MacCannell K L, Giraud G D, Hamilton P L, Groves G
Pharmacology. 1983;26(1):29-39. doi: 10.1159/000137766.
In normal animals, dopamine and dobutamine produce similar haemodynamic effects. However, clinical observations on patients in heart failure suggest that dobutamine produces a more favourable and stable haemodynamic effect. One explanation is that the inotropic action of dopamine is largely an indirect one mediated through noradrenaline release, while that of dobutamine is direct. If this were true, one would predict that the haemodynamic effects of dopamine and dobutamine would be similar over short-term infusions, but that the response to dopamine would be attenuated with time as a result of noradrenaline depletion. Experiments are reported which are consistent with this explanation. 15-min infusions of graded doses of dopamine and dobutamine produced indistinguishable haemodynamic effects in a dog model in which the haemodynamic characteristics of heart failure were produced by a chronic aorta-left atrial shunt: dopamine also produced the expected increase in mesenteric and renal flows with this short-term exposure. With long-term infusions of dopamine (5 h), the specific mesenteric/renal vasodilatation was lost with time, and indices of myocardial contractility also were attenuated with time. In contrast, the haemodynamic actions of dobutamine were well maintained. Both amines lowered total peripheral resistance and ventricular filling pressures over the entire period. These results suggest that the haemodynamic responses to dopamine change with time, and that some of the discrepancies between animal observations (short term) and those in patients (invariably long term) can be explained on this basis rather than on the basis of species differences or underlying pathology. They also suggest that dopamine is a less suitable 'inotropic' drug than dobutamine.
在正常动物中，多巴胺和多巴酚丁胺产生相似的血流动力学效应。然而，对心力衰竭患者的临床观察表明，多巴酚丁胺产生更有利且稳定的血流动力学效应。一种解释是，多巴胺的正性肌力作用很大程度上是通过去甲肾上腺素释放介导的间接作用，而多巴酚丁胺的正性肌力作用是直接的。如果这是真的，那么可以预测，多巴胺和多巴酚丁胺在短期输注时血流动力学效应相似，但由于去甲肾上腺素耗竭，随着时间推移对多巴胺的反应会减弱。本文报道了与该解释相符的实验。在通过慢性主动脉 - 左心房分流产生心力衰竭血流动力学特征的犬模型中，静脉输注不同剂量的多巴胺和多巴酚丁胺15分钟，产生了难以区分的血流动力学效应：短期输注多巴胺也使肠系膜和肾血流量出现预期的增加。长期输注多巴胺（5小时）后，肠系膜/肾血管的特异性扩张随时间消失，心肌收缩力指标也随时间减弱。相比之下，多巴酚丁胺的血流动力学作用保持良好。在整个实验期间，两种胺类药物均降低了总外周阻力和心室充盈压。这些结果表明，对多巴胺的血流动力学反应随时间变化，动物（短期）观察结果与患者（通常为长期）观察结果之间的一些差异可以基于此而非物种差异或潜在病理来解释。它们还表明，与多巴酚丁胺相比，多巴胺是一种不太合适的“正性肌力”药物。
