Digitalis glycosides accentuate the depressant effect of anoxia and reoxygenation on the cardiac myocyte: antagonism by amiloride.

The purpose of this study was to determine whether digitalis glycosides alter the effect of anoxia and reoxygenation on the cardiac myocytes and whether it could be modified by inhibition with amiloride. Cardiac myocytes aggregates were prepared from ventricles of 7 day old chick embryos and were maintained in culture. They were exposed to a 2 hr anoxia period followed by reoxygenation. Anoxia produced a significant reduction in contractile frequency. Ouabain, at low doses (10(-7) M and 10(-8) M), produced little effect in the absence of anoxia but produced a marked and significant (p less than 0.05) reduction in contractile frequency in the presence of anoxia. Myocytes exposed to anoxia stopped beating only in the presence of 10(-7) M and 10(-6) M ouabain and the time to cessation of spontaneous contraction was dependent on ouabain dose. Amiloride (10(-7) M or 10(-6) M) significantly (p less than 0.05) reduced but did not completely prevent the effect of ouabain. During reoxygenation, beating rate returned to base line in control cells and those exposed to ouabain (10(-8) M and 10(-7) M) but ouabain slowed the rate of recovery. This slowing of recovery, produced by ouabain, was prevented by amiloride. These findings indicate the potentially deleterious effects of digitalis glycosides in myocardial anoxia and reoxygenation and the ability of amiloride to oppose these adverse effects.