The Effect of Isoproterenol, Dobutamine, and Milrinone on Pulmonary Vasoconstriction in Isolated Rat Lungs

Abstract

Background: Dobutamine, isoproterenol, and milrinone are inotropic agents with vasodilatory properties, and are frequently used perioperatively. We undertook to examine the effects of these three drugs on the pulmonary vasculature, excluding cardiovascular effects, by determining their effects on pulmonary artery pressure and hypoxic pulmonary vasoconstriction in an isolated rat lung model. Methods: Thirty Sprague-Dawley rats were divided into a dobutamine group (n = 10), an isoproterenol group (n = 10) and a milrinone group (n = 10). Dobutamine 50, 500, and 5,000, isoproterenol 0.4, 4, and 40, and milrinone 2.5, 25, and 250 were added to perfusate sequentially during normoxic ventilation (21% -5% -balanced N2). Baseline pulmonary artery pressure changes and subsequent hypoxic pressor responses during hypoxic ventilation (5% O2-5% -balanced N2) were observed. Results: Dobutamine, isoproterenol, and milrinone all decreased baseline pulmonary artery pressures and hypoxic pressor responses in a dose-dependent manner (P (95% CI: 80-263) for dobutamine, 0.23 (95% CI: 0.011-0.75 ) for isoproterenol and 6.31 (95% CI: 3.1-10.8) for milrinone. The relative potency of the drugs on HPV, based on ED50 was dobutamine 10: isoproterenol 0.015: and milrinone 0.41. Conclusions: Dobutamine, isoproterenol, and milrinone all reduced pulmonary vascular resistance and hypoxic pulmonary vasoconstriction in a dose dependent manner.