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.
Neurobiology Research Unit 9201, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark.
Rasmus
R
Linde
Steen G
SG
Hasselbalch
Simon
S
Topp
Olaf B
OB
Paulson
Peter L
PL
Madsen
D020155:3-Hydroxybutyric Acid / Q000008:administration & dosage / Q000097:blood; D000208:Acute Disease; D000758:Anesthesia; D000818:Animals; D001921:Brain / Q000098:blood supply* / Q000187:drug effects / Q000378:metabolism*; D002560:Cerebrovascular Circulation / Q000187:drug effects / Q000502:physiology*; D004195:Disease Models, Animal; D006863:Hydrogen-Ion Concentration; D007262:Infusions, Intravenous; D007657:Ketone Bodies / Q000097:blood / Q000378:metabolism*; D009682:Magnetic Resonance Spectroscopy / Q000379:methods; D008297:Male; D010759:Phosphorus Isotopes; D051381:Rats; D017207:Rats, Sprague-Dawley; D012680:Sensitivity and Specificity; D017693:Sodium Bicarbonate / Q000008:administration & dosage / Q000097:blood; D014851:Wakefulness / Q000502:physiology*
D007657:Ketone Bodies; D010759:Phosphorus Isotopes; D017693:Sodium Bicarbonate; D020155:3-Hydroxybutyric Acid