Increases in lung expansion alter pulmonary hemodynamics in fetal sheep

Abstract

Prolonged increases in fetal lung expansion stimulate fetal lung growth and development, but the effects on pulmonary hemodynamics are unknown. Our aim was to determine the effect of increased fetal lung expansion, induced by tracheal obstruction (TO), on pulmonary blood flow (PBF) and vascular resistance (PVR). Chronically catheterized fetal sheep (n = 6) underwent TO from 120 to 127 days of gestational age (term approximately 147 days); tracheas were not obstructed in control fetuses (n = 6). PBF, PVR, and changes to the PBF waveform were determined. TO significantly increased lung wet weight compared with control (166.3 +/- 20.2 vs. 102.0 +/- 18.8 g; P < 0.05). Despite the increase in intraluminal pressure caused by TO (5.0 +/- 0.9 vs. 2.4 +/- 1.0 mmHg; P < 0.001), PBF and PVR were similar between groups after 7 days (TO 28.1 +/- 3.2 vs. control 34.1 +/- 10.0 ml.min(-1).100 g lung wt(-1)). However, TO markedly altered pulmonary hemodynamics associated with accentuated fetal breathing movements, causing a reduction rather than an increase in PBF at 7 days of TO. To account for the increase in intraluminal pressure, the pressure was equalized by draining the lungs of liquid on day 7 of TO. Pressure equalization increased PBF from 36.8 +/- 5.2 to 112.4 +/- 22.8 ml/min (P = 0.01) and markedly altered the PBF waveform. These studies provide further evidence to indicate that intraluminal pressure is an important determinant of PBF and PVR in the fetus. We suggest that the increase in PBF associated with pressure equalization following TO reflects an increase in growth of the pulmonary vascular bed, leading to an increase in its cross-sectional area.