title: Effect of valproic acid on survival and neurologic outcomes in an asphyxial cardiac arrest model of rats.
abstract: OBJECTIVE
  Valproic acid (VPA) has been known to reduce neuronal injury, has anti-inflammatory and anti-apoptotic effects as a histone deacetylase (HDAC) inhibitor. Thus, this study was performed to investigate the effects of VPA on survival and neurological outcomes in an asphyxial cardiac arrest model of rats.
  
  
  METHODS
  Male Sprague-Dawley rats were subjected to asphyxial cardiac arrest. For survival study, rats were subjected to 450s of asphyxial cardiac arrest. Cardiopulmonary resuscitation (CPR) was performed and then rats were blindly allocated to one of two groups (control group, n=10; VPA group, n=10). Valproic acid (300mgkg(-1)) or vehicle (normal saline) was administered via tail vein immediately after return of spontaneous circulation (ROSC) and observed for 72h. For neurological outcome study, rats (n=7 for each group) were subjected to same experimental procedures except duration of cardiac arrest of 360s. Neurological deficit scale (NDS) score was measured every 24h after ROSC for 72h and was ranged from 0 (brain dead) to 80 (normal). Brain tissues were harvested at 72h for evaluation of apoptotic injury and acetylation status of histone H3.
  
  
  RESULTS
  In survival study, 2 rats in VPA group were excluded because cardiac arrest was not achieved in predetermined time. Thus, 10 rats were allocated to control group and 8 rats were allocated to VPA group. The survival rates at 72h after cardiac arrest were significantly higher in VPA group than in control group (6/8 in VPA group, 3/10 rats in control group; log rank test, p<0.05). In neurological outcome study, all rats survived for 72h and NDS at 72h were significantly higher in VPA group than in control group (p<0.05). In brain tissues, expressions of acetylated histone H3 were not significantly different. However, expressions of cleaved caspase-3 were significantly lower in VPA group than in control group (p<0.05).
  
  
  CONCLUSIONS
  VPA increased survival rates and improved neurologic outcome in asphyxial cardiac arrest model of rats while decreasing expressions of cleaved caspase-3.
authors: Department of Emergency Medicine, Seoul National University Bundang Hospital, Gyeonggi-do, Republic of Korea.
authors: Jae Hyuk
authors: JH
authors: Lee
authors: Kyuseok
authors: K
authors: Kim
authors: You Hwan
authors: YH
authors: Jo
authors: Soo Hoon
authors: SH
authors: Lee
authors: Changwoo
authors: C
authors: Kang
authors: Joonghee
authors: J
authors: Kim
authors: Chan Jong
authors: CJ
authors: Park
authors: Min A
authors: MA
authors: Kim
authors: Min Ji
authors: MJ
authors: Lee
authors: Joong Eui
authors: JE
authors: Rhee
mesh_terms: D000818:Animals; D001237:Asphyxia / Q000150:complications / Q000188:drug therapy* / Q000401:mortality; D001927:Brain Diseases / Q000209:etiology / Q000517:prevention & control*; D004195:Disease Models, Animal; D004791:Enzyme Inhibitors / Q000627:therapeutic use*; D006323:Heart Arrest / Q000188:drug therapy* / Q000209:etiology / Q000401:mortality; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D015996:Survival Rate; D014635:Valproic Acid / Q000627:therapeutic use*
chemical_list: D004791:Enzyme Inhibitors; D014635:Valproic Acid
keywords: Apoptosis; Cardiac arrest; Histone deacetylase inhibitor; Valproic acid