Combined effects of hypoxia, hyperkalemia and acidosis on membrane action potential and excitability of guinea-pig ventricular muscle

Abstract

The effects of hypoxia (with and without acidosis) on membrane action potentials and recovery kinetics of their upstroke velocity (Vmax) were studied in isolated guinea-pig papillary muscles at various extracellular K+ concentrations. At 5 mM [K+]0, hypoxia (hypoxic and glucose-free perfusate) at pH 7.4 caused a progressive shortening of action potential duration and a slight decrease in Vmax and resting potential. The recovery kinetics of Vmax assessed by premature stimuli were not affected by hypoxia. At high [K+]0 of 10 or 12 mM, hypoxia caused a marked decrease in Vmax, while the shortening of the action potential and the decrease in resting potential were similar to those at 5 mM [K+]0. However, the recovery kinetics of Vmax were markedly slowed by hypoxia. When hypoxia was added in the presence of mild acidosis (pH 6.8), the shortening of the action potential due to hypoxia was appreciably less. However, other hypoxia-induced changes in action potential and in recovery kinetics of Vmax under normal and high [K+]0 were not influenced by the concomitant acidosis. These results show that the depressant effect of hypoxia on the action potential upstroke and on the recovery of excitability of ventricular myocardium is increased when the muscles are partly depolarized at high K+. Slight differences in extracellular K+ in the presence of hypoxia have a marked effect on the time course of recovery of excitability. This inhomogeneity in refractoriness could be important for the occurrence of re-entrant arrhythmias in ischemic myocardium.