Regional blood flow and hemodynamics in the rabbit with adriamycin cardiomyopathy: effects of isosorbide dinitrate, dobutamine and captopril

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.