions. When coupled with software that fully supports mission planning and execution, an integrated solution can be developed that leverages state assessment and estimation for the purposes of delivering autonomous operations. The authors have been applying this integrated, model-based approach to the autonomous loading of cryogenic spacecraft propellants at Kennedy Space Center.

Autonomous Control of Space Reactor Systems

International Nuclear Information System (INIS)

Belle R. Upadhyaya; K. Zhao; S.R.P. Perillo; Xiaojia Xu; M.G. Na

2007-01-01

Autonomous and semi-autonomous control is a key element of space reactor design in order to meet the mission requirements of safety, reliability, survivability, and life expectancy. Interrestrial nuclear power plants, human operators are available to perform intelligent control functions that are necessary for both normal and abnormal operational conditions

Autonomous Control of Space Reactor Systems

Energy Technology Data Exchange (ETDEWEB)

Belle R. Upadhyaya; K. Zhao; S.R.P. Perillo; Xiaojia Xu; M.G. Na

2007-11-30

Autonomous and semi-autonomous control is a key element of space reactor design in order to meet the mission requirements of safety, reliability, survivability, and life expectancy. Interrestrial nuclear power plants, human operators are avilable to perform intelligent control functions that are necessary for both normal and abnormal operational conditions.

The treatment of autonomic dysfunction in tetanus

Directory of Open Access Journals (Sweden)

T van den Heever

2017-07-01

Full Text Available We report a case of generalised tetanus in a 50-year-old female patient after sustaining a wound to her right lower leg. She developed autonomic dysfunction, which included labile hypertension alternating with hypotension and sweating. The autonomic dysfunction was treated successfully with a combination of morphine sulphate infusion, magnesium sulphate, and clonidine. She also received adrenaline and phenylephrine infusions as needed for hypotension. We then discuss the pathophysiology, clinical features and treatment options of autonomic dysfunction.

Swarm autonomic agents with self-destruct capability

Science.gov (United States)

Hinchey, Michael G. (Inventor); Sterritt, Roy (Inventor)

2011-01-01

Systems, methods and apparatus are provided through which in some embodiments an autonomic entity manages a system by generating one or more stay alive signals based on the functioning status and operating state of the system. In some embodiments, an evolvable synthetic neural system is operably coupled to one or more evolvable synthetic neural systems in a hierarchy. The evolvable neural interface receives and generates heartbeat monitor signals and pulse monitor signals that are used to generate a stay alive signal that is used to manage the operations of the synthetic neural system. In another embodiment an asynchronous Alice signal (Autonomic license) requiring valid credentials of an anonymous autonomous agent is initiated. An unsatisfactory Alice exchange may lead to self-destruction of the anonymous autonomous agent for self-protection.

A Primer on Autonomous Aerial Vehicle Design

Directory of Open Access Journals (Sweden)

Hugo H. G. Coppejans

2015-12-01

Full Text Available There is a large amount of research currently being done on autonomous micro-aerial vehicles (MAV, such as quadrotor helicopters or quadcopters. The ability to create a working autonomous MAV depends mainly on integrating a simultaneous localization and mapping (SLAM solution with the rest of the system. This paper provides an introduction for creating an autonomous MAV for enclosed environments, aimed at students and professionals alike. The standard autonomous system and MAV automation are discussed, while we focus on the core concepts of SLAM systems and trajectory planning algorithms. The advantages and disadvantages of using remote processing are evaluated, and recommendations are made regarding the viability of on-board processing. Recommendations are made regarding best practices to serve as a guideline for aspirant MAV designers.

F-18-FDG-PET in autonomous goiter

International Nuclear Information System (INIS)

Boerner, A.R.; Voth, E.; Schicha, H.

1999-01-01

Aim: Gain-of-function mutations of the thyrotropin receptor (TSHR) gene have been invoked as one of the major causes of toxic thyroid adenomas. This study evaluates F-18-FDG-PET in these patients. Methods: Twenty patients with focal autonomous nodules and ten with disseminated autonomy were investigated the day before radioiodine therapy. Twenty patients with cancer of the head or neck and normal thyroid function served as controls. Results: F-18-FDG-Uptake was higher in patients than in controls. Focal autonomous nodules were associated with focally enhanced glucose metabolism. Disseminated autonomous goiters showed various patterns of focal or global hypermetabolism. Conclusion: Autonomous thyroid tissue caused by constitutive mutations of the TSH receptor is characterised by simultaneous increases in glucose and iodine metabolism which are correlated. (orig.) [de

Autonomic symptoms in idiopathic REM behavior disorder

DEFF Research Database (Denmark)

Ferini-Strambi, Luigi; Oertel, Wolfgang; Dauvilliers, Yves

2014-01-01

Patients with idiopathic REM sleep behavior disorder (iRBD) are at very high risk of developing neurodegenerative synucleinopathies, which are disorders with prominent autonomic dysfunction. Several studies have documented autonomic dysfunction in iRBD, but large-scale assessment of autonomic...... symptoms has never been systematically performed. Patients with polysomnography-confirmed iRBD (318 cases) and controls (137 healthy volunteers and 181 sleep center controls with sleep diagnoses other than RBD) were recruited from 13 neurological centers in 10 countries from 2008 to 2011. A validated scale...

Nature's Autonomous Oscillators

Science.gov (United States)

Mayr, H. G.; Yee, J.-H.; Mayr, M.; Schnetzler, R.

2012-01-01

Nonlinearity is required to produce autonomous oscillations without external time dependent source, and an example is the pendulum clock. The escapement mechanism of the clock imparts an impulse for each swing direction, which keeps the pendulum oscillating at the resonance frequency. Among nature's observed autonomous oscillators, examples are the quasi-biennial oscillation and bimonthly oscillation of the Earth atmosphere, and the 22-year solar oscillation. The oscillations have been simulated in numerical models without external time dependent source, and in Section 2 we summarize the results. Specifically, we shall discuss the nonlinearities that are involved in generating the oscillations, and the processes that produce the periodicities. In biology, insects have flight muscles, which function autonomously with wing frequencies that far exceed the animals' neural capacity; Stretch-activation of muscle contraction is the mechanism that produces the high frequency oscillation of insect flight, discussed in Section 3. The same mechanism is also invoked to explain the functioning of the cardiac muscle. In Section 4, we present a tutorial review of the cardio-vascular system, heart anatomy, and muscle cell physiology, leading up to Starling's Law of the Heart, which supports our notion that the human heart is also a nonlinear oscillator. In Section 5, we offer a broad perspective of the tenuous links between the fluid dynamical oscillators and the human heart physiology.

Bilateral human-robot control for semi-autonomous UAV navigation

NARCIS (Netherlands)

Wopereis, Han Willem; Fumagalli, Matteo; Stramigioli, Stefano; Carloni, Raffaella

2015-01-01

This paper proposes a semi-autonomous bilateral control architecture for unmanned aerial vehicles. During autonomous navigation, a human operator is allowed to assist the autonomous controller of the vehicle by actively changing its navigation parameters to assist it in critical situations, such as

Effects of insula resection on autonomic nervous system activity

NARCIS (Netherlands)

de Morree, Helma; Rutten, Geert-Jan; Szabo, B.M.; Sitskoorn, Margriet; Kop, Wijo

2016-01-01

Background: The insula is an essential component of the central autonomic network and plays a critical role in autonomic regulation in response to environmental stressors. The role of the insula in human autonomic regulation has been primarily investigated following cerebrovascular accidents, but

Autonomous Cryogenics Loading Operations Simulation Software: Knowledgebase Autonomous Test Engineer

Science.gov (United States)

Wehner, Walter S., Jr.

2013-01-01

Working on the ACLO (Autonomous Cryogenics Loading Operations) project I have had the opportunity to add functionality to the physics simulation software known as KATE (Knowledgebase Autonomous Test Engineer), create a new application allowing WYSIWYG (what-you-see-is-what-you-get) creation of KATE schematic files and begin a preliminary design and implementation of a new subsystem that will provide vision services on the IHM (Integrated Health Management) bus. The functionality I added to KATE over the past few months includes a dynamic visual representation of the fluid height in a pipe based on number of gallons of fluid in the pipe and implementing the IHM bus connection within KATE. I also fixed a broken feature in the system called the Browser Display, implemented many bug fixes and made changes to the GUI (Graphical User Interface).

Demonstration of Autonomous Rendezvous Technology (DART) Project Summary

Science.gov (United States)

Rumford, TImothy E.

2003-01-01

Since the 1960's, NASA has performed numerous rendezvous and docking missions. The common element of all US rendezvous and docking is that the spacecraft has always been piloted by astronauts. Only the Russian Space Program has developed and demonstrated an autonomous capability. The Demonstration of Autonomous Rendezvous Technology (DART) project currently funded under NASA's Space Launch Initiative (SLI) Cycle I, provides a key step in establishing an autonomous rendezvous capability for the United States. DART's objective is to demonstrate, in space, the hardware and software necessary for autonomous rendezvous. Orbital Sciences Corporation intends to integrate an Advanced Video Guidance Sensor and Autonomous Rendezvous and Proximity Operations algorithms into a Pegasus upper stage in order to demonstrate the capability to autonomously rendezvous with a target currently in orbit. The DART mission will occur in April 2004. The launch site will be Vandenburg AFB and the launch vehicle will be a Pegasus XL equipped with a Hydrazine Auxiliary Propulsion System 4th stage. All mission objectives will be completed within a 24 hour period. The paper provides a summary of mission objectives, mission overview and a discussion on the design features of the chase and target vehicles.

Examining accident reports involving autonomous vehicles in California.

Directory of Open Access Journals (Sweden)

Francesca M Favarò

Full Text Available Autonomous Vehicle technology is quickly expanding its market and has found in Silicon Valley, California, a strong foothold for preliminary testing on public roads. In an effort to promote safety and transparency to consumers, the California Department of Motor Vehicles has mandated that reports of accidents involving autonomous vehicles be drafted and made available to the public. The present work shows an in-depth analysis of the accident reports filed by different manufacturers that are testing autonomous vehicles in California (testing data from September 2014 to March 2017. The data provides important information on autonomous vehicles accidents' dynamics, related to the most frequent types of collisions and impacts, accident frequencies, and other contributing factors. The study also explores important implications related to future testing and validation of semi-autonomous vehicles, tracing the investigation back to current literature as well as to the current regulatory panorama.

Examining accident reports involving autonomous vehicles in California.

Science.gov (United States)

Favarò, Francesca M; Nader, Nazanin; Eurich, Sky O; Tripp, Michelle; Varadaraju, Naresh

2017-01-01

Autonomous Vehicle technology is quickly expanding its market and has found in Silicon Valley, California, a strong foothold for preliminary testing on public roads. In an effort to promote safety and transparency to consumers, the California Department of Motor Vehicles has mandated that reports of accidents involving autonomous vehicles be drafted and made available to the public. The present work shows an in-depth analysis of the accident reports filed by different manufacturers that are testing autonomous vehicles in California (testing data from September 2014 to March 2017). The data provides important information on autonomous vehicles accidents' dynamics, related to the most frequent types of collisions and impacts, accident frequencies, and other contributing factors. The study also explores important implications related to future testing and validation of semi-autonomous vehicles, tracing the investigation back to current literature as well as to the current regulatory panorama.

Examining accident reports involving autonomous vehicles in California

Science.gov (United States)

Nader, Nazanin; Eurich, Sky O.; Tripp, Michelle; Varadaraju, Naresh

2017-01-01

Autonomous Vehicle technology is quickly expanding its market and has found in Silicon Valley, California, a strong foothold for preliminary testing on public roads. In an effort to promote safety and transparency to consumers, the California Department of Motor Vehicles has mandated that reports of accidents involving autonomous vehicles be drafted and made available to the public. The present work shows an in-depth analysis of the accident reports filed by different manufacturers that are testing autonomous vehicles in California (testing data from September 2014 to March 2017). The data provides important information on autonomous vehicles accidents’ dynamics, related to the most frequent types of collisions and impacts, accident frequencies, and other contributing factors. The study also explores important implications related to future testing and validation of semi-autonomous vehicles, tracing the investigation back to current literature as well as to the current regulatory panorama. PMID:28931022

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.

