Radiofrequency Renal Denervation Research Articles

Safety of catheter-based radiofrequency renal denervation on branch renal arteries in a porcine model.

ObjectivesWe aimed to investigate the safety of radiofrequency (RF)‐renal denervation (RDN) on branch renal arteries (RAs) in a porcine model.BackgroundThe efficacy of RF‐RDN was enhanced by treatment of the branch RA, in addition to the main RA. However, there are concerns regarding the safety of RF‐RDN on branch RA because of their smaller diameter and proximity to the kidney.MethodsRF was delivered to 24 RA from 12 swine. A total of 8 RA from 4 swine were untreated. Treated RA were examined by angiography and histopathology at 7, 30, and 90 days. Serum creatinine concentration, biophysical parameters during RF delivery, and renal norepinephrine concentration were also assessed.ResultsAngiography revealed minimal late lumen loss and diameter stenosis in the main and branch RA at any time point. There was no change in serum creatinine after RF‐RDN. Histopathologically, no augmentation of medial damage or neointimal formation was found in branch RA compared with main RA. No or minimal damage to surrounding tissues including the kidneys, ureters, lymph nodes, and muscles was observed at any time point in both the main and branch RA. Equivalent electrode temperature in the main and branch RA was achieved by automatic adjustment of output power by the generator. The renal norepinephrine concentration was significantly lower in the treated group compared with the untreated group.ConclusionsRF‐RDN on branch RA was safe in a porcine model, with stenosis‐free healing of treated arteries and negligible kidney damage at 7, 30, and 90 days.

Renal Denervation Prevents Heart Failure Progression Via Inhibition of the Renin-Angiotensin System

BackgroundPreviously, we have shown that radiofrequency (RF) renal denervation (RDN) reduces myocardial infarct size in a rat model of acute myocardial infarction (MI) and improves left ventricular (LV) function and vascular reactivity in the setting of heart failure following MI. ObjectivesThe authors investigated the therapeutic efficacy of RF-RDN in a clinically relevant normotensive swine model of heart failure with reduced ejection fraction (HFrEF). MethodsYucatan miniswine underwent 75 min of left anterior descending coronary artery balloon occlusion to induce MI followed by reperfusion (R) for 18 weeks. Cardiac function was assessed pre- and post-MI/R by transthoracic echocardiography and every 3 weeks for 18 weeks. HFrEF was classified by an LV ejection fraction <40%. Animals who met inclusion criteria were randomized to receive bilateral RF-RDN (n = 10) treatment or sham-RDN (n = 11) at 6 weeks post-MI/R using an RF-RDN catheter. ResultsRF-RDN therapy resulted in significant reductions in renal norepinephrine content and circulating angiotensin I and II. RF-RDN significantly increased circulating B-type natriuretic peptide levels. Following RF-RDN, LV end-systolic volume was significantly reduced when compared with sham-treated animals, leading to a marked and sustained improvement in LV ejection fraction. Furthermore, RF-RDN improved LV longitudinal strain. Simultaneously, RF-RDN reduced LV fibrosis and improved coronary artery responses to vasodilators. ConclusionsRF-RDN provides a novel therapeutic strategy to reduce renal sympathetic activity, inhibit the renin-angiotensin system, increase circulating B-type natriuretic peptide levels, attenuate LV fibrosis, and improve left ventricular performance and coronary vascular function. These cardioprotective mechanisms synergize to halt the progression of HFrEF following MI/R in a clinically relevant model system.

