VERAPAMIL PREVENTS SLOWING OF TRANSMURAL CONDUCTION AND SUPPRESSES ARRHYTHMIAS IN AN ISOLATED GUINEA-PIG VENTRICULAR MODEL OF ISCHEMIA AND REPERFUSION

Transmembrane electrical activity was recorded from endocardium and ep icardium of isolated segments of guinea pig right ventricular free wal ls. An electrocardiogram was recorded by electrodes at opposite ends o f the tissue bath. Endocardium was stimulated. Tissues were exposed to "ischemic" conditions (e.g., acidosis, hyperkalemia, hypoxia, and lac tate) for 15 minutes and then were reperfused with "normal" Tyrode's s olution. Arrhythmias with characteristics of transmural reentry occurr ed in ischemic conditions and early reperfusion in 30% and 70% of 20 c ontrol hearts, respectively. Arrhythmias were associated with prolonga tion of transmural conduction time (CT) and abbreviation of endocardia l effective refractory period. Verapamil significantly suppressed repe rfusion arrhythmias at 0.1-1.0-mu-M but not at 3.0-mu-M. Verapamil als o significantly decreased the incidence of arrhythmias during ischemic conditions at 0.5-mu-M but significantly promoted ischemic arrhythmia s at 3.0-mu-M. Action potential duration and effective refractory peri od were not altered by verapamil during ischemic conditions or reperfu sion. However, at 0.1-1.0-mu-M, verapamil prevented or attenuated prol ongation of transmural CT by ischemic conditions and reperfusion. Tran smural CT was further prolonged at 3-mu-M verapamil. In epicardial sli ces, 1-mu-M verapamil shortened CT transverse to fiber orientation dur ing reperfusion but had no effect on longitudinal CT. Our results indi cate that verapamil may suppress arrhythmias through differential effe cts on CT transverse and longitudinal to fiber orientation in anisotro pic ventricular tissues and thus by specifically improving transmural conduction.