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

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.

Renal sympathetic denervation in therapy resistant hypertension-pathophysiological aspects and predictors for treatment success

Many forms of human hypertension are associated with an increased systemic sympathetic activity. Especially the renal sympathetic nervous system has been found to play a prominent role in this context. Therefore, catheterinterventional renal sympathetic denervation(RDN) has been established as a treatment for patients suffering from therapy resistant hypertension in the past decade. The initial enthusiasm for this treatment was markedly dampened by the results of the Symplicity-HTN-3 trial, although the transferability of the results into clinical practice to date appears to be questionable. In contrast to the extensive use of RDN in treating hypertensive patients within or without clinical trial settings over the past years, its effects on the complex pathophysiological mechanisms underlying therapy resistant hypertension are only partly understood and are part of ongoing research. Effects of RDN have been described on many levels in human trials: From altered systemic sympathetic activity across cardiac and metabolic alterations down to changes in renal function. Most of these changes could sustainably change long-term morbidity and mortality of the treated patients, even if blood pressure remains unchanged. Furthermore, a number of promising predictors for a successful treatment with RDN have been identified recently and further trials are ongoing. This will certainly help to improve the preselection of potential candidates for RDN and thereby optimize treatment outcomes. This review summarizes important pathophysiologic effects of renal denervation and illustrates the currently known predictors for therapy success.

Renal sympathetic denervation in resistant hypertension

Resistant hypertension remains a major clinical problem despite the available multidrug therapy.Over the next decades,its incidence will likely increase given that it is strongly associated with older age and obesity.Resistant hypertension patients have an increased cardiovascular risk,thus effective antihypertensive treatment will provide substantial health benefits.The crosstalk between sympathetic nervous system and kidneys plays a crucial role in hypertension.It influences several pathophysiological mechanisms such as the central sympathetic tone,the sodium balance and the systemic neurohumoral activation.In fact,studies using several animal models demonstrated that the renal denervation prevented and attenuated hypertension in multiple species.Large reductions in blood pressure were also observed in malignant hypertension patients submitted to sympathectomy surgeries.However,these approaches had an unacceptably high rates of periprocedural complications and disabling adverse events.Recently,an innovative non-pharmacological therapy that modulates sympathetic activation has been successfully developed.Renal sympathetic percutaneous denervation is an endovascular procedure that uses radiofrequency energy to destroy the autonomic renal nerves running inside the adventitia of renal arteries.This method represents a promising new approach to the strategy of inhibiting the sympathetic nervous system.The aim of this review is to examine the background knowledge that resulted in the development of this hypertension treatment and to critically appraise the available clinical evidence.

The Effect of Renal Sympathetic Denervation (RSD) in Atrial Fibrillation (AF) Inducibility

Objective: The purpose of this study is to investigate the effects of renal sympathetic nerve stimulation (RSN-S) and ablation (RSN-A) on atrial effective refractory period (ERP) and AF in normal canine heart. Atrial Fibrillation (AF) is a complex disease and one of the most frequent arrhythmias, especially in elderly patients. Multiple mechanisms are involved including interaction between the autonomic nervous system (ANS), electrophysiological properties of the atria, and vulnerability for AF. Cardiac overload increases the incidence of AF. In lone AF the triggers are in the pulmonary veins. AF caused by underlying disease has different mechanism. Atrial fibrillation (AF) is associated with activity of renin-angiotensin-aldosterone system (RAAS). Reduction in renal nor-adrenaline spillover could be achieved after renal sympathetic denervation (RSD). Methods: 1) Establish of atrial fibrillation model;2) Ventricular rate analysis of AF;3) Statistical analysis. Results: 1) The establishment of atrial fibrillation model;2) Inducibility and duration of AF;3) The changes of AERP dispersion. Conclusion: Left RSN-S shortened left atrial ERP, increased ERP dispersion, but did not change right atrial ERP. Bilateral RSN-A produced significant prolongation in both atrial ERP, but did not affect ERP dispersion. The on time of RD effect is at 4 hrs after RD procedure and the RD effect on AF will last for 20 hrs after RD procedure.

