The effect of glucose during ischemia on brain ATP, lactate, and glutamate in piglets.
Glucose worsens hypoxic-ischemic brain injury in 0- to 3-day-old piglets. Piglets were randomly assigned to have blood glucose increased with glucose infusion (n = 12), or decreased with insulin (n = 13), or a sham group (n = 10). In the insulin and glucose groups at time 0, both carotid arteries were clamped, and blood was withdrawn to reduce the blood pressure one third. At time 15 min FiO2 was reduced to 6%. At time 30 min cerebrospinal fluid (CSF) was taken for glutamate, and the brains were frozen. The shams had CSF removed and brains frozen without hypoxia or ischemia. Brain ATP was 1.7 +/- 0.09 mumol/g wet weight in the shams, 0.98 +/- 0.09 in the glucose group (p < 0.01 vs. sham), and 0.52 +/- 0.10 in the insulin group (p < 0.01 vs. glucose). Brain lactate levels were 4.3 +/- 1.0 mumol/g wet weight in the shams, 18.3 +/- 1.9 in the insulin group (p < 0.01 vs. sham), and 29.4 +/- 2.6 in the glucose group (p < 0.01 vs. insulin). CSF glutamate was 9.3 +/- 3.6 microM in the glucose group, 9.6 +/- 3.5 in the insulin group, and 2.2 +/- 0.9 in the shams (p < 0.05, glucose and insulin > sham). The Bmax for MK-801 binding was 2.3 +/- 0.2 pmol/mg protein in the glucose group, 2.6 +/- 0.1 in the insulin group (p < 0.05 vs. sham), and 2.0 +/- 0.2 in the shams, and the Kd was the same in the three groups (p = nonsignificant). Brain Na+,K(+)-ATPase was the same in the three groups (p = nonsignificant). Providing additional glucose preserves ATP during hypoxic-ischemic brain injury in the piglet but does not change CSF glutamate or brain-801 binding and probably worsens outcome by elevating brain lactate levels above the threshold for cellular injury.
LeBlanc
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MH
Department of Pediatrics, University of Mississippi Medical Center, Jackson 39216-4505, USA. mleblanc@ped.umsmed.edu
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D000255:Adenosine Triphosphate / Q000032:analysis*; D000818:Animals; D000831:Animals, Newborn; D001831:Body Temperature; D001921:Brain / Q000473:pathology; D001923:Brain Chemistry / Q000187:drug effects*; D002545:Brain Ischemia / Q000503:physiopathology*; D005947:Glucose / Q000008:administration & dosage / Q000494:pharmacology*; D015309:Glucose Clamp Technique; D018698:Glutamic Acid / Q000134:cerebrospinal fluid* / Q000187:drug effects; D007004:Hypoglycemic Agents / Q000008:administration & dosage / Q000494:pharmacology; D002534:Hypoxia, Brain / Q000503:physiopathology*; D007328:Insulin / Q000008:administration & dosage / Q000494:pharmacology; D019344:Lactic Acid / Q000032:analysis*; D011897:Random Allocation; D013552:Swine; D013997:Time Factors
D007004:Hypoglycemic Agents; D007328:Insulin; D019344:Lactic Acid; D018698:Glutamic Acid; D000255:Adenosine Triphosphate; D005947:Glucose