Breithaupt K, Belz G G, Kempinski S, Schicketanz K H, Dieterich H A
Zentrum für kardiovaskuläre Pharmakologie, Mainz--Wiesbaden.
Z Kardiol. 1991;80 Suppl 4:15-20.
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.
在一项针对10名健康志愿者的安慰剂对照、交叉、双盲试验中,研究了依诺昔酮对心脏和外周血管的影响。在口服3mg/kg依诺昔酮之前以及之后1、2、3和4小时,通过机电收缩期(QS2c)显示出直接的正性肌力作用,并采用静脉阻塞体积描记法测量小腿动脉血流量。测量了人浅表手部静脉的去甲肾上腺素(7 - 640ng/min)剂量反应曲线,并在相同时间点测定依诺昔酮和依诺昔酮 - 亚砜的血浆浓度。所有测量的峰值效应在1小时时观察到,且与血浆浓度峰值一致:QS2c缩短36±13ms(平均值±标准差;与安慰剂相比,p<0.01);动脉血流量从2.10±0.58增加至4.32±1.26ml·100ml⁻¹·min⁻¹(平均值±标准差;与安慰剂相比,p<0.01);去甲肾上腺素剂量反应曲线右移(与基线相比,20 - 320ng/min时p<0.01),即与依诺昔酮给药前达到相同血管收缩程度需要高3至5倍剂量的去甲肾上腺素。除了其正性肌力作用外,依诺昔酮还可引起外周动脉扩张,并减弱去甲肾上腺素诱导的静脉血管收缩。这些药理学特性的组合可能是依诺昔酮对心力衰竭有益作用的原因。