Tactical Decision Aids High Bandwidth Links Using Autonomous Vehicles

Science.gov (United States)

2004-01-01

1 Tactical Decision Aids (High Bandwidth Links Using Autonomous Vehicles ) A. J. Healey, D. P. Horner, Center for Autonomous Underwater Vehicle...SUBTITLE Tactical Decision Aids (High Bandwidth Links Using Autonomous Vehicles ) 5a. CONTRACT NUMBER 5b. GRANT NUMBER 5c. PROGRAM ELEMENT NUMBER 6

Autonomous Cryogenic Load Operations: Knowledge-Based Autonomous Test Engineer

Science.gov (United States)

Schrading, J. Nicolas

2013-01-01

The Knowledge-Based Autonomous Test Engineer (KATE) program has a long history at KSC. Now a part of the Autonomous Cryogenic Load Operations (ACLO) mission, this software system has been sporadically developed over the past 20 years. Originally designed to provide health and status monitoring for a simple water-based fluid system, it was proven to be a capable autonomous test engineer for determining sources of failure in the system. As part of a new goal to provide this same anomaly-detection capability for a complicated cryogenic fluid system, software engineers, physicists, interns and KATE experts are working to upgrade the software capabilities and graphical user interface. Much progress was made during this effort to improve KATE. A display of the entire cryogenic system's graph, with nodes for components and edges for their connections, was added to the KATE software. A searching functionality was added to the new graph display, so that users could easily center their screen on specific components. The GUI was also modified so that it displayed information relevant to the new project goals. In addition, work began on adding new pneumatic and electronic subsystems into the KATE knowledge base, so that it could provide health and status monitoring for those systems. Finally, many fixes for bugs, memory leaks, and memory errors were implemented and the system was moved into a state in which it could be presented to stakeholders. Overall, the KATE system was improved and necessary additional features were added so that a presentation of the program and its functionality in the next few months would be a success.

Design of Autonomous Gel Actuators

Directory of Open Access Journals (Sweden)

Shuji Hashimoto

2011-01-01

Full Text Available In this paper, we introduce autonomous gel actuators driven by chemical energy. The polymer gels prepared here have cyclic chemical reaction networks. With a cyclic reaction, the polymer gels generate periodical motion. The periodic motion of the gel is produced by the chemical energy of the oscillatory Belouzov-Zhabotinsky (BZ reaction. We have succeeded in making synthetic polymer gel move autonomously like a living organism. This experimental fact represents the great possibility of the chemical robot.

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

Longitudinal Control for Mengshi Autonomous Vehicle via Gauss Cloud Model

Directory of Open Access Journals (Sweden)

Hongbo Gao

2017-12-01

Full Text Available Dynamic robustness and stability control is a requirement for self-driving of autonomous vehicle. Longitudinal control technique of autonomous vehicle is basic theory and one key complex technique which must have the reliability and precision of vehicle controller. The longitudinal control technique is one of the foundations of the safety and stability of autonomous vehicle control. In our paper, we present a longitudinal control algorithm based on cloud model for Mengshi autonomous vehicle to ensure the dynamic stability and tracking performance of Mengshi autonomous vehicle. The longitudinal control algorithm mainly uses cloud model generator to control the acceleration of the autonomous vehicle to achieve the goal that controls the speed of Mengshi autonomous vehicle. The proposed longitudinal control algorithm based on cloud model is verified by real experiments on Highway driving scene. The experiments results of the acceleration and speed show that the algorithm is validity and stability.

Biologically-Inspired Concepts for Autonomic Self-Protection in Multiagent Systems

Science.gov (United States)

Sterritt, Roy; Hinchey, Mike

2006-01-01

Biologically-inspired autonomous and autonomic systems (AAS) are essentially concerned with creating self-directed and self-managing systems based on metaphors &om nature and the human body, such as the autonomic nervous system. Agent technologies have been identified as a key enabler for engineering autonomy and autonomicity in systems, both in terms of retrofitting into legacy systems and in designing new systems. Handing over responsibility to systems themselves raises concerns for humans with regard to safety and security. This paper reports on the continued investigation into a strand of research on how to engineer self-protection mechanisms into systems to assist in encouraging confidence regarding security when utilizing autonomy and autonomicity. This includes utilizing the apoptosis and quiescence metaphors to potentially provide a self-destruct or self-sleep signal between autonomic agents when needed, and an ALice signal to facilitate self-identification and self-certification between anonymous autonomous agents and systems.

Autonomic dysfunction in cirrhosis and portal hypertension

DEFF Research Database (Denmark)

Dümcke, Christine Winkler; Møller, Søren

2008-01-01

Liver cirrhosis and portal hypertension are frequently associated with signs of circulatory dysfunction and peripheral polyneuropathy, which includes defects of the autonomic nervous system. Autonomic dysfunction, which is seen in both alcoholic and non-alcoholic liver cirrhosis and increases...

Symmetries and solutions of the non-autonomous von Bertalanffy equation

Science.gov (United States)

Edwards, Maureen P.; Anderssen, Robert S.

2015-05-01

For growth in a closed environment, which is indicative of the situation in laboratory experiments, autonomous ODE models do not necessarily capture the dynamics under investigation. The importance and impact of a closed environment arise when the question under examination relates, for example, to the number of the surviving microbes, such as in a study of the spoilage and contamination of food, the gene silencing activity of fungi or the production of a chemical compound by bacteria or fungi. Autonomous ODE models are inappropriate as they assume that only the current size of the population controls the growth-decay dynamics. This is reflected in the fact that, asymptotically, their solutions can only grow or decay monotonically or asymptote. Non-autonomous ODE models are not so constrained. A natural strategy for the choice of non-autonomous ODEs is to take appropriate autonomous ones and change them to be non-autonomous through the introduction of relevant non-autonomous terms. This is the approach in this paper with the focus being the von Bertalanffy equation. Since this equation has independent importance in relation to practical applications in growth modelling, it is natural to explore the deeper relationships between the introduced non-autonomous terms through a symmetry analysis, which is the purpose and goal of the current paper. Infinitesimals are derived which allow particular forms of the non-autonomous von Bertalanffy equation to be transformed into autonomous forms for which some new analytic solutions have been found.

Central melanin-concentrating hormone influences liver and adipose metabolism via specific hypothalamic nuclei and efferent autonomic/JNK1 pathways.

Science.gov (United States)

Imbernon, Monica; Beiroa, Daniel; Vázquez, María J; Morgan, Donald A; Veyrat-Durebex, Christelle; Porteiro, Begoña; Díaz-Arteaga, Adenis; Senra, Ana; Busquets, Silvia; Velásquez, Douglas A; Al-Massadi, Omar; Varela, Luis; Gándara, Marina; López-Soriano, Francisco-Javier; Gallego, Rosalía; Seoane, Luisa M; Argiles, Josep M; López, Miguel; Davis, Roger J; Sabio, Guadalupe; Rohner-Jeanrenaud, Françoise; Rahmouni, Kamal; Dieguez, Carlos; Nogueiras, Ruben

2013-03-01

Specific neuronal circuits modulate autonomic outflow to liver and white adipose tissue. Melanin-concentrating hormone (MCH)-deficient mice are hypophagic, lean, and do not develop hepatosteatosis when fed a high-fat diet. Herein, we sought to investigate the role of MCH, an orexigenic neuropeptide specifically expressed in the lateral hypothalamic area, on hepatic and adipocyte metabolism. Chronic central administration of MCH and adenoviral vectors increasing MCH signaling were performed in rats and mice. Vagal denervation was performed to assess its effect on liver metabolism. The peripheral effects on lipid metabolism were assessed by real-time polymerase chain reaction and Western blot. We showed that the activation of MCH receptors promotes nonalcoholic fatty liver disease through the parasympathetic nervous system, whereas it increases fat deposition in white adipose tissue via the suppression of sympathetic traffic. These metabolic actions are independent of parallel changes in food intake and energy expenditure. In the liver, MCH triggers lipid accumulation and lipid uptake, with c-Jun N-terminal kinase being an essential player, whereas in adipocytes MCH induces metabolic pathways that promote lipid storage and decreases lipid mobilization. Genetic activation of MCH receptors or infusion of MCH specifically in the lateral hypothalamic area modulated hepatic lipid metabolism, whereas the specific activation of this receptor in the arcuate nucleus affected adipocyte metabolism. Our findings show that central MCH directly controls hepatic and adipocyte metabolism through different pathways. Copyright © 2013 AGA Institute. Published by Elsevier Inc. All rights reserved.

Autonomy Level Specification for Intelligent Autonomous Vehicles

Science.gov (United States)

2003-09-01

Autonomy Level Specification for Intelligent Autonomous Vehicles : Interim Progress Report Hui-Min Huang, Elena Messina, James Albus...Level Specification for Intelligent Autonomous Vehicles : Interim Progress Report 5a. CONTRACT NUMBER 5b. GRANT NUMBER 5c. PROGRAM ELEMENT NUMBER 6

CSIR eNews: Mobile Intelligent Autonomous Systems

CSIR Research Space (South Africa)

CSIR

2008-03-01

Full Text Available autonomous systems Distinguished scientist from India to share knowledge with CSIR An esteemed scientist from India, Dr Jitendra Raol, will spend the next 14 months at the CSIR, specifically in the mobile intelligence autonomous systems (MIAS) emerging...

12th International Conference on Intelligent Autonomous Systems

CERN Document Server

Cho, Hyungsuck; Yoon, Kwang-Joon; Lee, Jangmyung

2013-01-01

Intelligent autonomous systems are emerged as a key enabler for the creation of a new paradigm of services to humankind, as seen by the recent advancement of autonomous cars licensed for driving in our streets, of unmanned aerial and underwater vehicles carrying out hazardous tasks on-site, and of space robots engaged in scientific as well as operational missions, to list only a few. This book aims at serving the researchers and practitioners in related fields with a timely dissemination of the recent progress on intelligent autonomous systems, based on a collection of papers presented at the 12th International Conference on Intelligent Autonomous Systems, held in Jeju, Korea, June 26-29, 2012. With the theme of “Intelligence and Autonomy for the Service to Humankind, the conference has covered such diverse areas as autonomous ground, aerial, and underwater vehicles, intelligent transportation systems, personal/domestic service robots, professional service robots for surgery/rehabilitation, rescue/security ...

Multiple Autonomous Vehicles for Minefield Reconnaissance and Mapping

Science.gov (United States)

1997-12-01

NPS-ME-97-008 NAVAL POSTGRADUATE SCHOOL Monterey, California ItC A D- 19980421 131 =C QUALTY Ui Ji.CTEJ) THESIS MULTIPLE AUTONOMOUS VEHICLES FOR...MULTIPLE AUTONOMOUS VEHICLES FOR MINEFIELD 5. FUNDING NUMBERS RECONNAISSANCE AND MAPPING N0001497WX30039 6. AUTHOR(S) Jack A. Starr 7. PERFORMING... AUTONOMOUS VEHICLES FOR MINEFIELD RECONNAISSANCE AND MAPPING Jack A. Starr Lieutenant, United States Navy B.S., Oregon State University, 1991 Submitted in

Autonomous execution of the Precision Immobilization Technique

Science.gov (United States)

Mascareñas, David D. L.; Stull, Christopher J.; Farrar, Charles R.

2017-03-01

Over the course of the last decade great advances have been made in autonomously driving cars. The technology has advanced to the point that driverless car technology is currently being tested on publicly accessed roadways. The introduction of these technologies onto publicly accessed roadways not only raises questions of safety, but also security. Autonomously driving cars are inherently cyber-physical systems and as such will have novel security vulnerabilities that couple both the cyber aspects of the vehicle including the on-board computing and any network data it makes use of, with the physical nature of the vehicle including its sensors, actuators, and the vehicle chassis. Widespread implementation of driverless car technology will require that both the cyber, as well as physical security concerns surrounding these vehicles are addressed. In this work, we specifically developed a control policy to autonomously execute the Precision Immobilization Technique, a.k.a. the PIT maneuver. The PIT maneuver was originally developed by law enforcement to end high-speed vehicular pursuits in a quasi-safe manner. However, there is still a risk of damage/roll-over to both the vehicle executing the PIT maneuver as well as to the vehicle subject to the PIT maneuver. In law enforcement applications, it would be preferable to execute the PIT maneuver using an autonomous vehicle, thus removing the danger to law-enforcement officers. Furthermore, it is entirely possible that unscrupulous individuals could inject code into an autonomously-driving car to use the PIT maneuver to immobilize other vehicles while maintaining anonymity. For these reasons it is useful to know how the PIT maneuver can be implemented on an autonomous car. In this work a simple control policy based on velocity pursuit was developed to autonomously execute the PIT maneuver using only a vision and range measurements that are both commonly collected by contemporary driverless cars. The ability of this

Technologies for highly miniaturized autonomous sensor networks

NARCIS (Netherlands)

Baert, K.; Gyselinckx, B.; Torfs, T.; Leonov, V.; Yazicioglu, F.; Brebels, S.; Donnay, S.; Vanfleteren, J.; Beyne, E.; Hoof, C. van

2006-01-01

Recent results of the autonomous sensor research program HUMAN++ will be summarized in this paper. The research program aims to achieve highly miniaturized and (nearly) autonomous sensor systems that assist our health and comfort. Although the application examples are dedicated to human

[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.

