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

ARTERIAL HYPERTENSION IN YOUNG PEOPLE: EFFICACY OF SYMPATHOLYTIC THERAPY

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N. N. Nikitina

2015-12-01

Full Text Available Aim. To evaluate the effect of imidasoline agonist, rilmenidine (Albarel, on 24-hour blood pressure (BP profile and autonomic regulation of cardiovascular system in young patients with arterial hypertension (HT and exogenous constitutional obesity (ECO.Material and methods. The study included 80 men aged 18-32 ( average age 20,5 years, including 34 patients with HT and normal body weight, 36 patients with HT and ECO, 10 healthy men as a control group. All hypertensive patients were treated with rilmenidine 1-2 mg daily during 12 weeks. BP 24-hour profile and heart rate variability (HRV were estimated before and after therapy.Results. Rilmenidine monotherapy resulted in significant reduction in average 24-hour, day-time and night-time BP as well as indices of BP loading in both groups. Indices of HRV proved the initial sympathetic overdrive among hypertensive patients especially among those with ECO. This sympathetic overdrive significantly reduced after 12 weeks of therapy.Conclusion. Rilmenidine effectively controls BP and reduces sympathetic system overdrive in young hypertensive patients with ECO.

ARTERIAL HYPERTENSION IN YOUNG PEOPLE: EFFICACY OF SYMPATHOLYTIC THERAPY

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N. N. Nikitina

2007-01-01

Full Text Available Aim. To evaluate the effect of imidasoline agonist, rilmenidine (Albarel, on 24-hour blood pressure (BP profile and autonomic regulation of cardiovascular system in young patients with arterial hypertension (HT and exogenous constitutional obesity (ECO.Material and methods. The study included 80 men aged 18-32 ( average age 20,5 years, including 34 patients with HT and normal body weight, 36 patients with HT and ECO, 10 healthy men as a control group. All hypertensive patients were treated with rilmenidine 1-2 mg daily during 12 weeks. BP 24-hour profile and heart rate variability (HRV were estimated before and after therapy.Results. Rilmenidine monotherapy resulted in significant reduction in average 24-hour, day-time and night-time BP as well as indices of BP loading in both groups. Indices of HRV proved the initial sympathetic overdrive among hypertensive patients especially among those with ECO. This sympathetic overdrive significantly reduced after 12 weeks of therapy.Conclusion. Rilmenidine effectively controls BP and reduces sympathetic system overdrive in young hypertensive patients with ECO.

Management of neuropathic pain following treatment for breast cancer in the absence of recurrence: a challenge for the radiation oncologist

International Nuclear Information System (INIS)

Clubb, B.

2004-01-01

This report reviews various management options for treatment-induced neuropathic pain in breast cancer. First-line options include tricyclic antidepressants and anticonvulsant drugs. Opioids should be prescribed according to published guidelines. Second-line treatments include lignocaine, mexiletine and ketamine. Sympatholytic therapies are available to patients with features of chronic regional pain syndrome. Anti-inflammatory agents are used for neurogenic inflammation. Surgical interventions are considered for refractory neuropathic pain. Interdisciplinary management is appropriate when persisting pain causes physical and psychosocial disabilities. Copyright (2004) Blackwell Science Pty Ltd

Spinal cord stimulation: Current applications for treatment of chronic pain.

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Vannemreddy, Prasad; Slavin, Konstantin V

2011-01-01

Spinal cord stimulation (SCS) is thought to relieve chronic intractable pain by stimulating nerve fibers in the spinal cord. The resulting impulses in the fibers may inhibit the conduction of pain signals to the brain, according to the pain gate theory proposed by Melzack and Wall in 1965 and the sensation of pain is thus blocked. Although SCS may reduce pain, it will not eliminate it. After a period of concern about safety and efficacy, SCS is now regaining popularity among pain specialists for the treatment of chronic pain. The sympatholytic effect of SCS is one of its most interesting therapeutic properties. This effect is considered responsible for the effectiveness of SCS in peripheral ischemia, and at least some cases of complex regional pain syndrome. The sympatholytic effect has also been considered part of the management of other chronic pain states such as failed back surgery syndrome, phantom pain, diabetic neuropathy, and postherpetic neuralgia. In general, SCS is part of an overall treatment strategy and is used only after the more conservative treatments have failed. The concept of SCS has evolved rapidly following the technological advances that have produced leads with multiple contact electrodes and battery systems. The current prevalence of patients with chronic pain requiring treatment other than conventional medical management has significantly increased and so has been the need for SCS. With the cost benefit analysis showing significant support for SCS, it may be appropriate to offer this as an effective alternative treatment for these patients.

