Comparison of the Effect of the Regional Ischemia, Hypoxia, Hyperkalemia, and Acidosis on Intracellular and Extracellular Potentials and Metabolism in the Isolated Porcine Heart

DC electrograms and transmembrane potentials were recorded from isolated perfused pig hearts.Regional ischemia was produced by clamping the left anterior dascending artery (LOD), and after a reperfusion period, regional hypoxic, glucose-free solutions (with or without acidification, or high K+) or with normoxic high K+ solutions. In transmural biosies, nucleotides, lactate, and K+ were determined. During ischemia, resting potential decrease (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, decrease 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). Hypoxin (Poz=7 mm Hg, no glucose) causes a moderate decrease in resting potential, marked action potential shortening, and some of loss of amplitude but no or only minor delay in activation (slight T-Q depression and S-T elevation, positive T waves). Acidle perfusate does not influence changes fin transm,embrane 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 minutes of perfusion, like that seen during maintained LAD occlusion. The time course of metabolic changes was the same in hypoxia and ischemia. Results indicate (1) that there is no direct relationship between metabolic and electrical changes, (2)that electrical changes during ischemia are caused by a combination of lack of perfusion (hypoxia, no substrate) and lack of washout (hyperkalemia, acidosis), and (3) that action potentils of ischemic cells are more “depressed” than those of normoxic cells, at similar reduced levels of resting membrane potential. Circ Res 46: 634-646, 1980.