1662 INDOMETHACIN, IMMATURE FETAL PULMONARY VASCULAR RESISTANCE (PVR), AND LUNG INFLATION

Abstract

Indomethacin (I) was studied in the isolated, perfused immature (27 days' gestation) fetal rabbit lung. Lungs contained normal volume of fetal pulmonary fluid (FPF) during pulmonary vascular perfusion with either balanced, buffered electrolyte solution (BES), 3% 02 (C, control, n=5) or BES, 3% 02, plus .50 μg/ml I (n=5). Within 5 min of start of perfusion, the ductus was ligated and after 1.5-2 h, the lungs were inflated to maximal volume, then deflated to atmospheric pressure, the first air volume-pressure (VP) diagram. PVR was the same in both groups at the start and immediately after ductal ligation when PVR increased. However, after 1.5-2 h C PVR had returned to pre-ligation level, whereas I PVR remained elevated. When the lungs were inflated, PVR decreased in C, but increased in I. With deflation C PVR did not change and I PVR decreased to pre-inflation level. Comparison of VP diagrams with age-matched, but unperfused fetal lungs showed larger volumes and greater air retention in C, but no difference from I. These studies indicate that (1) “resting” prostaglandin (PG) activity is minimal in the isolated, perfused immature fetal lung; (2) normal accommodation to volume load produced by ductal closure may be mediated by PG and is blocked by I; (3) pulmonary vascular perfusion itself may induce surfactant release (which is blocked indirectly by I) into FPF; and (4) PVR decrease during inflation is related, in part, to PG activity and/or surfactant release. (Supported by NIH HL 07060).