Autonomous Industrial Mobile Manipulation (AIMM)

DEFF Research Database (Denmark)

Hvilshøj, Mads; Bøgh, Simon; Nielsen, Oluf Skov

2012-01-01

Purpose - The purpose of this paper is to provide a review of the interdisciplinary research field Autonomous Industrial Mobile Manipulation (AIMM), with an emphasis on physical implementations and applications. Design/methodology/approach - Following an introduction to AIMM, this paper investiga......Purpose - The purpose of this paper is to provide a review of the interdisciplinary research field Autonomous Industrial Mobile Manipulation (AIMM), with an emphasis on physical implementations and applications. Design/methodology/approach - Following an introduction to AIMM, this paper......; sustainability, configuration, adaptation, autonomy, positioning, manipulation and grasping, robot-robot interaction, human-robot interaction, process quality, dependability, and physical properties. Findings - The concise yet comprehensive review provides both researchers (academia) and practitioners (industry......) with a quick and gentle overview of AIMM. Furthermore, the paper identifies key open issues and promising research directions to realize real-world integration and maturation of the AIMM technology. Originality/value - This paper reviews the interdisciplinary research field Autonomous Industrial Mobile...

Autonomic neuropathy in diabetes mellitus

Directory of Open Access Journals (Sweden)

Alberto eVerrotti

2014-12-01

Full Text Available Diabetic autonomic neuropathy (DAN is a serious and common complication of diabetes, often overlooked and misdiagnosed. It is a systemic-wide disorder that may be asymptomatic in the early stages. The most studied and clinically important form of DAN is cardiovascular autonomic neuropathy (CAN defined as the impairment of autonomic control of the cardiovascular system in patients with diabetes after exclusion of other causes. The reported prevalence of DAN varies widely depending on inconsistent definition, different diagnostic method, different patient cohorts studied. The pathogenesis is still unclear and probably multifactorial. Once DAN becomes clinically evident, no form of therapy has been identified which can effectively stop or reverse it. Prevention strategies are based on strict glycemic control with intensive insulin treatment, multifactorial intervention and lifestyle modification including control of hypertension, dyslipidemia, stop smoking, weight loss and adequate physical exercise. The present review summarizes the latest knowledge regarding clinical presentation, epidemiology, pathogenesis and management of DAN, with some mention to childhood and adolescent population.

3-D Vision Techniques for Autonomous Vehicles

Science.gov (United States)

1988-08-01

TITLE (Include Security Classification) W 3-D Vision Techniques for Autonomous Vehicles 12 PERSONAL AUTHOR(S) Martial Hebert, Takeo Kanade, inso Kweoni... Autonomous Vehicles Martial Hebert, Takeo Kanade, Inso Kweon CMU-RI-TR-88-12 The Robotics Institute Carnegie Mellon University Acession For Pittsburgh

Hard-real-time resource management for autonomous spacecraft

Science.gov (United States)

Gat, E.

2000-01-01

This paper describes tickets, a computational mechanism for hard-real-time autonomous resource management. Autonomous spacecraftcontrol can be considered abstractly as a computational process whose outputs are spacecraft commands.

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

Directory of Open Access Journals (Sweden)

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

College English Students’ Autonomous Learning Motivation and Cultivation Model Research

Institute of Scientific and Technical Information of China (English)

王艳荣; 李娥

2015-01-01

Studying the autonomous learning motivation and excitation model can stimulate intrinsic motivation of foreign language learners,develop students self-management strategy evaluation are very necessary.The purpose of this paper is to give students the skills of listening and speaking for their autonomous learning.Then study the cultivation and motivation of college English students autonomous learning,hoping to make students to learn autonomous learning and stimulate their motivation fully.

Tracked robot controllers for climbing obstacles autonomously

Science.gov (United States)

Vincent, Isabelle

2009-05-01

Research in mobile robot navigation has demonstrated some success in navigating flat indoor environments while avoiding obstacles. However, the challenge of analyzing complex environments to climb obstacles autonomously has had very little success due to the complexity of the task. Unmanned ground vehicles currently exhibit simple autonomous behaviours compared to the human ability to move in the world. This paper presents the control algorithms designed for a tracked mobile robot to autonomously climb obstacles by varying its tracks configuration. Two control algorithms are proposed to solve the autonomous locomotion problem for climbing obstacles. First, a reactive controller evaluates the appropriate geometric configuration based on terrain and vehicle geometric considerations. Then, a reinforcement learning algorithm finds alternative solutions when the reactive controller gets stuck while climbing an obstacle. The methodology combines reactivity to learning. The controllers have been demonstrated in box and stair climbing simulations. The experiments illustrate the effectiveness of the proposed approach for crossing obstacles.

Autonomic Cluster Management System (ACMS): A Demonstration of Autonomic Principles at Work

Science.gov (United States)

Baldassari, James D.; Kopec, Christopher L.; Leshay, Eric S.; Truszkowski, Walt; Finkel, David

2005-01-01

Cluster computing, whereby a large number of simple processors or nodes are combined together to apparently function as a single powerful computer, has emerged as a research area in its own right. The approach offers a relatively inexpensive means of achieving significant computational capabilities for high-performance computing applications, while simultaneously affording the ability to. increase that capability simply by adding more (inexpensive) processors. However, the task of manually managing and con.guring a cluster quickly becomes impossible as the cluster grows in size. Autonomic computing is a relatively new approach to managing complex systems that can potentially solve many of the problems inherent in cluster management. We describe the development of a prototype Automatic Cluster Management System (ACMS) that exploits autonomic properties in automating cluster management.

Elements of Autonomous Self-Reconfigurable Robots

DEFF Research Database (Denmark)

Christensen, David Johan

In this thesis, we study several central elements of autonomous self-reconfigurable modular robots. Unlike conventional robots such robots are: i) Modular, since robots are assembled from numerous robotic modules. ii) Reconfigurable, since the modules can be combined in a variety of ways. iii) Self......-reconfigurable, since the modules themselves are able to change how they are combined. iv) Autonomous, since robots control themselves without human guidance. Such robots are attractive to study since they in theory have several desirable characteristics, such as versatility, reliability and cheapness. In practice...... however, it is challenging to realize such characteristics since state-of-the-art systems and solutions suffer from several inherent technical and theoretical problems and limitations. In this thesis, we address these challenges by exploring four central elements of autonomous self-reconfigurable modular...

Cooperative Control of Multiple Unmanned Autonomous Vehicles

Science.gov (United States)

2005-06-03

I I Final Report 4. TITLE AND SUBTITLE 5. FUNDING NUMBERS Cooperative Control of Multiple Unmanned Autonomous Vehicles F49620-01-1-0337 6. AUTHOR(S... Autonomous Vehicles Final Report Kendall E. Nygard Department of Computer Science and Operations Research North Dakota State University Fargo, ND 58105-5164

A System for Fast Navigation of Autonomous Vehicles

Science.gov (United States)

1991-09-01

AD-A243 523 4, jj A System for Fast Navigation of Autonomous Vehicles Sanjiv Singh, Dai Feng, Paul Keller, Gary Shaffer, Wen Fan Shi, Dong Hun Shin...FUNDING NUMBERS A System for Fast Navigation of Autonomous Vehicles 6. AUTHOR(S) S. Singh, D. Feng, P. Keller, G. Shaffer, W.F. Shi, D.H. Shin, J. West...common in the control of autonomous vehicles to establish the necessary kinematic models but to ignore an explicit representation of the vehicle dynamics

Towards autonomous vehicles.

Science.gov (United States)

2013-11-01

We are moving towards an age of autonomous vehicles. Cycles of innovation initiated in the public and private sectors : have led one into another since the 1990s; and out of these efforts have sprung a variety of Advanced Driver Assistance : Systems ...

Autonomous Flight in Unknown Indoor Environments

OpenAIRE

Bachrach, Abraham Galton; He, Ruijie; Roy, Nicholas

2009-01-01

This paper presents our solution for enabling a quadrotor helicopter, equipped with a laser rangefinder sensor, to autonomously explore and map unstructured and unknown indoor environments. While these capabilities are already commodities on ground vehicles, air vehicles seeking the same performance face unique challenges. In this paper, we describe the difficulties in achieving fully autonomous helicopter flight, highlighting the differences between ground and helicopter robots that make it ...

High-frequency autonomic modulation: a new model for analysis of autonomic cardiac control.

Science.gov (United States)

Champéroux, Pascal; Fesler, Pierre; Judé, Sebastien; Richard, Serge; Le Guennec, Jean-Yves; Thireau, Jérôme

2018-05-03

Increase in high-frequency beat-to-beat heart rate oscillations by torsadogenic hERG blockers appears to be associated with signs of parasympathetic and sympathetic co-activation which cannot be assessed directly using classic methods of heart rate variability analysis. The present work aimed to find a translational model that would allow this particular state of the autonomic control of heart rate to be assessed. High-frequency heart rate and heart period oscillations were analysed within discrete 10 s intervals in a cohort of 200 healthy human subjects. Results were compared to data collected in non-human primates and beagle dogs during pharmacological challenges and torsadogenic hERG blockers exposure, in 127 genotyped LQT1 patients on/off β-blocker treatment and in subgroups of smoking and non-smoking subjects. Three states of autonomic modulation, S1 (parasympathetic predominance) to S3 (reciprocal parasympathetic withdrawal/sympathetic activation), were differentiated to build a new model of heart rate variability referred to as high-frequency autonomic modulation. The S2 state corresponded to a specific state during which both parasympathetic and sympathetic systems were coexisting or co-activated. S2 oscillations were proportionally increased by torsadogenic hERG-blocking drugs, whereas smoking caused an increase in S3 oscillations. The combined analysis of the magnitude of high-frequency heart rate and high-frequency heart period oscillations allows a refined assessment of heart rate autonomic modulation applicable to long-term ECG recordings and offers new approaches to assessment of the risk of sudden death both in terms of underlying mechanisms and sensitivity. © 2018 The Authors. British Journal of Pharmacology published by John Wiley & Sons Ltd on behalf of British Pharmacological Society.

An autonomous weeding robot for organic farming

NARCIS (Netherlands)

Bakker, T.; Asselt, van C.J.; Bontsema, J.; Müller, J.; Straten, van G.

2006-01-01

The objective of this research is the replacement of hand weeding in organic farming by a device working autonomously at ¯eld level. The autonomous weeding robot was designed using a structured design approach, giving a good overview of the total design. A vehicle was developed with a diesel engine,

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.

Alterations in cardiac autonomic control in spinal cord injury.

Science.gov (United States)

Biering-Sørensen, Fin; Biering-Sørensen, Tor; Liu, Nan; Malmqvist, Lasse; Wecht, Jill Maria; Krassioukov, Andrei

2018-01-01

A spinal cord injury (SCI) interferes with the autonomic nervous system (ANS). The effect on the cardiovascular system will depend on the extent of damage to the spinal/central component of ANS. The cardiac changes are caused by loss of supraspinal sympathetic control and relatively increased parasympathetic cardiac control. Decreases in sympathetic activity result in heart rate and the arterial blood pressure changes, and may cause arrhythmias, in particular bradycardia, with the risk of cardiac arrest in those with cervical or high thoracic injuries. The objective of this review is to give an update of the current knowledge related to the alterations in cardiac autonomic control following SCI. With this purpose the review includes the following subheadings: 2. Neuro-anatomical plasticity and cardiac control 2.1 Autonomic nervous system and the heart 2.2 Alteration in autonomic control of the heart following spinal cord injury 3. Spinal shock and neurogenic shock 3.1 Pathophysiology of spinal shock 3.2 Pathophysiology of neurogenic shock 4. Autonomic dysreflexia 4.1 Pathophysiology of autonomic dysreflexia 4.2 Diagnosis of autonomic dysreflexia 5. Heart rate/electrocardiography following spinal cord injury 5.1 Acute phase 5.2 Chronic phase 6. Heart rate variability 6.1 Time domain analysis 6.2 Frequency domain analysis 6.3 QT-variability index 6.4 Nonlinear (fractal) indexes 7. Echocardiography 7.1 Changes in cardiac structure following spinal cord injury 7.2 Changes in cardiac function following spinal cord injury 8. International spinal cord injury cardiovascular basic data set and international standards to document the remaining autonomic function in spinal cord injury. Copyright © 2017 Elsevier B.V. All rights reserved.

Design of an Autonomous Transport System for Coastal Areas

Directory of Open Access Journals (Sweden)

Andrzej Lebkowski

2018-03-01

Full Text Available The article presents a project of an autonomous transport system that can be deployed in coastal waters, bays or between islands. Presented solutions and development trends in the transport of autonomous and unmanned units (ghost ships are presented. The structure of the control system of autonomous units is discussed together with the presentation of applied solutions in the field of artificial intelligence. The paper presents the concept of a transport system consisting of autonomous electric powered vessels designed to carry passengers, bikes, mopeds, motorcycles or passenger cars. The transport task is to be implemented in an optimal way, that is, most economically and at the same time as safe as possible. For this reason, the structure of the electric propulsion system that can be found on such units is shown. The results of simulation studies of autonomous system operation using simulator of marine navigational environment are presented.

Longitudinal Control for Mengshi Autonomous Vehicle via Cloud Model

Science.gov (United States)

Gao, H. B.; Zhang, X. Y.; Li, D. Y.; Liu, Y. C.

