Hemodynamic effects of MDL 17,043, a new cardiotonic agent, in patients with congestive heart failure: comparison with sodium nitroprusside.
MDL 17,043 (MDL), a new cardiotonic agent, was given intravenously at a single dose of 0.5 mg/kg to 14 patients with congestive heart failure (stages II-III). The mean half-life of plasma elimination of the parent compound determined in eight subjects was 81 min. MDL is rapidly metabolized to the sulfoxide with a maximum plasma metabolite concentration reached at 15 min after parent drug infusion and a metabolite half-life of 164 min. In eight patients, the hemodynamic effects of MDL were compared with those of sodium nitroprusside (SN) given at a dose lowering mean blood pressure by 20 mm Hg. Both agents increased cardiac output (p less than 0.001 for MDL, p = 0.06 for SN) and decreased total peripheral resistance values (p less than 0.001 for both) and left ventricular end-diastolic pressure (wedge pressure) (p less than 0.001 for MDL, p less than 0.01 for SN). However, MDL was able to increase left ventricular stroke work, whereas SN failed. As both agents induced comparable changes in loading conditions, it can be assumed that MDL not only acts by peripheral vasodilation but also has a direct positive inotropic action on the heart muscle. Myocardial oxygen uptake, assessed indirectly by tension-time index, was not affected by MDL (p greater than 0.2) despite the improvement in myocardial contractile state, thus making this new agent suitable for the treatment of congestive heart failure secondary to ischemic heart disease.
D000328:Adult; D000368:Aged; D002316:Cardiotonic Agents / Q000009:adverse effects / Q000494:pharmacology*; D017335:Enoximone; D005260:Female; D005292:Ferricyanides / Q000494:pharmacology*; D006333:Heart Failure / Q000188:drug therapy*; D006439:Hemodynamics / Q000187:drug effects*; D006801:Humans; D007093:Imidazoles / Q000009:adverse effects / Q000494:pharmacology*; D008297:Male; D008875:Middle Aged; D009599:Nitroprusside / Q000009:adverse effects / Q000494:pharmacology*
D002316:Cardiotonic Agents; D005292:Ferricyanides; D007093:Imidazoles; D009599:Nitroprusside; D017335:Enoximone