Valoración de la variabilidad de la frecuencia cardiaca en pacientes con hipertensión arterial sistémica tratados mediante ablación renal por radiofrecuencia. Serie de casos

Introduction: Refractory systemic arterial hypertension is the blood pressure above the appropriate goal despite the use of three or more antihypertensive drugs, one of which is a diuretic; renal denervation by radiofrequency ablation, is a treatment for this condition, which is effective and safe. We consider that denervation decreases the tone of the autonomic nervous system at the renal level (renin angiotensin aldosterone axis), so that the result will be a decrease in blood pressure without affecting the variability of the heart rate. Objective: To determine if there is a change in the variability of heart rate in patients with refractory systemic arterial hypertension who are treated by radiofrequency renal denervation with catheter. Material and methods: Observational, descriptive and analytical study of patients with refractory systemic arterial hypertension who were treated by radiofrequency renal ablation with catheter. The variability of the heart rate in the temporal and frequency domain was measured before and two months after the procedure. The statistical analysis of results was by Student’s t-test for related samples. Results: Nine patients were eligible, only six patients with refractory systemic arterial hypertension treated by radiofrequency renal ablation were included, in the domain temporal domain for the standard deviation of the NN intervals (SDNN), a statistically nonsignificant increase was observed (7 ms, p = 0.58). Conclusion: In the six patients with refractory systemic arterial hypertension treated by radiofrequency renal ablation, it was observed two months after the procedure, that the variability of the heart rate in the time domain for the standard deviation of the NN intervals (SDNN), it increased 7 ms, being statistically non-significant (p = 0.58).

P5369The effect of a hypotensive challenge before and after catheter-based radio-frequency renal nerve denervation in obese hypertensive swine model

P5369The effect of a hypotensive challenge before and after catheter-based radio-frequency renal nerve denervation in obese hypertensive swine model

Procedural and anatomical predictors of renal denervation efficacy using two radiofrequency renal denervation catheters in a porcine model

Introduction:Several renal denervation (RDN) systems are currently under investigation for treatment of hypertension by ablation of renal sympathetic nerves. The procedural efficacy of devices, however, is variable and incompletely understood. This study aimed at investigating procedural and anatomical predictors of RDN efficacy by comparing two radiofrequency catheter systems in a porcine model.Methods:Domestic swine were assigned into two treatment groups (n = 10) and one sham group (n = 3). Bilateral RDN in main and in branch segments of renal arteries was performed using two different multielectrode catheter systems [Symplicity Spyral (SPY) and IberisBloom (IBB)]. After 7 days, measurement of norepinephrine (NEPI) tissue concentrations and histological analyses have been performed.Results:Renal NEPI tissue concentration following RDN was significantly reduced when compared with Sham (SPY: −95 ± 3% vs. Sham, P < 0.001; IBB: −88 ± 11% vs. Sham, P < 0.001). Histological evaluation showed comparable lesion depth and lesion area (lesion depth: SPY-main 6.26 ± 1.62 mm vs. SPY-branch 3.49 ± 1.11 mm; IBB-main 5.93 ± 1.88 mm vs. IBB-branch: 3.26 ± 1.26 mm, P < 0.001; lesion area: SPY-main 43.5 ± 29.5 mm2 vs. SYP-branch 45.0 ± 38.0 mm2; IBB-main 52.3 ± 34.8 mm2 vs. IBB-branch 44.0 ± 42.6 mm2, P = 0.77; intergroup SPY vs. IBB, P = 0.73). Histological investigations documented a significant correlation between number of ablations per millimeter length of renal artery and reduction in NEPI tissue concentration.Conclusion:The two devices under investigation demonstrated similar histopathological lesion characteristics and similar reduction of renal NEPI levels. An increase in number of ablations per millmeter length of renal artery resulted in improved efficacy and reduced variability in treatment effects.