Renal artery denervation suppresses intractable ventricular arrhythmia in patients with left heart thrombosis

Transcutaneous renal artery denervation （RND） has beeninitially developed for destruction of efferent nerve fireswith luminal delivery of radiofrequency or ultrasonic energyaiming blood pressure reduction in patients with refractoryhypertension. However, other positive results of RNDwere described afterwards, and they include suppression ofatrial fibrillation and ventricular tachycardia （VT） storm.

Computed tomography-guided chemical renal sympathetic nerve modulation in the treatment of resistant hypertension: A case report

BACKGROUND Resistant hypertension(RH)has always been a difficult problem in clinical diagnosis and treatment.At present,there is no recognized safe and effective minimally invasive treatment.CASE SUMMARY An 80-year-old woman was admitted to hospital due to trigeminal neuralgia(TN).The patient had a history of RH for more than 10 years and her blood pressure(BP)was not well-controlled.Before the treatment for TN,we decided to perform chemical renal sympathetic denervation with ethanol in the Pain Department of our hospital.One year after the operation,she stopped taking antihypertensive drugs,and her BP was satisfactorily controlled within 4 years after surgery.CONCLUSION Computed tomography-guided chemical renal sympathetic modulation may be a feasible method for the treatment of RH.

Comparison of a 5 F Microtube-Irrigated Ablation Catheter and a General Ablation Catheter in the Treatment of Resistant Hypertension with Renal Denervation

Objective:To assess the effectiveness of catheter-based renal denervation for reducing blood pressure in patients with resistant hypertension using a 5 F microtube-irrigated ablation catheter.Methods:Sixty patients with resistant hypertension were divided into two groups:a microtube-irrigated ablation catheter group and a general ablation catheter group.We conducted 12-month follow-up of all patients and recorded clinical blood pressure,ambulatory blood pressure,medication use,and biochemistry test results in both groups at the baseline and at the 12-month follow-up.Results:All patients underwent renal denervation.At the 6-month follow-up,ambulatory blood pressure in the mi-crotube-irrigated ablation catheter group was signifi cantly lower than in the general ablation catheter group(systolic blood pressure 142.0±14.4 mmHg vs.150.8±17.9 mmHg,P=0.04;diastolic blood pressure 81.2±7.0 mmHg vs.87.6±8.0 mmHg,P=0.002).At the 12-month follow-up,the between-group difference in ambulatory blood pressure was not statistically signifi cant.At the 12-month follow-up,the number of antihypertensive drugs and diuretics used in the microtube-irrigated ablation catheter group was less than in the general ablation catheter group(P=0.043).There was no statistical difference between the two groups in the results of biochemistry tests and echocardiography.Conclusion:The microtube-irrigated ablation catheter is more effective in treating hypertension than the general ablation catheter at the 6-month follow up and thus fewer antihypertensive drugs were used in the microtube-irrigated ablation catheter group than in the general ablation catheter group.

Main Renal Artery Plus Branch Ablation in the Treatment of Resistant Hypertension with Renal Denervation

Objective:To study the safety and effi cacy of denervation of renal artery branches in the treatment of resistant hy-pertension.Methods:Sixty patients with resistant hypertension were enrolled.The patients were randomly assigned to the main renal artery plus branch ablation group or the main renal artery ablation group.The clinical data and operation-related parameters,including number of ablation points,temperature,and average energy,were recorded.Ambulatory blood pressure was taken for all patients at the baseline and at 6 months after treatment.Offi ce blood pressure was recorded before treatment and after treatment every 3 months for 2 years.Results:Sixty patients with resistant hypertension were enrolled in this study.There were 30 patients in each group.Angiography was performed after ablation.No renal artery complications,such as stenosis and dissection,occurred in the two groups.There was no signifi cant difference in age,sex,BMI,comorbid disease,and medication between the two groups(P>0.05).The number of ablation points for the main renal artery plus branch ablation group was greater than that for the main renal artery ablation group.The offi ce blood pressure and 24-hour blood pressure were signifi cantly lower 6 months after treatment than before treatment in both groups(P<0.05).Offi ce blood pressure in the main renal artery plus branch ablation group was lower than that in the main renal artery ablation group during the 3-12-month follow-up period,with a statistical difference.However,as the follow-up time increased,the difference disappeared.Conclusion:The results of this study show that main renal artery plus branch ablation is a safe interventional method,but there was no obvious advantage on long-term follow-up compared with only main renal artery ablation.

