OBJECTIVE: The purpose of the present study was to determine whether endotoxins (lipopolysaccharides, LPS) affect the fetal cardiovascular system in a may likely to cause brain damage. METHODS: Thirteen fetal sheep were chronically instrumented at a mean gestational age of 107 +/- 1 days. After control measurements of organ flow (microscphere method), blood gases, and acid base balance were obtained, seven of 13 fetuses received LPS (53 +/- 3 mug/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. RESULTS: 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 a 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. CONCLUSIONS: Endotoxemia severely impaired fetal cardiovascular control during normoxia and asphyxia, resulting in a considerable decrease in cerebral oxygen delivery. Theses effects might have important effects in the development of fetal brain damage associated with intrauterine infection. (J Soc Gynecol Investig 2001; 8:134-42) Copyright (C) 2001 by the Society for Gynecologic Investigation.