2267 Radiofrequency renal denervation attenuates kidney fibrosis in spontaneously hypertensive rats

OBJECTIVES/SPECIFIC AIMS: The goal of this study was to investigate whether RF-RDN attenuates renal fibrosis and inflammation in SHR with established hypertension. METHODS/STUDY POPULATION: Twenty-two-week-old SHR received bilateral RF-RDN or Sham-RDN (Biosense Webster Stockert 70 generator and RF-probe). Four weeks later, SHR were sacrificed and paraffin sections of kidneys were stained for fibrosis by Masson’s trichrome staining. Kidney tissue were homogenized for measurement of cytokines levels by ELISA. RESULTS/ANTICIPATED RESULTS: The results showed that Sham-RDN treated SHR had extensive fibrosis as demonstrated by moderate thickening of Bowman’s capsule, collagen deposition in glomerulus, extensive tubulointerstitial fibrosis, and segmental glomerulosclerosis. In contrast, RF-RDN significantly reduced each of these pathological components of fibrosis in kidney cortex and medulla as compared with Sham-RDN treated kidneys. In other studies, RF-RDN decreased B cells, CD4+ T cells, and CD8+ T cells in the kidney of SHR as measured by flow cytometry. Meanwhile, kidney tissue levels of IL-17, INF-γ, MIP-3a, TNF-α, and TGF-β were decreased as compared with respective levels in Sham-RDN. DISCUSSION/SIGNIFICANCE OF IMPACT: Together, these findings demonstrate that removal of the influence of heightened renal sympathetic activity by RF-RDN decreases kidney inflammatory markers and attenuates renal fibrosis in hypertensive SHR.

Blood Pressure and Renal Responses to Orthostatic Stress Before and After Radiofrequency Renal Denervation in Patients with Resistant Hypertension.

Background/AimsIn patients with resistant hypertension, renal denervation (RDN) studies have mainly focused their outcomes on blood pressure (BP). The aim of this study was to evaluate the long-term effect of RDN on neurohormonal profiles, renal hemodynamics and sodium excretion in a resting state and during stress induced by lower body negative pressure (LBNP).Materials and methodsThis was a single center prospective observational study. Norepinephrine, plasma renin activity (PRA), glomerular filtration rate (GFR), renal plasma flow (RPF) and sodium excretion were measured in unstimulated conditions (rest) and after one hour of LBNP at three different time points: before (M0), one (M1) and twelve months (M12) after RDN.ResultsThirteen patients with resistant hypertension were included. In the resting state, no differences were observed in norepinephrine, PRA, sodium excretion and mean BP levels after RDN. GFR (78 ± 32 ml/min at M0 vs 66 ± 26 ml/min at M12 (p = 0.012) and filtration fraction (22.6 ±5.4% at M0 vs 15.1 ±5.3% at M12 (p = 0.002)) both decreased after RDN. During LBNP, the magnitude of the mean BP increase was reduced from +6.8 ± 6.6 mm Hg at M0 to +2.3 ± 1.3 mm Hg at M12 (p = 0.005). The LBNP-induced increase in norepinephrine and decrease in GFR and sodium excretion observed before RDN were blunted after the procedure.ConclusionA decrease in GFR and filtration fraction was observed one year after RDN. In addition, our results suggest that RDN blunts not only the norepinephrine but also the mean BP, the GFR and the sodium excretion responses to an orthostatic stress one year after the intervention.Registry numberNCT01734096

Radiofrequency Renal Denervation Decreases Fibrosis in Kidney Cortex and Medulla in Spontaneously Hypertensive Rats (SHR)

