Metoprolol Reduces Cerebral Tissue Oxygen Tension after Acute Hemodilution in Rats
Autor: | Melissa Noronha, Howard Leong-Poi, David F. Wilson, Tenille E Ragoonanan, W. Scott Beattie, Albert K. Y. Tsui, Julie Yu, C. David Mazer, Neil D. Dattani, Elaine Liu, Gordon Tait, Nicholas Mitsakakis, Gregory M. T. Hare |
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Rok vydání: | 2009 |
Předmět: |
Male
medicine.medical_specialty Cardiac output Adrenergic beta-Antagonists Blood volume Rats Sprague-Dawley Catecholamines Internal medicine medicine Animals Cardiac Output Erythropoietin Metoprolol Pentastarch Hemodilution business.industry Angiotensin II Brain Stroke volume Hypoxia-Inducible Factor 1 alpha Subunit Rats Oxygen tension Oxygen Stroke Anesthesiology and Pain Medicine Endocrinology Cerebral blood flow Cerebrovascular Circulation Anesthesia business medicine.drug |
Zdroj: | Anesthesiology. 111:988-1000 |
ISSN: | 0003-3022 |
Popis: | 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. |
Databáze: | OpenAIRE |
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