2018-03-01

Dynamic robustness and stability control is a requirement for self-driving of autonomous vehicle. Longitudinal control method of autonomous is a key technique which has drawn the attention of industry and academe. In this paper, we present a longitudinal control algorithm based on cloud model for Mengshi autonomous vehicle to ensure the dynamic stability and tracking performance of Mengshi autonomous vehicle. An experiments is applied to test the implementation of the longitudinal control algorithm. Empirical results show that if the longitudinal control algorithm based Gauss cloud model are applied to calculate the acceleration, and the vehicles drive at different speeds, a stable longitudinal control effect is achieved.

Autonomous Propellant Loading Project

Data.gov (United States)

National Aeronautics and Space Administration — The AES Autonomous Propellant Loading (APL) project consists of three activities. The first is to develop software that will automatically control loading of...

Autonomous Systems and Operations

Data.gov (United States)

National Aeronautics and Space Administration — The AES Autonomous Systems and Operations (ASO) project will develop an understanding of the impacts of increasing communication time delays on mission operations,...

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.

Cooperative Control of Distributed Autonomous Vehicles in Adversarial Environments

Science.gov (United States)

2006-08-14

COOPERATIVE CONTROL OF DISTRIBUTED AUTONOMOUS VEHICLES IN ADVERSARIAL ENVIRONMENTS Grant #F49620–01–1–0361 Final Report Jeff Shamma Department of...CONTRACT NUMBER F49620-01-1-0361 5b. GRANT NUMBER 4. TITLE AND SUBTITLE COOPERATIVE CONTROL OF DISTRIBUTED AUTONOMOUS VEHICLES IN...single dominant language or a distribution of languages. A relation to multivehicle systems is understanding how highly autonomous vehicles on extended

THE STUDY OF THE AUTONOMOUS SYNCHRONOUS GENERATOR MODES

Directory of Open Access Journals (Sweden)

V. S. Safaryan

2017-01-01

Full Text Available The importance of the problem of the static stability of the stationary mode of the power system for its operation is extremely high. The investigation of the static stability of the power system is a subject of a number of works, but the problems of static stability of the stationary points of an autonomous synchronous generator are given little attention. The article considers transient and resonant (stationary modes of the generator under active-inductive and active-capacitive loads. Mathematical model of transients in a natural form and in the coordinate system d, q are plotted. It is discovered that the mathematical model of the transition process of an autonomous synchronous generator is identical to the mathematical model of the transition process of the synchronous machine under three-phase short circuit. Electromagnetic transients of an autonomous synchronous generator are described by a system of linear autonomous differential equations with constant coefficients. However, the equivalent circuit of a generator contains dependent sources. We investigated the stability of stationary motion of an autonomous synchronous generator at a given angular velocity of rotation of the rotor. The condition for the existence and stability of stationary points of an autonomous synchronous generator is derived. The condition for the existence of stationary points of such a generator does not depend on the active load resistance and stator windings, and inductance of the rotor. The determining of stationary points of the generator is reduced to finding roots of a polynomial of the fourth degree. The graphs of electromagnetic torque dependencies on the angular velocity of rotation of the rotor (mechanical characteristics are plotted. The equivalent circuits, corresponding to the equations of the transition process of an autonomous synchronous generator, are featured as well.

Are Turkish University Students Autonomous or Not?

Directory of Open Access Journals (Sweden)

Büşra Kırtık

2017-01-01

Full Text Available The present study tried to determine Turkish learners’ attitudes, and the Turkish education system’s approach towards learner autonomy with regard to three main points: 1 whether Turkish university students are aware of learner autonomy or not 2 whether Turkish university students have the characteristics of autonomous learners (whether they are autonomous learners or not, and 3 if the Turkish education system is suitable for fostering learner autonomy or not from the viewpoint of the participants. Participants were 50 second grade learners in the English Language Teaching Departments of Hacettepe University (N=10, Mehmet Akif Ersoy University (N=10, and Uludag University (N=30 who had already taken courses about learner autonomy.  The data were collected by means of a questionnaire which had two Likert-scale sections and an open-ended questions section. The first Likert-scale section contained 15 characteristics of autonomous learners each of which was rated by the participants in a scale from strongly disagree to agree, from 1 to 5. In the second Likert-scale section, the participants were asked to rate the Turkish education system’s five basic elements such as school curriculums, course materials, approaches used by the teachers in classrooms, learning activities, and classroom settings. Additionally, learners’ opinions about their awareness and understanding of learner autonomy were gathered by five open ended questions. The results proposed that the participants were aware of learner autonomy, and had the characteristics of autonomous learners. On the other hand, results showed that the Turkish education system was not suitable for autonomous learners and did not foster learner autonomy. The findings suggested that the Turkish education system should be designed again in such a way to support the autonomous learners and to foster learner autonomy in all sections of the education.

Are Autonomous and Controlled Motivations School-Subjects-Specific?

Science.gov (United States)

Chanal, Julien; Guay, Frédéric

2015-01-01

This research sought to test whether autonomous and controlled motivations are specific to school subjects or more general to the school context. In two cross-sectional studies, 252 elementary school children (43.7% male; mean age = 10.7 years, SD = 1.3 years) and 334 junior high school children (49.7% male, mean age = 14.07 years, SD = 1.01 years) were administered a questionnaire assessing their motivation for various school subjects. Results based on structural equation modeling using the correlated trait-correlated method minus one model (CTCM-1) showed that autonomous and controlled motivations assessed at the school subject level are not equally school-subject-specific. We found larger specificity effects for autonomous (intrinsic and identified) than for controlled (introjected and external) motivation. In both studies, results of factor loadings and the correlations with self-concept and achievement demonstrated that more evidence of specificity was obtained for autonomous regulations than for controlled ones. These findings suggest a new understanding of the hierarchical and multidimensional academic structure of autonomous and controlled motivations and of the mechanisms involved in the development of types of regulations for school subjects. PMID:26247788

Improving Human/Autonomous System Teaming Through Linguistic Analysis

Science.gov (United States)

Meszaros, Erica L.

2016-01-01

An area of increasing interest for the next generation of aircraft is autonomy and the integration of increasingly autonomous systems into the national airspace. Such integration requires humans to work closely with autonomous systems, forming human and autonomous agent teams. The intention behind such teaming is that a team composed of both humans and autonomous agents will operate better than homogenous teams. Procedures exist for licensing pilots to operate in the national airspace system and current work is being done to define methods for validating the function of autonomous systems, however there is no method in place for assessing the interaction of these two disparate systems. Moreover, currently these systems are operated primarily by subject matter experts, limiting their use and the benefits of such teams. Providing additional information about the ongoing mission to the operator can lead to increased usability and allow for operation by non-experts. Linguistic analysis of the context of verbal communication provides insight into the intended meaning of commonly heard phrases such as "What's it doing now?" Analyzing the semantic sphere surrounding these common phrases enables the prediction of the operator's intent and allows the interface to supply the operator's desired information.

Autonomous biomorphic robots as platforms for sensors

Energy Technology Data Exchange (ETDEWEB)

Tilden, M.; Hasslacher, B.; Mainieri, R.; Moses, J.

1996-10-01

The idea of building autonomous robots that can carry out complex and nonrepetitive tasks is an old one, so far unrealized in any meaningful hardware. Tilden has shown recently that there are simple, processor-free solutions to building autonomous mobile machines that continuously adapt to unknown and hostile environments, are designed primarily to survive, and are extremely resistant to damage. These devices use smart mechanics and simple (low component count) electronic neuron control structures having the functionality of biological organisms from simple invertebrates to sophisticated members of the insect and crab family. These devices are paradigms for the development of autonomous machines that can carry out directed goals. The machine then becomes a robust survivalist platform that can carry sensors or instruments. These autonomous roving machines, now in an early stage of development (several proof-of-concept prototype walkers have been built), can be developed so that they are inexpensive, robust, and versatile carriers for a variety of instrument packages. Applications are immediate and many, in areas as diverse as prosthetics, medicine, space, construction, nanoscience, defense, remote sensing, environmental cleanup, and biotechnology.

Autonomous operation of distributed storages in microgrids

DEFF Research Database (Denmark)

Loh, Poh Chiang; Chai, Yi Kai; Li, Ding

2014-01-01

Operation of distributed generators in microgrids has been widely discussed, but would not be fully autonomous if distributed energy storages are not considered. Storages are important since they provide energy buffering to load changes, energy levelling to source variations and ride-through enha......Operation of distributed generators in microgrids has been widely discussed, but would not be fully autonomous if distributed energy storages are not considered. Storages are important since they provide energy buffering to load changes, energy levelling to source variations and ride......-through enhancement to the microgrids. Recognising their importance, this study presents a scheme for sharing power among multiple distributed storages in coordination with the distributed sources and loads. The scheme prompts the storages to autonomously sense for local operating conditions, requesting for maximum...... to help with meeting the extra load demand. The described process takes place autonomously with energy eventually shared among the storages in proportion to their ratings. To test the concepts discussed, experiments have been performed with favourable results obtained for performance verification....

Autonomous biomorphic robots as platforms for sensors

International Nuclear Information System (INIS)

Tilden, M.; Hasslacher, B.; Mainieri, R.; Moses, J.

1996-01-01

The idea of building autonomous robots that can carry out complex and nonrepetitive tasks is an old one, so far unrealized in any meaningful hardware. Tilden has shown recently that there are simple, processor-free solutions to building autonomous mobile machines that continuously adapt to unknown and hostile environments, are designed primarily to survive, and are extremely resistant to damage. These devices use smart mechanics and simple (low component count) electronic neuron control structures having the functionality of biological organisms from simple invertebrates to sophisticated members of the insect and crab family. These devices are paradigms for the development of autonomous machines that can carry out directed goals. The machine then becomes a robust survivalist platform that can carry sensors or instruments. These autonomous roving machines, now in an early stage of development (several proof-of-concept prototype walkers have been built), can be developed so that they are inexpensive, robust, and versatile carriers for a variety of instrument packages. Applications are immediate and many, in areas as diverse as prosthetics, medicine, space, construction, nanoscience, defense, remote sensing, environmental cleanup, and biotechnology

Blood pressure regulation in diabetic autonomic neuropathy

DEFF Research Database (Denmark)

Hilsted, J

1985-01-01

Defective blood pressure responses to standing, exercise and epinephrine infusions have been demonstrated in diabetic patients with autonomic neuropathy. The circulatory mechanisms underlying blood pressure responses to exercise and standing up in these patients are well characterized: In both...... which may contribute to exercise hypotension in these patients. During hypoglycemia, blood pressure regulation seems intact in patients with autonomic neuropathy. This is probably due to release of substantial amounts of catecholamines during these experiments. During epinephrine infusions a substantial...... blood pressure fall ensues in patients with autonomic neuropathy, probably due to excessive muscular vasodilation. It is unresolved why blood pressure regulation is intact during hypoglycemia and severely impaired--at similar catecholamine concentrations--during epinephrine infusions....

Dynamics control of autonomous vehicle at driving limits and experiment on an autonomous formula racing car

Science.gov (United States)

Ni, Jun; Hu, Jibin

2017-06-01

In this paper, a novel dynamics controller for autonomous vehicle to simultaneously control it to the driving limits and follow the desired path is proposed. The dynamics controller consists of longitudinal and lateral controllers. In longitudinal controller, the G-G diagram is utilized to describe the driving and handling limits of the vehicle. The accurate G-G diagram is obtained based on phase plane approach and a nonlinear vehicle dynamic model with accurate tyre model. In lateral controller, the tyre cornering stiffness is estimated to improve the robustness of the controller. The stability analysis of the closed-looped error dynamics shows that the controller remains stable against parameters uncertainties in extreme condition such as tyre saturation. Finally, an electric autonomous Formula race car developed by the authors is used to validate the proposed controller. The autonomous driving experiment on an oval race track shows the efficiency and robustness of the proposed controller.

Control of autonomous ground vehicles: a brief technical review

Science.gov (United States)

Babak, Shahian-Jahromi; Hussain, Syed A.; Karakas, Burak; Cetin, Sabri

2017-07-01

This paper presents a brief review of the developments achieved in autonomous vehicle systems technology. A concise history of autonomous driver assistance systems is presented, followed by a review of current state of the art sensor technology used in autonomous vehicles. Standard sensor fusion method that has been recently explored is discussed. Finally, advances in embedded software methodologies that define the logic between sensory information and actuation decisions are reviewed.

Gas House Autonomous System Monitoring

Science.gov (United States)

Miller, Luke; Edsall, Ashley

2015-01-01

Gas House Autonomous System Monitoring (GHASM) will employ Integrated System Health Monitoring (ISHM) of cryogenic fluids in the High Pressure Gas Facility at Stennis Space Center. The preliminary focus of development incorporates the passive monitoring and eventual commanding of the Nitrogen System. ISHM offers generic system awareness, adept at using concepts rather than specific error cases. As an enabler for autonomy, ISHM provides capabilities inclusive of anomaly detection, diagnosis, and abnormality prediction. Advancing ISHM and Autonomous Operation functional capabilities enhances quality of data, optimizes safety, improves cost effectiveness, and has direct benefits to a wide spectrum of aerospace applications.

