TY - JOUR
T1 - Acute and chronic effects of endotoxin on cerebral circulation in lambs
AU - Feng, Susan
AU - Samarasinghe, Thilini
AU - Phillips, David James
AU - Alexiou, Theodora
AU - Hollis, Jacob
AU - Yu, Victor
AU - Walker, Adrian
PY - 2010
Y1 - 2010
N2 - 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.
AB - 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.
UR - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=20071615
U2 - 10.1152/ajpregu.00398.2009
DO - 10.1152/ajpregu.00398.2009
M3 - Article
SN - 0363-6119
VL - 298
SP - 760
EP - 766
JO - American Journal of Physiology - Regulatory Integrative and Comparative Physiology
JF - American Journal of Physiology - Regulatory Integrative and Comparative Physiology
IS - 3
ER -