Muscle interstitial ATP and norepinephrine concentrations in the human leg during exercise and ATP infusion

DEFF Research Database (Denmark)

Mortensen, Stefan P.; Gonzalez-Alonso, Jose; Nielsen, Jens Jung

2009-01-01

ATP and NE concentrations to gain insight into the interstitial and intravascular mechanisms by which ATP causes muscle vasodilation and sympatholysis. Leg hemodynamics and muscle interstitial nucleotide and norepinephrine (NE) concentrations were measured during: 1) femoral arterial ATP infusion (0......, respectively (Pcontracting muscle (Pmuscle, whereas interstitial NE concentrations increased similarly in both active...... and inactive muscles. These results suggest that the vasodilatory and sympatholytic effects of intraluminal ATP are mainly mediated via endothelial prinergic receptors. Intraluminal ATP and muscle contractions appear to modulate sympathetic nerve activity by inhibiting the effect of NE rather than blunting its...

[Mechanism of the diuretic effect of eufillin].

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Kantariia, V A; Lebedev, A A

1975-01-01

In acute experiments on rats the xanthine diuretic euphylline did not block the short-circuited current in the proximal tubule, nor did it lower the transtubular potential and the transepithelial resistance of the nephron wall. The diuretic speeded up significantly the passage of the tubular fluid along the proximal region of the nephron and Henle's loop. The dihydroergotoxin and inderal blocking of adrenoreceptors did not produce any influence on the renal effects of the xanthine agent. Reserpine totally blocked the diuretic and saluretic effects of euphylline, whereas other sympatholytics, such as alpha-methyl-dofa, anthabus and hemedin, did not modify the action of the diuretic.

Sympatholytic properties of several AT(1)-receptor antagonists in the isolated rabbit thoracic aorta

NARCIS (Netherlands)

Nap, Alexander; Balt, Jippe C.; Pfaffendorf, Martin; van Zwieten, Pieter A.

2002-01-01

Objective To evaluate the facilitating effect of angiotensin II on sympathetic neurotransmission to quantitatively compare the sympatho-inhibitory potencies of the selective AT(1)-receptor antagonists losartan, irbesartan and telmisartan in the isolated rabbit thoracic aorta. Design To investigate

Functional sympatholysis during exercise in patients with type 2 diabetes with intact response to acetylcholine

DEFF Research Database (Denmark)

Thaning, Pia; Bune, Laurids T; Zaar, Morten

2011-01-01

Sympathetic vasoconstriction is blunted in contracting human skeletal muscles (functional sympatholysis). In young subjects, infusion of adenosine and ATP increases blood flow, and the latter compound also attenuates α-adrenergic vasoconstriction. In patients with type 2 diabetes and age-matched ......Sympathetic vasoconstriction is blunted in contracting human skeletal muscles (functional sympatholysis). In young subjects, infusion of adenosine and ATP increases blood flow, and the latter compound also attenuates α-adrenergic vasoconstriction. In patients with type 2 diabetes and age......-matched healthy subjects, we tested 1) the sympatholytic capacity during one-legged exercise, 2) the vasodilatory capacity of adenosine and ATP, and 3) the ability to blunt α-adrenergic vasoconstriction during ATP infusion....

Regulation of Blood Flow in Contracting Skeletal Muscle in Aging

DEFF Research Database (Denmark)

Piil, Peter Bergmann

Oxygen delivery to skeletal muscle is regulated precisely to match the oxygen demand; however, with aging the regulation of oxygen delivery during exercise is impaired. The present thesis investigated mechanisms underlying the age-related impairment in regulation of blood flow and oxygen delivery......GMP) was used as intervention, and skeletal muscle blood flow, oxygen delivery, and functional sympatholysis was examined. The two studies included 53 healthy, habitually active, male subjects. All subjects participated in an experimental day in which femoral arterial blood flow and blood pressure were assessed...... that improving sympatholytic capacity by training may be a slower process in older than in young men. In conclusion, this thesis provides new important knowledge related to the regulation of skeletal muscle blood flow in aging. Specifically, it demonstrates that changes in cGMP signaling is an underlying cause...

Skeletal blood flow: implications for bone-scan interpretation

International Nuclear Information System (INIS)

Charkes, N.D.