There are over 8.3 million people in the US that have chronic kidney disease (CKD), which ultimately can progress to end stage renal fibrosis. Despite an increasing prevalence of CKD, there are no new therapies targeting fibrosis. Our previous studies showed that removal of the renal nerves by radiofrequency renal denervation (RF‐RDN) decreases blood pressure, sympathetic activity, and renal inflammation in hypertensive SHR. Renal fibrosis is a common consequence of chronic kidney inflammation. Therefore, these studies investigated whether RF‐RDN will attenuate renal fibrosis in hypertensive SHR. 22‐week old SHR (n=7/group) received bilateral RF‐RDN or Sham‐RDN (Biosense Webster Stockert 70 generator and RF‐probe). Four weeks later, rat kidneys from all animals were harvested and paraffin sections were stained for fibrosis by Masson's trichrome staining. A pathologist, who was blinded to treatment groups, evaluated each kidney section for fibrosis. The results showed that Sham‐RDN treated SHR had extensive fibrosis demonstrated by moderate thickening of Bowman's capsule, collagen deposition in glomerulus, extensive tubulointerstitial fibrosis, and segmental glomerulosclerosis. In contrast, RF‐RDN significantly reduced each of these pathological components of fibrosis in kidney cortex and medulla. Chemokines play a critical role in mediating the infiltration of immune cells and subsequent fibrosis formation. Therefore, in other studies we measured (ELISA) expression levels of Chemokine ligand 5 (CCL5), CCL2 and CXCL16 in kidney homogenates from RF‐RDN or Sham‐RDN SHR. RF‐RDN decreased CCL5 expression in kidney of SHR compared to Sham‐RDN (78.9±1.7 vs 87.9±2.7 pg/mg protein). RF‐RDN did not alter CCL5 expression in normotensive WKY (68.0±2.2 vs 68.4±3.3 pg/mg protein). These findings suggest that RF‐RDN may offer a novel therapy for renal fibrosis and CCL5 may serve as a potential therapeutic target to treat CKD.Support or Funding InformationNIGMS of NIH U54 GM104940 LA CaTS Roadmap Scholar to JG. NIH P30GM106392 to DRK &amp; Pilot project to JG.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

The place of intervention methods of treatment of patients with resistant hypertension in clinical practice

Every year scientific interest in studying of interventional methods of treatment of resistant hypertension steadily increases. Row of high technology device are created for performance of such procedures as well as techniques of their management are also developed. Non-pharmacological ways of treatment are described in this article, which are widely used in clinical practice: baroreflex activation therapy, radiofrequency renal denervation, and central iliac arteriovenous anastomosis.

TRANSCATHETER MICROWAVE ABLATION CAN PRODUCE DEEP CIRCUMFERENTIAL PERIVASCULAR ABLATION AND EFFECTIVE RENAL DENERVATION WITHOUT SIGNIFICANT ARTERIAL INJURY

Radiofrequency renal denervation does not have consistent and durable efficacy. Microwave denervation may enable circumferential perivascular ablation while the renal arterial wall is protected by cooling blood flow. 9 sheep underwent unilateral renal denervation using a novel microwave catheter

CRT-200.22 Safety And Efficacy Of Renal Sympathetic Denervation Using Circumferential Ultrasound: 12-month Results of the ACHIEVE Study

The efficacy of first-generation radiofrequency renal denervation devices may have been limited due to incomplete circumferential denervation and dependence on individual operator technique. The Paradise Renal Denervation System (ReCor Medical, Palo Alto, CA) was designed to maximize nerve coverage

Denervação simpática renal por cateter com ponta irrigada: estudo de viabilidade

ABSTRACT Background: Catheter-based radiofrequency renal denervation has emerged as a promising tool for blood pressure control in patients with resistant hypertension. The aim of the present study was to evaluate the feasibility and safety of percutaneous renal sympathetic denervation by radiofrequency ablation using an irrigated-tip catheter in patients with true resistant hypertension. Methods: A saline-irrigated catheter was used for renal sympathetic denervation. The sample consisted of a consecutive series of 11 patients with resistant hypertension based on office blood pressure [...]

Radiofrequency Renal Denervation Decreases Renal Fibrosis in Spontaneously Hypertensive Rats (SHR)

Radiofrequency Renal Denervation Decreases Renal Fibrosis in Spontaneously Hypertensive Rats (SHR)

Renal Sympathetic Denervation Protects the Failing Heart Via Inhibition of Neprilysin Activity in the Kidney

