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Canadian Journal of Anesthesia/Journal canadien d'anesthésie

Published in:

01-07-2009 | Reports of Original Investigations

A potential role for inducible nitric oxide synthase in the cerebral response to acute hemodilution

Authors: Anya T. McLaren, MSc, C. David Mazer, MD, Haibo Zhang, MD, PhD, Elaine Liu, MD, Lillian Mok, BSc, Gregory M. T. Hare, MD, PhD

Published in: Canadian Journal of Anesthesia/Journal canadien d'anesthésie | Issue 7/2009

Abstract

Purpose

Acute anemia increases the cerebral expression of hypoxic molecules including neuronal nitric oxide synthase (nNOS) and hypoxia inducible factor-1α (HIF-1α). This study assessed the effects of acute hemodilution on inducible NOS (iNOS) and systemic inflammatory cytokines.

Methods

Anesthetized rats (n = 5–7 per group) underwent 50% hemodilution with pentastarch, whole blood exchange or no fluid exchange. Cerebral cortical nNOS and iNOS protein levels were characterized using Western blot analysis and immunostaining (1 and 18 h). Plasma cytokine levels were assessed by enzyme-linked immunosorbent assay (1, 4, and 18 h). Data were analyzed by two-way analysis of variance to determine significance (P < 0.05, mean ± SD).

Results

No differences in mean arterial blood pressure or arterial blood gases were observed between groups after hemodilution. A comparable hemoglobin target (~70 g · L⁻¹) was achieved in all groups following hemodilution. Cerebral cortical iNOS protein levels were increased in anemic rats, relative to controls. The nNOS protein levels increased to a greater degree (P < 0.05 for both). Immunostaining demonstrated that iNOS localized to endothelium, glial fibrillary acidic protein (GFAP) positive (astrocytes) and GFAP negative cells within the brain. Plasma cytokine levels (tumour necrosis factor α, interleukin (IL)-1β and IL-6) increased transiently, to the same levels, in both control and hemodiluted rats.

Conclusions

Cerebral cortical iNOS and nNOS protein levels were both increased in anemic rats. The nNOS response was predominant. This suggests that NOS-derived NO may be an important signalling pathway which is activated in the brain during anemia. These cellular responses could maintain cerebral homeostasis, or contribute to neuronal injury, during acute hemodilutional anemia.

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Title: A potential role for inducible nitric oxide synthase in the cerebral response to acute hemodilution
Authors: Anya T. McLaren, MSc
C. David Mazer, MD
Haibo Zhang, MD, PhD
Elaine Liu, MD
Lillian Mok, BSc
Gregory M. T. Hare, MD, PhD
Publication date: 01-07-2009
Publisher: Springer-Verlag
Published in: Canadian Journal of Anesthesia/Journal canadien d'anesthésie / Issue 7/2009
Print ISSN: 0832-610X
Electronic ISSN: 1496-8975
DOI: https://doi.org/10.1007/s12630-009-9104-z

Keynote webinar | Spotlight on medication adherence

Springer Medicine

A potential role for inducible nitric oxide synthase in the cerebral response to acute hemodilution

Abstract

Purpose

Methods

Results

Conclusions

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Purpose

Methods

Results

Conclusions

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