Renal, Cardiac, and Autonomic Effects of Catheter-Based Renal Denervation in Ovine Heart Failure

Abstract

A growing number of clinical studies suggest that in heart failure renal denervation (RDN) has beneficial effects on the autonomic control of the heart. There is also experimental evidence that surgical RDN improves sodium handling and clearance in heart failure. The aim of this study was to determine the effects of catheter-based RDN on the sympathetic and parasympathetic control of the heart, and salt and water handling capacity of the kidneys, in sheep with established heart failure. A randomized, controlled study was conducted in 10 sheep with heart failure (ejection fraction<40%) induced by rapid ventricular pacing. Sheep underwent either bilateral RDN using the Symplicity denervation system or sham denervation and were studied 1 and 6 weeks after RDN. In established ovine heart failure, at 6 weeks after catheter-based RDN, heart rate significantly decreased, estimates of resting and maximal parasympathetic control of heart rate increased, and cardiac sympathetic nerve activity decreased. Compared with sham denervation, there was an increase in the resting sodium and water excretion 6 weeks after catheter-RDN and an improved ability of the kidneys to excrete a nonhypertensive saline load. After catheter-based RDN, renal norepinephrine levels were reduced by 70% compared with sham denervation. In established heart failure, RDN induced a beneficial shift in both arms of the autonomic nervous control of the heart and improved the ability of the kidneys to excrete sodium and water. Thus, effective catheter-based RDN may be beneficial to both the heart and kidneys in heart failure.

Effects of Renal Denervation on the Enhanced Renal Vascular Responsiveness to Angiotensin II in High-Output Heart Failure: Angiotensin II Receptor Binding Assessment and Functional Studies in Ren-2 Transgenic Hypertensive Rats

“…Therefore, it is tempting to propose that the beneficial actions of RDN are not mediated by renal mechanism(s). However, two recent studies, in ovine HF model and in sheep with hypertensive CKD, showed that RDN not only lowered blood pressure but also improved the glomerular filtration rate (GFR) and sodium and water excretion [ 59 , 60 ]. In addition, RDN was recently reported to attenuate the increased expression of renal epithelial sodium channels (ENaC) and the water channel aquaporin 2 (AQP2) in rats with MI-induced HF [ 61 ].…”

Neural and central mechanisms of kidney fibrosis after relief of ureteral obstruction

“…The nerve activity was expressed in spikes per second (Hz), as commonly used by previous studies that compare multifiber nerve recording among different groups. 36 , 38 , 39 , 40 , 41 In optogenetic experiments, nerve activity was expressed as percentage relative to values just before optical silence of RVLM-projection PVN neurons.…”

Renal Sodium Avidity in Heart Failure

“…Many guideline-directed medical therapies (GDMT) for HF target this neurohumoral axis (i.e., β-blockers and renin-angiotensin blockers) to slow the progression of HF. Specific modulation of renal efferent neurons by catheter-based renal denervation augments renal sodium and water excretion in a sheep model of HF, yet more definitive human data are needed [19].…”