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Pharmacologically induced hypothermia with cannabinoid receptor agonist WIN55, 212-2 after cardiopulmonary resuscitation.

 Shijie Sun  ;  Wanchun Tang  ;  Fengqing Song  ;  Sung Phil Chung  ;  Yinlun Weng  ;  Tao Yu  ;  Max Harry Weil 
 CRITICAL CARE MEDICINE, Vol.38(12) : 2282-2286, 2010 
Journal Title
Issue Date
Analysis of Variance ; Animals ; Benzoxazines/pharmacology* ; Cannabinoid Receptor Agonists* ; Cardiac Output/drug effects ; Cardiopulmonary Resuscitation/methods* ; Disease Models, Animal ; Drug Administration Schedule ; Electric Countershock/methods ; Hemodynamics/drug effects* ; Hemodynamics/physiology ; Hypothermia, Induced/methods* ; Male ; Morpholines/pharmacology* ; Myocardial Contraction/drug effects ; Naphthalenes/pharmacology* ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Reference Values ; Stroke Volume/drug effects ; Survival Rate ; Time Factors ; Ventricular Fibrillation/mortality ; Ventricular Fibrillation/therapy*
OBJECTIVE: To investigate whether hypothermia could be induced pharmacologically after resuscitation with the cannabinoid CB1/CB2 receptor agonist in a rat model and its effects on outcomes of cardiopulmonary resuscitation. DESIGN: Prospective, randomized, placebo-controlled experimental study. SETTING: University-affiliated animal research laboratory. SUBJECTS: Ten healthy male Sprague-Dawley rats. INTERVENTIONS: Ventricular fibrillation was induced and untreated for 6 mins. Defibrillation was attempted after 8 mins of cardiopulmonary resuscitation. Thirty minutes after resuscitation, animals were randomized to receive either WIN55, 212-2 (1.0 mg/kg/hr) or vehicle placebo (1.4 mL/kg/hr) for 6 hrs. Before infusion, the temperature was maintained at 37°C in all the animals with the help of a heating lamp. The same temperature environment was maintained for both groups after infusion. MEASUREMENTS AND MAIN RESULTS: Hemodynamic measurements and cardiac output, ejection fraction, and myocardial performance index were measured at baseline and hourly for 6 hrs after resuscitation. Survival time up to 72 hrs was observed. RESULTS: Blood temperature decreased progressively after infusion of WIN55, 212-2 from 37°C to 34°C 4 hrs after resuscitation. There was no significant change in blood temperature after 6 hrs of placebo infusion of the same volume and same infusate temperature. Significantly better postresuscitation myocardial function and longer durations of survival were observed in WIN55, 212-2-treated animals. CONCLUSIONS: The selective cannabinoid agonist, WIN55, 212-2, produced a significant reduction in blood temperature and improved postresuscitation myocardial functions and survival after cardiopulmonary resuscitation. The study results may provide a further option for early and effective induction of therapeutic hypothermia in settings of cardiopulmonary resuscitation.
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1. College of Medicine (의과대학) > Dept. of Emergency Medicine (응급의학교실) > 1. Journal Papers
Yonsei Authors
Chung, Sung Pil(정성필) ORCID logo https://orcid.org/0000-0002-3074-011X
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