Safe and Autonomous Drones for Urban Flight

Science.gov (United States)

Krishnakumar, Kalmanje

2016-01-01

Autonomous vehicles are no longer futuristic technology; in fact, there are already cars with self-driving features on the road. Over the next five years, the connected vehicles will disrupt the entire automotive and UAS ecosystems. The industry will undergo fundamental change as semi-autonomous driving and flying emerges, followed by an eventual shift to full autonomy.

Autonomous underwater vehicle for research and rescue operations

CSIR Research Space (South Africa)

Holtzhausen S

2008-11-01

Full Text Available Autonomous under water vehicles are ideal platforms for search and rescue operations. They can also be used for inspection of underwater terrains. These vehicles need to be autonomous and robust to cope with unpredictable current and high pressures...

Future of Autonomous Ground Logistics: Convoys in the Department of Defense

Science.gov (United States)

2011-02-13

operations. Figure 3 History of Autonomous Vehicles44 Civilian car manufactures have included elements of autonomous vehicles in their...in the area of autonomous vehicles , equal to the capabilities of civilian robotics programs. These contests and competitions inspire new ideas...data into the vehicles , loaded the vehicles with the supplies and drove them to the staging area. From the staging area, the autonomous vehicles self

Evaluating the autonomic nervous system in patients with laryngopharyngeal reflux.

Science.gov (United States)

Huang, Wan-Ju; Shu, Chih-Hung; Chou, Kun-Ta; Wang, Yi-Fen; Hsu, Yen-Bin; Ho, Ching-Yin; Lan, Ming-Ying

2013-06-01

The pathogenesis of laryngopharyngeal reflux (LPR) remains unclear. It is linked to but distinct from gastroesophageal reflux disease (GERD), which has been shown to be related to disturbed autonomic regulation. The aim of this study is to investigate whether autonomic dysfunction also plays a role in the pathogenesis of LPR. Case-control study. Tertiary care center. Seventeen patients with LPR and 19 healthy controls, aged between 19 and 50 years, were enrolled in the study. The patients were diagnosed with LPR if they had a reflux symptom index (RSI) ≥ 13 and a reflux finding score (RFS) ≥ 7. Spectral analysis of heart rate variability (HRV) analysis was used to assess autonomic function. Anxiety and depression levels measured by the Beck Anxiety Inventory (BAI) and Beck Depression Inventory II (BDI-II) were also conducted. In HRV analysis, high frequency (HF) represents the parasympathetic activity of the autonomic nervous system, whereas low frequency (LF) represents the total autonomic activity. There were no significant differences in the LF power and HF power between the 2 groups. However, significantly lower HF% (P = .003) and a higher LF/HF ratio (P = .012) were found in patients with LPR, who demonstrated poor autonomic modulation and higher sympathetic activity. Anxiety was also frequently observed in the patient group. The study suggests that autonomic dysfunction seems to be involved in the pathogenesis of LPR. The potential beneficial effect of autonomic nervous system modulation as a therapeutic modality for LPR merits further investigation.

Autonomic Function Impairment and Brain Perfusion Deficit in Parkinson’s Disease

Directory of Open Access Journals (Sweden)

Wei-Che Lin

2017-06-01

Full Text Available IntroductionAutonomic disorders have been recognized as important Parkinson’s disease (PD components. Some vulnerable structures are related to the central autonomic network and have also been linked to autonomic function alterations. The aims of the study are to evaluate the severity of the autonomic dysfunction and the cortical hypoperfusion using arterial spin labeling (ASL MRI. And then, possible relationships of significant between-group differences in perfusion pattern to clinical variables and autonomic functions were examined to determine the pharmaceutical effects of dopaminergic treatment on cerebral blood flow (CBF in patients with PD.MethodsBrain ASL MRI was carried out in 20 patients with PD (6 men and 14 women, mean age: 63.3 ± 6.4 years and 22 sex- and age-matched healthy volunteers to assess whole-brain CBF and the effects of dopaminergic therapy on perfusion. All subjects underwent a standardized evaluation of cardiovagal and adrenergic function including a deep breathing, Valsalva maneuver, and 5-min head-up tilt test. Perfusion MRI data were acquired on a 3.0 T scanner with a pulsed continuous ASL technique. The CBF, autonomic parameters, and clinical data were analyzed after adjusting for age and sex.ResultsPatients exhibited a decline in autonomic function (rapid heart rate in response to deep breathing, low baroreflex sensitivity, high systolic and diastolic pressure, and altered tilting test response, widespread low CBF, and robust response to dopaminergic therapy. Lower perfusion in the middle frontal gyrus was associated with increased clinical disease severity (Unified Parkinson’s Disease Rating Scale I score, P < 0.001. Lower perfusion in autonomic control areas, such as the frontal lobe and insula, were significantly associated with autonomic impairment (P < 0.001.ConclusionsOur study indicates that PD is a progressive neurodegenerative disorder that changes the perfusion of central nervous system

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.

Autonomous Vehicles: Disengagements, Accidents and Reaction Times.

Directory of Open Access Journals (Sweden)

Vinayak V Dixit

Full Text Available Autonomous vehicles are being viewed with scepticism in their ability to improve safety and the driving experience. A critical issue with automated driving at this stage of its development is that it is not yet reliable and safe. When automated driving fails, or is limited, the autonomous mode disengages and the drivers are expected to resume manual driving. For this transition to occur safely, it is imperative that drivers react in an appropriate and timely manner. Recent data released from the California trials provide compelling insights into the current factors influencing disengagements of autonomous mode. Here we show that the number of accidents observed has a significantly high correlation with the autonomous miles travelled. The reaction times to take control of the vehicle in the event of a disengagement was found to have a stable distribution across different companies at 0.83 seconds on average. However, there were differences observed in reaction times based on the type of disengagements, type of roadway and autonomous miles travelled. Lack of trust caused by the exposure to automated disengagements was found to increase the likelihood to take control of the vehicle manually. Further, with increased vehicle miles travelled the reaction times were found to increase, which suggests an increased level of trust with more vehicle miles travelled. We believe that this research would provide insurers, planners, traffic management officials and engineers fundamental insights into trust and reaction times that would help them design and engineer their systems.

Autonomous Vehicles: Disengagements, Accidents and Reaction Times.

Science.gov (United States)

Dixit, Vinayak V; Chand, Sai; Nair, Divya J

2016-01-01

Autonomous vehicles are being viewed with scepticism in their ability to improve safety and the driving experience. A critical issue with automated driving at this stage of its development is that it is not yet reliable and safe. When automated driving fails, or is limited, the autonomous mode disengages and the drivers are expected to resume manual driving. For this transition to occur safely, it is imperative that drivers react in an appropriate and timely manner. Recent data released from the California trials provide compelling insights into the current factors influencing disengagements of autonomous mode. Here we show that the number of accidents observed has a significantly high correlation with the autonomous miles travelled. The reaction times to take control of the vehicle in the event of a disengagement was found to have a stable distribution across different companies at 0.83 seconds on average. However, there were differences observed in reaction times based on the type of disengagements, type of roadway and autonomous miles travelled. Lack of trust caused by the exposure to automated disengagements was found to increase the likelihood to take control of the vehicle manually. Further, with increased vehicle miles travelled the reaction times were found to increase, which suggests an increased level of trust with more vehicle miles travelled. We believe that this research would provide insurers, planners, traffic management officials and engineers fundamental insights into trust and reaction times that would help them design and engineer their systems.

Autonomous Vehicles: Disengagements, Accidents and Reaction Times

Science.gov (United States)

Dixit, Vinayak V.; Chand, Sai; Nair, Divya J.

2016-01-01

Autonomous vehicles are being viewed with scepticism in their ability to improve safety and the driving experience. A critical issue with automated driving at this stage of its development is that it is not yet reliable and safe. When automated driving fails, or is limited, the autonomous mode disengages and the drivers are expected to resume manual driving. For this transition to occur safely, it is imperative that drivers react in an appropriate and timely manner. Recent data released from the California trials provide compelling insights into the current factors influencing disengagements of autonomous mode. Here we show that the number of accidents observed has a significantly high correlation with the autonomous miles travelled. The reaction times to take control of the vehicle in the event of a disengagement was found to have a stable distribution across different companies at 0.83 seconds on average. However, there were differences observed in reaction times based on the type of disengagements, type of roadway and autonomous miles travelled. Lack of trust caused by the exposure to automated disengagements was found to increase the likelihood to take control of the vehicle manually. Further, with increased vehicle miles travelled the reaction times were found to increase, which suggests an increased level of trust with more vehicle miles travelled. We believe that this research would provide insurers, planners, traffic management officials and engineers fundamental insights into trust and reaction times that would help them design and engineer their systems. PMID:27997566

Passive and Self-Powered Autonomous Sensors for Remote Measurements

Directory of Open Access Journals (Sweden)

Mauro Serpelloni

2009-02-01

Full Text Available Autonomous sensors play a very important role in the environmental, structural, and medical fields. The use of this kind of systems can be expanded for several applications, for example in implantable devices inside the human body where it is impossible to use wires. Furthermore, they enable measurements in harsh or hermetic environments, such as under extreme heat, cold, humidity or corrosive conditions. The use of batteries as a power supply for these devices represents one solution, but the size, and sometimes the cost and unwanted maintenance burdens of replacement are important drawbacks. In this paper passive and self-powered autonomous sensors for harsh or hermetical environments without batteries are discussed. Their general architectures are presented. Sensing strategies, communication techniques and power management are analyzed. Then, general building blocks of an autonomous sensor are presented and the design guidelines that such a system must follow are given. Furthermore, this paper reports different proposed applications of autonomous sensors applied in harsh or hermetic environments: two examples of passive autonomous sensors that use telemetric communication are proposed, the first one for humidity measurements and the second for high temperatures. Other examples of self-powered autonomous sensors that use a power harvesting system from electromagnetic fields are proposed for temperature measurements and for airflow speeds.

Passive and self-powered autonomous sensors for remote measurements.

Science.gov (United States)

Sardini, Emilio; Serpelloni, Mauro

2009-01-01

Autonomous sensors play a very important role in the environmental, structural, and medical fields. The use of this kind of systems can be expanded for several applications, for example in implantable devices inside the human body where it is impossible to use wires. Furthermore, they enable measurements in harsh or hermetic environments, such as under extreme heat, cold, humidity or corrosive conditions. The use of batteries as a power supply for these devices represents one solution, but the size, and sometimes the cost and unwanted maintenance burdens of replacement are important drawbacks. In this paper passive and self-powered autonomous sensors for harsh or hermetical environments without batteries are discussed. Their general architectures are presented. Sensing strategies, communication techniques and power management are analyzed. Then, general building blocks of an autonomous sensor are presented and the design guidelines that such a system must follow are given. Furthermore, this paper reports different proposed applications of autonomous sensors applied in harsh or hermetic environments: two examples of passive autonomous sensors that use telemetric communication are proposed, the first one for humidity measurements and the second for high temperatures. Other examples of self-powered autonomous sensors that use a power harvesting system from electromagnetic fields are proposed for temperature measurements and for airflow speeds.

Digital Watermarking of Autonomous Vehicles Imagery and Video Communication

Science.gov (United States)

2005-10-01

Watermarking of Autonomous Vehicles Imagery and Video Communications Executive Summary We have developed, implemented and tested a known-host-state methodology...2005 Final 01-06-2004->31-08-2005 4. TITLE AND SUBTITLE 5a. CONTRACT NUMBER Digital Watermarking of Autonomous Vehicles Imagery 5b. GRANTNUMBER and...college of ENGINEERING Center for Advanced VI LLANOVA Communications U N I V E R S I T Y FINAL TECHNICAL REPORT Digital Watermarking of Autonomous

Autonomic Symptoms in Migraineurs: Are They of Clinical Importance

Directory of Open Access Journals (Sweden)

Aysel Milanl›o¤lu

2012-06-01

Full Text Available Aim: The aim of this study was to evaluate the presence of autonomic symptoms in migraine patients with and without aura and to investigate whether there is an association between expression of autonomic symptoms and disease duration, headache side, attack duration and frequency. Methods: The study sample comprised 82 subjects in headachefree phase including 20 migraine with aura patients and 62 - without aura; 61 were females (74.39% and 21 were males (25.61%. The mean headache frequency was 2.63±1.29 per month and the mean duration of headache occurrence was 10.04±7.26 years from the first episode. The subjects were asked whether or not they had autonomic symptoms like diaphoresis, diarrhea, eyelid oedema, pallor, flushing, syncope or syncope-like episode, constipation, palpitation, diuresis, blurred vision, sensation of chills and coldness during each migraine headache. Results: Of all 82 migraine patients, 50 (60.98% experienced at least one of the autonomic symptoms during the attack periods. The most common symptom was flushing (39.2%. Among the autonomic symptoms, syncope or syncope-like episode was significantly more in patients without aura compared to those with aura (p<0.05. In this study, patients who experienced autonomic symptoms during their headache attack had statistically significantly higher attack frequency (p=0.019. Conclusion: This result indicate that migraine patients with autonomic nervous system involvement have more frequent headaches, therefore these patients should be particularly and cautiously investigated. (The Medical Bulletin of Haseki 2011; 49: 62-6

Theoretical foundations for the responsibility of autonomous agents

NARCIS (Netherlands)

Hage, Jaap

This article argues that it is possible to hold autonomous agents themselves, and not only their makers, users or owners, responsible for the acts of these agents. In this connection autonomous systems are computer programs that interact with the outside world without human interference. They

[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.

