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

Abstract

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. Key words: Ketamine; Hypothermia, induced; Asphyxia; Heart arrest; Reperfusion injury; Brain