title: Effect of valproic acid combined with therapeutic hypothermia on neurologic outcome in asphyxial cardiac arrest model of rats.
abstract: BACKGROUND
  Valproic acid (VPA) has been reported to have survival and neuroprotective effects in a cardiac arrest rat model. This study was designed to investigate the effect of VPA combined with therapeutic hypothermia (HT) in an asphyxial cardiac arrest rat model.
  
  
  METHODS
  Rats were subjected to 6 minutes of asphyxial cardiac arrest. Cardiopulmonary resuscitation was performed and then the randomly allocated to 1 of 4 groups (normal saline [NS]/normothermia [NT], VPA/NT, NS/HT, and VPA/HT). Hypothermia (32.5°C ± 0.5°C, 4 hours of HT and 2 hours of rewarming) or NT (37°C ± 0.5°C for 6 hours) was applied, and VPA (300 mg/kg) or NS was administered immediately after the return of spontaneous circulation. Neurologic deficit score was measured, and a tape removal test was performed for 3 days. Histologic injury of hippocampus was evaluated.
  
  
  RESULTS
  Valproic acid significantly improved neurologic deficit score at 48 and 72 hours in the NT-treated rats and at 72 hours in the HT-treated rats (all P < .05). Although the latency and success rate were not significantly different between the VPA/NT and NS/NT groups, the VPA/HT group showed significantly lower latency and higher success rates compared to the NS/HT group (P < .05). The histologic injury score in the hippocampal CA1 sector was significantly lower in the VPA/NT group than the NS/NT group (P < .05) and showed a tendency to be decreased in the VPA/HT group compared with the NS/HT group (P = .06).
  
  
  CONCLUSIONS
  In an asphyxial cardiac arrest rat model, administration of VPA improved neurologic outcomes and added a neuroprotective effect to HT.
authors.affiliation: Department of Emergency Medicine, Seoul National University Bundang Hospital, Gyeonggi-do, Republic of Korea.
authors.forename: Jae Hyuk
authors.initials: JH
authors.lastname: Lee
authors.affiliation: Department of Emergency Medicine, Seoul National University Bundang Hospital, Gyeonggi-do, Republic of Korea. Electronic address: dremkks@snubh.org.
authors.forename: Kyuseok
authors.initials: K
authors.lastname: Kim
authors.affiliation: Department of Emergency Medicine, Seoul National University Bundang Hospital, Gyeonggi-do, Republic of Korea.
authors.forename: You Hwan
authors.initials: YH
authors.lastname: Jo
authors.affiliation: Department of Emergency Medicine, Seoul National University Bundang Hospital, Gyeonggi-do, Republic of Korea.
authors.forename: Min Ji
authors.initials: MJ
authors.lastname: Lee
authors.affiliation: Department of Emergency Medicine, Seoul National University Bundang Hospital, Gyeonggi-do, Republic of Korea.
authors.forename: Ji Eun
authors.initials: JE
authors.lastname: Hwang
authors.affiliation: Department of Pathology, Seoul National University, Seoul, Republic of Korea.
authors.forename: Min A
authors.initials: MA
authors.lastname: Kim
mesh_terms: D000818:Animals; D001237:Asphyxia / Q000150:complications; D001927:Brain Diseases / Q000209:etiology / Q000473:pathology / Q000517:prevention & control*; D003131:Combined Modality Therapy; D004195:Disease Models, Animal; D004791:Enzyme Inhibitors / Q000627:therapeutic use*; D006323:Heart Arrest / Q000150:complications* / Q000628:therapy; D006624:Hippocampus / Q000473:pathology; D007036:Hypothermia, Induced; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D014635:Valproic Acid / Q000627:therapeutic use*
chemical_list: D004791:Enzyme Inhibitors; D014635:Valproic Acid