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 PO2 < 50 mm Hg. During the initial 10 minutes of superfusion with altered Tyrode's solution, reduction of action potential (AP) amplitude and dV/dt(max) 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 minutes, only 3 of 18 epicardial and 5 of 16 papillary cells were excitable, whereas 14 of 16 endocardial muscle cells and 13 of 13 PF still were 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 minutes 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- to 60-minute period of continued superfusion. Tetrodotoxin (TTX, 5 x 10-6 M) depressed AP amplitude and dV/dt(max) 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 x 10-6M) had equivalent effects on endocardium and epicardium. These data indicate that excitability is more easily depressed by a combination of hyperkalemia, hypoxia, and acidosis, and by TTX, in epicardium and papillary muscle tip than in endocardium and PF. Responsiveness of endocardial muscle during exposure to altered Tyrode's solution of TTX may be enhanced by contact with PF.
ASJC Scopus subject areas
- Cardiology and Cardiovascular Medicine