Different electrophysiological responses of canine endocardium and epicardium to combined hyperkalemia, hypoxia, and acidosis.

Abstract

To determine whether canine epicardium and endocardium show intrinsically different electrophysiological responses to metabolic alterations that occur during acute myocardial ischemia in vivo, endocardial, epicardial, papillary muscle tip and Purkinje fibers (PF) were superfused in vitro with Tyrode''s solution containing 8.0 mM KCl at a pH of 6.85 and a P[partial pressure]O2 < 50 mm Hg. During the initial 10 min of superfusion with altered Tyrode''s solution, reduction of action potential (AP) amplitude and dV/dtmax [1st derivative of left ventricular pressure] and prolongation of activation times were greater in epicardium than in endocardium or in PF, despite similar changes in resting membrane potential. After superfusion for 15 min, only 3 of 18 epicardial and 5 of 16 papillary muscle cells were excitable; 14 of 16 endocardial muscle cells and 13 of 13 PF were still responsive. Membrane responsiveness at takeoff potentials < -65mV was lower in epicardium and papillary muscle than in endocardium during superfusion with normal or altered Tyrode''s solution. The effects produced by the initial 15 min of superfusion with altered Tyrode''s solution were partially reversed in endocardium and PF but not in epicardium or papillary muscle during a subsequent 20-60 min period of continued superfusion. Tetrodotoxin (TTX, 5 .times. 10-6 M) depressed AP amplitude and dV/dtmax more in epicardium than in endocardium. TTX had only a small effect on the upstroke of PF AP, but shortened AP duration by 30-40%. Verapamil (2 .times. 10-6 M) had equivalent effects on endocardium and epicardium. Excitability is more easily depressed by a combination of hyperkalemia, hypoxia, acidosis and TTX in epicardium and papillary muscle tip than in endocardium and PF. Responsiveness of endocardial muscle during exposure to altered Tyrode''s solution or TTX may be enhanced by contact with PF.