经皮去肾神经术:最新证据与患者筛选

尽管有许多药物和非药物治疗可降低血压,但难治性高血压仍是一个重要的健康问题。经皮去肾神经术(RDN)已成为有发展前景、临床证据最多的用于改善血压、提高血压控制率的器械治疗方法。现总结目前RDN治疗高血压的机制,同时总结关于RDN的多项随机假手术对照的临床研究和优化患者选择。

肾动脉去交感神经消融术在高血压治疗中的评价

全球约有12.8亿的高血压患者,在成年人口中约1/3患有高血压,目前我国30~79岁人群中高血压的患病人数为2.57亿^([1])。《中国心血管健康与疾病报告2021》指出,我国25~45岁居民血压正常高值的检出粗率已经高达42.9%~45.5%^([2])。近年多项研究证实,进一步将目标血压降至130/80mm Hg,可以使患者进一步获益。然而,与之形成鲜明对比的是,全球平均高血压控制率仅在13.8%,我国高血压控制率约在16.8%。因此,进一步丰富降压药物与手段,优化血管管理策略,是目前的临床需求。高血压治疗长期以来是“二驾马车”,即生活方式干预和药物治疗,但研究发现,我国高血压药物治疗的依从性一直不容乐观,仅44.8%的高血压患者能坚持每月就诊1次,63.9%能在家中自测血压,而50%在1年内停用降压药物,12.4%每周漏服降压药物≥1次。

肾神经消融术治疗高血压的病理生理学基础和临床研究进展

高血压是严重危害人类健康的慢性心血管疾病,尽管有多种治疗药物,但大多数患者的血压仍未达到指南推荐的理想水平。交感神经过度激活在高血压发病中起重要作用,肾动脉交感神经消融术通过使用导管消融技术去除肾神经包括肾交感传出神经和传入神经,从而降低交感神经活动,成为高血压重要的补充和非药物治疗方法,特别是用于顽固性高血压的治疗。临床研究显示了肾动脉交感神经消融术的安全性和有效性,可以降低顽固性高血压患者的动脉血压、改善高血压预后。

经皮去肾神经术治疗高血压的临床获益:证据和争议

高血压是全球心血管疾病发病率和死亡率增加重要的可改变的危险因素之一。尽管目前有多种药物治疗和非药物治疗方法,高血压的控制率仍较低。经皮去肾神经术是一种微创介入手术,其作为一种新兴的高血压治疗方法备受关注,十余年来开展了一系列的临床研究。现总结当前经皮去肾神经术治疗高血压临床获益的证据和争议,旨在指导临床实践并推动相关研究的进展。

Renal sympathetic denervation reduces left ventricular hypertrophy and improves cardiac function in patients with resistant hypertension

This study investigated the effect of catheter-based renal sympathetic denervation （RD） on left ventricular hypertrophy （LVH） and systolic and diastolic function in patients with resistant hypertension. LVH and diastolic dysfunction are associated with elevated sympathetic activity and increased morbidity and mortality. The effect of RD on LVH and LV function is unclear

Catheter-based renal denervation： treating hypertension or beyond？

The sympathetic nervous system regulates cardiac output,blood pressure(BP)and volume,electrolyte balance,and the composition of body fluids.The afferent nervous signals to the brain are regulated by mechano-sensitive

Short-term Safety and Efficiency of Cryoablation for Rena Sympathetic Denervation in a Swine Model

Background:Renal sympathetic nerves are involved in the reflective activation of the sympathetic nervous system in circulatory control.Catheter-based renal denervation (RDN) ameliorated treatment-resistant hypertension safely,but 10％-20％ of treated patients are nonresponders to radiofrequency denervation.The purpose of this study was to investigate the safety and efficiency of cryoablation for sympathetic denervation in a swine model and to explore a new way of RDN.Methods:Seven swines randomly assigned to two groups:Renal cryoablation (CR) group and control group.The control group underwent renal angiogram only.The CR group underwent renal angiogram plus bilateral renal cryoablation.Renal angiograms via femoral were performed before denervation,after denervation and prior to the sacrifice to access the diameter of renal arterial and the pressure of aorta abdominalis.Euthanasia of the swine was performed on 28-day to access norepinephrine (NE) changes of the renal cortex and the changes of renal nerves.Results:Cryoablation did not induce severe complications at any time point.There was no significant change in diameter of renal artery.CR reduced systolic blood pressure (BP) from 145.50 ± 9.95 mmHg at baseline to 119.00 ± 14.09 mmHg.There was a slight but insignificant decrease in diastolic BP.The main nerve changes at 28-day consisted of necrosis with perineurial fibrosis at the site of CR exposure in conjunction with the nerve vacuolation.Compared with the control group,renal tissue NE of CR group decreased by 89.85％.Conclusions:Percutaneous catheter-based cryoablation of the renal artery is safe.CR could effectively reduce NE storing in the renal cortex,and the efficiency could be maintained 28-day at least.