BackgroundSustained sympathetic activation contributes to the progression of myocardial cell injury, cardiac fibrosis, and left ventricular (LV) dysfunction in heart failure (HF). ObjectivesThis study investigated the effects of radiofrequency renal nerve denervation (RF-RDN) on the pathobiology of HF and the interaction between the renal sympathetic nerves and natriuretic peptide (NP) metabolism. MethodsSpontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto rats (WKY) were subjected to 45 min of coronary artery ligation and reperfusion for 12 weeks. At 4 weeks post-reperfusion, SHR and WKY underwent either bilateral RF-RDN or sham-RDN. ResultsFollowing RF-RDN in both strains, LV ejection fraction remained significantly above those levels in respective sham-RDN rats, and at the end of the 12-week study, rats in both strains had significantly reduced LV fibrosis and improved vascular function. RF-RDN therapy significantly improved vascular reactivity to endothelium-dependent and -independent vasodilators as well as vascular compliance in the setting of severe HF. Improvements in LV function were accompanied by significant elevations in circulating NP as compared to those associated with sham-RDN. Further investigation into the cause of increased circulating NP levels demonstrated that RF-RDN significantly inhibited renal neprilysin activity in SHR and WKY with HF. Likewise, chronic treatment with the beta1 antagonist bisoprolol inhibited renal neprilysin activity and increased circulation NP levels in WKY with HF. ConclusionsThis study identifies a novel endogenous pathway by which the renal nerves participate in the degradation of cardioprotective NP. Furthermore, removal of the influence of the renal nerves on kidney function attenuates renal neprilysin activity, augments circulating NP levels, reduces myocardial fibrosis, and improves LV function in the setting of HF.

Changes in renal artery dimensions are associated with clinical response to radiofrequency renal denervation: a series of studies using quantitative angiography and intravascular ultrasound.

Renal denervation (RDN) can cause focal (notches) and global (spasms) changes in renal artery dimensions. We quantified these changes and related them to renal norepinephrin tissue content in animals and to blood pressure (BP) changes in patients. We measured renal artery dimensions pre-RDN and post-RDN, utilizing quantitative renal angiography (QRA) in a porcine model and in a retrospective patient cohort, and intravascular ultrasound (IVUS) in a prospective patient cohort. Focal and global measurements were minimum and mean diameter/area/volume with QRA, minimum lumen/vessel/wall area and volume with IVUS. BP was assessed with 24-h ambulatory monitoring, norepinephrin content with liquid chromatography. In 36 pigs treated unilaterally with RDN, norepinephrin content of the treated right kidney was 48.2% of the untreated left kidney. QRA measurements following RDN were associated with norepinephrin content only of the (treated) right kidney. In the human QRA study (n = 43 patients), mean 24-h BP fell by 8/4 and 12/6 mmHg at 1 and 12 months, respectively. More pronounced changes in QRA measurements were associated with a more pronounced BP drop. In multiple regression models, the change in minimum diameter was independently associated with BP changes at 12 months. In the prospective IVUS study (n = 17 patients), a larger decrease in minimum lumen/vessel area and larger increase of wall area/volume were associated with a larger BP drop. Focal and global changes in renal arteries following RDN can be quantified, using QRA or IVUS, and may serve as markers of a successful procedure.

PP.25.28] RENALASE PLASMA CONCENTRATION BEFORE AND AFTER RADIOFREQUENCY RENAL DENERVATION IN PATIENTS WITH RESISTANT HYPERTENSION

Objective: Renalase is a catecholamine-metabolizing enzyme produced by proximal tubular cells in kidney which is supposed to be involved in blood pressure regulation. The aim of the study was to evaluate plasma renalase concentration before and after radiofrequency renal denervation (RDN) in patients with resistant arterial hypertension. Design and method: 19 patients (10 men, median age 56 (48; 57) years; BMI 30.9 ± 4.4 kg/m2 and eGFR 89 ± 17.7 ml/min/1.73 m2) with resistant hypertension were enrolled in the study. In all patient plasma renalase concentration was measured before and 1, 3, 6 and 12 months after RDN by ELISA method (Cloud-Clone Corp, Houston, USA). Results: A significant decrease of both office systolic and diastolic blood pressure 6 months after RDN was found (192 ± 31 vs. 177 ± 28 mmHg, p = 0.03; 113 ± 23 vs. 99 ± 21 mmHg, p = 0.002, respectively). One and 3 months after RDN plasma renalase concentration decreased significantly (p < 0.05 vs. baseline), with a subsequent return to values comparable with baseline at 6 and 12 months after RDN (NS vs. baseline) (median plasma renalase concentration 22100 vs. 18550 vs. 17600 vs. 20750 vs. 20500 ng/ml, respectively; Friedman analysis of variance p = 0.054). Conclusions: 1. Renal denervation leads to the temporary decrease of plasma renalase concentration in patients with resistant hypertension. 2. Lower plasma renalase concentrations seems to reflect a counteract reaction to blood pressure decline after successful renal denervation.

