STUDIES ON DIGITALIS. VIII. EFFECT OF AUTONOMIC INNERVATION AND OF MYOCARDIAL CATECHOLAMINE STORES UPON THE CARDIAC ACTION OF OUABAIN

¹ Cardiology Branch, National Heart Institute, Bethesda, Maryland

The effects of autonomic innervation and of myocardial catecholamine stores on the action of ouabain on myocardial contractile force, the functional refractory period of the A-V conduction system, and on the dose required to produce multiple ventricular premature contractions were determined in pentoharbital anesthetized, open-chest dogs. The mean increment in contractile force produced by ouabain in groups of dogs which had been vagotomized, reserpine-pre-treated, acutely cardiac denervated, and chronically cardiac denervated, was not significantly different from the mean change produced by ouabain in the control dogs. Similarly, the mean cumulative doses of ouabain required to produce multiple ventricular premature contractions did not differ significantly among the five groups of animals. The mean prolongation in AVFRP produced by a cumulative dose of 42 µg/kg ouabain was 46 milliseconds in the control dogs, 21 milliseconds in the vagotomized dogs, and 10 milliseconds in the chronically cardiac denervated dogs.

These results indicate that the inotropic and arrhythmic doses of ouabain are independent of autonomic innervation and myocardial catecholamine stores, but that a major portion of the prolongation of the functional refractory period of the atrioventricular conduction system produced by ouabain is dependent upon intact autonomic innervation. However, by studying dogs after chronic cardiac denervation and myocardial catecholamine depletion, it was shown that there is a significant though small direct effect of this glycoside on the functional refractory period of the A-V conduction system. Since the magnitude of the prolongation of the AVFRP produced by ouabain was inversely proportional to the AVFRP existing prior to the infusion of the glycoside, the possibility was considered that the state of cardiac innervation modified the effects of ouabain on atrioventricular conduction by affecting the resting level of the AVFRP.

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