Renal Denervation in male rats attenuates changes in cardiac sympathetic innervation in post‐infarction heart failure

Following myocardial infarction (MI) a decrease in the expression of sympathetic nerves in the myocardium remote from the infarct has been observed. Reduced sympathetic innervation of the cardiac ventricles is implicated in attenuated contractility and arrhythmia development, contributing to the development and progression of heart failure. Renal denervation is currently being investigated both clinically and experimentally as a treatment for heart failure, yet the precise mechanisms by which renal denervation may be beneficial are not completely understood. In the current study we set out to determine the effects of renal denervation on the expression of sympathetic nerves in the cardiac ventricles of rats with post‐infarction heart failure. MI or sham MI was performed in male Wistar rats and 4 weeks later renal denervation or sham surgery was performed. 7 weeks post‐MI, left ventricle function was assessed and then the hearts were removed and post‐fixed overnight in paraformaldehyde (4%). The hearts were then embedded in paraffin wax and stored until processing. Tyrosine‐hydroxylase (TH) immunoreactivity (IR) was used to visualize the sympathetic nerves and PGP 9.5 IR was used to visualize total nerves. The area density of the target nerves was quantitatively assessed using threshold discrimination. In sham MI animals, renal denervation did not alter the density or distribution of sympathetic and total nerves in the left and right ventricles. In the MI groups, the myocardium directly adjacent to the infarct border zone (peri‐infarct) displayed significantly reduced nerve density, almost complete denervation, when compared to areas remote from the infarct and this effect was unaltered by renal denervation. In both MI groups, particular areas within the infarct were observed to have a high density of sympathetic innervation. In animals with intact renal nerves, post‐infarction heart failure resulted in reduced expression of sympathetic and total nerves in the left and right ventricles, remote from the infarct. Renal denervation in animals with post‐infarction heart failure increased the sympathetic and total nerve density in the left and right ventricles remote from the infarct thereby abolishing the statistically significant difference in nerve density when compared to sham MI group. The current findings suggest that renal denervation may be beneficial in heart failure via attenuating adverse changes in cardiac innervation. In particular, renal denervation resulted in the conservation of sympathetic nerves in the ventricles consistent with improved contractility and reduced arrythmogenisis. Support or Funding Information This research was supported by a grant from The National Heart Foundation of New Zealand