TY - JOUR

T1 - Global cerebral blood flow and metabolism during acute hyperketonemia in the awake and anesthetized rat

AU - Linde, Rasmus

AU - Hasselbalch, Steen G

AU - Topp, Simon

AU - Paulson, Olaf B

AU - Madsen, Peter L

PY - 2006/2

Y1 - 2006/2

N2 - 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.

AB - 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.

KW - 3-Hydroxybutyric Acid/administration & dosage

KW - Acute Disease

KW - Anesthesia

KW - Animals

KW - Brain/blood supply

KW - Cerebrovascular Circulation/drug effects

KW - Disease Models, Animal

KW - Hydrogen-Ion Concentration

KW - Infusions, Intravenous

KW - Ketone Bodies/blood

KW - Magnetic Resonance Spectroscopy/methods

KW - Male

KW - Phosphorus Isotopes

KW - Rats

KW - Rats, Sprague-Dawley

KW - Sensitivity and Specificity

KW - Sodium Bicarbonate/administration & dosage

KW - Wakefulness/physiology

U2 - 10.1038/sj.jcbfm.9600177

DO - 10.1038/sj.jcbfm.9600177

M3 - Journal article

C2 - 16001018

VL - 26

SP - 170

EP - 180

JO - Journal of Cerebral Blood Flow and Metabolism

JF - Journal of Cerebral Blood Flow and Metabolism

SN - 0271-678X

IS - 2

ER -