1980-01-01

The dispersion of the skeleton throughout the body and its complex vascular anatomy require indirect methods for the measurement of skeletal blood flow. The results of one such method, compartmental analysis of skeletal tracer kinetics, are presented. The assumptions underlying the models were tested in animals and found to be in agreement with experimental observations. Based upon the models and the experimental results, inferences concerning bone-scan interpretation can be drawn: decreased cardiac output produces low-contrast (technically poor) scans; decreased skeletal flow produces photon-deficient lesions; increase of cardiac output or of generalized systemic blood flow is undetectable 1 to 2 h after dose; increased local skeletal blood flow results from disturbance of the bone microvasculature and can occur from neurologic (sympatholytic) disorders or in association with focal abnormalities that also incite the formation of reactive bone (e.g., metastasis, fracture, etc.). Mathematical solutions of tracer kinetic data thus become relevant to bone-scan interpretation

Design, synthesis, and evaluation of new organomedicinal radiopharmaceuticals. Progress report, March 1, 1981-February 28, 1982

International Nuclear Information System (INIS)

Hanson, R.N.

1982-01-01

The goal of this project is the development of radiopharmaceuticals which localize selectively in the normal myocardium and which can be used to assess myocardial perfusion and function with external detection systems. The availability of T1-201 as a myocardial imaging agent makes it possible to visualize compromised myocardium as an area of decreased radionuclide uptake. However, the long physical and biologic half-lives of this nuclide, as well as the low energy of its gamma emission and its cost, suggest a need to develop radiodiagnostic agents which have a similar myocardial distribution but employ a less expensive radioisotope with better decay properties. An approach developed in this proposal involves the use of cardioselective sympatholytic agents into which a suitable radionuclide can be incorporated. The two types of compounds to be investigated are the beta adrenoceptor antagonists and the catecholamine depleting agents. The radiolabeled products will be evaluated in normal and in experimentally infarcted animals, and their pharmacokinetics compared with those of T1-201. The most promising radiopharmaceuticals will subsequently be tested in larger animals having myocardial pathology

Posttraumatic stress disorder and anesthesia emergence.

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Lovestrand, Donnamarie; Phipps, Steven; Lovestrand, Steven

2013-06-01

Emergence agitation or delirium is a known phenomenon in the postanesthesia period. The underlying cause is not definitively understood. In a U.S. Army hospital's postanesthesia care unit, combat-related posttraumatic stress disorder (PTSD) can complicate interventions. Scant evidence-based research exists on the issue. By presenting case studies of 2 patients who underwent different surgical procedures, the authors argue that traditional modalities to reorient and calm patients experiencing emergence agitation who have PTSD are not shown to be effective. The first procedure demonstrates outcomes in a situation handled through traditional interventions. The second procedure demonstrates outcomes after incorporation of evidence-driven interventions. The authors conclude that best practice includes a proper identification of patients at risk of emergence agitation, a minimally stimulating environment, intraoperative sympatholytic therapy, and patient and staff education. Although the case studies presented support these principles, research is needed to provide stronger evidence. Military medical and research personnel can take the lead on this issue and be a source for improved outcomes and high-quality patient care.

Massage therapy: understanding the mechanisms of action on blood pressure. A scoping review.

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Nelson, Nicole L

2015-10-01

Massage therapy (MT) has shown potential in reducing blood pressure (BP); however, the psychophysiological pathways and structures involved in this outcome are unclear. The aims of this scoping review were twofold. (1) To summarize the current knowledge of the mechanisms of action of MT on BP. (2) To highlight the research gaps and challenges that researchers must overcome to further elucidate how MT attenuates BP. A scoping review was conducted to examine the evidence regarding the mechanisms of action of MT on BP. This review included the thematic analysis of 27 publications that considered the influence of MT on BP. Based on this analysis, six potential BP mediating pathways were identified Current theories suggest that MT exerts sympatholytic effects through physiologic and psychological mechanisms, improves hypothalamus-pituitary-adrenocortical axis function, and increases in blood flow, which, in turn, may improve endothelial function. Future study is needed, using more scientifically rigorous methodology, to fully elucidate the mechanism of action of MT. Copyright © 2015 American Society of Hypertension. Published by Elsevier Inc. All rights reserved.

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

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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.

