Effects of a new cardiotonic agent, MDL-17,043, on myocardial contractility and left ventricular performance in congestive heart failure.
MDL-17,043, a newly synthesized imidazole derivative, has been shown to manifest both inotropic and peripheral vasodilating properties in experimental animals and to be effective when administered orally. Although MDL-17,043 has been demonstrated to inhibit cyclic adenosine monophosphate (AMP) phosphodiesterase activity in vitro, whether its inotropic activity derives from increased myocellular levels of cyclic AMP is not yet known. After intravenous administration of MDL-17,043 to seven patients with severe congestive heart failure (CHF) at the time of cardiac catheterization, the rate of left ventricular (LV) pressure rise increased almost immediately from a control of 878 +/- 161 to a peak of 1010 +/- 217 mm Hg/sec (p less than 0.01), while cardiac index tended to increase but not significantly. Subsequently, as mean aortic pressure decreased from 86.4 +/- 15.9 at control to 75.6 +/- 16.4 mm Hg (p less than 0.01), cardiac index rose from 1.87 +/- 0.35 at control to 2.30 +/- 0.27 L/min/m2 at peak effect (p less than 0.01), while pulmonary capillary wedge pressure fell from 23.7 +/- 5.1 to 13.1 +/- 4.6 mm Hg (p less than 0.01). Concomitantly, the rate of LV pressure rise returned to control value. Thus, intravenous administration of MDL-17,043 improves myocardial contractility and LV performance in patients with severe CHF. This manifest improvement in LV performance most probably results from both the positive inotropic and direct vasodilating effects of MDL-17,043.
Strain
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J
Grose
R
R
Maskin
C S
CS
LeJemtel
T H
TH
D002316:Cardiotonic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D055598:Chemical Phenomena; D002621:Chemistry; D017335:Enoximone; D005260:Female; D006333:Heart Failure / Q000188:drug therapy*; D006352:Heart Ventricles / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology / Q000627:therapeutic use*; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects; D014664:Vasodilation / Q000187:drug effects
D002316:Cardiotonic Agents; D007093:Imidazoles; D017335:Enoximone