性激素在尖端扭转型室性心动过速发生机制中的作用

Role of Sex Hormones in the Development of Torsades De Pointes

目的 通过研究雌雄激素替代法对大鼠离体心室肌细胞单相动作电位 (MAP)的影响及奎尼丁诱导下致心律失常作用性别差异性的机制 ,阐明性激素在尖端扭转型室性心动过速 (TdP)发生中的作用。方法 制造苯甲酸雌二醇、丙酸睾酮替代的大鼠模型 ,Langendorff法灌流离体大鼠心脏 ,采用MAP技术记录 6组大鼠 (①去势雌性大鼠 ;②去势雌性大鼠 +雌激素 ;③去势雌性大鼠 +雄激素 ;④去势雄性大鼠 ;⑤去势雄性大鼠 +雌激素 ;⑥去势雄性大鼠+雄激素 )的MAP ,比较组间的性别差异 ,并观察奎尼丁诱发各组早期后除极 (EAD)、TdP发生率的差异。结果 去势雌性大鼠 +雌激素组的单向动作电位时程 (MAPD)显著长于去势雌性大鼠 +雄激素组 ,去势雄性大鼠 +雌激素组MAPD显著长于去势雄性大鼠 +雄激素组 ;雌激素替代组与单纯去势组相比MAPD也延长 ,雄激素组则相反 ;而去势雌性大鼠组和去势雄性大鼠组无差别。各组在应用奎尼丁后MAPD都有显著延长 ,EAD发生率均较高 ;而雌激素替代组的EAD、TdP发生率都高于雄激素组。结论 雌雄大鼠发生TdP的性别差异性与性别本身无关 ,关键在于性激素的差异 ,雌激素可通过使心肌细胞在复极延长的基础上EAD发生增加 ,导致触发活动 ,从而发生TdP ;雄激素的作用则相反。

Objective To investigate the effects of estrogen and androgen replacement treatment on castrated rat ventricular monophasic action potential (MAP) and the mechanism of gender differences in quinidine-induced proarrhythmic effect in order to demonstrate the role of sex hormones in the development of torsades de pointes (TdP). Methods After making the rat models of estradiol benzoate and testosterone propionate replacement and perfusing heart by Langendorff method, by using the MAP recording technique, the MAPs of epicardium of left ventricular free walls in 6 groups (castrated female rat, castrated female rat+estrogen, castrated female rat+androgen, castrated male rat, castrated male rat+estrogen, castrated male rat+androgen) were recorded and the gender differences in early afterdepolarization (EAD) induced by quinidine and TdP incidence among groups were compared. Results The MAPD was significantly prolonged in castrated female rat+estrogen group as compared with that in castrated female rat+androgen group; the MAPD prolonged in castrated male rat+estrogen group significantly as compared with that in castrated male rat+androgen group; the MAPD in estrogen replacement groups was prolonged as compared with castrated rat groups, but the MAPD in androgen groups was shortened; no significant difference was found between castrated female groups and castrated male groups. The MAPDs in each group was prolonged significantly when the hearts were perfused with quinidine solution and the incidence of EAD was also significantly elevated. The incidence of EAD and TdP in estrogen replacement groups was significantly higher than in androgen groups. Conclusion The gender difference of TdP incidence between female and male rats wasn't related with gender itself, but the role that sex hormones played was important. Estrogen could produce more EADs in myocytes via repolarization prolongation, which induced triggering activities and TdP, but the effects of androgen were contrary.