Grant: Travel Awards - Institute Community Support

Beta-blockers are drugs that are prescribed to treat high blood pressure and to reduce the risk of heart attacks. However, recent findings have shown that these benefits may be offset by an increase in death and ischemic stroke (due to an inadequate supply of oxygen to the brain) when surgical patients using beta-blockers undergo blood loss and fluid resuscitation. This results in a condition called hemodilution, where there is a decrease in the concentration of red blood cells (acute anemia). Beta-blockers have been shown to limit oxygen delivery to the brain during hemodilution by attenuating both cardiac output (beta-1 effect) and cerebral vasodilatory responses (beta-2 effect). We hypothesized that low dose treatment with a highly beta-1 specific blocker (nebivolol) would control heart rate while maintaining oxygen delivery to the brain during hemodilution. Anesthetized rats were treated with vehicle or nebivolol (1.25 or 2.5 mg/kg) intravenously prior to hemodilution to a hemoglobin concentration of approximately 60 g/L. Mean arterial pressure, heart rate, cardiac output, regional cerebral blood flow (rCBF, laser Doppler), and brain tissue oxygen values (G2 oxyphor) were measured. Both nebivolol doses reduced heart rate and attenuated the cardiac output response to hemodilution. Low dose nebivolol did not attenuate the increase in rCBF following hemodilution and brain tissue oxygen values remained at higher levels, relative to rats treated with high dose nebivolol. Brain hypoxic protein levels were increased in rats treated with high dose nebivolol. Our data support the hypothesis that lower dose nebivolol can confer cardiac protection while reducing the risk of cerebral hypoxia during hemodilution.