Haemodynamic responses to dopamine and dobutamine infusions as a function of duration of infusion

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.