Document Detail


Metoprolol reduces cerebral tissue oxygen tension after acute hemodilution in rats.
MedLine Citation:
PMID:  19809291     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
BACKGROUND: Perioperative beta-blockade and anemia are independent predictors of increased stroke and mortality by undefined mechanisms. This study investigated the effect of beta-blockade on cerebral tissue oxygen delivery in an experimental model of blood loss and fluid resuscitation (hemodilution). METHODS: Anesthetized rats were treated with metoprolol (3 mg x kg) or saline before undergoing hemodilution with pentastarch (1:1 blood volume exchange, 30 ml x kg). Outcomes included cardiac output, cerebral blood flow, and brain (PBrO2) and kidney (PKO2) tissue oxygen tension. Hypoxia inducible factor-1alpha (HIF-1alpha) protein levels were assessed by Western blot. Systemic catecholamines, erythropoietin, and angiotensin II levels were measured. RESULTS: Hemodilution increased heart rate, stroke volume, cardiac output (60%), and cerebral blood flow (50%), thereby maintaining PBrO2 despite an approximately 50% reduction in blood oxygen content (P < 0.05 for all). By contrast, PKO2 decreased (50%) under the same conditions (P < 0.05). Beta-blockade reduced baseline heart rate (20%) and abolished the compensatory increase in cardiac output after hemodilution (P < 0.05). This attenuated the cerebral blood flow response and reduced PBrO2 (50%), without further decreasing PKO2. Cerebral HIF-1alpha protein levels were increased in beta-blocked hemodiluted rats relative to hemodiluted controls (P < 0.05). Systemic catecholamine and erythropoietin levels increased comparably after hemodilution in both groups, whereas angiotensin II levels increased only after beta-blockade and hemodilution. CONCLUSIONS: Cerebral tissue oxygen tension is preferentially maintained during hemodilution, relative to the kidney, despite elevated systemic catecholamines. Acute beta-blockade impaired the compensatory cardiac output response to hemodilution, resulting in a reduction in cerebral tissue oxygen tension and increased expression of HIF-1alpha.
Authors:
Tenille E Ragoonanan; W Scott Beattie; C David Mazer; Albert K Y Tsui; Howard Leong-Poi; David F Wilson; Gordon Tait; Julie Yu; Elaine Liu; Melissa Noronha; Neil D Dattani; Nicholas Mitsakakis; Gregory M T Hare
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Anesthesiology     Volume:  111     ISSN:  1528-1175     ISO Abbreviation:  Anesthesiology     Publication Date:  2009 Nov 
Date Detail:
Created Date:  2009-10-28     Completed Date:  2009-11-13     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  1300217     Medline TA:  Anesthesiology     Country:  United States    
Other Details:
Languages:  eng     Pagination:  988-1000     Citation Subset:  AIM; IM    
Affiliation:
Department of Anesthesia, Keenan Research Centre of the Li Ka Shing Knowledge Institute, St. Michael's Hospital, University of Toronto, Toronto, Ontario, Canada.
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MeSH Terms
Descriptor/Qualifier:
Adrenergic beta-Antagonists / pharmacology*
Angiotensin II / blood
Animals
Brain / drug effects*,  metabolism
Cardiac Output / drug effects
Catecholamines / blood
Cerebrovascular Circulation / drug effects
Erythropoietin / blood
Hemodilution*
Hypoxia-Inducible Factor 1, alpha Subunit / analysis
Male
Metoprolol / adverse effects,  pharmacology*
Oxygen / metabolism*
Rats
Rats, Sprague-Dawley
Stroke / etiology
Grant Support
ID/Acronym/Agency:
NS-31465/NS/NINDS NIH HHS
Chemical
Reg. No./Substance:
0/Adrenergic beta-Antagonists; 0/Catecholamines; 0/Hif1a protein, rat; 0/Hypoxia-Inducible Factor 1, alpha Subunit; 11096-26-7/Erythropoietin; 11128-99-7/Angiotensin II; 37350-58-6/Metoprolol; 7782-44-7/Oxygen

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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