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


METHODS
Prospective, randomized, placebo-controlled experimental study.


METHODS
University-affiliated animal research laboratory.


METHODS
Ten healthy male Sprague-Dawley rats.


METHODS
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.


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.
Sun
Shijie
S
Weil Institute of Critical Care Medicine, Rancho Mirage, CA, USA.
Tang
Wanchun
W
Song
Fengqing
F
Chung
Sung Phil
SP
Weng
Yinlun
Y
Yu
Tao
T
Weil
Max Harry
MH
D000704:Analysis of Variance; D000818:Animals; D048588:Benzoxazines / Q000494:pharmacology*; D063386:Cannabinoid Receptor Agonists; D002302:Cardiac Output / Q000187:drug effects; D016887:Cardiopulmonary Resuscitation / Q000379:methods*; D004195:Disease Models, Animal; D004334:Drug Administration Schedule; D004554:Electric Countershock / Q000379:methods; D006439:Hemodynamics / Q000187:drug effects* / Q000502:physiology; D007036:Hypothermia, Induced / Q000379:methods*; D008297:Male; D009025:Morpholines / Q000494:pharmacology*; D009200:Myocardial Contraction / Q000187:drug effects; D009281:Naphthalenes / Q000494:pharmacology*; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D012016:Reference Values; D013318:Stroke Volume / Q000187:drug effects; D015996:Survival Rate; D013997:Time Factors; D014693:Ventricular Fibrillation / Q000401:mortality / Q000628:therapy*
D048588:Benzoxazines; D063386:Cannabinoid Receptor Agonists; D009025:Morpholines; D009281:Naphthalenes; C070417:(3R)-((2,3-dihydro-5-methyl-3-((4-morpholinyl)methyl)pyrrolo-(1,2,3-de)-1,4-benzoxazin-6-yl)(1-naphthalenyl))methanone