Pharmacological prevention of sudden cardiac death

心脏性猝死(SCD)是心血管疾病患者的一个严重问题，但研究SCD预防的动物模型尚未建立。我们使用冠状动脉结扎/再灌注性心律失常和氟烷-肾上腺素心律失常来评估各种心脏保护药物，不包括经典的抗心律失常药物，这些药物已被证明增加了SCD。在这三年中，我们已经证明了Na/H交换抑制剂在减少动物体内心律失常死亡方面是有效的，而Na/Ca交换抑制剂和KATP通道开放剂或阻断剂显示了不同的保护作用。然而，这些药物的电生理学特性已经通过电压钳和转基因离子通道蛋白得到了更详细的阐明。我们还评估了缺乏交感神经α或β受体的转基因小鼠模型，发现其中一些模型的寿命较短，但部分由于评估小鼠长期心电记录的问题，我们尚未证明这些动物是否可用于SCD的预防研究。

Sudden cardiac death (SCD) is a serious problem in cardiovascular patients, but the animal models for studying prevention of SCD have not yet establishd. We used coronary ligation/reperfusion induced and halothane-adrenaline arrhythmias to evaluate various cardioprotective drugs not including classical antiarrhythmic drugs, which have been shown to increase SCD. In these 3 years, we have demonstrated that Na/H exchange inhibitors are effective in decreasing arrhythmia death in in vivo animals, however Na/Ca exchange inhibitors and KATP channel openers or blockers have shown variable and mariginal protective effects.However electophysiological characteristics of these drugs have been clarified in more detail using voltage clamp and genetically modified ion channel proteins. We also evaluated transgeneic mice models which lacks sympathetic alpha or beta receptors and found shorter lives in some of these models, but partly due to the problems of evaluating mice long term ECG recordig we have not yet demonstrated whether these animals can be used to study preention of SCD.