This study was designed to test the hypothesis that verapamil has an effect on ischemia-initiated arrhythmias related to its regional influences on recovery of excitability and conduction time. Using a coronary perfused preparation of cat left ventricle that allows simultaneous electrophysiologic monitoring of both endocardium and epicardium, we studied the effect of verapamil on ischemia-induced changes in transmembrane action potentials, conduction properties, and refractory periods of endocardial and epicardial muscle cells. Oxygenated Tyrode's solution was perfused through the left anterior descending coronary artery, while the preparation was superfused with Tyrode's solution gassed with 95% N2 and 5% CO2. 'Ischemia' was produced by stopping coronary perfusion. During 30 min of ischemia, resting potential, action potential amplitude (APA), and action potential duration (APD) were reduced, and conduction time was prolonged in both endocardial and epicardial cells, but the changes were greater in the epicardial cells. Endocardial refractory periods shortened in parallel with APD shortening throughout 30 min of ischemia, whereas epicardial refractory periods shortened for the first 10 min and then increased due to development of longer postrepolarization refractoriness. As a result, there were significant differences in refractory periods between endocardial and epicardial cells at 10 and 30 min of ischemia, and rapid ventricular activity could be induced at these times. Exposure to verapamil (1 mg/liter) before cessation of coronary perfusion significantly limited the reduction of APA and the prolongation of conduction time during the first 10 min of ischemia in epicardial cells, but did not influence endocardial cells. During the remaining 20 min of ischemia, verapamil enhanced the reduction of APD of both epicardial and endocardial cells. Verapamil abolished the significant differences in refractory period between endocardial and epicardial cells at 30 min of ischemia, because it enhanced ischemia-induced APD shortening to a greater degree in epicardial cells. Rapid ventricular activity was no longer inducible by extrastimuli at 30 min of ischemia in the presence of verapamil. These results lead us to suggest that verapamil may prevent some ischemic arrhythmias by limiting conduction disturbances and dispersion of endo-epicardial refractoriness. Our data also indicate that verapamil has multiple actions in the different regions of the heart under pathophysiologic conditions.
ASJC Scopus subject areas
- Cardiology and Cardiovascular Medicine
- Physiology (medical)