The Effects of the Rate of Postresuscitation Rewarming Following Hypothermia on Outcomes of Cardiopulmonary Resuscitation in a Rat Model*

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Objective:To investigate the optimal rewarming rate following therapeutic hypothermia in a rate model of cardiopulmonary resuscitation. Both clinical and laboratory studies have demonstrated that mild therapeutic hypothermia following cardiopulmonary resuscitation improves myocardial and neurologic outcomes of cardiac arrest. However, the optimal rewarming strategy following therapeutic hypothermia remains to be explored.Design:Prospective randomized controlled experimental study.Setting:University-affiliated research institution.Subjects:Twenty-three healthy male Sprague-Dawley rats.Interventions:Four groups of Sprague-Dawley rats were randomized: 1) normothermia group (control), 2) rewarming rate at 2°C/hr, 3) rewarming rate at 1°C/hr, and 4) rewarming rate at 0.5°C/hr. Ventricular fibrillation was induced and untreated for 8 minutes, and defibrillation was attempted after 8 minutes of cardiopulmonary resuscitation. For the 2, 1, and 0.5°C/hr groups, rapid cooling was started at the beginning of cardiopulmonary resuscitation. On reaching the target cooling temperature of 33°C ± 0.2°C, the temperature was maintained with the aid of a cooling blanket until 4 hours after resuscitation. Rewarming was then initiated at the rate of 2.0, 1.0, or 0.5°C/hr, respectively, until the body temperature reached 37°C ±0.2°C. Blood samples were drawn at baseline and postresuscitation of 4, 6, 8, 10, and 12 hours for the measurements of blood gas and serum biomarkers.Measurements and Main Results:Blood temperature significantly decreased in the hypothermic groups from cardiopulmonary resuscitation to postresuscitation 4 hours. Significantly better cardiac output, ejection fraction, myocardial performance index, reduced neurologic deficit scores, and longer duration of survival were observed in the 1 and 0.5°C/hr groups. The increased serum concentration of troponin I, interleukin-6, and tumor necrosis factor-α was partly attenuated in the 1 and 0.5°C/hr groups when compared with the control and 2°C/hr groups.Conclusions:This study demonstrated that the severity of myocardial, cerebral injuries, and inflammatory reaction after cardiopulmonary resuscitation was reduced when mild therapeutic hypothermia was applied. A rewarming rate at 0.5–1°C/hr did not alter the beneficial effects of therapeutic hypothermia. However, a rapid rewarming rate at 2°C/hr abolished the beneficial effects of hypothermia.

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