Knapp Jürgen, Schneider Andreas, Nees Corinna, Bruckner Thomas, Böttiger Bernd W, Popp Erik
Department of Anaesthesiology, University of Heidelberg, Im Neuenheimer Feld 110, D-69120 Heidelberg, Germany.
Department of Anaesthesiology and Postoperative Intensive Care Medicine, University of Cologne, Kerpener Str. 62, D-50937 Köln, Germany.
Resuscitation. 2014 Sep;85(9):1291-7. doi: 10.1016/j.resuscitation.2014.05.030. Epub 2014 Jun 27.
Animal studies and pathophysiological considerations suggest that therapeutic hypothermia after cardiopulmonary resuscitation is the more effective the earlier it is induced. Therefore this study is sought to examine whether pharmacological facilitated hypothermia by administration of 5'-adenosine monophosphate (AMP) is neuroprotective in a rat model of cardiac arrest (CA) and resuscitation.
Sixty-one rats were subjected to CA. After 6 min of ventricular fibrillation advanced cardiac life support was started. After successful return of spontaneous circulation (ROSC, n=40), animals were randomized either to placebo group (n=14) or AMP group (800 mg/kg body weight, n=14). Animals were kept at an ambient temperature of 18°C for 12 h after ROSC and core body temperature was measured using a telemetry temperature probe. Neuronal damage was analyzed by counting Nissl-positive (i.e. viable) neurons and TUNEL-positive (i.e. apoptotic) cells in coronal brain sections 7 days after ROSC. Functional status evaluated on days 1, 3 and 7 after ROSC by a tape removal test.
Time until core body temperature dropped to <34.0°C was 31 min [28; 45] in AMP-treated animals and 125 min [90; 180] in the control group (p=0.003). Survival until 7 days after ROSC was comparable in both groups. Also number of Nissl-positive cells (AMP: 1 [1; 7] vs. placebo: 2 [1; 3] per 100 pixel; p=0.66) and TUNEL-positive cells (AMP: 56 [44; 72] vs. placebo: 53 [41; 67] per 100 pixel; p=0.70) did not differ. Neither did AMP affect functional neurological outcome up to 7 days after ROSC. Mean arterial pressure 20 min after ROSC was 49 [45; 55] mmHg in the AMP group in comparison to 91 [83; 95] mmHg in the control group (p<0.001).
Although application of AMP reduced the time to reach a core body temperature of <34°C neither survival was improved nor neuronal damage attenuated. Reason for this is probably induction of marked hypotension as an adverse reaction to AMP treatment.
动物研究和病理生理学考量表明，心肺复苏后进行治疗性低温，诱导时间越早效果越好。因此，本研究旨在探讨通过给予5'-单磷酸腺苷（AMP）进行药物辅助性低温在大鼠心脏骤停（CA）及复苏模型中是否具有神经保护作用。
61只大鼠经历心脏骤停。室颤6分钟后开始进行高级心脏生命支持。自主循环成功恢复（ROSC，n = 40）后，将动物随机分为安慰剂组（n = 14）或AMP组（800mg/kg体重，n = 14）。ROSC后，动物在18°C环境温度下饲养12小时，并使用遥测温度探头测量核心体温。复苏后7天，通过计数冠状脑切片中尼氏染色阳性（即可存活）神经元和TUNEL阳性（即凋亡）细胞来分析神经元损伤情况。在ROSC后第1、3和7天，通过胶带去除试验评估功能状态。
AMP治疗组动物核心体温降至<34.0°C的时间为31分钟[28；45]，而对照组为125分钟[90；180]（p = 0.003）。两组ROSC后存活至第7天的情况相当。尼氏染色阳性细胞数量（AMP组：每100像素1[1；7]个，安慰剂组：每100像素2[1；3]个；p = 0.66）和TUNEL阳性细胞数量（AMP组：每100像素56[44；72]个，安慰剂组：每100像素53[41；67]个；p = 0.70）也无差异。ROSC后长达7天，AMP对神经功能结局也无影响。ROSC后20分钟，AMP组平均动脉压为49[45；55]mmHg，而对照组为91[83；95]mmHg（p<0.001）。
尽管应用AMP缩短了达到<34°C核心体温的时间，但既未提高存活率，也未减轻神经元损伤。原因可能是AMP治疗引发明显低血压这一不良反应。
