Dopaminergic drugs in congestive heart failure: Hemodynamic and neuroendocrine responses to ibopamine, dopamine, and dihydroergotoxine

Marco Metra, Cristina Missale, Pier Franco Spano, Livio Dei Cas

Research output: Contribution to journalArticle

Abstract

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 dopaminergic receptor stimulation in the hemodynamic and neurohumoral activity of ibopamine, we compared the effects of ibopamine, 100 mg orally (p.o.) with those of dopamine 2, 4, and 6 μg/kg/min intravenously (i.v.) and of the DA2 agonist dihydroergotoxine 6 μg/kg i.v. in 13 patients with chronic CHF [left ventricular ejection fraction (LVEF) ±35%]. All patients underwent right heart Swan-Ganz catheterization with determination of hemodynamic parameters at baseline, after 30 min of infusion of each dose of dopamine (DA) and ±6 h after ibopamine and dihydroergotoxine administration. Blood samples for the assessment of plasma renin activity (PRA), aldosterone, norepinephrine (NE), and epinephrine (Epi) were also obtained. Ibopamine induced a peak 21% increase of cardiac index (CI) with a 23 and 25% increase in stroke volume (SV) and stroke work indexes (SWI), respectively, and an 18% reduction in systemic vascular resistance (SVR). Similar changes were observed after DA infused at the doses of 2 and 4 μg/kg/min, whereas with the dose of 6 μg/kg/min heart rate (HR) increased by 23% and SV index (SVI) did not change further. Dihydroergotoxine administration induced only a significant 9% decrease in mean arterial pressure (MAP), with a 13% reduction in SVR. Plasma NE levels were reduced by 24% after ibopamine and by 20% after dihydroergotoxine; in contrast, DA did not significantly change NE levels at the doses of 2 and 4 μg/kg/min and increased them at 6 μg/kg/min. Plasma aldosterone levels were significantly decreased by all three agents. The effects of ibopamine on systemic hemodynamics are similar to those of DA infused at 2-4 μg/kg/min, whereas the DA2 agonist dihydroergotoxine 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, hemodynamic effects of ibopamine probably can be ascribed mainly to the stimulation of DA1 and DA2 receptors, whereas its neuroendocrine effects are produced by DA2 receptor stimulation.

Original languageEnglish
Pages (from-to)732-740
Number of pages9
JournalJournal of Cardiovascular Pharmacology
Volume25
Issue number5
Publication statusPublished - 1995

Keywords

  • Congestive heart failure
  • DA2 receptor stimulation
  • Dihydroergotoxine
  • Dopamine
  • Ibopamine
  • Norepinephrine
  • Systemic hemodynamics

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Pharmacology

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