Abstract 3727: Beta-1 Adrenergic Antagonism Inhibits Cardiovascular Adaptation to Hemodilution Causing Cerebral Hypoxia

Abstract

A recent clinical study (POISE) demonstrated an increased incidence of stroke in surgical patients treated with a beta-1 adrenergic antagonist. This stroke risk may be attributed to reduced cerebral perfusion in treated patients who are exposed to hemodynamic stress during surgery, including acute blood loss and fluid resuscitation. We tested the hypothesis that acute beta-1 adrenergic antagonism attenuates cardiovascular responses to acute hemodilution causing cerebral tissue hypoxia. After ACC approval, anesthetized rats (1–2% isoflurane) were treated with metoprolol (3 mg kg −1 i.v.) or saline vehicle (n=8/outcome). Acute hemodilution was then performed by exchanging 50% of estimated blood volume (30 ml kg −1 ) with pentastarch (1:1). Experimental outcomes included heart rate (HR), mean arterial blood pressure (MAP), cardiac output (CO, echocardiography), carotid and cerebral tissue blood flow (CBF, Doppler), and hippocampal and kidney tissue oxygen tension (P Br O 2 , P Ki O 2 , phosphorescence quenching). Arterial blood gases (ABGs), and hemoglobin concentration (Co- oximetry) were also measured. Data was analyzed by two-way ANOVA (mean ± SD). Acute beta blockade reduced baseline HR (334 ± 31 vs. 291 ± 22 bpm, p<0.05). No differences in ABG and co-oximetry values were observed between groups and a target hemoglobin concentration near 50 g.L −1 was achieved. MAP was maintained near 70 mmHg and was not different between groups at any time. After hemodilution CO and CBF increased, P Br O 2 was maintained and P Ki O 2 decreased in control rats. In beta blocked rats, the CO and CBF responses were greatly attenuated leading to a significant reduction in P Br O 2 (15 ± 4 vs. 30 ± 12 mmHg, p<0.05). P Ki O 2 was reduced comparably to the control group. Acute metoprolol treatment attenuated the cardiovascular response to acute hemodilution resulting in cerebral tissue hypoxia. Acute beta-1 adrenergic blockade may increase the risk of cerebral hypoxia in surgical patients who are exposed to blood loss and fluid resuscitation (CAS and PSI support).