心肺复苏大鼠模型中应用辣椒素结合通道受体激活剂olvanil和rinvanil诱导低温及复苏的疗效评价

Differential cardiovascular response to TRPV1 receptor agonist - induced hypothermia in a rat model of cardiopulmonary resuscitation

目的 通过在心肺复苏大鼠模型中应用辣椒素结合通道受体激活剂olvanil和rinvanil,评价其诱导低温的疗效、心血管反应和大鼠生存时间.方法 15只大鼠随机分为3组：诱导6 min的心脏骤停,然后进行6 min的心肺复苏,复苏后30 min,3组大鼠分别接受olvanil、rinvanil和安慰剂持续治疗6 h.药物浓度逐步提高.检测体温、心电图、血流动力学参数、心功能和7天生存率.结果 药物组均成功诱导亚低温,体温约下降3 ℃.各组均出现了短时间的心律失常,表现为室性心动过速和室性早搏.药物组还出现了三度房室传导阻滞伴室性逸搏.在生存时间方面,rinvanil组有明显改善而olvanil组没有.结论 相对于olvanil和对照组,rinvanil能改善心功能,从而延长生存时间.

Objective To investigate cardiovascular response to TRPV1 agonists upon induction of hypothermia in a rat model of cardiopulmonary resuscitation. In addition, survival of the rats was determined. Methods The fifteen rats were randomized into three experimental groups and subjected to 6 min of ventricular fibrillation induced cardiac arrest and cardiopulmonary resuscitation. 30 min post - resuscitation the rats were treated with increasing concentrations of TRPV1 agonist olvanil and rinvanil or vehicle for 6 h. Outcomes were assessed as blood temperature, ECG recordings, hemodynamic values, cardiac function and 7 days survival. Results All the tested compounds induced hypothermia of about 3℃. In all the groups, including vehicle, micro - episodes of arrhythmias in a form of ventricular tachycardia and premature ventricular beats were observed. Infusion of rinvanil and olvanil induced additional micro - episodes of arrhythmias in a form of A - V block and ventricular escape. Survival time in the rinvanil groups was prolonged compared to the vehicle group. No effect on survival was determined after olvanil treatment. Conclusion The TRPV1 agonist rinvanil showed more favourable cardiovascular profile compared to olvanil and vehicle, and increased survival.