COMBINED EFFECTS OF OUABAIN AND HYPOXIA ON THE TRANSMEMBRANE POTENTIAL OF CANINE CARDIAC PURKINJE-FIBERS

The effects of hypoxia on the transmembrane potential of dog Purkinje cells in isolated, superfused fiber bundles pretreated with ouabain were studied. Cells stimulated electrically at 93/min were exposed to ouabain, 2.1 .times. 10-7 M, until the magnitude of phase 4 depolarization increased to 7-12 mV. Arrhythmias did not occur. Following a 10-min washout period, hypoxic solution (PO2 = 15-50 mm Hg) was applied for 2-5 min. This caused decreases in maximum diastolic potential, overshoot, rising velocity of phase 0 and duration of the action potential. The slope of depolarization during phase 4 increased markedly. Arrhythmias characterized by escape rhythms or single and multiple bursts of premature excitations occurred in > 90% of the experiments. None of these changes was noted when identical levels of hypoxia were applied for a similar period to normal cells. Blockade of the .beta.-adrenergic receptors with propranolol 0.3 mg/l, did not alter the response of ouabain-pretreated cells to hypoxia in any manner, ruling out release of endogenous catecholamines as essential for the observed effects. Evidently ouabain and hypoxia have a synergistic effect directly on the cells and produce the observed changes in membrane potential. The ventricular arrhythmias observed in digitalized humans or animals that become hypoxemic may result either from the induction of oscillatory afterpotentials in Purkinje cells causing triggered spontaneous excitations or from reentry of excitation.