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Abstract

Introduction: To determine the mechanisms of improved myocardial function and survival following administration of cannabinoid receptor agonist, WIN55, 212-2 in a rat post-cardiac arrest model. Hypothesis: We hypothesize that myocardial and neurological protective effects of WIN55, 212-2 are resulted from its temperature reduction effect. Methods: Ventricular fibrillation (VF) was electrically induced in 30 male Sprague-Dawley rats weighing between 450 - 550g. CPR was initiated after 6 min of untreated VF. After 8 min of CPR, up to three 2-J defibrillations were attempted. Restoration of spontaneous circulation (ROSC) was defined as return of supra ventricular rhythm with a mean aortic pressure above 50 mmHg for 5 min. If ROSC was not achieved, a 30 sec interval of CPR was performed prior to attempt a subsequent sequence of up to 3 shocks until successful resuscitation or for a maximum of 3 cycle attempts. Five min after post-resuscitation, the animals were randomized into 3 groups: (1) WIN55, 212-2 with normothermia; (2) WIN55, 212-2 alone; (3) control. Thirty mins after ROSC, the animals received continuous intravenous infusion of WIN55, 212-2 (1.0 mg/kg.h) for 2 hrs while control animals received a placebo. Except for the group in WIN55, 212-2 alone, the body temperature in the other 2 groups were maintained at 37.0 ± 0.2°C with the aid of a heating lamp to prevent spontaneous or pharmacologically induced hypothermia. The room temperature was identical in all animals. Neurological deficit scores (NDS) and survival time were observed for up to 72 hrs. Results: Blood temperatures decreased progressively in animals treated with WIN55, 212-2 alone from 37°C to 33°C in 4 hrs. Post-resuscitation myocardial function, NDS and survival time were significantly better in this group when compared with the control group. However, in animals treated with WIN55, 212-2 and normothermia, there were no statistical differences in post-resuscitation myocardial function, NDS and survival time when compared with the control group. Conclusions: In a rat model of cardiac arrest, better post-resuscitation myocardial function, neurological deficit scores and longer duration of survival were observed by the pharmacologically induced hypothermia with WIN55, 212-2. However, the protective effects of WIN55, 212-2 were diminished when body temperature was maintained at the normal level.