Effect of carbon dioxide on cerebral metabolism during hypoxia-ischemia in the immature rat.
We previously have demonstrated that hypocapnia aggravates and hypercapnia protects the immature rat from hypoxic-ischemic brain damage. To ascertain cerebral blood flow (CBF) and metabolic correlates, 7-d postnatal rats were subjected to hypoxia-ischemia during which they were rendered either hypo-(3.5 kPa), normo- (5.1 kPa), or hypercapnic (7.3 kPa) by the inhalation of either 0, 3, or 6% CO2, 8% O2, balance N2. CBF during hypoxia-ischemia was better preserved in the normo- and hypercapnic rat pups; these animals also exhibited a stimulation of cerebral glucose utilization. Brain glucose concentrations were higher and lactate lower in the normo- and hypercapnic animals, indicating that glucose was consumed oxidatively in these groups rather than by anaerobic glycolysis, as apparently occurred in the hypocapnic animals. ATP and phosphocreatine were better preserved in the normo- and hypercapnic rats compared with the hypocapnic animals. Cerebrospinal fluid glutamate, as a reflection of the brain extracellular fluid concentration, was lowest in the hypercapnic rats at 2 h of hypoxia-ischemia. The data indicate that during hypoxia-ischemia in the immature rat, CBF is better preserved during normo- and hypercapnia; the greater oxygen delivery promotes cerebral glucose utilization and oxidative metabolism for optimal maintenance of tissue high energy phosphate reserves. An inhibition of glutamate secretion into the synaptic cleft and its attenuation of N-methyl-D-aspartate receptor activation would further protect the hypercapnic animal from hypoxic-ischemic brain damage.
Vannucci
R C
RC
Department of Pediatrics (Pediatric Neurology), The Pennsylvania State University College of Medicine, The Milton S. Hershey Medical Center, Hershey 17033-0850, USA.
Brucklacher
R M
RM
Vannucci
S J
SJ
D000818:Animals; D001921:Brain / Q000378:metabolism*; D001930:Brain Injuries / Q000517:prevention & control; D002545:Brain Ischemia / Q000150:complications / Q000378:metabolism*; D002245:Carbon Dioxide / Q000378:metabolism*; D002560:Cerebrovascular Circulation; D002952:Citric Acid Cycle; D005947:Glucose / Q000378:metabolism; D018698:Glutamic Acid / Q000134:cerebrospinal fluid; D006019:Glycolysis; D006863:Hydrogen-Ion Concentration; D006935:Hypercapnia / Q000150:complications / Q000378:metabolism; D016857:Hypocapnia / Q000150:complications / Q000378:metabolism; D002534:Hypoxia, Brain / Q000150:complications / Q000378:metabolism*; D010710:Phosphates / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley
D010710:Phosphates; D002245:Carbon Dioxide; D018698:Glutamic Acid; D005947:Glucose