COMPARISON OF POSITIVE INOTROPIC EFFECTS OF MILRINONE, DOBUTAMINE AND OUABAIN

This study compared the positive inotropic actions of milrinone in isolated rabbit myocardium with that of the conventional positive inotropic drug, dobutamine, and a cardiac glycoside, ouabain. Maximal increase in developed tension (g/mm(2)) was significantly (p < 0.05) greater with ouabain (from 2.0 to 4.4; 132 +/- 11%) than with dobutamine (from 3.9 to 6.0; 77.8 +/- 22.4%) or milrinone (from 2.4 to 3.6; 54.0 +/- 12.0%) Maximal augmentation of the rate of tension development (g/s/mm(2)), however, was similar with ouabain (from 14.3 to 39.7; 187 +/- 20%) and dobutamine (from 25.9 to 64.4; 174 +/- 35%), and both were significantly (p < 0.05) greater than with milrinone (from 18.2 to 30; 73.1 +/- 14.7%). In combination with dobutamine, however, the dose-response curve of milrinone was shifted to the left, and its ED(10) was significantly (p < 0.001) reduced by 100-fold to 1.6 x 10(-7) M. Thus, milrinone is significantly less potent than dobutamine or ouabain in vitro and is without contractile effect at clinically relevant concentrations. However, data from the combined application of a catecholamine and milrinone in isolated myocardium suggest that milrinone may induce a direct positive inotropic effect at clinical concentrations in the presence of augmented sympathetic neurohumoral stimulation.