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.

Maladaptive autonomic regulation in PTSD accelerates physiological aging

Directory of Open Access Journals (Sweden)

John B Williamson

2015-01-01

Full Text Available A core manifestation of posttraumatic stress disorder is a disconnection between physiological state and psychological and behavior processes necessary to adequately respond to environmental demands. Patients with PTSD experience oscillations in autonomic states that support either fight and flight behaviors or withdrawal, immobilization, and dissociation without an intervening calm state that would provide opportunities for positive social interactions. This defensive autonomic disposition is adaptive in dangerous and life threatening situations, but in the context of every-day life may lead to significant psychosocial distress and deteriorating social relationships. The perpetuation of these maladaptive autonomic responses, may contribute to the development of comorbid mental health issues such as depression, loneliness, and hostility that further modify the nature of cardiovascular behavior in the context of internal and external stressors. Over time, changes in autonomic, endocrine, and immune function contribute to deteriorating health, which is potently expressed in brain dysfunction and cardiovascular health. In this theoretical review paper, we review the literature on the chronic health effects of post-traumatic stress disorder. We discuss the brain networks underlying post-traumatic stress disorder in the context of autonomic efferent and afferent contributions and how disruption of these networks leads to poor health outcomes. Finally, we discuss treatments based on our theoretical model of posttraumatic stress disorder.

Autonomous Motivation and Fruit/Vegetable Intake in Parent–Adolescent Dyads

Science.gov (United States)

Dwyer, Laura A.; Bolger, Niall; Laurenceau, Jean-Philippe; Patrick, Heather; Oh, April Y.; Nebeling, Linda C.; Hennessy, Erin

2017-01-01

Introduction Autonomous motivation (motivation to engage in a behavior because of personal choice, interest, or value) is often associated with health behaviors. The present study contributes to research on motivation and eating behaviors by examining: (1) how autonomous motivation is correlated within parent–adolescent dyads; and (2) whether parent- and adolescent-reported autonomous motivation predicts the parent–adolescent correlation in fruit and vegetable (FV) intake frequency. Methods Data were drawn from the Family Life, Activity, Sun, Health, and Eating (FLASHE) Study, a cross-sectional U.S. survey of parent–adolescent dyads led by the National Cancer Institute and fielded between April and October 2014. In 2016, data were analyzed from dyads who had responses on a six-item self-report measure of daily frequency of FV consumption and a two-item self-report measure of autonomous motivation for consuming FVs. Results Parents' and adolescents' reports of autonomous motivation and FV intake frequency were positively correlated. Both parents' and adolescents' autonomous motivation predicted higher levels of their own FV intake frequency and that of their dyad partner (p-values ≤0.001). These effects of autonomous motivation explained 22.6% of the parent–adolescent correlation in FV intake frequency. Actor effects (one's motivation predicting their own FV intake frequency) were stronger than partner effects (one's motivation predicting their partner's FV intake frequency). Conclusions Parent–adolescent similarity in autonomous motivation for healthy eating may contribute to similarity in eating behaviors. Future research should further examine how individual-level health behavior correlates influence health behaviors within dyads. PMID:28526363

Autonomous Motivation and Fruit/Vegetable Intake in Parent-Adolescent Dyads.

Science.gov (United States)

Dwyer, Laura A; Bolger, Niall; Laurenceau, Jean-Philippe; Patrick, Heather; Oh, April Y; Nebeling, Linda C; Hennessy, Erin

2017-06-01

Autonomous motivation (motivation to engage in a behavior because of personal choice, interest, or value) is often associated with health behaviors. The present study contributes to research on motivation and eating behaviors by examining (1) how autonomous motivation is correlated within parent-adolescent dyads and (2) whether parent- and adolescent-reported autonomous motivation predicts the parent-adolescent correlation in fruit and vegetable (FV) intake frequency. Data were drawn from the Family Life, Activity, Sun, Health, and Eating (FLASHE) Study, a cross-sectional U.S. survey of parent-adolescent dyads led by the National Cancer Institute and fielded between April and October 2014. In 2016, data were analyzed from dyads who had responses on a six-item self-report measure of daily frequency of FV consumption and a two-item self-report measure of autonomous motivation for consuming FVs. Parents' and adolescents' reports of autonomous motivation and FV intake frequency were positively correlated. Both parents' and adolescents' autonomous motivation predicted higher levels of their own FV intake frequency and that of their dyad partner (p-values ≤0.001). These effects of autonomous motivation explained 22.6% of the parent-adolescent correlation in FV intake frequency. Actor effects (one's motivation predicting their own FV intake frequency) were stronger than partner effects (one's motivation predicting their partner's FV intake frequency). Parent-adolescent similarity in autonomous motivation for healthy eating may contribute to similarity in eating behaviors. Future research should further examine how individual-level health behavior correlates influence health behaviors within dyads. Published by Elsevier Inc.

Commande prédictive pour conduite autonome et coopérative

OpenAIRE

Qian , Xiangjun

2016-01-01

Autonomous driving has been gaining more and more attention in the last decades, thanks to its positive social-economic impacts including the enhancement of traffic efficiency and the reduction of road accidents. A number of research institutes and companies have tested autonomous vehicles in traffic, accumulating tens of millions of kilometers traveled in autonomous driving. With the vision of massive deployment of autonomous vehicles, researchers have also started to envision cooperative st...

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.)

An autonomous control framework for advanced reactors

Directory of Open Access Journals (Sweden)

Richard T. Wood

2017-08-01

Full Text Available Several Generation IV nuclear reactor concepts have goals for optimizing investment recovery through phased introduction of multiple units on a common site with shared facilities and/or reconfigurable energy conversion systems. Additionally, small modular reactors are suitable for remote deployment to support highly localized microgrids in isolated, underdeveloped regions. The long-term economic viability of these advanced reactor plants depends on significant reductions in plant operations and maintenance costs. To accomplish these goals, intelligent control and diagnostic capabilities are needed to provide nearly autonomous operations with anticipatory maintenance. A nearly autonomous control system should enable automatic operation of a nuclear power plant while adapting to equipment faults and other upsets. It needs to have many intelligent capabilities, such as diagnosis, simulation, analysis, planning, reconfigurability, self-validation, and decision. These capabilities have been the subject of research for many years, but an autonomous control system for nuclear power generation remains as-yet an unrealized goal. This article describes a functional framework for intelligent, autonomous control that can facilitate the integration of control, diagnostic, and decision-making capabilities to satisfy the operational and performance goals of power plants based on multimodular advanced reactors.

An autonomous control framework for advanced reactors

International Nuclear Information System (INIS)

Wood, Richard T.; Upadhyaya, Belle R.; Floyd, Dan C.

2017-01-01

Several Generation IV nuclear reactor concepts have goals for optimizing investment recovery through phased introduction of multiple units on a common site with shared facilities and/or reconfigurable energy conversion systems. Additionally, small modular reactors are suitable for remote deployment to support highly localized microgrids in isolated, underdeveloped regions. The long-term economic viability of these advanced reactor plants depends on significant reductions in plant operations and maintenance costs. To accomplish these goals, intelligent control and diagnostic capabilities are needed to provide nearly autonomous operations with anticipatory maintenance. A nearly autonomous control system should enable automatic operation of a nuclear power plant while adapting to equipment faults and other upsets. It needs to have many intelligent capabilities, such as diagnosis, simulation, analysis, planning, reconfigurability, self-validation, and decision. These capabilities have been the subject of research for many years, but an autonomous control system for nuclear power generation remains as-yet an unrealized goal. This article describes a functional framework for intelligent, autonomous control that can facilitate the integration of control, diagnostic, and decision-making capabilities to satisfy the operational and performance goals of power plants based on multimodular advanced reactors

An autonomous control framework for advanced reactors

Energy Technology Data Exchange (ETDEWEB)

Wood, Richard T.; Upadhyaya, Belle R.; Floyd, Dan C. [Dept. of Nuclear Engineering, University of Tennessee, Knoxville (United States)

2017-08-15

Several Generation IV nuclear reactor concepts have goals for optimizing investment recovery through phased introduction of multiple units on a common site with shared facilities and/or reconfigurable energy conversion systems. Additionally, small modular reactors are suitable for remote deployment to support highly localized microgrids in isolated, underdeveloped regions. The long-term economic viability of these advanced reactor plants depends on significant reductions in plant operations and maintenance costs. To accomplish these goals, intelligent control and diagnostic capabilities are needed to provide nearly autonomous operations with anticipatory maintenance. A nearly autonomous control system should enable automatic operation of a nuclear power plant while adapting to equipment faults and other upsets. It needs to have many intelligent capabilities, such as diagnosis, simulation, analysis, planning, reconfigurability, self-validation, and decision. These capabilities have been the subject of research for many years, but an autonomous control system for nuclear power generation remains as-yet an unrealized goal. This article describes a functional framework for intelligent, autonomous control that can facilitate the integration of control, diagnostic, and decision-making capabilities to satisfy the operational and performance goals of power plants based on multimodular advanced reactors.

Heterogeneous Teams of Autonomous Vehicles: Advanced Sensing & Control

Science.gov (United States)

2009-03-01

Final Technical 3. DATES COVERED (From To) 7/1/05-12/31708 4. TITLE AND SUBTITLE Heterogeneous Teams of Autonomous Vehicles Advanced Sensing...assimilating data from underwater and surface autonomous vehicles in addition to the usual sources of Eulerian and Lagrangian systems into a small scale

Cold Regions Issues for Off-Road Autonomous Vehicles

Science.gov (United States)

2004-04-01

the operation of off-road autonomous vehicles . Low-temperature effects on lubricants, materials, and batteries can impair a robot’s ability to operate...demanding that off-road autonomous vehicles must be designed for and tested in cold regions if they are expected to operate there successfully.

Experimental and numerical study of an autonomous flap

NARCIS (Netherlands)

Bernhammer, L.O.; Navalkar, S.T.; Sodja, J.; De Breuker, R.; Karpel, M.

2015-01-01

This paper presents the experimental and numerical study of an autonomous load alleviation concept using trailing edge flaps. The flaps are autonomous units, which for instance can be used for gust load alleviation. The unit is self-powered and self-actuated through trailing edge tabs which are

Political accountability and autonomous weapons

Directory of Open Access Journals (Sweden)

James Igoe Walsh

2015-09-01

Full Text Available Autonomous weapons would have the capacity to select and attack targets without direct human input. One important objection to the introduction of such weapons is that they will make it more difficult to identify and hold accountable those responsible for undesirable outcomes such as mission failures and civilian casualties. I hypothesize that individuals can modify their attribution of responsibility in predicable ways to accommodate this new technology. The results of a survey experiment are consistent with this; subjects continue to find responsible and hold accountable political and military leaders when autonomous weapons are used, but also attribute responsibility to the designers and programmers of such weapons.

Autonomic Regulation of Splanchnic Circulation

Directory of Open Access Journals (Sweden)

Kathleen A Fraser

1991-01-01

Full Text Available The role of the autonomic nervous system in circulatory regulation of the splanchnic organs (stomach, small intestine, colon, liver, pancreas and spleen is reviewed. In general, the sympathetic nervous system is primarily involved in vasoconstriction, while the parasympathetic contributes to vasodilation. Vasoconstriction in the splanchnic circulation appears to be mediated by alpha-2 receptors and vasodilation by activation of primary afferent nerves with subsequent release of vasodilatory peptides, or by stimulation of beta-adrenergic receptors. As well, an important function of the autonomic nervous system is to provide a mechanism by which splanchnic vascular reserve can be mobilized during stress to maintain overall cardiovascular homeostasis.

Experimental Autonomous Road Vehicle with Logical Artificial Intelligence

Directory of Open Access Journals (Sweden)

Sergey Sergeevich Shadrin

2017-01-01

Full Text Available This article describes some technical issues regarding the adaptation of a production car to a platform for the development and testing of autonomous driving technologies. A universal approach to performing the reverse engineering of electric power steering (EPS for the purpose of external control is also presented. The primary objective of the related study was to solve the problem associated with the precise prediction of the dynamic trajectory of an autonomous vehicle. This was accomplished by deriving a new equation for determining the lateral tire forces and adjusting some of the vehicle parameters under road test conductions. A Mivar expert system was also integrated into the control system of the experimental autonomous vehicle. The expert system was made more flexible and effective for the present application by the introduction of hybrid artificial intelligence with logical reasoning. The innovation offers a solution to the major problem of liability in the event of an autonomous transport vehicle being involved in a collision.

