At birth, with the initiation of ventilation there is an increase in pulmonary blood flow and a decrease in pulmonary vascular resistance. Prostaglandins probably, at least in part, mediate this ventilation induced fall in pulmonary vasular resistance and indomethacin, an inhibitor of prostaglandin synthesis, produces pulmonary hypertension in the fetus and newborn. Recent evidence suggests that PGD?2? may be important in the regulation of pulmonary blood flow in the perinatal period. PGD?2? specifically lowers pulmonary arterial pressure in pump perfused fetal goat lungs and in newborn lambs with hypoxic pulmonary hypertension. It produces mild pulmonary vasoconstriction in older animals. Histamine has similar effects. In some newborns, pulmonary blood flow remains low secondary to respiratory distress, meconium aspiration or sepsis. Hypoxia increases pulmonary vascular resistance and thereby reduces pulmonary blood flow further by constriction of the small pulmonary arteries. The elevation of pulmonary vascular resistance enhances right to left shunting through the foramen ovale or ductus arteriosus. Persistent pulmonary hypertension of the newborn accounts for one percent of admissions to newborn intensive care units. There is no specific treatment and the mortality approaches fifty percent. The purpose of this study is (1) to further define the role of PGD?2? and histamine, possibly released from lung mast cells, in the normal fall in pulmonary vascular resistance at birth; (2) to develop a model of pulmonary hypertension with increased pulmonary artery medial smooth muscle and define the morphologic and physiologic changes; (3) to induce pulmonary hypertension by infusion of endotoxin and define the role of platelets and prostaglandins in its pathogenesis; (4) to determine whether PGD?2? will lower pulmonary arterial pressure and resistance in these two models of pulmonary hypertension. If PGD?2? is important in the regulation of pulmonary blood flow in the normal and abnormal perinatal pulmonary circulations then it may be useful in the treatment of newborn pulmonary hypertension.
| Schreiber, M D; Heymann, M A; Soifer, S J (1987) The differential effects of leukotriene C4 and D4 on the pulmonary and systemic circulations in newborn lambs. Pediatr Res 21:176-82 |
| Soifer, S J; Kaslow, D; Roman, C et al. (1987) Umbilical cord compression produces pulmonary hypertension in newborn lambs: a model to study the pathophysiology of persistent pulmonary hypertension in the newborn. J Dev Physiol 9:239-52 |
| Schreiber, M D; Heymann, M A; Soifer, S J (1986) Increased arterial pH, not decreased PaCO2, attenuates hypoxia-induced pulmonary vasoconstriction in newborn lambs. Pediatr Res 20:113-7 |
| Schreiber, M D; Heymann, M A; Soifer, S J (1985) Leukotriene inhibition prevents and reverses hypoxic pulmonary vasoconstriction in newborn lambs. Pediatr Res 19:437-41 |
| Soifer, S J; Loitz, R D; Roman, C et al. (1985) Leukotriene end organ antagonists increase pulmonary blood flow in fetal lambs. Am J Physiol 249:H570-6 |
