[Effect of oral administration of enoximone on cardiac performance, arterial circulation at rest and on the vasoconstrictor effect of local noradrenaline infusions into the human hand vein].
Cardiac and peripheral vascular effects of enoximone were investigated in a placebo-controlled, crossover, double-blind trial in 10 healthy volunteers. Electromechanical systole (QS2c) revealed direct positive inotropic effects and venous occlusion plethysmography of the calf arterial blood flow before and 1, 2, 3, and 4 h following 3 mg/kg of enoximone orally. Norepinephrine (7-640 ng/min) dose-response curves of a superficial human hand vein were measured, and enoximone and enoximone-sulfoxide plasma concentrations were determined at the same time points. Peak effects on all measurements were observed at 1 h and coincided with peak plasma concentrations: QS2c shortened by 36 +/- 13 ms (mean +/- SD; p less than 0.01 compared to placebo); arterial blood flow increased from 2.10 +/- 0.58 to 4.32 +/- 1.26 ml 100 ml-1 min-1 (mean +/- SD; p less than 0.01 compared to placebo); norepinephrine dose-response curves shifted to the right (p less than 0.01 with 20-320 ng/min compared to baseline), i.e., to achieve the same vasoconstriction as before enoximone a 3-to-5-times higher dose of norepinephrine was needed. In addition to its positive inotropic effects, enoximone exerts peripheral arterial dilation and diminishes the venous vasoconstriction induced by norepinephrine. The combination of these pharmacological properties could be responsible for the beneficial effects of enoximone in heart failure.
Breithaupt
K
K
Zentrum für kardiovaskuläre Pharmakologie, Mainz--Wiesbaden.
Belz
G G
GG
Kempinski
S
S
Schicketanz
K H
KH
Dieterich
H A
HA
D000284:Administration, Oral; D000328:Adult; D002302:Cardiac Output / Q000187:drug effects; D002316:Cardiotonic Agents; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004562:Electrocardiography / Q000187:drug effects; D017335:Enoximone; D006225:Hand / Q000098:blood supply; D006439:Hemodynamics / Q000187:drug effects*; D006801:Humans; D007093:Imidazoles / Q000493:pharmacokinetics / Q000494:pharmacology*; D007262:Infusions, Intravenous; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D009200:Myocardial Contraction / Q000187:drug effects*; D009638:Norepinephrine / Q000494:pharmacology*; D010726:Phosphodiesterase Inhibitors; D010991:Plethysmography; D013599:Systole / Q000187:drug effects; D014661:Vasoconstriction / Q000187:drug effects*
D002316:Cardiotonic Agents; D007093:Imidazoles; D010726:Phosphodiesterase Inhibitors; D017335:Enoximone; D009638:Norepinephrine
Einfluss von oral verabreichtem Enoximon auf Herzleistung, arterielle Ruhedurchblutung und auf die vasokonstriktorische Wirkung von lokalen Noradrenalininfusionen in die menschliche Handvene.