Fang Xiangshao, Tang Wanchun, Sun Shijie, Huang Lei, Huang Zitong, Weil Max Harry
Weil Institute of Critical Care Medicine, Rancho Mirage, CA, USA.
Crit Care Med. 2006 Oct;34(10):2607-12. doi: 10.1097/01.CCM.0000228916.81470.E1.
Postresuscitation myocardial dysfunction has been recognized as a leading cause of early death after initially successful cardiopulmonary resuscitation. We have previously demonstrated that opening adenosine triphosphate (ATP)-sensitive K (KATP) channels or activation of delta-opioid receptors minimized the severity of postresuscitation myocardial dysfunction and increased the duration of postresuscitation survival. In the present study, we investigated the potential mechanism of myocardial protection following delta-opioid receptor activation in a rat model of cardiac arrest and cardiopulmonary resuscitation.
Randomized prospective animal study.
Animal research laboratory.
Male Sprague-Dawley rats.
Ventricular fibrillation was induced in 24 Sprague-Dawley rats. Mechanical ventilation and precordial compression were initiated after 8 mins of untreated ventricular fibrillation. Defibrillation was attempted after 6 mins of cardiopulmonary resuscitation. The animals were randomized to four groups: a) pentazocine (0.3 mg/kg), a delta-opioid receptor agonist; b) pentazocine pretreated with KATP channel blocker, glibenclamide (0.3 mg/kg), administered 45 mins before induction of ventricular fibrillation; c) glibenclamide pretreated alone 45 mins before induction of ventricular fibrillation; and d) placebo. Pentazocine or saline placebo was injected into the right atrium after 5 mins of untreated ventricular fibrillation.
Postresuscitation myocardial function, as measured by the rate of left ventricular pressure increase at 40 mm Hg, left ventricular end-diastolic pressure, and cardiac index, was significantly improved in pentazocine-treated animals. This was associated with significantly prolonged duration of survival. Except for ease of defibrillation, the beneficial effects of pentazocine were abolished by pretreatment with the KATP channel blocker glibenclamide.
The postresuscitation myocardial protective effects provided by activation of delta-opioid receptor may be mediated via opening KATP channels.
复苏后心肌功能障碍已被公认为是初始心肺复苏成功后早期死亡的主要原因。我们之前已经证明，开放三磷酸腺苷（ATP）敏感性钾（KATP）通道或激活δ-阿片受体可将复苏后心肌功能障碍的严重程度降至最低，并延长复苏后的存活时间。在本研究中，我们在大鼠心脏骤停和心肺复苏模型中研究了激活δ-阿片受体后心肌保护的潜在机制。
随机前瞻性动物研究。
动物研究实验室。
雄性Sprague-Dawley大鼠。
对24只Sprague-Dawley大鼠诱发室颤。在未治疗的室颤8分钟后开始机械通气和胸外按压。心肺复苏6分钟后尝试除颤。将动物随机分为四组：a）喷他佐辛（0.3mg/kg），一种δ-阿片受体激动剂；b）在诱发室颤前45分钟用KATP通道阻滞剂格列本脲（0.3mg/kg）预处理的喷他佐辛；c）在诱发室颤前45分钟单独用格列本脲预处理；d）安慰剂。在未治疗的室颤5分钟后将喷他佐辛或生理盐水安慰剂注入右心房。
通过40mmHg时左心室压力上升速率、左心室舒张末期压力和心脏指数测量的复苏后心肌功能，在喷他佐辛治疗的动物中显著改善。这与存活时间显著延长相关。除了易于除颤外，喷他佐辛的有益作用被KATP通道阻滞剂格列本脲预处理所消除。
激活δ-阿片受体提供的复苏后心肌保护作用可能通过开放KATP通道介导。
