Wann Shue-ren, Weil Max Harry, Sun Shijie, Tang Wanchun, Pellis Tommaso
Institute of Critical Care Medicine, Palm Springs, CA, USA.
Crit Care Med. 2002 Apr;30(4 Suppl):S154-6. doi: 10.1097/00003246-200204001-00007.
Ventricular fibrillation (VF) is generally sustained. The mechanism is, at least in part, caused by progressive accumulation of intracellular sodium and calcium ions during untreated ventricular fibrillation, which subsequently increases defibrillation threshold. Cariporide, a potent and specific inhibitor of the sodium-hydrogen exchanger, has been shown to reduce intracellular sodium and calcium concentration in the setting of myocardial ischemia and reperfusion. We hypothesized that cariporide would facilitate defibrillation from prolonged ventricular fibrillation in a rodent model of cardiac arrest and resuscitation. Fifteen Sprague-Dawley rats were randomized to receive bolus injections of cariporide or placebo in a dose of 3 mg/kg into the right atrium either 5 mins before or at 8 mins after onset of ventricular fibrillation. Ventricular fibrillation was electrically induced and untreated for 8 mins. Precordial compression together with mechanical ventilation was then started and continued for an interval of 8 mins before attempted electrical defibrillation. All but one placebo-treated animal were successfully resuscitated. Spontaneous defibrillation with restoration of circulation was observed in both cariporide pretreatment and treatment groups but in none of the placebo-treated animals. The duration of postresuscitation survival was significantly increased in animals pretreated with cariporide. Therefore, sodium-hydrogen exchanger inhibitors may provide new options in settings of cardiopulmonary resuscitation to facilitate defibrillation.
心室颤动（VF）通常是持续性的。其机制至少部分是由于在未经治疗的心室颤动期间细胞内钠和钙离子的逐渐积累，这随后会增加除颤阈值。卡立泊来德是一种强效且特异性的钠氢交换体抑制剂，已被证明在心肌缺血和再灌注情况下可降低细胞内钠和钙浓度。我们假设卡立泊来德会在心脏骤停和复苏的啮齿动物模型中促进从长时间心室颤动中除颤。15只Sprague-Dawley大鼠被随机分为两组，在心室颤动发作前5分钟或发作后8分钟经右心房给予3mg/kg剂量的卡立泊来德或安慰剂推注。通过电诱导心室颤动并持续8分钟不予治疗。然后开始进行心前区按压并同时进行机械通气，持续8分钟后尝试进行电除颤。除一只接受安慰剂治疗的动物外，其他所有动物均成功复苏。在卡立泊来德预处理组和治疗组中均观察到自发除颤并恢复循环，但在接受安慰剂治疗的动物中均未观察到。卡立泊来德预处理的动物复苏后存活时间显著延长。因此，钠氢交换体抑制剂可能为心肺复苏提供促进除颤的新选择。
