DOPAMINERGIC DRUGS IN CONGESTIVE-HEART-FAILURE - HEMODYNAMIC AND NEUROENDOCRINE RESPONSES TO IBOPAMINE, DOPAMINE, AND DIHYDROERGOTOXINE

Ibopamine has hemodynamic and neurohumoral effects potentially useful for the treatment of congestive heart failure (CHF), but its mechanism of action is not completely clear. To evaluate the role of dopaminerg ic receptor stimulation in the hemodynamic and neurohumoral activity o f ibopamine, we compared the effects of ibopamine, 100 mg orally (p.o. ) with those of dopamine 2, 4, and 6 mu g/kg/min intravenously (i.v.) and of the DA2 agonist dihydroergotoxine 6 mu g/kg i.v. in 13 patients with chronic CHF [left ventricular ejection fraction (LVEF) less than or equal to 35%]. All patients underwent right heart Swan-Ganz cathet erization with determination of hemodynamic parameters at baseline, af ter 30 min of infusion of each dose of dopamine (DA) and less than or equal to 6 h after ibopamine and dihydroergotoxine administration. Blo od samples for the assessment of plasma renin activity (PRA), aldoster one, norepinephrine (NE), and epinephrine (Epi) were also obtained. Ib opamine induced a peak 21% increase of cardiac index (CI) with a 23 an d 25% increase in stroke volume (SV) and stroke work indexes (SWI), re spectively, and an 18% reduction in systemic vascular resistance (SVR) . Similar changes were observed after DA infused at the doses of 2 and 4 mu g/kg/min, whereas with the dose of 6 mu g/kg/min heart rate (HR) increased by 23% and SV index (SVI) did not change further. Dihydroer gotoxine administration induced only a significant 9% decrease in mean arterial pressure (MAP), with a 13% reduction in SVR. Plasma NE level s were reduced by 24% after ibopamine and by 20% after dihydroergotoxi ne; in contrast, DA did not significantly change NE levels at the dose s of 2 and 4 mu g/kg/min and increased them at 6 mu g/kg/min. Plasma a ldosterone levels were significantly decreased by all three agents. Th e effects of ibopamine on systemic hemodynamics are similar to those o f DA infused at 2-4 mu g/kg/min, whereas the DA2 agonist dihydroergoto xine reduced arterial pressure and SVR. Plasma aldosterone levels were decreased by all three agents, whereas plasma NE levels were reduced by ibopamine and dihydroergotoxine but not by DA. Therefore, hemodynam ic effects of ibopamine probably can be ascribed mainly to the stimula tion of DA1 and DA2 receptors, whereas its neuroendocrine effects are produced by DA2 receptor stimulation.