Dose-response effects of milrinone on hemodynamics of newborn pigs with hypoxia-reoxygenation.

Abstract

Neonatal asphyxia causes cardiogenic shock and pulmonary hypertension with decreased brain perfusion. We examined the dose-response of milrinone on systemic, pulmonary, and carotid circulations in a model of neonatal hypoxia-reoxygenation. Controlled, block-randomized study in a university research laboratory. Mixed breed piglets (1-3 days, 1.5-2.3 kg). In acutely instrumented piglets normocapnic alveolar hypoxia (10-15% oxygen) was induced for 2 h followed by reoxygenation with 100% oxygen (1 h) then 21% oxygen (3 h). At 2 h of reoxygenation after a volume loading (10 ml/kg) either saline or milrinone (bolus and infusion at 0.25, 0.5, or 0.75 microg/kg per minute) was given for 2 h in a blinded-randomized fashion (n = 7/group). All milrinone-treated groups had higher cardiac output and stroke volume than those of saline-treated hypoxic controls, which showed progressive decline in these measurements. At 2 h of infusion plasma milrinone levels were significantly correlated with cardiac output (r = 0.6), which increased from pretreatment value in the group receiving 0.75 microg/kg per minute. Milrinone maintained mean arterial pressure; heart rate and pulmonary arterial pressure did not differ between groups. Milrinone prevented continued increases in systemic and pulmonary vascular resistances after hypoxia-reoxygenation. Milrinone infusion at higher doses increased common carotid flow. Milrinone-treated piglets had increased systemic and carotid oxygen delivery, with no difference in plasma and myocardial lactate levels among groups. When used to treat shock in newborn piglets with hypoxia-reoxygenation, milrinone improved cardiac output and carotid flow while maintaining systemic blood pressure. Pulmonary hypertension was not aggravated. Further studies are needed to confirm these findings in asphyxiated neonates.