PP.15.25] REDO RENAL DENERVATION WITH NON-INVASIVE THERAPEUTIC ULTRASOUND

Objective: Safety and preliminary effectiveness evaluation of non-invasive ultrasound (US) renal denervation system in patients who were previously treated with catheter-based radiofrequency renal denervation. Design and method: The Surround Sound system delivers therapeutic US non-invasively to create a field of energy around the renal artery. This mode of delivery is very different from other catheter-based systems which deliver (radiofrequency) energy at concentrated ablation spots. Pre-clinical animal data showed no discernible effects on the renal artery in a repeated treatment model even at doses much higher than used in the clinic. The hypothesis underpinning these data was that the Surround Sound treatment could be safely applied to patients with prior denervation and is potentially well suited for repeated treatments. Eleven patients with uncontrolled hypertension who were previously treated with catheter based renal denervation were treated with the Surround System at 4 centres [U.K (5), Czech Republic (3), Poland (1) and New Zealand (2). Treatment criteria were: office systolic blood pressure (SBP) >160 mm, 24 hour ambulatory SBP > 135 mm Hg, and patients were required to be taking three antihypertensive medications. The patients may or may not have responded to prior renal denervation treatment but all met entry BP criteria. Results: There were no mortality or major adverse events, no significant device related AEs including significant back pain, change in renal function, renal artery stenosis, or other events. At 3 months (11 patients), the average office SBP change was −27.4 mm Hg. At one year (8 patients), the average change in office SBP was −33.4 mm Hg. Average ambulatory SBP change at 6 months (8 patients) was −21.5 mm Hg and −17.2 mm Hg at 1 year (5 patients). Conclusions: These clinical data serve as the initial pilot safety data for redo US renal denervation. Larger randomized trials are needed in this patient population to assess efficacy as well as a treatment regimen in a treatment naïve patient cohort in which planned denervation with the Surround Sound system is studied.

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

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

Radiofrequency Renal Denervation Improves Vascular Reactivity in a Rodent Model of Heart Failure

