Effect of renal denervation in a porcine model of myocardial infarction
D Martinez-Falguera, E Fadeuilhe, E Jorge, G Iraola, M Kalil, J Aranyo, F Bisbal, V Crisostomo, C Baez-Diaz, F M Sanchez-Margallo, A Teis, S Roura, A Bayes-Genis, O Rodriguez-Leor, C Galvez-MontonAbstract
Background
Activation of the sympathetic nervous system following myocardial infarction (MI) contributes to adverse cardiac remodelling, ventricular dysfunction, heart failure, and ventricular arrhythmias. Catheter-based renal sympathetic denervation (RDN) lowers systemic sympathetic activity by ablating renal nerves and is currently indicated only for patients with arterial hypertension that remains uncontrolled despite pharmacological treatment.
Purpose
This study aimed to evaluate the effect of early RDN on cardiac function, arrhythmic substrate, and myocardial scar characteristics in a porcine model of MI.
Methods
Ten pigs with MI were randomized to a Control group or an RDN-treated group (n=5 per group). RDN was performed immediately after MI induction by radiofrequency ablation. Cardiac function was assessed by magnetic resonance imaging at days 2 and 29 post-MI. On day 30, an electrophysiological study with programmed electrical stimulation and high-density mapping was performed to evaluate electrophysiological properties and ventricular tachycardia (VT) inducibility. Myocardial samples from infarcted and remote regions were collected for histological and immunohistochemical analysis of fibrosis and vascularization, as well as RNA-seq evaluation.
Results
At day 2 post-MI, the RDN group showed an attenuated left ventricular systolic dysfunction without differences in scar size compared to controls. By day 29, LVEF was similar between groups, but total and dense scar mass was significantly smaller in RDN-treated animals. At 30 days, the RDN group tended to have fewer deceleration zones and exhibited markedly reduced VT inducibility (0% vs. 60% in controls). Analyses of myocardial infarcted tissue showed no differences in type I or III collagen content, whereas vascular density within the scar was higher in the RDN group. RNA-seq of infarcted tissue identified 143 differentially expressed genes between groups, revealing broad down-regulation of inflammatory pathways, including those related to lymphocyte activation and migration in the RDN group.
Conclusions
Early RDN after MI down-regulates inflammatory and lymphocyte-related pathways, which is associated with a smaller and more vascularized myocardial scar, and reduced arrhythmic susceptibility, suggesting a protective effect on post-infarction remodelling.