Acute hemodynamic effects of MDL 19205 in mild congestive heart failure.
MDL 19205 4-ethyl-1-,3-dihydro-5-(4-pyridinylcarbonyl)-2H-imidazol-2-one, a new cardioactive agent, has been shown to increase myocardial contractile force in animals. It is effective by both oral and intravenous routes. We studied 11 patients with congestive heart failure--in 10 cases owing to coronary artery disease, and in one to cardiomyopathy. All patients had symptoms of NYHA class II or III, left ventricular ejection fractions (LVEF) less than 55%, and left ventricular end-diastolic pressures (LVEDP) greater than 15 mm Hg. Following routine coronary angiography and ventriculography, 0.5 mg/kg MDL 19205 was administered intravenously over 5 min to six patients. Thirty minutes after injection, hemodynamic measurements and ventriculography were repeated. Mean LVEF increased from 42 to 49% (p less than 0.05 for baseline vs. 30 min). In five patients ventriculography was repeated 60 min after placebo administration: LVEF decreased from 45 to 40%. LVEDP decreased from 29 +/- 8 to 16 +/- 8 mm Hg after MDL 19205 administration (p less than 0.05) and remained constant at 24 mm Hg in the placebo group. The small although nonsignificant increase of LVdP/dt after MDL 19205 administration (10 +/- 33%), together with a considerable decrease in LVEDP, was consistent with a positive inotropic effect. LVdP/dt/total pressure developed (VPM), a measure of contractility relatively independent of changes in pre- and afterload, increased from 1.0 +/- 0.3 to 1.3 +/- 0.3 s-1 (p less than 0.05). Neither parameter of contractility (LVdP/dt and VPM) changed significantly in the placebo group.(ABSTRACT TRUNCATED AT 250 WORDS)
D002316:Cardiotonic Agents / Q000097:blood / Q000494:pharmacology / Q000627:therapeutic use*; D006333:Heart Failure / Q000188:drug therapy* / Q000503:physiopathology; D006439:Hemodynamics / Q000187:drug effects*; D006801:Humans; D007093:Imidazoles / Q000097:blood / Q000494:pharmacology / Q000627:therapeutic use*; D007275:Injections, Intravenous; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects*
D002316:Cardiotonic Agents; D007093:Imidazoles; C039686:piroximone