Influence of the calcium-sensitizer UDCG-115 on hemodynamics and myocardial energetics in patients with idiopathic dilated cardiomyopathy. Comparison with nitroprusside.
UDCG-115 is a new cardiotonic agent which in vitro increases the sensitivity of the contractile proteins to calcium ions, inhibits the activity of phosphodiesterase, and prolongs the duration of the action potential. The influence of UDCG-115 (i.v.) on hemodynamics and myocardial energetics was investigated in patients with idiopathic dilated cardiomyopathy (NYHA II-III) and compared to the effects of the pure vasodilator nitroprusside. UDCG-115 increased cardiac index from 3.2 +/- 0.4 to 4.2 +/- 0.8 l/min/m2 (p less than 0.01) and decreased left ventricular end-diastolic wall stress (preload) from 52 +/- 21 to 28 +/- 18 10(3) dyn/cm2 (p less than 0.01) and end-systolic wall stress (afterload) from 201 +/- 61 to 129 +/- 43 10(3) dyn/cm2 (p less than 0.01) compared to control conditions. Compared to nitroprusside, for a similar decrease in preload and afterload. UDCG-115 increased cardiac index by 40% (p less than 0.01), stroke volume index by 37% (p less than 0.01) and maximum rate of left ventricular pressure rise by 23% (p less than 0.05). Heart rate did not significantly change with either drug. Myocardial oxygen consumption per beat decreased by 33% (p less than 0.05) with UDCG-115 and by 30% (p less than 0.01) with nitroprusside. With both drugs, the decrease of myocardial oxygen consumption correlated significantly with the decrease of left ventricular systolic stress-time integral. The slopes of the respective linear regression lines were not significantly different. Thus, UDCG-115 given intravenously in patients with idiopathic dilated cardiomyopathy and moderate congestive heart failure exhibits significant inotropic and vasodilating properties. The systemic hemodynamic actions are associated with favorable effects on myocardial energetics.
Hasenfuss
G
G
Medizinische Universitätsklinik, Innere Medizin III, Kardiologie, Universität Freiburg, FRG.
Holubarsch
C
C
Heiss
H W
HW
Rattert
B
B
Just
H
H
D000328:Adult; D002311:Cardiomyopathy, Dilated / Q000503:physiopathology*; D002316:Cardiotonic Agents / Q000494:pharmacology*; D004734:Energy Metabolism / Q000187:drug effects*; D005260:Female; D005292:Ferricyanides / Q000494:pharmacology*; D006439:Hemodynamics / Q000187:drug effects*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009206:Myocardium / Q000378:metabolism*; D009599:Nitroprusside / Q000494:pharmacology*; D011724:Pyridazines / Q000494:pharmacology*
D002316:Cardiotonic Agents; D005292:Ferricyanides; D011724:Pyridazines; D009599:Nitroprusside; C041648:pimobendan