Acute and chronic effects of endotoxin on cerebral circulation in lambs

Susan Feng, Thilini Samarasinghe, David James Phillips, Theodora Alexiou, Jacob Hollis, Victor Yu, Adrian Walker

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27 Citations (Scopus)


The impact of endotoxemia on cerebral endothelium and cerebral blood flow (CBF) regulation was studied in conscious newborn lambs. Bacterial endotoxin [LPS, 2 microg/kg iv] was infused on 3 consecutive days. Cerebrovascular function was assessed by monitoring CBF and cerebral vascular resistance (CVR) over 12 h each day and by the endothelium-dependent vasodilator bradykinin (BK) (n = 10). Inflammatory responses were assessed by plasma tumor necrosis factor-alpha (TNF-alpha, n = 5). Acutely, LPS disrupted the cerebral circulation within 1 h, with peak cerebral vasoconstriction at 3 h (CBF -28 and CVR +118 , P <0.05) followed by recovery to baseline by 12 h. TNF-alpha and body temperature peaked approximately 1 h post-LPS. BK-induced vasodilatation (CVR -20 , P <0.05) declined with each LPS infusion, was abolished after 3 days, and remained absent for at least the subsequent 5 days. Histological evidence of brain injury was found in four of five LPS-treated newborns. We conclude that endotoxin impairs cerebral perfusion in newborn lambs via two mechanisms: 1) acute vasoconstriction (over several hours); and 2) persistent endothelial dysfunction (over several days). Endotoxin-induced circulatory impairments may place the newborn brain at prolonged risk of CBF dysregulation and injury as a legacy of endotoxin exposure.
Original languageEnglish
Pages (from-to)760 - 766
Number of pages7
JournalAmerican Journal of Physiology - Regulatory Integrative and Comparative Physiology
Issue number3
Publication statusPublished - 2010

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