Effect of Dexmedetomidine on Intraoperative Haemodynamics and Postoperative Analgesia in Laparoscopic Cholecystectomy

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Yojan Trikhatri

2018-03-01

Full Text Available Background and objectives:Dexmedetomidine is an α2 agonist with sympatholytic, anxiolytic, sedative and analgesic effect used as adjunct during surgeries for its haemodynamic stabilizing effect and analgesic effect. Primary aims of the study were to evaluate the haemodynamic effect of intravenous dexmedetomidine and the duration and quality of analgesia in laparoscopic cholecystectomy. Secondary aims were sedation levels and occurrence of side effects.Materials and methods:Eighty four patients, American society of Anaesthesiologists physical status I and II, aged 18-60 years of either gender undergoing laparoscopic cholecystectomy in general anaesthesia were randomly allocated into two equal groups. Group C patient received Normal Saline and Group S patient received dexmedetomidine loading dose infusion of 1µg/kg over 10 minutes before induction and maintained with 0.4µg/kg/hr till the removal of gall bladder. Induction with propofol and fentanyl was done. Standard monitoring including Heart Rate, Mean arterial pressure, oxygen saturation were monitored perioperatively. Postoperative analgesia requirement and sedation score were assessed.Results: In Group S, the haemodynamic responses were significantly attenuated. During postoperative period, 24 hours analgesic requirement of diclofenac sodium was 141.43mg in group S as compared to 217.50mg in group C(p<0.001. Side effects were treatable. Sedation was better in Group S.Conclusion:Dexmedetomidine effectively attenuates haemodynamic stress response during laparoscopic surgery with reduction in postoperative analgesic requirements.

Actions of rilmenidine on neurogenic hypertension in BPH/2J genetically hypertensive mice.

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Jackson, Kristy L; Palma-Rigo, Kesia; Nguyen-Huu, Thu-Phuc; Davern, Pamela J; Head, Geoffrey A

2014-03-01

BPH/2J hypertensive mice have an exaggerated sympathetic contribution to blood pressure (BP). Premotor sympathetic neurons within the rostroventrolateral medulla (RVLM) are a major source of sympathetic vasomotor tone and major site of action of the centrally acting sympatholytic agent, rilmenidine. The relative cardiovascular effect of rilmenidine in BPH/2J versus normotensive BPN/3J mice was used as an indicator of the involvement of the RVLM in the sympathetic contribution to hypertension in BPH/2J mice. BPH/2J and BPN/3J mice were pre-implanted with telemetry devices to measure BP in conscious unrestrained mice. Rilmenidine was administered acutely (n=7-9/group), orally for 14 days, at a wide range of doses (n=5/group), and also infused intracerebroventricularly for 7 days (n=6/group). Acute intraperitoneal rilmenidine induced greater depressor and bradycardic responses in BPH/2J than BPN/3J mice (PstrainBPH/2J mice during the dark (active) period (-6.5 ± 2 mmHg; P=0.006). Chronic orally administered rilmenidine (1-12 mg/kg per day) also had minimal effect on 24-h BP in both strains (P>0.16). The sympathetic vasomotor inhibitory effect of rilmenidine is minimal in both strains and similar in hypertensive BPH/2J and BPN/3J mice. Thus, hypertension in BPH/2J mice is not likely mediated by greater neuronal activity in the RVLM, and agents such as rilmenidine would be an ineffective treatment for this form of neurogenic hypertension.

Moxonidine-induced central sympathoinhibition improves prognosis in rats with hypertensive heart failure.

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Honda, Nobuhiro; Hirooka, Yoshitaka; Ito, Koji; Matsukawa, Ryuichi; Shinohara, Keisuke; Kishi, Takuya; Yasukawa, Keiji; Utsumi, Hideo; Sunagawa, Kenji

2013-11-01

Enhanced central sympathetic outflow is an indicator of the prognosis of heart failure. Although the central sympatholytic drug moxonidine is an established therapeutic strategy for hypertension, its benefits for hypertensive heart failure are poorly understood. In the present study, we investigated the effects of central sympathoinhibition by intracerebral infusion of moxonidine on survival in a rat model of hypertensive heart failure and the possible mechanisms involved. As a model of hypertensive heart failure, we fed Dahl salt-sensitive rats an 8% NaCl diet from 7 weeks of age. Intracerebroventricular (ICV) infusion of moxonidine (moxonidine-ICV-treated group [Mox-ICV]) or vehicle (vehicle-ICV-treated group [Veh-ICV]) was performed at 14-20 weeks of age, during the increased heart failure phase. Survival rates were examined, and sympathetic activity, left ventricular function and remodelling, and brain oxidative stress were measured. Hypertension and left ventricular hypertrophy were established by 13 weeks of age. At around 20 weeks of age, Veh-ICV rats exhibited overt heart failure concomitant with increased urinary norepinephrine (uNE) excretion as an index of sympathetic activity, dilated left ventricle, decreased percentage fractional shortening, and myocardial fibrosis. Survival rates at 21 weeks of age (n = 28) were only 23% in Veh-ICV rats, and 76% (n = 17) in Mox-ICV rats with concomitant decreases in uNE, myocardial fibrosis, collagen type I/III ratio, brain oxidative stress, and suppressed left ventricular dysfunction. Moxonidine-induced central sympathoinhibition attenuated brain oxidative stress, prevented cardiac dysfunction and remodelling, and improved the prognosis in rats with hypertensive heart failure. Central sympathoinhibition can be effective for the treatment of hypertensive heart failure.

