Activation-Induced Resetting of Cerebral Metabolism and Flow Is Abolished by β-Adrenergic Blockade With Propranolol

Abstract

Background and Purpose — It has previously been shown that activation will increase cerebral blood flow (CBF) and cerebral glucose uptake (CMR glc ) in excess of cerebral oxygen uptake (CMRO 2 ). Our purpose was to investigate the influence of β-adrenergic blockade with propranolol on the activation-induced uncoupling of cerebral glucose and oxygen metabolism. Methods — Using awake rats, we determined the cerebral arteriovenous differences of oxygen [(a−v) O2 ], glucose [(a−v) glc ], and lactate [(a−v) lac ] both under baseline conditions and during activation. The molar ratio between CMRO 2 and CMR glc , the oxygen-glucose index (OGI), was calculated. Results — Without β-adrenergic blockade, activation decreased the (a−v) O2 but not the (a−v) glc , reducing the OGI from 6.1 during baseline conditions to 4.0 under activation ( P <0.01). The (a−v) O2 decreased, indicating that the ratio CBF/CMRO 2 had increased. Under baseline conditions, a slight flux of lactate from the brain was observed. Activation increased the arterial lactate concentration, and during this condition, the lactate flux from the brain was reversed into a slight lactate uptake. Propranolol administration did not change the behavior of the animals during activation. After administration of propranolol, baseline values were unaffected, but β-adrenergic blockade totally abolished the activation-induced uncoupling of (a−v) O2 from (a−v) glc , because both remained constant with an unchanged OGI. The unchanged (a−v) O2 indicates that CBF remained unchanged compared with CMRO 2 . Conclusions — β-Adrenergic blockade by propranolol abolishes the activation-induced uncoupling of cerebral oxygen to glucose metabolism and the changes in (a−v) O2 . This may be of most significance to studies of cerebral activation by the blood oxygen level–dependent fMRI method.