Gestational changes in pulmonary vascular responses in fetal lambs in utero

Pulmonary arterial (PA) blood flow patterns, changes in pulmonary blood flow, and pulmonary vascular responses to graded hypoxemia and intravenous acetylcholine (ACh) were studied in 15 fetal lambs in utero 3-12 days after surgical implantation of an electromagnetic flow transducer and PA catheter. Phasic PA flow in the fetus was forward only during the first third of systole, almost zero during midsystole, and backward during late systole and early diastole. In contrast, neonatal lambs showed forward PA flow throughout systole. The constriction of the fetal pulmonary vasculature in response to progressive hypoxemia varied with gestational age. At 103 days there was no significant drop in PA flow and only a small increase in pulmonary vascular resistance (Rp) with hypoxemia. The greatest increase in Rp was seen in fetuses after 121 days of gestation. This response was unaffected by alpha- and beta-sympathetic and parasympathetic blockade. Similarly, the pulmonary vascular response to ACh injected into the fetal jugular vein depended on gestational age. Little or no increase in pulmonary flow was noted in the youngest fetus, whereas ACh produced a marked increase in pulmonary flow in festuses over 120 days of gestation. These data suggest that the mechanisms by which hypoxemia constricts and ACh relaxes the pulmonary vascular smooth muscle are not fully developed in fetal lambs at 100 days of gestation and furthermore, that these mechanisms progressively develop during the last third of gestation.