Global cerebral blood flow and metabolism during acute hyperketonemia in the awake and anesthetized rat.

In the human setting, it has been shown that acute increase in the concentration of ketone bodies by infusion of beta-hydroxybutyrate increased the cerebral blood flow (CBF) without affecting the overall cerebral metabolic activity. The mechanism by which this effect of ketone bodies was mediated is not known. Alterations in several parameters may possibly explain the increase in CBF and the resetting of the relation between CBF and cerebral metabolism. To study this phenomenon further, we measured global CBF and global cerebral metabolism with the Kety-Schmidt technique in the wakeful rat before and during infusion of ketone bodies. During acute hyperketonemia (average concentration of beta-hydroxybutyrate: 6 mmol/L), global CBF increased 65% from 108 to 178 mL/100 g min and the cerebral metabolic rates for both oxygen and glucose remained constant. This resetting of the relation between CBF and cerebral metabolism could not be explained by alterations in blood pH or arterial CO2 tension. By measuring cerebral intracellular pH by 31P nuclear magnetic resonance spectroscopy, it could further be concluded that the brain pH was unchanged during acute hyperketonemia. These observations indicate that the mechanism responsible for the increase in CBF is rather a direct effect on the cerebral endothelium than via some metabolic interactions.

Activation-induced resetting of cerebral metabolism and flow is abolished by beta-adrenergic blockade with propranolol.

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 beta-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 beta-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 beta-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: beta-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.