Alpha-2A Adrenoceptor Agonist Guanfacine Restores Diuretic Efficiency in Experimental Cirrhotic Ascites: Comparison with Clonidine.

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Giovanni Sansoè

Full Text Available In human cirrhosis, adrenergic hyperfunction causes proximal tubular fluid retention and contributes to diuretic-resistant ascites, and clonidine, a sympatholytic drug, improves natriuresis in difficult-to-treat ascites.To compare clonidine (aspecific α2-adrenoceptor agonist to SSP-002021R (prodrug of guanfacine, specific α2A-receptor agonist, both associated with diuretics, in experimental cirrhotic ascites.Six groups of 12 rats were studied: controls (G1; controls receiving furosemide and potassium canrenoate (G2; rats with ascitic cirrhosis due to 14-week CCl4 treatment (G3; cirrhotic rats treated (over the 11th-14th CCl4 weeks with furosemide and canrenoate (G4, furosemide, canrenoate and clonidine (G5, or diuretics and SSP002021R (G6. Three rats of each group had their hormonal status and renal function assessed at the end of 11th, 12th, 13th, and 14th weeks of respective treatments.Cirrhotic rats in G3 and G4 gained weight over the 12th-14th CCl4 weeks. In G4, brief increase in sodium excretion over the 11th-12th weeks preceded worsening of inulin clearance and natriuresis (diuretic resistance. In comparison with G4, the addition of clonidine (G5 or guanfacine (G6 to diuretics improved, respectively, sodium excretion over the 11th-12th CCl4 weeks, or GFR and electrolytes excretion over the 13th-14th CCl4 weeks. Natriuretic responses in G5 and G6 were accompanied by reduced catecholamine serum levels.α2A-receptor agonists restore glomerular filtration rate and natriuresis, and delay diuretic-resistant ascites in experimental advanced cirrhosis. Clonidine ameliorates diuretic-dependent natriuresis just for a short time.

Raynaud’s phenomenon

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F. Ingegnoli

2011-09-01

Full Text Available Raynaud’s phenomenon (RP is a vasospastic disorder characterized by episodic color changes of blanching, cyanosis, and hyperemia in response to cold and/or emotional stress. Although most typically noted in the fingers, the circulation of the toes, ears, nose and tongue is also frequently affected. Population studies have shown that RP in adults is more common in women than men, with prevalence estimates ranging from 4% to 30%. Geographic variations in the prevalence reflect differences in climate. RP may be a primary or a secondary process. LeRoy and Medsger suggested criteria for primary RP: symmetric attacks, the absence of tissue necrosis, ulceration or gangrene, the absence of a secondary cause, negative antinuclear antibodies, normal nailfold capillaroscopy and a normal erythrocyte sedimentation rate. Secondary RP is characterized by an age of onset of more than 30 years, painful and asymmetric attacks, ischemic skin lesions, positive autoautoantibodies, capillaroscopic abnormalities and/or clinical features suggestive of connective tissue diseases (CTDs. Among the CTDs, systemic sclerosis has the highest frequency of RP. Finding a cause for RP requires a knowledge of the patient’s occupational, smoking, drug history, physical examination, nailfold capillaroscopy, routine laboratory tests and autoantibodies. Furthermore, RP should be distinguished from acrocyanosis, a condition characterized by continuous cyanosis of the hands or feet that is aggravated by cold temperature. The most important instruction to the patient is abstinence from any smoking, offending drugs should be discontinued, and abrupt changes in temperature. If these measures are inadequate, calcium-channel blockers are the most widely used (nifedipine 30 mg up to 90 mg daily. Alternatively, sympatholytic agent (prazosin, angiotensin II -receptor type I antagonist (losartan, selective sertonin-reuptake inhibitor (fluoxetine may be useful. In the severe cases the role of