Effect of cannabinoid receptor agonist, WIN55, 212-2 on inflammatory factor levels and prognosis in a rat model of cardiac arrest

Zhu Yan; Lin Zhao-fen; Ma Lin-hao

doi:10.3969/j.issn.1002-1949.2017.03.018

Abstract：Objective To investigate the mechanisms of improved inflammatory factor levels and prognosis following intravenously administration of non-selective cannabinoid receptor agonist,WIN55,212-2 in a rat model of cardiac arrest.Methods Ventricular fibrillation (VF) was electrically induced in 30 male Sprague-Dawley rats.Cardiopulmonary resuscitation (CPR) was initiated after 6 minutes of untreated VF.After eight min of CPR,up to three 2 J defibrillations were attempted.After successful recovery for 30 min,the animals were then randomized into 3 groups:①WIN55,212-2 with normal body temperature;②WIN55,212-2 hypothermia;③Placebo control.Either WIN55,212-2 [1.0mg/(kg· h)]or saline placebo was continuously infused for two hrs.Except for the WIN55,212-2 hypothermia group,the body temperature in the other two groups was maintained at (37.0±0.2)℃ using an external heating lamp.Monitor interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) levels after 4 hours of recovery,and record each animal's survival after 72 hours of recovery.Results WIN55,212-2 hypothermia group was associated with significant decline in levels of IL-6 and TNF-α and significantly improved NDS and survival time when compared with placebo control group and WIN55,212-2 with normal body temperature group.Conclusion In a rat model of cardiac arrest,better post-resuscitation myocardial function,neurological deficit scores and longer duration of survival are observed by the pharmacologically induced hypothermia with WIN55,212-2.But when hypothermia induced by drugs disappears,effects on inflammatory factors and prognosis of rats also decrease significantly.Therefore,the improved outcomes of CPR following administration of WIN55,212-2 appear to be the results from its temperature reduction effects.