Verapamil prevents slowing of transmural conduction and suppresses arrhythmias in an isolated guinea pig ventricular model of ischemia and reperfusion

Abstract

Transmembrane electrical activity was recorded from endocardium and epicardium of isolated segments of guinea pig right ventricular free walls. An electrocardiogram was recorded by electrodes at opposite ends of the tissue bath. Endocardium was stimulated. Tissues were exposed to 'ischemic' conditions (e.g., acidosis, hyperkalemia, hypoxia, and lactate) for 15 minutes and then were reperfused with 'normal' Tyrode's solution. Arrhythmias with characteristics of transmural reentry occurred in ischemic conditions and early reperfusion in 30% and 70% of 20 control hearts, respectively. Arrhythmias were associated with prolongation of transmural conduction time (CT) and abbreviation of endocardial effective refractory period. Verapamil significantly suppressed reperfusion arrhythmias at 0.1-1.0 μM but not at 3.0 μM. Verapamil also significantly decreased the incidence of arrhythmias during ischemic conditions at 0.5 μM but significantly promoted ischemic arrhythmias at 3.0 μM. Action potential duration and effective refractory period were not altered by verapamil during ischemic conditions or reperfusion. However, at 0.1-1.0 μM, verapamil prevented or attenuated prolongation of transmural CT by ischemic conditions and reperfusion. Transmural CT was further prolonged at 3 μM verapamil. In epicardial slices, 1 μM verapamil shortened CT transverse to fiber orientation during reperfusion but had no effect on longitudinal CT. Our results indicate that verapamil may suppress arrhythmias through differential effects on CT transverse and longitudinal to fiber orientation in anisotropic ventricular tissues and thus by specifically improving transmural conduction.