Effects of amrinone and dobutamine on PGF2 alpha-induced pulmonary hypertension in dogs.
The hemodynamic benefits and pulmonary vascular selectivity of amrinone, dobutamine and amrinone + dobutamine were assessed in a canine model of vasoconstrictive pulmonary hypertension. Dogs were equipped with central and peripheral catheters and with an electromagnetic flow probe placed around the ascending aorta for the measurement of cardiac function. Through a laparotomy, an arteriovenous fistula was created between the abdominal aorta and the inferior vena cava. Gradual opening of this fistula, which permitted construction of pressure-flow curves (mean pulmonary artery pressure over the cardiac index, PAP/CI), was utilized to identify the pulmonary vascular effects of amrinone and dobutamine. PGF2 alpha, prostaglandin derivative, induced stable pulmonary hypertension along with significant reduction in CI. The resultant pulmonary hypertension translated into a significant increase in both the slope and pressure intercept of the PAP/CI curve. The bipyridine derivative, amrinone, did not reverse the CI reduction observed with PGF2 alpha: both mean arterial pressure and PAP were decreased as was the intercept of the PAP/CI curve. Dobutamine, a beta-agonist, reversed the CI decline elicited by PGF2 alpha but the elevated pulmonary pressure remained unaffected; dobutamine reduced the slope of the PAP/CI curve. When combined, amrinone and dobutamine demonstrated additive beneficial hemodynamic effects and improved lung perfusion. Their additive effects were also indicated by data on the PAP/CI curve: both the slope and the pressure intercept were significantly reduced. These results suggest that amrinone and dobutamine interact at different sites of the pulmonary vasculature and that their association might be beneficial in vasoconstrictive pulmonary hypertension although no significant pulmonary vascular selectivity could be observed.
Département de Pharmacologie, Faculté de Médecine, Université de Montréal, Qué., Canada.
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Dumont
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Dagher
D000676:Amrinone / Q000627:therapeutic use*; D000818:Animals; D015237:Dinoprost; D004195:Disease Models, Animal; D004280:Dobutamine / Q000627:therapeutic use*; D004285:Dogs; D004359:Drug Therapy, Combination; D006439:Hemodynamics / Q000187:drug effects; D006976:Hypertension, Pulmonary / Q000139:chemically induced / Q000188:drug therapy*; D012129:Respiratory Function Tests
D004280:Dobutamine; D015237:Dinoprost; D000676:Amrinone