Endotoxin has acute and chronic effects on the cerebral circulation of fetal sheep

We studied the impact of endotoxemia on cerebral blood flow (CBF), cerebral vascular resistance (CVR), and cerebral oxygen transport ([O.sub.2] transport) in fetal sheep. We hypothesized that endotoxemia impairs CBF regulation and [O.sub.2] transport, exposing the brain to hypoxicischemic injury. Responses to lipopolysaccharide (LPS; 1 [micro]g/kg iv on 3 consecutive days, n = 9) or normal saline (n = 5) were studied. Of LPS-treated fetuses, five survived and four died; in surviving fetuses, transient cerebral vasoconstriction at 0.5 h ([DELTA]CVR approximately +50%) was followed by vasodilatation maximal at 5-6 h ([DELTA]CVR approximately -50%) when CBF had increased (approximately +60%) despite reduced ABP (approximately -20%). Decreased CVR and increased CBF persisted 24 h post-LPS and the two subsequent LPS infusions. Cerebral 02 transport was sustained, although arterial [O.sub.2] saturation was reduced (P < 0.05). Histological evidence of neuronal injury was found in all surviving LPS-treated fetuses; one experienced grade IV intracranial hemorrhage. Bradykinin-induced cerebral vasodilatation ([DELTA]CVR approximately -20%, P < 0.05) was abolished after LPS. Fetuses that died post-LPS (n = 4) differed from survivors in three respects: CVR did not fall, CBF did not rise, and [O.sub.2] transport fell progressively. In conclusion, endotoxin disrupts the cerebral circulation in two phases: 1) acute vasoconstriction (1 h) and 2) prolonged vasodilatation despite impaired endothelial dilatation (24 h). In surviving fetuses, LPS causes brain injury despite cerebral [O.sub.2] transport being maintained by elevated cerebral perfusion; thus sustained O2 transport does not prevent brain injury in endotoxemia. In contrast, cerebral hypoperfusion and reduced [O.sub.2] transport occur in fetuses destined to die, emphasizing the importance of sustaining [O.sub.2] transport for survival. cerebral blood flow; fetus; oxygen transport