Cardiac depressant and circulatory effects of prostaglandin D₂ in developing lambs

Pulmonary and systemic vascular and cardiac effects of intravenous prostaglandin D₂ (PGD₂), given at 0.1, 1.0, and 10 μg/kg, were measured in chronically instrumented lambs during normoxia and hypoxia at ages 2-3, 9-14, and ≥21 days. During normoxia, PGD₂ was not a pulmonary vasodilator at low dose and caused mild pulmonary vasoconstrictor changes at 10 μg/kg in young lambs; normoxic older lambs had pulmonary vasoconstriction at both 1 μg/kg and 10 μg/kg doses. With hypoxemia, PGD₂ caused mild pulmonary vasodilation at all doses in the youngest lambs, converted the normoxic 9-14-day-old lambs' pressor response to a nonresponse, and attenuated the high-dose pulmonary vasoconstriction in the ≥21 day lambs. PGD₂ was a directly dose-related systemic pressor (+5 - 20 mmHg) at all ages during both normoxia and hypoxia. Heart rate and cardiac output decreased in a dose-dependent fashion during both normoxia and hypoxia. The PGD₂-induced cardiac depression was unaltered by age or ventilatory hypoxemia. PGD₂ response of the lamb pulmonary circulation changes from marginal dilation to constriction during the late postnatal development. During the same period, PGD₂ dose-related systemic pressure and cardiac depressant effects remain stable. Thus the circulatory effects of PGD₂ are complexly interrelated with age, dose, and presence of hypoxemia.