Renal Denervation Decreases Susceptibility to Arrhythmogenic Cardiac Alternans and Ventricular Arrhythmia in a Rat Model of Post-Myocardial Infarction Heart Failure

Abstract

Summary: Several studies have shown the beneficial effect of renal denervation (RDN) in the treatment of ventricular arrhythmia, especially in the setting of heart failure (HF). However, the underlying mechanism of antiarrhythmic effect of RDN is unknown. Arrhythmogenic cardiac alternans, particularly spatially discordant repolarization alternans, characterized by simultaneous prolongation and shortening of action potential duration (APD) in different myocardial regions, is central to the genesis of ventricular fibrillation in HF. Whether RDN decreases the susceptibility to arrhythmogenic cardiac alternans in HF has never been addressed before. The authors used a rat model of post-myocardial infarction HF and dual voltage-calcium optical mapping to investigate whether RDN could attenuate arrhythmogenic cardiac alternans that predisposes to ventricular arrhythmias, as well as the hemodynamic effect of RDN in HF. The HF rats had increased body weights, dilated hearts, and lower blood pressure. The HF rats also had longer ventricular APDs and a delay in the decay of the calcium transient, typical electrophysiological features of human HF. Susceptibility to calcium transient alternans, APD alternans, and spatially discordant APD alternans was increased in the HF hearts. RDN significantly attenuated a delay in the decay of the calcium transient, calcium transient and APD alternans, and importantly, the discordant APD alternans, and thereby decreased the incidence of induced ventricular arrhythmia in HF. RDN did not further decrease blood pressure in HF rats. In conclusion, RDN improves calcium cycling and prevents spatially discordant APD alternans and ventricular arrhythmia in HF. RDN does not aggravate hemodynamics in HF. Key Words: alternans, arrhythmia mechanism, heart failure, renal denervation