title: Elevated brain lactate accumulation and increased neurologic deficit are associated with modest hyperglycemia in global brain ischemia.
abstract: This study determined if hyperglycemia: (1) augments ischemic cerebral cortical lactate accumulation during complete cerebral ischemia; and (2) exacerbates subsequent neurologic morbidity and mortality. Dextrose (D5W, n = 8) or normal saline (n = 6) was administered i.v. prior to 10 min of global cerebral ischemia induced by normothermic cardiac arrest in dogs. Before arrest plasma glucose was significantly higher in the D5W-treated group than saline-infused (407 +/- 31 vs. 11 9 +/- 20 mg/dl, P less than 0.05). By 6 h post-arrest, seven of eight D5W-infused dogs died, compared to one of six saline-infused dogs (P = 0.002). D5W-infused dogs showed significantly greater neurologic deficit at 2, 6, and 12 h post-arrest. In a complementary protocol, dogs were pretreated in the same manner, however, six cerebral cortical brain biopsies were taken before, during, and immediately after cardiac arrest. Plasma glucose was 320 +/- 17 mg/dl in the D5W-infused dogs and lower (P less than 0.001), 140 +/- 5 mg/dl, in the saline-infused group. Cerebral cortical lactate accumulation was slightly but significantly greater during ischemia and early reperfusion in animals receiving dextrose. Neither plasma nor cerebrospinal fluid (CSF) creatine kinase isoenzymes nor plasma or CSF lactate concentrations, measured during and for 25 min after cardiac arrest, served as a good prognostic indicator of 24 h neurologic morbidity or mortality. Therefore, induction of complete cerebral ischemia in the presence of moderate hyperglycemia is associated with profound neurologic dysfunction and striking mortality. A qualitative but not quantitative increase in brain lactate accumulation is consistent with the hypothesis that lactate may contribute to the increased severity of neurologic dysfunction with hyperglycemia.
authors.affiliation: Department of Physiology, University of Michigan Medical School, Ann Arbor.
authors.forename: J E
authors.initials: JE
authors.lastname: Natale
authors.forename: S M
authors.initials: SM
authors.lastname: Stante
authors.forename: L G
authors.initials: LG
authors.lastname: D'Alecy
mesh_terms: D000818:Animals; D001921:Brain / Q000378:metabolism* / Q000503:physiopathology; D002545:Brain Ischemia / Q000150:complications / Q000378:metabolism* / Q000503:physiopathology; D004285:Dogs; D006943:Hyperglycemia / Q000150:complications / Q000378:metabolism* / Q000503:physiopathology; D007773:Lactates / Q000097:blood / Q000378:metabolism*; D008297:Male
chemical_list: D007773:Lactates