Wanless R B, Anand I S, Gurden J, Harris P, Poole-Wilson P A
Department of Cardiac Medicine, Cardiothoracic Institute, London, UK.
J Pharmacol Exp Ther. 1987 Dec;243(3):1101-6.
We have studied the effects of captopril, nitrates and dobutamine on hemodynamics and regional blood flow in the conscious rabbit with adriamycin cardiomyopathy. Rabbits were injected twice weekly with adriamycin (1 mg.kg-1 bw.) for 8 weeks and subsequently maintained for 2 weeks without adriamycin in order to allow recovery from any noncardiac effects. Doses of drug for investigation (captopril, 300 micrograms.kg-1.min-1; isosorbide dinitrate, 10 micrograms.kg-1.min-1; and dobutamine, 10.9 micrograms.kg-1.min-1) were chosen in anticipation of a 20% increase of cardiac output in animals with heart failure. In animals with heart failure myocardial blood flow was increased by dobutamine and to a lesser extent by captopril. Renal blood flow was increased only by captopril and nitrates. Cerebral blood flow was reduced by captopril in control animals but unaltered in animals with heart failure. The observed alterations of blood flow were similar to those known to occur in humans and indicate that this is a useful model of heart failure for the evaluation of new drugs.
我们研究了卡托普利、硝酸盐和多巴酚丁胺对阿霉素诱导的心肌病清醒兔血流动力学和局部血流的影响。每周两次给兔子注射阿霉素（1毫克/千克体重），持续8周，随后在不注射阿霉素的情况下维持2周，以便从任何非心脏效应中恢复。为了预期心力衰竭动物的心输出量增加20%，选择了用于研究的药物剂量（卡托普利，300微克/千克体重·分钟；异山梨醇二硝酸酯，10微克/千克体重·分钟；多巴酚丁胺，10.9微克/千克体重·分钟）。在心力衰竭动物中，多巴酚丁胺可增加心肌血流量，卡托普利的作用较小。只有卡托普利和硝酸盐可增加肾血流量。在对照动物中，卡托普利可降低脑血流量，但在心力衰竭动物中未改变。观察到的血流变化与已知在人类中发生的变化相似，表明这是一种用于评估新药的有用的心力衰竭模型。
