Effects of indomethacin in utero on the pulmonary vasculature of the newborn guinea pig.
The clinical syndrome of persistent pulmonary hypertension of the newborn results from failure of the normal perinatal vascular adaptation, and functionally is characterized by persistent right to left shunting of blood through the foramen ovale and ductus arteriosus. Exposure of the fetus to drugs that inhibit prostaglandin synthesis and cause closure of the ductus arteriosus has been suggested as one cause of persistent pulmonary hypertension of the newborn. We attempted to produce a functional and structural model of persistent pulmonary hypertension of the newborn by administration of indomethacin, a cyclooxygenase inhibitor, to pregnant guinea pigs. Five pregnant guinea pigs received 3.5 mg/kg indomethacin intravenously twice each day for the 12 to 19 days before delivery and seven controls received saline. Hemodynamic studies were performed in eight "treated" newborns and in 12 controls. After sacrifice, the ductus was ligated and, for morphometric studies, the pulmonary arteries were distended with barium/gelatin. The treated animals did not show the intraacinar structural or hemodynamic changes of persistent pulmonary hypertension of the newborn. It seems that the indomethacin did cross the placenta because lung structure was modified. The radical alveolar count and alveolar/artery ratio were increased and the preacinar arteries dilated, with more increase in muscle mass. This could be explained by increased pulmonary blood flow because of ductal constriction but direct effect of indomethacin cannot be excluded.
Demello
D E
DE
Department of Pathology, Children's Hospital, Boston, Massachusetts, 02115.
Murphy
J D
JD
Aronovitz
M J
MJ
Davies
P
P
Reid
L M
LM
D000818:Animals; D000831:Animals, Newborn; D004373:Ductus Arteriosus / Q000187:drug effects; D005260:Female; D006168:Guinea Pigs; D006801:Humans; D007213:Indomethacin / Q000494:pharmacology*; D007231:Infant, Newborn; D010547:Persistent Fetal Circulation Syndrome / Q000209:etiology* / Q000473:pathology / Q000503:physiopathology; D011247:Pregnancy; D011651:Pulmonary Artery / Q000187:drug effects / Q000473:pathology; D011652:Pulmonary Circulation / Q000187:drug effects*
D007213:Indomethacin