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

Sun, Shijie MD, FCCM; Tang, Wanchun MD, FCCM; Song, Fengqing MD; Chung, Sung Phil MD; Weng, Yinlun MD; Yu, Tao MD; Weil, Max Harry MD, PhD, FCCM

doi: 10.1097/CCM.0b013e3181f9f9e3
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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.

From the Weil Institute of Critical Care Medicine (SS, WT, FS, SPC, YW, TY, MHW), Rancho Mirage, CA; and Keck School of Medicine of the University of Southern California (SS, WT, MHW), Los Angeles, CA.

This project was funded by the Weil Institute of Critical Care Medicine, Rancho Mirage, CA.

The work was performed at the Weil Institute of Critical Care Medicine, Rancho Mirage, CA.

The authors have not disclosed any potential conflicts of interest.

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© 2010 by the Society of Critical Care Medicine and Lippincott Williams & Wilkins