Age-dependent effects of sodium nitroprusside and dopamine in lambs

Vasodilators and cardiotonic agents are frequently used in hypoxemic newborn infants with persistent pulmonary hypertension. We studied the effects of sodium nitroprusside and dopamine on hypoxia-induced pulmonary hypertension in seven newborn (0-3 d) and seven young (10-14 d) lambs under chloralose anesthesia. Pulmonary blood flow, pulmonary arterial pressure, systemic arterial pressure, and left atrial pressure were measured during the experimental states of hypoxia, hypoxia plus nitroprusside, and hypoxia plus both nitroprusside and dopamine. Pulmonary and systemic arterial pressure and cardiac output all decreased significantly when hypoxemic newborn lambs were given nitroprusside; in contrast, when hypoxemic young lambs were given nitroprusside, cardiac output did not change, whereas both pulmonary and systemic arterial pressure decreased significantly. Calculated pulmonary vascular resistance was unchanged in the newborn lambs but fell in the young lambs, implying that active pulmonary vasodilation by nitroprusside occurred only in the latter group. Systemic vascular resistance was not significantly affected by nitroprusside in either group. The addition of dopamine resulted in qualitatively similar changes in both groups of lambs, with increased pulmonary blood flow and no significant change in pulmonary or systemic arterial pressures. Maturation in vascular smooth muscle responsiveness to nitrovasodilators may explain the age-related differences that we found in lambs, and could also account for the variable clinical responses to vasodilators observed in hypoxemic human infants.