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

Title

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

Creator

Feng Susan YS; Phillips DJ; Stockx EM; Yu Victor YH; Walker AM

Publisher

American Journal Of Physiology. Regulatory, Integrative And Comparative Physiology

Date

2009

Subject

Female; Fetal Death; Pregnancy; Animals; Statistical; Data Interpretation; Cerebrovascular Circulation/de [Drug Effects]; Endotoxins/pd [Pharmacology]; Fetus/bs [Blood Supply]; Lipopolysaccharides/pd [Pharmacology]; Blood Pressure/ph [Physiology]; Cerebrospinal Fluid/me [Metabolism]; Cytokines/bi [Biosynthesis]; Endothelial Cells/ph [Physiology]; Endotoxins/bl [Blood]; Lipopolysaccharides/bl [Blood]; Nitrates/bl [Blood]; Nitrites/bl [Blood]; Oxygen Consumption/ph [Physiology]; Sheep; Tumor Necrosis Factor-alpha/bl [Blood]; Vasodilation/de [Drug Effects]

Description

We studied the impact of endotoxemia on cerebral blood flow (CBF), cerebral vascular resistance (CVR), and cerebral oxygen transport (O(2) transport) in fetal sheep. We hypothesized that endotoxemia impairs CBF regulation and O(2) transport, exposing the brain to hypoxic-ischemic injury. Responses to lipopolysaccharide (LPS; 1 microg/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 (DeltaCVR approximately +50%) was followed by vasodilatation maximal at 5-6 h (DeltaCVR 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 O(2) transport was sustained, although arterial O(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 (DeltaCVR 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(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(2) transport being maintained by elevated cerebral perfusion; thus sustained O(2) transport does not prevent brain injury in endotoxemia. In contrast, cerebral hypoperfusion and reduced O(2) transport occur in fetuses destined to die, emphasizing the importance of sustaining O(2) transport for survival.
2009

Rights

Article information provided for research and reference use only. PedPalASCNET does not hold any rights over the resource listed here. All rights are retained by the journal listed under publisher and/or the creator(s).

Type

Journal Article

Citation List Month

Backlog

Pages

R640-50

Issue

3

Volume

296

Citation

Feng Susan YS; Phillips DJ; Stockx EM; Yu Victor YH; Walker AM, “Endotoxin has acute and chronic effects on the cerebral circulation of fetal sheep.,” Pediatric Palliative Care Library, accessed October 16, 2021, https://pedpalascnetlibrary.omeka.net/items/show/14126.

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