INFLUENCE OF ENDOGENOUS CARDIAC CATECHOLAMINE DEPLETION ON THE FORCE AND RATE OF ISOLATED HEART PREPARATIONS AND THEIR RESPONSE TO OUABAIN

¹ Department of Pharmacology, Geigy Research Laboratories, Ardsley, New York

The action of ouabain on cardiac tissue from cats pretreated with reserpine or guanethidine was studied. In addition, the inotropic and chronotropic effects of reserpine and guanethidine on in vitro cat cardiac preparations was reevaluated. Reserpine (administered every day for 3 days) reduced ventricular catecholamines to less than 2% of the controls. In cat Langendorff preparations no significant difference was observed in initial contractile force, heart rate or histology between hearts from treated or control animals. However, prior reserpinization significantly depressed the inotropic action of ouabain. Guanethidine (administered every day for 2 days) reduced ventricular catecholamine content to 8.6% of the controls. In the cat papillary muscle and Langendorff preparations there was no discernible difference between control and treated hearts with respect to contractile force or rate. Nevertheless, ouabain-induced augmentation was significantly depressed in preparations from guanethidinized animals. These data indicate that the positive inotropic action of ouabain is in some way dependent upon the availability of adequate myocardial catecholamine stores, and adds support to previous reports from this laboratory which suggested that the mechanism of the positive inotropic action of ouabain might be related (at least in part) to its ability to release endogenous catecholamines.