Endotoxemia severely affects circulation during normoxia and asphyxia in immature fetal sheep

The purpose of the present study was to determine whether endotoxins (lipopolysaccharides, LPS) affect the fetal cardiovascular system in a way likely to cause brain damage.

Thirteen fetal sheep were chronically instrumented at a mean gestational age of 107 +/- 1 days. After control measurements of organ blood flow (microsphere method), blood gases, and acid base balance were obtained, seven of 13 fetuses received LPS (53 +/- 3 microg/kg fetal weight) intravenously. Sixty minutes later, asphyxia was induced by occlusion of the maternal aorta for 2 minutes. Measurements of organ blood flows were made at -60, -1, +2, +4, +30, and +60 minutes.

Unlike in the control group, after LPS infusion there was a significant decrease in arterial oxygen saturation (-46%; P <.001) and pH (P <.001). In LPS-treated fetuses the portion of combined ventricular output directed to the placenta decreased significantly (-76%; P <.001), whereas output to the fetal body (+60%; P <.001), heart (+167%; P <.05), and adrenals (+229%; P <.01) increased. Furthermore, during asphyxia circulatory centralization was impaired considerably in LPS-treated fetuses, and there was clear evidence of circulatory decentralization. This decentralization caused a severe decrease in cerebral oxygen delivery by 70%. Within 30 minutes after induction of asphyxia five of seven LPS-treated fetuses died, whereas all control fetuses recovered completely.

Endotoxemia severely impaired fetal cardiovascular control during normoxia and asphyxia, resulting in a considerable decrease in cerebral oxygen delivery. These effects might have important effects in the development of fetal brain damage associated with intrauterine infection.