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.

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 µg, 500 µg, and 5,000 µg, isoproterenol 0.4 µg, 4 µg, and 40 µg, and milrinone 2.5 µg, 25 µg, and 250 µg 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.

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 155 µg (95% CI: 80-263 µg) for dobutamine, 0.23 µg (95% CI: 0.011-0.75 µg) for isoproterenol and 6.31 µg (95% CI: 3.1-10.8 µg) for milrinone. The relative potency of the drugs on HPV, based on ED50 was dobutamine 10: isoproterenol 0.015: and milrinone 0.41.

Dobutamine, isoproterenol, and milrinone all reduced pulmonary vascular resistance and hypoxic pulmonary vasoconstriction in a dose dependent manner.