BackgroundWe have previously reported that radiofrequency (RF) renal denervation (RDN) exerts cardioprotective effects in the setting of myocardial ischemia‐reperfusion (MI‐R) injury. The protective actions of RF‐RDN in MI‐R injury are related in part to attenuated oxidative stress and increased nitric oxide (NO) bioavailability. More recently we have demonstrated that RF‐RDN protects the failing heart independent of reductions in blood pressure. The mechanisms by which RF‐RDN affords these benefits have not been fully described, including the effects on vascular function.MethodsMale Wistar‐Kyoto (WKY) rats and spontaneously hypertensive rats (SHR) at 20 weeks of age were subjected to 45 minutes of transient LAD coronary artery ligation followed by reperfusion for 12 weeks. Four weeks following reperfusion animals were subjected to either bilateral RF‐RDN or a sham procedure (SHAM) with n=12 in all groups. At 12 weeks after reperfusion, thoracic aorta was harvested and vascular reactivity was evaluated. Vasoactivity was assessed for the endothelium‐dependent vasodilators acetylcholine (ACh, 0.1nM–10mM) and the calcium ionophore A23187 (A23187, 10nM‐1mM). In addition, vascular reactivity to the endothelium‐independent vasodilator sodium nitroprusside (SNP, 0.1nM–10 mM) was investigated. The effects of RF‐RDN therapy on cardiac structure and function were also determined via biweekly 2‐D serial echocardiography.ResultsRF‐RDN significantly improved cardiovascular function as reflected in improved left ventricle (LV) ejection fraction at 12 weeks following reperfusion in both SHRs (46.8 ± 2.4% vs. 30.4 ± 2.5%, p&lt;0.01) and WKYs (50.4 ± 3.0% vs 35.4 ± 2.7%; p&lt;0.05). RF‐RDN treatment significantly improved endothelium mediated vasorelaxation in both hypertensive and normotensive animals as reflected in ACh EC50 (SHR: 98.8 ± 19.2 nM vs. 349.6 ± 25.0 nM, p&lt;0.0001; WKY: 10.03 ± 1.32 nM vs. 44.97 ± 12.03 nM, p&lt;0.01). Similar improvements were seen in smooth muscle mediated vasorelaxation due to SNP (SHR: 29.4 ± 4.2 nM vs. 145.3 ± 14.2 nM, p&lt;0.0001; WKY: 11.68 ± 1.28 nM vs 39.68 ± 7.47 nM, p&lt;0.01). RF‐RDN also improved vasorelaxation to the direct endothelium‐dependent vasodilator, A23187, in hypertensive animals (SHR: 10.8 ± 1.3 nM vs. 23.2 ± 2.7 nM, p&lt;0.001) but not normotensive animals. We did not observe any significant reductions in blood pressure in either the SHR or WKY rats following RF‐RDN at anytime during the experimental protocol.ConclusionRF‐RDN significantly improved LV function in the setting of heart failure independent of blood pressure reductions. Therapy improved vascular function suggesting that the cardiovascular benefits afforded by RF‐RDN may be partially due to improved vascular function. The improved vascular reactivity and cardiac function observed following RF‐RDN may be a result of reduced oxidative stress and increased NO bioavailability. Experiments are currently underway to evaluate this possibility. Our results reveal a novel mechanism related to the beneficial effects of RF‐RDN in heart failure.

Catheter-Based Renal Denervation Exacerbates Blood Pressure Fall During Hemorrhage

BackgroundClinical trials applying catheter-based radiofrequency renal denervation (RDN) demonstrated a favorable safety profile with minimal acute or procedural adverse events. Whether ablation of renal nerves adversely affects compensatory responses to hemodynamic challenge has not been extensively investigated. ObjectivesThe aim of this study was to examine the effect of RDN on mean arterial pressure, renal function, and the reflex response to hemorrhage in sheep with normotension (control) or with hypertensive chronic kidney disease (CKD). MethodsSheep underwent RDN (control-RDN, n = 8; CKD-RDN, n = 7) or sham procedures (control-intact, n = 6; CKD-intact, n = 7). Response to hemorrhage (20% loss of blood volume), including plasma renin activity, was assessed at 2 and 5 months post-procedure. ResultsRDN caused a complete reversal of hypertension and improved renal function in CKD-RDN sheep (p < 0.0001 for 2 and 5 months vs. pre-RDN). In response to hemorrhage, mean arterial pressure fell in all groups, with the fall being greater in the RDN than the intact group (2-month fall in mean arterial pressure: control-intact, −10 ± 1 mm Hg; control-RDN, −15 ± 1 mm Hg; p < 0.05; CKD-intact, −11 ± 3 mm Hg; CKD-RDN, −19 ± 9 mm Hg; p < 0.001). Hemorrhage increased heart rate and plasma renin activity in intact sheep, but these responses were significantly attenuated in control-RDN and CKD-RDN animals. Responses to hemorrhage were remarkably similar at 2 and 5 months post-RDN, which suggests that nerve function had not returned within this time frame. ConclusionsIn hypertensive CKD sheep, RDN reduced blood pressure and improved basal renal function but markedly compromised compensatory hemodynamic responses to hemorrhage. Therefore, the capacity to respond to a physiological challenge to body fluid homeostasis may be compromised following RDN.