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Cholecystokinin octapeptide induces hypothermia and improves outcomes in a rat model of cardiopulmonary resuscitation*

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

doi: 10.1097/CCM.0b013e3182257660
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Objectives: To investigate the effects of cholecystokinin octapeptide on thermoregulation, postresuscitation myocardial function, neurologic outcome, and duration of survival in a rat model of cardiopulmonary resuscitation.

Design: Prospective, randomized, placebo-controlled experimental study.

Setting: University-affiliated animal research laboratory.

Subjects: Ten male Sprague-Dawley rats.

Interventions: Ventricular fibrillation was induced and untreated for 6 mins. Defibrillation was attempted after 8 mins of cardiopulmonary resuscitation. Animal temperature was adjusted to 37.0°C with the aid of a heating lamp. At 30 mins after resuscitation, animals were randomized to receive an intravenous injection of either cholecystokinin octapeptide (200 μg/kg in 0.3 mL saline) or vehicle placebo (0.3 mL saline). The ambient temperature settings and that of the distance of the heating lamp from the animal remained the same in both groups throughout the entire experiment.

Measurements and Main Results: Body temperature, hemodynamic measurements, and postresuscitation myocardial function, including cardiac output, left ventricular ejection fraction, and myocardial performance index, were measured together with neurologic deficit scores and duration of survival.

Results: After injection of cholecystokinin octapeptide, blood temperature decreased progressively from 37.0°C to 34.8°C 5 hrs after resuscitation and returned to 37.0°C at 9 hrs after injection. In the control group, blood temperature was sustained at 37.0°C ± 0.2°C during the same period of observation. Myocardial and neurologic function and duration of survival were significantly better in the cholecystokinin octapeptide-treated animals when compared to the control group.

Conclusions: In a rat model of cardiopulmonary resuscitation, cholecystokinin octapeptide induced mild hypothermia, attenuated postresuscitation myocardial dysfunction, and improved neurologic outcome and duration of survival.

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

Supported, in part, by American Heart Association grant 11IRG487001.

The authors have not disclosed any potential conflicts of interest.

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© 2011 by the Society of Critical Care Medicine and Lippincott Williams & Wilkins