The effect of systemic administration of lipopolysaccharide on cerebral haemodynamics and oxygenation in the 0.65 gestation ovine fetus in utero.

Abstract

To investigate the effect of intravenous lipopolysaccharide on systemic and cerebral haemodynamics and oxygenation in the preterm ovine fetus. Prospective observational study. Research centre for perinatal brain injury. Nine fetal sheep at circa 93 days of gestation (0.65). Fetal sheep were chronically instrumented with arterial and venous catheters and a flow probe in the carotid artery. Near-infrared spectroscopy was used to measure changes in cerebral oxygenation and total haemoglobin concentration. Three days after surgery, each fetus was given 100 ng/kg Escherichia coli lipopolysaccharide. Observations were continued for 48 hours post-injection and compared with baseline control values. Fetal heart rate, mean arterial pressure, carotid blood flow. Three fetuses died after administration of the lipopolysaccharide. In the survivors fetal heart rate rose from 193 (SEM 7) to a mean maximal level of 226 (SEM 31 bpm) (P = 0.01) after 6.5 (SEM 1.0) hours. The mean arterial pressure decreased from 40.5 (SEM 4.2) to 29.4 (SEM 1.6) mmHg (P < 0.05) after 7.0 (SEM 2.0) hours, and carotid blood flow increased from 29.6 (SEM 1.6) to 45.8 (SEM 5.7) mL/min (P = 0.0002) at 12 (SEM 3) hours. All values returned to control levels by 48 hours. Histological assessment showed evidence of periventricular leucomalacia in three out of six brains studied. These data do not suggest that cerebral ischaemia is the main aetiological factor in endotoxin-related fetal brain injury. Fetal tachycardia and cerebral vasodilation may indicate endotoxaemia in fetuses exposed to prenatal infection.