经皮去肾神经术治疗高血压中国专家科学声明

高血压是心脑血管疾病最主要的危险因素之一。虽然改善生活方式和药物治疗是有效的降压方式,但是高血压的控制率依然很低。经皮去肾神经术(RDN)治疗已经成为有发展前景、临床证据最多的器械治疗改善血压、提高血压控制率的方法。多项随机、假手术对照的临床研究表明RDN可以持久、有效降压,且安全性良好。RDN治疗高血压中国专家科学声明旨在介绍RDN目前国内外的临床证据、治疗进展,阐述对RDN治疗高血压的观点和目前的应用建议,希望借此指导在中国健康、有序、安全和规范地开展RDN治疗高血压的临床实践。

交感神经激活在自体动静脉内瘘新生内膜增生中的作用

自体动静脉内瘘(arteriovenous fistula,AVF)是血液透析治疗最常用的血管通路。然而,AVF失功问题严重制约着其临床应用,静脉流出道狭窄是AVF失功的常见原因,其病理基础是新生内膜增生(neointimal hyperplasia,NIH)。NIH的发生发展与血管内病理机制有关,包括炎症、氧化应激等一系列级联反应和血管重塑,导致血管狭窄、失功。终末期肾病患者存在交感神经的过度激活,而交感神经的激活可能通过不同的机制参与NIH的发生而导致AVF的失功。本综述重点阐述交感神经激活参与NIH发生发展的可能机制,旨在为AVF失功提供新的理论解释及其防治提供新的干预靶点。

基于自抗扰控制器的射频消融电极温度控制系统仿真研究

目的将自抗扰控制器(active disturbance rejection controller,ADRC)应用于射频电极并探讨温度控制效果。方法在MATLAB Simulink仿真平台,建立基于ADRC的射频电极温度控制系统,进行阶跃信号实验。加入幅值为2的阶跃信号扰动,以模拟不稳定的人体内环境。最后,将温度滞后时间τ、温度转换时间T和增益系数K值增加20%和50%,与同条件比例-积分-微分(proportion integration differentiation,PID)控制性能对比。结果(1)ADRC调节时间(15.38 s)较PID(18.68 s)短且超调为0。(2)τ与T值变化时,PID超调最大增量分别为3.55%和8.55%,但ADRC超调均为0;K值变化时,ADRC虽出现超调,但同参数下的超调均较PID小。(3)各种参数变化下,两者受干扰后均能在30 s内平稳快速达到设定值。结论ADRC控制技术在射频电极温度控制中显示超调小、稳定速度快、一定的抗干扰性及参数变化适应性,具有良好的调节能力。

肾去交感神经术治疗植入型心律转复除颤器植入术后电风暴的研究进展

植入型心律转复除颤器(ICD)能有效预防和治疗因恶性心律失常导致的心源性猝死。但ICD植入术后患者发生电风暴不可预料且极其危险,目前针对ICD植入术后电风暴的治疗方法效果欠佳。近几年肾去交感神经术(RDN)为ICD植入术后电风暴的预防和治疗提供了新的思路和方法,RDN这一新的治疗方法能降低整个机体交感神经系统活性、明显抑制和逆转心肌重构,对改善和治疗心律失常有积极的效果。现对RDN治疗ICD植入术后电风暴的研究进展做一综述。

Renal denervation： a new therapeutic approach for resistant hypertension

Objective To review the advances in studies on renal denervation. Data sources 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. Study selection Articles with keywords ＂renal denervation＂ and ＂resistant hypertension＂ were selected. Results 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 Conformite Europ6enne mark is also included in this review. Conclusions 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.