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

Oh, Ah Young; Park, Hee Yeon; Kim, Koung Ok; Kim, Seong Deok

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 50microgram, 500microgram, and 5,000microgram, isoproterenol 0.4microgram, 4microgram, and 40microgram, and milrinone 2.5microgram, 25microgram, and 250microgram were added to perfusate sequentially during normoxic ventilation (21% O2-5% CO2-balanced N2). Baseline pulmonary artery pressure changes and subsequent hypoxic pressor responses during hypoxic ventilation (5% O2-5% CO2-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 < 0.05). The last dose listed for each of the three drugs reversed hypoxic pulmonary vasoconstriction nearly completely. The calculated dose required to reduce the hypoxic pressor response to 50% of the initial response before drug administration (ED50) was 155microgram (95% CI: 80-263microgram) for dobutamine, 0.23microgram (95% CI: 0.011-0.75 microgram) for isoproterenol and 6.31microgram (95% CI: 3.1-10.8microgram) 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. (Korean J Anesthesiol 2004; 46: 454~461)