Abstract 16488: ERK is Invovled in Neuroprotection of Win55,212-2 Pharmacological Hypothermia After CPR in a Rat Cardiac Arrest Model

• Published in: Circulation (New York, N.Y.) Vol. 134; no. Suppl_1 Suppl 1; p. A16488
• Main Authors: Song, Feng-Qing, Yu, Tao, Fang, Xiangshao, Zheng, Guanghui, Jiang, Longyuan, Huang, Zitong, Zuo, Yanfang, Yang, Zhengfei
• Format: Journal Article
• Language: English
• Published: by the American College of Cardiology Foundation and the American Heart Association, Inc 11-11-2016
• ISSN: 0009-7322; 1524-4539

ERK is involved in the neuroprotection of Win55,212-2 pharmacological hypothermia after CPR in a rat cardiac arrest modelThis study was supported by National Natural Science Foundation of China (No.81201447, 81460289)IntroductionStudies have demonstrated that Win55,212-2 induced pharmacological hypothermia and improved the outcome of CPR. However, the mechanism is still unclear.HypothesisIn this study, we hypothesize extracellular signal-regulated kinase (ERK) will take part in the neuroprotection of WIN55,212-2 pharmacological hypothermia after CPR in a rat cardiac arrest (CA) model.MethodsCA was induced by transoesophageal ventricular pacing in SD rats. 5min after onset of CA, CPR was started. At 5 min post-resuscitation, 30 animals were randomized into 3 groups (n=10 in each group)(1) Win55, 212-2 group; (2) Normothermia group; (3) Win55, 212-2 + ERK blocker PD98059. Animals received PD98059 (3mg/kg) or placebo. After 30 min of ROSC, animals in drug groups were received continuous intravenous infusion of Win55,212-2 (1 mg/kg/h ) for 4 h while which in normothermia group were received 5% DMSO. Rats in normothermia group were maintained at 37°C with warming lamp though the whole experiment. Rats in drug group were warmed to 37°C increasingly after 4h of Win55,212-2 treatment. The survival time and neurological deficit score (NDS) were observed.ResultsTemperatures of rats in Win55,212-2 group decreased from 37°C to 34°C in 4 hours, which could not be blocked by ERK blocker PD98059. Accumulate survival rate was higher and NDS was significantly improved in Win55 group than those of the normothermia group (P<0.05). However, these effects disappeared with PD98059.ConclusionsWin55, 212-2 inducing pharmacologically hypothermia prolonged survival and improved cerebral function in a rat cardiac arrest model. The beneficial effects of WIN55, 212-2 were associated with ERK signal pathway.