Weil Institute of Critical Care Medicine, Rancho Mirage, CA, USA.
Crit Care Med. 2010 Dec;38(12):2282-6. doi: 10.1097/CCM.0b013e3181f9f9e3.
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.
Prospective, randomized, placebo-controlled experimental study.
University-affiliated animal research laboratory.
Ten healthy male Sprague-Dawley rats.
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.
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.
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.
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.
在大鼠模型中，通过使用大麻素 CB1/CB2 受体激动剂复律来探讨是否可以诱导低温，并观察其对心肺复苏后结局的影响。
前瞻性、随机、安慰剂对照的实验研究。
大学附属动物研究实验室。
10 只健康雄性 Sprague-Dawley 大鼠。
心室颤动诱导后未经治疗 6 分钟。心肺复苏 8 分钟后尝试除颤。复苏 30 分钟后，动物随机接受 WIN55,212-2（1.0mg/kg/hr）或载体安慰剂（1.4mL/kg/hr）6 小时输注。在输注前，所有动物均在加热灯的帮助下将体温维持在 37°C。输注后两组均保持相同的温度环境。
在复苏前和复苏后 6 小时内每小时测量血流动力学测量和心输出量、射血分数和心肌收缩性能指数。观察 72 小时的存活时间。
WIN55,212-2 输注后，体温从 37°C逐渐下降至复苏后 4 小时的 34°C。输注相同体积和相同输注液温度的安慰剂 6 小时后，体温无明显变化。WIN55,212-2 治疗组复苏后心肌功能明显改善，存活时间延长。
选择性大麻素激动剂 WIN55,212-2 可显著降低体温，并改善心肺复苏后心肌功能和存活率。该研究结果可能为心肺复苏后早期和有效诱导治疗性低温提供了进一步的选择。
