氯胺酮联合亚低温对窒息性心跳骤停大鼠复苏后脑缺血再灌注损伤的影响

目的 探讨氯胺酮联合亚低温对窒息性心跳骤停大鼠复苏后脑缺血再灌注损伤的影响.方法 健康Wistar大鼠50只,4.0～4.5个月,雌雄各半,体重410～510 g,随机分为5组(n=10):假手术组(S组)仅经动、静脉穿刺置管;窒息性心跳骤停组(ACA组)制备窒息性脑缺血模型;氯胺酮组(K组)窒息前5 min腹腔注射氯胺酮100 mg/kg;亚低温组(MH组):窒息开始后维持直肠温30～35℃;氯胺酮+亚低温组(K+MH组):窒息前5 min腹腔注射氯胺酮100 mg/kg,窒息开始后维持直肠温30～35 ℃.成功复苏后,取脑组织,测定脑含水量和海马神经元p-caspase-3的表达水平.结果 与S组比较,ACA组和K组脑含水量升高,p-caspase-3表达上调,MH组和K+MH组p-caspase-3表达上调(P＜0.01),脑含水量差异无统计学意义(P＞0.05);与ACA组比较,MH组和K+MH组脑含水量降低,p-caspase-3表达下调,K组p-caspase-3表达下调(P＜0.01),脑含水量差异无统计学意义(P＞0.05);与K组比较,K+MH组脑含水量降低,p-caspase-3表达下凋,MH组脑含水量降低(P＜0.01),p-caspase-3表达差异无统计学意义(P＞0.05);与MH组比较,K+MH组p-caspase-3表达下调(P＜0.01),脑含水量差异无统计学意义(P＞0.05).结论 氯胺酮联合亚低温可减轻窒息性心跳骤停大鼠复苏后的脑缺血再灌注损伤,该效应较两者单独应用时增强.

Effects of ketamine combined with moderate hypothermia on brain ischemia-reperfusion injury in a rat model of asphyxial cardiac arrest

Objective To investigate the effects of ketamine combined with moderate hypothermia on brain ischemia-reperfusion (I/R) injury in a rat model of asphyxial cardiac arrest. Methods Fifty healthy Wistar rats of both sexes aged 4.0-4.5 months, weighing 410-510 g were randomly allocated into 5 groups (n = 10each): group Ⅰ sham operation (group S), group Ⅱ asphyxial cardiac arrest (group ACA), group Ⅲ ketamine (group K), group Ⅳ moderate hypothermia (group MH) and group Ⅴ K + MH. The animals were anesthetized with intraperitoneal (IP) phenobarbital 20 mg/100 g, tracheostomized and mechanically ventilated (RR 60 bpm,FiO2 50%), PaCO2 was maintained at 35-45 mm Hg. Cardiac arrest was induced by clamping tracheal tube until ECG activity disappeared and MAP ＜ 15 mm Hg. Resuscitated was started 5 min later. MAP ＞ 60 mm Hg and HR ＞ 250 bpm were considered to be signs of successful resuscitation. Dead animals and animals in which resuscitation time was longer than 5 min were excluded from the study. In group K ketamine 100 mg/kg was administered IP at 5 min before asphyxia. In group MH hypothermia was started as soon as asphyxia was started and body temperature was maintained at 30-35 ℃. After successful resuscitation, the animals were sacrificed. Their brains were removed for determination of brain water content and p-caspase-3 expression in hippocampus. Results Brain I/Rsignificantly increased brain water content and p-caspase-3 expression in group ACA. MH alone significantly attenuated 1/R-induced brain edema and decreased p-caspase-3 expression, while ketamine alone only significantly decreased p-caspase-3 expression but did not decrease I/R-induced brain edema. MH + K decreased p-caspase-3expression further but did not reduce brain edema further as compared with MH alone. Conclusion Ketamine combined with moderate hypothermia provides better protection against brain I/R injury.