Metoprolol Reduces Cerebral Tissue Oxygen Tension after Acute Hemodilution in Rats

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 -1 ) or saline before undergoing hemodilution with pentastarch (1:1 blood volume exchange, 30 ml · kg -1 ). Outcomes included cardiac output, cerebral blood flow, and brain (P Br O 2 ) and kidney (P K O 2 ) 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 P Br O 2 despite an approximately 50% reduction in blood oxygen content (P < 0.05 for all). By contrast, P K O 2 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 P Br O 2 (50%), without further decreasing P K O 2 . 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 HIW-1α.