Abnormal Cardiac Autonomic Regulation in Mice Lacking ASIC3

Directory of Open Access Journals (Sweden)

Ching-Feng Cheng

2014-01-01

Full Text Available Integration of sympathetic and parasympathetic outflow is essential in maintaining normal cardiac autonomic function. Recent studies demonstrate that acid-sensing ion channel 3 (ASIC3 is a sensitive acid sensor for cardiac ischemia and prolonged mild acidification can open ASIC3 and evoke a sustained inward current that fires action potentials in cardiac sensory neurons. However, the physiological role of ASIC3 in cardiac autonomic regulation is not known. In this study, we elucidate the role of ASIC3 in cardiac autonomic function using Asic3−/− mice. Asic3−/− mice showed normal baseline heart rate and lower blood pressure as compared with their wild-type littermates. Heart rate variability analyses revealed imbalanced autonomic regulation, with decreased sympathetic function. Furthermore, Asic3−/− mice demonstrated a blunted response to isoproterenol-induced cardiac tachycardia and prolonged duration to recover to baseline heart rate. Moreover, quantitative RT-PCR analysis of gene expression in sensory ganglia and heart revealed that no gene compensation for muscarinic acetylcholines receptors and beta-adrenalin receptors were found in Asic3−/− mice. In summary, we unraveled an important role of ASIC3 in regulating cardiac autonomic function, whereby loss of ASIC3 alters the normal physiological response to ischemic stimuli, which reveals new implications for therapy in autonomic nervous system-related cardiovascular diseases.

ANALYTICAL SOLUTION OF THE K-TH ORDER AUTONOMOUS ORDINARY DIFFERENTIAL EQUATION

Directory of Open Access Journals (Sweden)

Ronald Orozco López

2017-04-01

Full Text Available The main objective of this paper is to find the analytical solution of the autonomous equation y(k = f (y and prove its convergence using autonomous polynomials of order k, define here in addition of the formula of Faá di Bruno for composition of functions and Bell polynomials. Autonomous polynomials of order k are defined in terms of the boundary values of the equation. Also special values of autonomous polynomials of order 1 are given.

Autonomous path planning solution for industrial robot manipulator using backpropagation algorithm

Directory of Open Access Journals (Sweden)

PeiJiang Yuan

2015-12-01

Full Text Available Here, we propose an autonomous path planning solution using backpropagation algorithm. The mechanism of movement used by humans in controlling their arms is analyzed and then applied to control a robot manipulator. Autonomous path planning solution is a numerical method. The model of industrial robot manipulator used in this article is a KUKA KR 210 R2700 EXTRA robot. In order to show the performance of the autonomous path planning solution, an experiment validation of path tracking is provided. Experiment validation consists of implementation of the autonomous path planning solution and the control of physical robot. The process of converging to target solution is provided. The mean absolute error of position for tool center point is also analyzed. Comparison between autonomous path planning solution and the numerical methods based on Newton–Raphson algorithm is provided to demonstrate the efficiency and accuracy of the autonomous path planning solution.

A Queueing Model for Supervisory Control of Unmanned Autonomous Vehicles

Science.gov (United States)

2013-09-01

Autonomous Vehicles Joseph DiVita, PhD Robert L. Morris Maria Olinda Rodas SSC Pacific Approved...298 (Rev. 8/98) Prescribed by ANSI Std. Z39.18 09–2013 Final A Queueing Model for Supervisory Control of Unmanned Autonomous Vehicles Joseph...Mission Area: Command and Control, Queueing Model; Supervisory Control; Unmanned Autonomous Vehicles M. O. Rodas U U U U 38 (619)

Learner Behaviors and Perceptions of Autonomous Language Learning

Science.gov (United States)

Bekleyen, Nilüfer; Selimoglu, Figen

2016-01-01

The purpose of the present study was to investigate the learners' behaviors and perceptions about autonomous language learning at the university level in Turkey. It attempts to reveal what type of perceptions learners held regarding teachers' and their own responsibilities in the language learning process. Their autonomous language learning…

Wireless IR Image Transfer System for Autonomous Vehicles

Science.gov (United States)

2003-12-01

the camera can operate between 0 and 500 C; this uniquely suites it for employment on autonomous vehicles in rugged environments. The camera is...system is suitable for used on autonomous vehicles under varying antenna orientations. • The third is the use of MDS transceivers allows the received

Physics-Aware Informative Coverage Planning for Autonomous Vehicles

Science.gov (United States)

2014-06-01

Physics-Aware Informative Coverage Planning for Autonomous Vehicles Michael J. Kuhlman1, Student Member, IEEE, Petr Švec2, Member, IEEE, Krishnanand...Physics-Aware Informative Coverage Planning for Autonomous Vehicles 5a. CONTRACT NUMBER 5b. GRANT NUMBER 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S) 5d

Cardiovascular autonomic dysfunction due to diabetes mellitus: An ...

African Journals Online (AJOL)

Cardiovascular autonomic neuropathy (CAN) is a common form of diabetes autonomic neuropathy, causes abnormalities in heart rate control as well as central and peripheral vascular dynamics, and may carry an increased risk of mortality. The aim of this article was to review the importance of identifying CAN and ...

Emerging Technologies for Autonomous Language Learning

Directory of Open Access Journals (Sweden)

Mark Warschauer

2011-09-01

Full Text Available Drawing on a lengthier review completed for the US National Institute for Literacy, this paper examines emerging technologies that are applicable to self-access and autonomous learning in the areas of listening and speaking, collaborative writing, reading and language structure, and online interaction. Digital media reviewed include podcasts, blogs, wikis, online writing sites, text-scaffolding software, concordancers, multiuser virtual environments, multiplayer games, and chatbots. For each of these technologies, we summarize recent research and discuss possible uses for autonomous language learning.

Sex differences in autonomic function following maximal exercise.

Science.gov (United States)

Kappus, Rebecca M; Ranadive, Sushant M; Yan, Huimin; Lane-Cordova, Abbi D; Cook, Marc D; Sun, Peng; Harvey, I Shevon; Wilund, Kenneth R; Woods, Jeffrey A; Fernhall, Bo

2015-01-01

Heart rate variability (HRV), blood pressure variability, (BPV) and heart rate recovery (HRR) are measures that provide insight regarding autonomic function. Maximal exercise can affect autonomic function, and it is unknown if there are sex differences in autonomic recovery following exercise. Therefore, the purpose of this study was to determine sex differences in several measures of autonomic function and the response following maximal exercise. Seventy-one (31 males and 40 females) healthy, nonsmoking, sedentary normotensive subjects between the ages of 18 and 35 underwent measurements of HRV and BPV at rest and following a maximal exercise bout. HRR was measured at minute one and two following maximal exercise. Males have significantly greater HRR following maximal exercise at both minute one and two; however, the significance between sexes was eliminated when controlling for VO2 peak. Males had significantly higher resting BPV-low-frequency (LF) values compared to females and did not significantly change following exercise, whereas females had significantly increased BPV-LF values following acute maximal exercise. Although males and females exhibited a significant decrease in both HRV-LF and HRV-high frequency (HF) with exercise, females had significantly higher HRV-HF values following exercise. Males had a significantly higher HRV-LF/HF ratio at rest; however, both males and females significantly increased their HRV-LF/HF ratio following exercise. Pre-menopausal females exhibit a cardioprotective autonomic profile compared to age-matched males due to lower resting sympathetic activity and faster vagal reactivation following maximal exercise. Acute maximal exercise is a sufficient autonomic stressor to demonstrate sex differences in the critical post-exercise recovery period.

Robotics and Autonomous Systems Laboratory

Data.gov (United States)

Federal Laboratory Consortium — FUNCTION: Provides an environment for developing and evaluating intelligent software for both actual and simulated autonomous vehicles. Laboratory computers provide...

Development of an autonomous power system testbed

International Nuclear Information System (INIS)

Barton, J.R.; Adams, T.; Liffring, M.E.

1985-01-01

A power system testbed has been assembled to advance the development of large autonomous electrical power systems required for the space station, spacecraft, and aircraft. The power system for this effort was designed to simulate single- or dual-bus autonomous power systems, or autonomous systems that reconfigure from a single bus to a dual bus following a severe fault. The approach taken was to provide a flexible power system design with two computer systems for control and management. One computer operates as the control system and performs basic control functions, data and command processing, charge control, and provides status to the second computer. The second computer contains expert system software for mission planning, load management, fault identification and recovery, and sends load and configuration commands to the control system

Control of autonomous robot using neural networks

Science.gov (United States)

Barton, Adam; Volna, Eva

2017-07-01

The aim of the article is to design a method of control of an autonomous robot using artificial neural networks. The introductory part describes control issues from the perspective of autonomous robot navigation and the current mobile robots controlled by neural networks. The core of the article is the design of the controlling neural network, and generation and filtration of the training set using ART1 (Adaptive Resonance Theory). The outcome of the practical part is an assembled Lego Mindstorms EV3 robot solving the problem of avoiding obstacles in space. To verify models of an autonomous robot behavior, a set of experiments was created as well as evaluation criteria. The speed of each motor was adjusted by the controlling neural network with respect to the situation in which the robot was found.

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.

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.

Multiculturalismo, interculturalismo y autonomía

OpenAIRE

Edwin Cruz Rodríguez

2014-01-01

Este artículo examina dos enfoques teóri- cos sobre la autonomía: el multiculturalis- mo liberal y el interculturalismo latinoa- mericano. El argumento principal es que el enfoque intercultural es idóneo para fun- damentar la autonomía que el multicultu- ralismo porque tiene un mayor alcance metodológico y sus horizontes normativos son más amplios. En primer lugar, se exa- minan las críticas del interculturalismo al multiculturalismo liberal de Kymlicka. Se- guidamente, se estudian sus concep...

Autonomously managed high power systems

International Nuclear Information System (INIS)

Weeks, D.J.; Bechtel, R.T.

1985-01-01

The need for autonomous power management capabilities will increase as the power levels of spacecraft increase into the multi-100 kW range. The quantity of labor intensive ground and crew support consumed by the 9 kW Skylab cannot be afforded in support of a 75-300 kW Space Station or high power earth orbital and interplanetary spacecraft. Marshall Space Flight Center is managing a program to develop necessary technologies for high power system autonomous management. To date a reference electrical power system and automation approaches have been defined. A test facility for evaluation and verification of management algorithms and hardware has been designed with the first of the three power channel capability nearing completion

Autonomous Vehicles Navigation with Visual Target Tracking: Technical Approaches

Directory of Open Access Journals (Sweden)

Zhen Jia

2008-12-01

Full Text Available This paper surveys the developments of last 10 years in the area of vision based target tracking for autonomous vehicles navigation. First, the motivations and applications of using vision based target tracking for autonomous vehicles navigation are presented in the introduction section. It can be concluded that it is very necessary to develop robust visual target tracking based navigation algorithms for the broad applications of autonomous vehicles. Then this paper reviews the recent techniques in three different categories: vision based target tracking for the applications of land, underwater and aerial vehicles navigation. Next, the increasing trends of using data fusion for visual target tracking based autonomous vehicles navigation are discussed. Through data fusion the tracking performance is improved and becomes more robust. Based on the review, the remaining research challenges are summarized and future research directions are investigated.

12th International Conference on Intelligent Autonomous Systems (IAS-12)

CERN Document Server

Yoon, Kwang-Joon; Lee, Jangmyung; Frontiers of Intelligent Autonomous Systems

2013-01-01

This carefully edited volume aims at providing readers with the most recent progress on intelligent autonomous systems, with its particular emphasis on intelligent autonomous ground, aerial and underwater vehicles as well as service robots for home and healthcare under the context of the aforementioned convergence. “Frontiers of Intelligent Autonomous Systems” includes thoroughly revised and extended papers selected from the 12th International Conference on Intelligent Autonomous Systems (IAS-12), held in Jeju, Korea, June 26-29, 2012. The editors chose 35 papers out of the 202 papers presented at IAS-12 which are organized into three chapters: Chapter 1 is dedicated to autonomous navigation and mobile manipulation, Chapter 2 to unmanned aerial and underwater vehicles and Chapter 3 to service robots for home and healthcare. To help the readers to easily access this volume, each chapter starts with a chapter summary introduced by one of the editors: Chapter 1 by Sukhan Lee, Chapter 2 by Kwang Joon Yoon and...

Autonomic Fuselet Specification and Composition

National Research Council Canada - National Science Library

Mills, Peter H

2006-01-01

A framework for autonomic fuselet business logic development was developed, using semantic web services and workflow technologies to specify fuselet information needs, to define an executable workflow...

