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 micrograms/kg, were measured in chronically instrumented lambs during normoxia and hypoxia at ages 2-3, 9-14, and greater than or equal to 21 days. During normoxia, PGD2 was not a pulmonary vasodilator at low dose and caused mild pulmonary vasoconstrictor changes at 10 micrograms/kg in young lambs; normoxic older lambs had pulmonary vasoconstriction at both 1 microgram/kg and 10 micrograms/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 greater than or equal to 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 pressor and cardiac depressant effects remain stable. Thus, the circulatory effects of PGD2 are complexly interrelated with age, dose, and presence of hypoxemia.