The search for a digitalis substitute II milrinone (Win 47203) its action on the heart-lung preparation of the dog

Abstract Milrinone (Win 47203) is a dipyridine related to amrinone, which is about 20–50 times as effective as amrinone when assayed on cardiac contractility. In dog heart-lung preparations, milrinone in a concentration of 0.25–0.5 μM produced a near maximal positive inotropic effect on a variety of acute heart failures. This dosage produced a minimal increase in heart rate and reduced the PR interval. Large doses of milrinone did not produce cardiac irregularities and in Nifedipine heart failure with ventricular irregularities, it eliminated these irregularities. Papaverine-induced heart failure was resistant to ouabain, epinephrine and milrinone therapy. In the presence of positive inotropic amounts of papaverine or theophylline, a pentobarbital heart failure was superimposed. This heart failure responded poorly to milrinone, although it responded to both the addition of epinephrine and ouabain. It is thus possible that milrinone, papaverine and theophyline have closely related sites of action.