title: Prevention of postischemic canine neurological injury through potentiation of brain energy metabolism by acetyl-L-carnitine.
abstract: OBJECTIVE
  Mechanisms of ischemia/reperfusion brain injury include altered patterns of energy metabolism that may be amenable to pharmacological manipulation. The purpose of this study was to test the effectiveness of postischemic acetyl-L-carnitine administration on potentiation of metabolic recovery and prevention of neurological morbidity in a clinically relevant model of complete, global cerebral ischemia and reperfusion.
  
  
  METHODS
  Neurological deficit scoring as well as spectrophotometric and fluorescent assays of frontal cortex lactate and pyruvate levels were used in a canine model employing 10 minutes of cardiac arrest followed by restoration of spontaneous circulation for 2 or 24 hours.
  
  
  RESULTS
  Dogs treated with acetyl-L-carnitine exhibited significantly lower neurological deficit scores (p = 0.0037) and more normal cerebral cortex lactate/pyruvate ratios than did vehicle-treated control animals.
  
  
  CONCLUSIONS
  Postischemic administration of acetyl-L-carnitine potentiates normalization of brain energy metabolites and substantially improves neurological outcome in a clinically relevant model of global cerebral ischemia and reperfusion.
authors.affiliation: Department of Emergency Medicine, George Washington University Medical Center, DC 20037.
authors.forename: R E
authors.initials: RE
authors.lastname: Rosenthal
authors.forename: R
authors.initials: R
authors.lastname: Williams
authors.forename: Y E
authors.initials: YE
authors.lastname: Bogaert
authors.forename: P R
authors.initials: PR
authors.lastname: Getson
authors.forename: G
authors.initials: G
authors.lastname: Fiskum
mesh_terms: D000108:Acetylcarnitine / Q000494:pharmacology*; D000818:Animals; D001921:Brain / Q000378:metabolism / Q000473:pathology*; D002545:Brain Ischemia / Q000473:pathology* / Q000517:prevention & control; D004285:Dogs; D004734:Energy Metabolism / Q000187:drug effects*; D005260:Female; D006323:Heart Arrest / Q000503:physiopathology; D007773:Lactates / Q000378:metabolism; D019344:Lactic Acid; D012151:Resuscitation; D012720:Severity of Illness Index
chemical_list: D007773:Lactates; D019344:Lactic Acid; D000108:Acetylcarnitine