Comparison of the effects of regional ischemia, hypoxia, hyperkalemia, and acidosis on intracellular and extracellular potentials and metabolism in the isolated porcine heart.

Abstract

DC electrograms and transmembrane potentials were recorded from isolated perfused pig hearts. Regional ischemia was produced by clamping the left anterior descending artery (LAD), and after a reperfusion period, regional hypoxia and/or hyperkalemia was produced by perfusing the LAD with hypoxic, glucose-free solutions (with or without acidification, or high K+) or with normoxic high K+ solutions. In transmural biopsies, nucleotides, lactate and K+ were determined. During ischemia, resting potential decreases (T-Q depression), action potential amplitude and upstroke velocity decrease and local activation is markedly delayed (S-T elevation, late intrinsic deflection, high R wave). A high K+ concentration, up to 13 mM, decreases resting potential (T-Q depression) and shortens the action potential (positive T wave) but has minor effect on amplitude (no S-T elevation) and activation (no delay). Hypoxia (P[partial pressure]O2 = 7 mm Hg, no glucose) causes a moderate decrease in resting potential, marked action potential shortening and some loss of amplitude but no or only minor delay in activation (slight T-Q depression and S-T elevation, positive T waves). Acidic perfusate does not influence changes in transmembrane potential during hypoxia. Potentials of similar configuration to those seen during ischemia could be obtained by LAD perfusion with hypoxic, glucose-free, high K+ (10 mM), acidic (pH 6.8) solutions. Most surprising was improvement of potentials after 20 min of perfusion, like that seen during maintained LAD occlusion. The time course of metabolic changes was the same in hypoxia and ischemia. Apparently, there is no direct relationship between metabolic and electrical changes. Electrical changes during ischemia may be caused by a combination of lack of perfusion (hypoxia, no substrate) and lack of washout (hyperkalemia, acidosis). Action potentials of ischemic cells evidently are more depressed than those of normoxic cells, at similar reduced levels of resting membrane potential.