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

摘要

In this study we aimed to clarify the uncertainty surrounding the changes of CBF and O2 transport in endotoxemia because of their importance in understanding the pathogenesis of brain injury in intrauterine infection. We hypothesized that endotoxin would impair cerebral perfusion and oxygenation, exposing the brain to hypoxic-ischemic injury. Because variability between studies might arise from intermittent measurements, we continuously monitored changes of CBF and O2 transport in fetal sheep exposed to LPS. Also, we repeated the study on successive days, because circulatory tolerance to endotoxin may develop with repeated LPS exposure (10, 70). In addition, because nitric oxide (NO) synthesis might be critical for sustaining CBF in endotoxemia (56), we included functional tests of the cerebral endothelium, a primary source of NO (18), in the study. LPS-induced responses of the vasoconstrictor and proinflammatory cytokine tumor necrosis factor-a (TNF-a) were also measured to assess its role in cerebral regulation in conditions of endotoxemia.