title: Comparison of positive inotropic effects of milrinone, dobutamine and ouabain.
abstract: 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/mm2) 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/mm2), 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 ED10 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.
authors.affiliation: Division of Cardiovascular Medicine, School of Medicine, University of California, Davis, Sacramento 95817.
authors.forename: S V
authors.initials: SV
authors.lastname: Rendig
authors.forename: E A
authors.initials: EA
authors.lastname: Amsterdam
mesh_terms: D000818:Animals; D002316:Cardiotonic Agents / Q000494:pharmacology*; D046508:Culture Techniques; D004280:Dobutamine / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D008297:Male; D020105:Milrinone; D008955:Models, Cardiovascular; D009200:Myocardial Contraction / Q000187:drug effects*; D010042:Ouabain / Q000494:pharmacology*; D010210:Papillary Muscles / Q000187:drug effects; D011728:Pyridones / Q000494:pharmacology*; D011817:Rabbits
chemical_list: D002316:Cardiotonic Agents; D011728:Pyridones; D004280:Dobutamine; D010042:Ouabain; D020105:Milrinone