Intrauterine inflammation alters fetal cardiopulmonary and cerebral haemodynamics in sheep

摘要

Intrauterine inflammation impairs fetal pulmonary vascular development and increases cerebral metabolic rate in fetal sheep. We hypothesized that these structural and metabolic effects of intrauterine inflammation would be accompanied by reduced fetal pulmonary blood flow and increased cerebral perfusion. Fetal sheep were instrumented at 112 days of gestation (term is 147 days) for measurement of cardiopulmonary and cerebral haemodynamics. At 118 days ewes were randomly assigned to receive intra-amniotic lipopolysaccharide (LPS, 20 mg from Escherichia coli; n= 7) or saline (control, 4 ml; n= 6). Fetal haemodynamic data were recorded continually from 1 h before intra-amniotic LPS or saline, until 144 h after. Fetal arterial blood was sampled before, and periodically after, intra-amniotic LPS or saline. End-diastolic and mean pulmonary blood flows were significantly lower than control from 48 and 96 h after LPS exposure, respectively, until the end of the experiment. Carotid blood flow was transiently increased at 96 and 120 h after LPS exposure. Carotid arterial oxygen content was lower than control from 48 h after intra-amniotic LPS. Fetal arterial lactate concentration was higher than control between 4 and 12 h after intra-amniotic LPS. Experimental intrauterine inflammation reduces pulmonary blood flow in fetal sheep, over a time course consistent with impaired pulmonary vascular development. Increased carotid blood flow after LPS administration may reflect an inflammation-induced increase in cerebral metabolic demand.