Metoprolol reduces cerebral tissue oxygen tension after acute hemodilution in rats

Abstract

BACKGROUND:: Perioperative β-blockade and anemia are independent predictors of increased stroke and mortality by undefined mechanisms. This study investigated the effect of β-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 • kg) or saline before undergoing hemodilution with pentastarch (1:1 blood volume exchange, 30 ml • kg). Outcomes included cardiac output, cerebral blood flow, and brain (PBrO2) and kidney (PKO2) tissue oxygen tension. Hypoxia inducible factor-1α (HIF-1α) 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). β-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-1α protein levels were increased in β-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 β-blockade and hemodilution. CONCLUSIONS:: Cerebral tissue oxygen tension is preferentially maintained during hemodilution, relative to the kidney, despite elevated systemic catecholamines. Acute β-blockade impaired the compensatory cardiac output response to hemodilution, resulting in a reduction in cerebral tissue oxygen tension and increased expression of HIF-1α. © 2009 the American Society of Anesthesiologists, Inc. Lippincott Williams & Wilkins, Inc.