Electrophysiological and Antiarrhythmic Properties of Potassium Canrenoate During Myocardial Ischemia–Reperfusion

Abstract

Introduction: Recent clinical studies have reported the potential benefit of an early mineralocorticoid receptor (MR) blockade with potassium canrenoate (PC) on ventricular arrhythmias (VAs) occurrence in patients experiencing an ST-segment elevation myocardial infarction (STEMI). However, most of the electrophysiological properties of PC demonstrated to date have been investigated in normoxic conditions, and therefore, in vitro experiments during an acute myocardial ischemia–reperfusion were lacking. Materials and Methods: We used rabbit in vitro models and standard microelectrode technique to assess the electrophysiological impact of PC during myocardial ischemia–reperfusion, including right ventricle mimicking the “border zone” existing between normal and ischemic/reperfused areas (1 µmol/L, 10 and 100 nmol/L), isolated right ventricle, and sinoatrial node (SAN) experiments (1 µmol/L, respectively). Results: During ischemia–reperfusion, acute superfusion of PC 100 nmol/L prevented the increase in action potential (AP) duration at 90% of repolarization (APD90) dispersion between ischemic and nonischemic areas and in VAs occurrence induced by aldosterone 10 nmol/L (86 ± 3 vs 114 ± 4 milliseconds for aldosterone alone, P < .05). Potassium canrenoate also induced conduction blocks and significantly decreased Vmax during simulated ischemia (from 25 ± 5 to 12 ± 4, 14 ± 3, and 14 ± 5 V/s, respectively, for PC 1 µmol/L, 100, and 10 nmol/L, P < .05). Potassium canrenoate 1 µmol/L demonstrated cycle length (CL)-dependent effects on APD90 and on Vmax, and it also reduced SAN beating CL (from 446 ± 28 to 529 ± 24 millisecond, P < .05). Conclusion: Our experimental study highlights new evidence for an antiarrhythmic impact of PC during myocardial ischemia–reperfusion via multiple channels modulation. These results are in line with recent clinical trials suggesting that an early MR blockade in STEMI may be preventive of VAs.