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

Neuronal degeneration in autonomic nervous system of Dystonia musculorum mice

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Liu Kang-Jen

2011-01-01

Full Text Available Abstract Background Dystonia musculorum (dt is an autosomal recessive hereditary neuropathy with a characteristic uncoordinated movement and is caused by a defect in the bullous pemphigoid antigen 1 (BPAG1 gene. The neural isoform of BPAG1 is expressed in various neurons, including those in the central and peripheral nerve systems of mice. However, most previous studies on neuronal degeneration in BPAG1-deficient mice focused on peripheral sensory neurons and only limited investigation of the autonomic system has been conducted. Methods In this study, patterns of nerve innervation in cutaneous and iridial tissues were examined using general neuronal marker protein gene product 9.5 via immunohistochemistry. To perform quantitative analysis of the autonomic neuronal number, neurons within the lumbar sympathetic and parasympathetic ciliary ganglia were calculated. In addition, autonomic neurons were cultured from embryonic dt/dt mutants to elucidate degenerative patterns in vitro. Distribution patterns of neuronal intermediate filaments in cultured autonomic neurons were thoroughly studied under immunocytochemistry and conventional electron microscopy. Results Our immunohistochemistry results indicate that peripheral sensory nerves and autonomic innervation of sweat glands and irises dominated degeneration in dt/dt mice. Quantitative results confirmed that the number of neurons was significantly decreased in the lumbar sympathetic ganglia as well as in the parasympathetic ciliary ganglia of dt/dt mice compared with those of wild-type mice. We also observed that the neuronal intermediate filaments were aggregated abnormally in cultured autonomic neurons from dt/dt embryos. Conclusions These results suggest that a deficiency in the cytoskeletal linker BPAG1 is responsible for dominant sensory nerve degeneration and severe autonomic degeneration in dt/dt mice. Additionally, abnormally aggregated neuronal intermediate filaments may participate in

Feasibility of Turing-Style Tests for Autonomous Aerial Vehicle "Intelligence"

Science.gov (United States)

Young, Larry A.

2007-01-01

A new approach is suggested to define and evaluate key metrics as to autonomous aerial vehicle performance. This approach entails the conceptual definition of a "Turing Test" for UAVs. Such a "UAV Turing test" would be conducted by means of mission simulations and/or tailored flight demonstrations of vehicles under the guidance of their autonomous system software. These autonomous vehicle mission simulations and flight demonstrations would also have to be benchmarked against missions "flown" with pilots/human-operators in the loop. In turn, scoring criteria for such testing could be based upon both quantitative mission success metrics (unique to each mission) and by turning to analog "handling quality" metrics similar to the well-known Cooper-Harper pilot ratings used for manned aircraft. Autonomous aerial vehicles would be considered to have successfully passed this "UAV Turing Test" if the aggregate mission success metrics and handling qualities for the autonomous aerial vehicle matched or exceeded the equivalent metrics for missions conducted with pilots/human-operators in the loop. Alternatively, an independent, knowledgeable observer could provide the "UAV Turing Test" ratings of whether a vehicle is autonomous or "piloted." This observer ideally would, in the more sophisticated mission simulations, also have the enhanced capability of being able to override the scripted mission scenario and instigate failure modes and change of flight profile/plans. If a majority of mission tasks are rated as "piloted" by the observer, when in reality the vehicle/simulation is fully- or semi- autonomously controlled, then the vehicle/simulation "passes" the "UAV Turing Test." In this regards, this second "UAV Turing Test" approach is more consistent with Turing s original "imitation game" proposal. The overall feasibility, and important considerations and limitations, of such an approach for judging/evaluating autonomous aerial vehicle "intelligence" will be discussed from a

An Expert System for Autonomous Spacecraft Control

Science.gov (United States)

Sherwood, Rob; Chien, Steve; Tran, Daniel; Cichy, Benjamin; Castano, Rebecca; Davies, Ashley; Rabideau, Gregg

2005-01-01

The Autonomous Sciencecraft Experiment (ASE), part of the New Millennium Space Technology 6 Project, is flying onboard the Earth Orbiter 1 (EO-1) mission. The ASE software enables EO-1 to autonomously detect and respond to science events such as: volcanic activity, flooding, and water freeze/thaw. ASE uses classification algorithms to analyze imagery onboard to detect chang-e and science events. Detection of these events is then used to trigger follow-up imagery. Onboard mission planning software then develops a response plan that accounts for target visibility and operations constraints. This plan is then executed using a task execution system that can deal with run-time anomalies. In this paper we describe the autonomy flight software and how it enables a new paradigm of autonomous science and mission operations. We will also describe the current experiment status and future plans.

Research on support effectiveness modeling and simulating of aviation materiel autonomic logistics system

Science.gov (United States)

Zhou, Yan; Zhou, Yang; Yuan, Kai; Jia, Zhiyu; Li, Shuo

2018-05-01

Aiming at the demonstration of autonomic logistics system to be used at the new generation of aviation materiel in our country, the modeling and simulating method of aviation materiel support effectiveness considering autonomic logistics are studied. Firstly, this paper introduced the idea of JSF autonomic logistics and analyzed the influence of autonomic logistics on support effectiveness from aspects of reliability, false alarm rate, troubleshooting time, and support delay time and maintenance level. On this basis, the paper studies the modeling and simulating methods of support effectiveness considering autonomic logistics, and puts forward the maintenance support simulation process considering autonomic logistics. Finally, taking the typical aviation materiel as an example, this paper analyzes and verifies the above-mentioned support effectiveness modeling and simulating method of aviation materiel considering autonomic logistics.

Autonomic dysfunction in Hodgkin and non-Hodgkin lymphoma. A paraneoplastic syndrome?

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Franca Bilora

2010-11-01

Full Text Available We wanted to determine whether autonomic dysfunction in patients with lymphoma is related to chemotherapy or represent a paraneoplastic syndrome. 40 patients with current or cured Hodgkin or non-Hodgkin lymphoma and 40 healthy controls, matched for age, gender, hypertension and diabetes mellitus underwent autonomic evaluation (Deep Breath, Valsalva Maneuver, Hand Grip, Lying to Standing, Tilt Test. Current patients also suffering from diabetes or hypertension, or still on chemotherapy revealed autonomic changes, while cured or healthy subjects did not. Autonomic dysfunction in lymphoma is a transient manifestation of a paraneoplastic syndrome.

Amplifying human ability through autonomics and machine learning in IMPACT

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Dzieciuch, Iryna; Reeder, John; Gutzwiller, Robert; Gustafson, Eric; Coronado, Braulio; Martinez, Luis; Croft, Bryan; Lange, Douglas S.

2017-05-01

Amplifying human ability for controlling complex environments featuring autonomous units can be aided by learned models of human and system performance. In developing a command and control system that allows a small number of people to control a large number of autonomous teams, we employ an autonomics framework to manage the networks that represent mission plans and the networks that are composed of human controllers and their autonomous assistants. Machine learning allows us to build models of human and system performance useful for monitoring plans and managing human attention and task loads. Machine learning also aids in the development of tactics that human supervisors can successfully monitor through the command and control system.

An Investigation of the Relationship between Autonomous Learning and Lifelong Learning

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Cengiz Yurdakul

2016-12-01

Full Text Available The present study aims to investigate the relationship between autonomous learning and lifelong learning. The study group consists of 657 secondary school students enrolled in three public schools, aged 11 – 16 from Sakarya, Turkey. In this study, relationships between the variables of autonomous learning and lifelong learning and the sub-dimensions of autonomous learning were investigated. Pearson Product Moment Correlation, Partial Correlation methods were utilized in order to investigate these relationships. Autonomous Learning Scale (12 items which was developed by Macaskill and Taylor (2010, was adapted to Turkish by Arslan and Yurdakul (2015 was conducted to measure autonomous learning. Lifelong Learning Scale (14 items which was developed by Kirby, Knapper, Lamon and Egnatoff (2010, was adapted to Turkish by Arslan and Akcaalan (2015 was carried out to assess lifelong learning level. In the light of the research findings, it can be purported that autonomous learning and lifelong learning scores were correlating significantly. According to the existing results, it can be argued that autonomous learning which can be defined as the capacity to take charge of one’s own learning, has a positive interaction with lifelong learning which can be found voice in one’s ongoing, voluntary, and self-motivated learning.

Modulation of autonomic activity in neurological conditions: Epilepsy and Tourette syndrome

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Yoko eNagai

2015-09-01

Full Text Available This manuscript considers the central but neglected role of the autonomic nervous system in the expression and control of seizures in Epilepsy and tics in Tourette Syndrome (TS. In epilepsy, consideration of autonomic involvement is typically confined to differential diagnoses (e.g. syncope, or in relation to Sudden Unexpected Death in Epilepsy (SUDEP. Investigation is more limited in Tourette Syndrome. The role of the autonomic nervous system in the generation and prevention of epileptic seizures is largely overlooked. Emotional stimuli such as anxiety and stress are potent causes of seizures and tic activity in TS, respectively. This manuscript will describe a possible neural mechanism by which afferent autonomic projections linked to cognition and behaviour influence central nervous system thalamo-cortical regulation, which appears to be an important means for controlling both seizure and tic activity. It also summarizes the link between the integrity of the default mode network and autonomic regulation in patients with epilepsy as well as the link between impaired motor control and autonomic regulation in patients with TS. Two neurological conditions; epilepsy and TS were chosen, as seizures and tics represent parameters that can be easily measured to investigate influences of autonomic functions. The EDA biofeedback approach is anticipated

Autonomous nutrient detection for water quality monitoring

OpenAIRE

Maher, Damien; Cleary, John; Cogan, Deirdre; Diamond, Dermot

2012-01-01

The ever increasing demand for real time environmental monitoring is currently being driven by strong legislative and societal drivers. Low cost autonomous environmental monitoring systems are required to meet this demand as current monitoring solutions are insufficient. This poster presents an autonomous nutrient analyser platform for water quality monitoring. Results from a field trial of the nutrient analyser are reported along with current work to expand the range of water quality targ...

Autonomous Car Parking System through a Cooperative Vehicular Positioning Network.

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Correa, Alejandro; Boquet, Guillem; Morell, Antoni; Lopez Vicario, Jose

2017-04-13

The increasing development of the automotive industry towards a fully autonomous car has motivated the design of new value-added services in Vehicular Sensor Networks (VSNs). Within the context of VSNs, the autonomous car, with an increasing number of on-board sensors, is a mobile node that exchanges sensed and state information within the VSN. Among all the value added services for VSNs, the design of new intelligent parking management architectures where the autonomous car will coexist with traditional cars is mandatory in order to profit from all the opportunities associated with the increasing intelligence of the new generation of cars. In this work, we design a new smart parking system on top of a VSN that takes into account the heterogeneity of cars and provides guidance to the best parking place for the autonomous car based on a collaborative approach that searches for the common good of all of them measured by the accessibility rate, which is the ratio of the free parking places accessible for an autonomous car. Then, we simulate a real parking lot and the results show that the performance of our system is close to the optimum considering different communication ranges and penetration rates for the autonomous car.

Autonomous Car Parking System through a Cooperative Vehicular Positioning Network

Science.gov (United States)

Correa, Alejandro; Boquet, Guillem; Morell, Antoni; Lopez Vicario, Jose

2017-01-01

The increasing development of the automotive industry towards a fully autonomous car has motivated the design of new value-added services in Vehicular Sensor Networks (VSNs). Within the context of VSNs, the autonomous car, with an increasing number of on-board sensors, is a mobile node that exchanges sensed and state information within the VSN. Among all the value added services for VSNs, the design of new intelligent parking management architectures where the autonomous car will coexist with traditional cars is mandatory in order to profit from all the opportunities associated with the increasing intelligence of the new generation of cars. In this work, we design a new smart parking system on top of a VSN that takes into account the heterogeneity of cars and provides guidance to the best parking place for the autonomous car based on a collaborative approach that searches for the common good of all of them measured by the accessibility rate, which is the ratio of the free parking places accessible for an autonomous car. Then, we simulate a real parking lot and the results show that the performance of our system is close to the optimum considering different communication ranges and penetration rates for the autonomous car. PMID:28406426

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.

Experimental Autonomous Vehicle Systems

DEFF Research Database (Denmark)

Ravn, Ole; Andersen, Nils Axel

1998-01-01

The paper describes the requirements for and a prototype configuration of a software architecture for control of an experimental autonomous vehicle. The test bed nature of the system is emphasised in the choice of architecture making re-configurability, data logging and extendability simple...

Not Deep Learning but Autonomous Learning of Open Innovation for Sustainable Artificial Intelligence

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JinHyo Joseph Yun

2016-08-01

Full Text Available What do we need for sustainable artificial intelligence that is not harmful but beneficial human life? This paper builds up the interaction model between direct and autonomous learning from the human’s cognitive learning process and firms’ open innovation process. It conceptually establishes a direct and autonomous learning interaction model. The key factor of this model is that the process to respond to entries from external environments through interactions between autonomous learning and direct learning as well as to rearrange internal knowledge is incessant. When autonomous learning happens, the units of knowledge determinations that arise from indirect learning are separated. They induce not only broad autonomous learning made through the horizontal combinations that surpass the combinations that occurred in direct learning but also in-depth autonomous learning made through vertical combinations that appear so that new knowledge is added. The core of the interaction model between direct and autonomous learning is the variability of the boundary between proven knowledge and hypothetical knowledge, limitations in knowledge accumulation, as well as complementarity and conflict between direct and autonomous learning. Therefore, these should be considered when introducing the interaction model between direct and autonomous learning into navigations, cleaning robots, search engines, etc. In addition, we should consider the relationship between direct learning and autonomous learning when building up open innovation strategies and policies.