DISSOCIATION OF THE POSITIVE INOTROPIC ACTION OF DIGITALIS FROM INHIBITION OF SODIUM- AND POTASSIUM-ACTIVATED ADENOSINE TRIPHOSPHATASE

¹ Department of Pharmacoloqy, Northwestern University Medical School, Chicago, Illinois

Experiments were undertaken to test the hypothesis that the mechanism of the positive inotropic action of digitalis is the result of inhibition of the transport enzyme. Na⁺, K⁺-activated adenosine triphosphatase (Na, K-ATPase). Initial studies utilizing strophanthidin-3-bromoacetate indicated indirert evidence for the dissociation of the short duration of the positive inotropic action from the long persistent inhibition in vivo of the transport enzyme. In an attempt to obtain direct evidence for this observed dissociation. ex vivo pharmacologic and biochemical studies were conducted on isolated Langendorff rabbit heart utilizing strophanthidin-3-bromoacetate. strophanthidin and ouabain. After positive inotropic effects with each of the cardiac steroids in the Langendorff hearts were obtained, the perfusate was changed to a drug-free buffer solution in order to effect "washout" of all pharmacologic effect. After return of contractile force to control levels, the hearts were extracted for Na, K-ATPase and assayed for enzyme activity. Up to 39% inhibition of Na, K-ATPase activity was noted in comparison to control values. Since the transport enzyme was inhibited when positive inotropic effect was no longer present, these findings indicate that inhibition of Na, K-ATPase may not be responsible for the positive inotropic action of the cardiac steroids.

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