The Effects of Oral Enoximone on Cardiac Performance, Calf Arterial Blood Flow, and Constrictor Effects of Norepinephrine Infused Into Hand Veins in Humans

Abstract

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 determined at the same time points. Peak effects on all measures 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/min (mean +/- SD; p less than 0.01 compared to placebo); and 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 three to five 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.