Myocardial metabolic and hemodynamic effects of intravenous MDL-17,043, a new cardiotonic drug, in patients with chronic severe heart failure.
MDL-17,043, a new inotropic drug with vasodilator properties, has been shown to produce salutary hemodynamic effects in severe heart failure, but its effects on myocardial metabolism are unknown. To determine whether such hemodynamic effects are associated with adverse effects on the myocardial oxygen demand and supply relationship, we evaluated the effects of intravenous MDL-17,043 given in incremental doses to a mean maximum dose of 2.1 mg/kg, in nine patients with severe chronic heart failure. Overall cardiac pump performance was significantly improved by MDL-17,043, as reflected by an 88% increase in stroke work index (17 +/- 11 to 32 +/- 19 gm-m/m2; p less than 0.001), a 43% reduction in left ventricular filling pressure (28 +/- 4 to 16 +/- 5 mm Hg; p less than 0.0001), a 49% reduction in systemic vascular resistance (1832 +/- 490 to 937 +/- 296 dynes-sec-cm-5; p less than 0.0001) with a slight (11%) decrease in mean arterial pressure (86 +/- 17 to 76 +/- 19 mm Hg; p = 0.005) and without significant changes in heart rate (88 +/- 14 to 91 +/- 12 bpm; p = NS). These hemodynamic effects were associated with an 18% reduction in myocardial oxygen consumption (17 +/- 5 to 14 +/- 5 ml/min p = 0.01), a 17% reduction in myocardial arteriovenous oxygen difference (13.2 +/- 2.4 to 10.9 +/- 1.8 volumes %; p = 0.01), and a 120% improvement in external myocardial efficiency (stroke work index/oxygen consumption) (1.0 +/- 0.6 to 2.2 +/- 0.9; p less than 0.0001).(ABSTRACT TRUNCATED AT 250 WORDS)
D000368:Aged; D001783:Blood Flow Velocity; D002316:Cardiotonic Agents / Q000627:therapeutic use*; D002908:Chronic Disease; D017335:Enoximone; D005260:Female; D006333:Heart Failure / Q000188:drug therapy / Q000378:metabolism / Q000503:physiopathology*; D006439:Hemodynamics / Q000187:drug effects*; D006801:Humans; D007093:Imidazoles / Q000627:therapeutic use*; D007263:Infusions, Parenteral; D007773:Lactates / Q000097:blood; D019344:Lactic Acid; D008297:Male; D008875:Middle Aged; D009206:Myocardium / Q000378:metabolism*; D010101:Oxygen Consumption / Q000187:drug effects
D002316:Cardiotonic Agents; D007093:Imidazoles; D007773:Lactates; D019344:Lactic Acid; D017335:Enoximone