Effect of amrinone on sodium-calcium exchange in cardiac sarcolemmal vesicles

The mechanism of action of amrinone, a synthetic cardiotonic drug, is unknown. It has been postulated that it increases cardiac contractility by increasing intracellular free Ca++ concentration, in some manner. Purified cardiac sarcolemmal vesicles have been shown capable of carrying out Ca++ transport in either direction by Na+/Ca++ exchange. We have observed that amrinone inhibits Ca++ uptake by Na+/Ca++ exchange in such vesicles prepared from both guinea pig and rat hearts. The inhibitory effect is dose-dependent and maximal at a concentration of about 300 micrograms/ml. If amrinone decreases the rate of Ca++ efflux from myocardial cells in vivo during diastole by this mechanism, this action may account, at least in part, for the observed positive inotropic effect of the drug.