Effects of prostacyclin and milrinone on pulmonary hemodynamics in newborn lambs with persistent pulmonary hypertension induced by ductal ligation

Prostacyclin (PGI2) stimulates adenyl cyclase to synthesize cAMP within the vascular smooth muscle resulting in vasodilatation. Milrinone inhibits cAMP clearance by phosphodiesterase type III. We studied the dose response of pulmonary and systemic hemodynamics to intratracheal (IT) PGI2 in newborn lambs with pulmonary hypertension (PH) and whether intravenous milrinone potentiate these effects. IT-PGI2 at varying doses was administered to lambs with PH induced by prenatal ductal ligation. IT-PGI2 doses were repeated in the presence of intravenous milrinone (bolus-100 μg/kg followed by infusion at 1 μg/kg/min). Increasing doses of IT-PGI2 significantly decreased mean pulmonary arterial pressures (PAP) and pulmonary vascular resistance (PVR) and increased pulmonary blood flow (PBF). Intravenous milrinone by itself produced a significant reduction in PVR and a significant increase in PBF. Intravenous milrinone significantly shortened the onset, prolonged the duration and degree of pulmonary vasodilation produced by PGI2. We conclude that intravenous milrinone potentiates the pulmonary vasodilator effects of PGI2 at lower doses.