Regional effects of verapamil on recovery of excitability and conduction time in experimental ischemia.
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.(ABSTRACT TRUNCATED AT 250 WORDS)
Kimura
S
S
Department of Medicine, University of Miami, School of Medicine, FL 33101.
Bassett
A L
AL
Kohya
T
T
Kozlovskis
P L
PL
Myerburg
R J
RJ
D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D002415:Cats; D003326:Coronary Circulation / Q000187:drug effects; D003327:Coronary Disease / Q000503:physiopathology*; D004594:Electrophysiology; D004699:Endocardium / Q000503:physiopathology; D005260:Female; D006321:Heart / Q000503:physiopathology*; D006329:Heart Conduction System / Q000503:physiopathology*; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D010496:Pericardium / Q000503:physiopathology; D014700:Verapamil / Q000494:pharmacology*
D014700:Verapamil