Ventricular fibrillation (VF) was induced and untreated for 6 min in 20 male Sprague-Dawley rats. Defibrillation was attempted after 8 min of Cardiopulmonary resuscitation (CPR). Five min post-resuscitation, resuscitated animals were randomized to receive an intramuscular injection of selective CB1 receptors antagonist, SR141716A (5 mg kg?1); selective CB2 receptors antagonist SR144528 (5 mg kg?1); or placebo. Thirty min after injection, animals received continuous intravenous infusion of WIN55, 212-2 (1.0 mg kg?1 h?1) for 4 h while control animals received placebo. The identical temperature environment was maintained in all animals.
In animals treated with WIN55, 212-2, blood temperatures decreased progressively from 37 ¡ãC to 34 ¡ãC within 4 h. This hypothermic effect was completely blocked by CB1 but not CB2 antagonist. Accordingly, significantly better cardiac output, ejection fraction and myocardial performance index, reduced neurological deficit scores, improved microcirculation and longer duration of survival were observed in WIN55, 212-2-treated animals, which were also completely abolished by pretreatment with CB1 antagonist.
Pharmacologically induced hypothermia with WIN55, 212-2 improved post-resuscitation myocardial and cerebral function, associated with a significantly increased duration of survival in a rat post-cardiac arrest model. The hypothermic and resulted beneficial effects of WIN55, 212-2 were mediated through CB1 receptors.