Yi Shao-lei, Zhong Jing-quan, Zhang Jing, Su Guo-ying, Li Jing-sha, Liu Hong-zhen, Zhang Yun
Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of Public Health, Department of Cardiology, Qilu Hospital of Shandong University, Jinan, Shandong 250012, People's Republic of China.
Tex Heart Inst J. 2012;39(6):784-91.
In ventricular fibrillation, the uncoupling of gap junctions slows conduction velocity and increases action-potential dispersion, which slows and diminishes defibrillation. We studied how the peptide ZP123, a gap-junction enhancer, might lower defibrillation-energy requirements during ventricular fibrillation in live pigs. We randomly assigned 33 pigs into 3 groups: ZP123 (receiving a 1-µg/kg bolus and 10 µg/kg/hr of ZP123), control (receiving saline solution), and sham (undergoing a sham operation). After a 30-min administration of agents, ventricular fibrillation was induced and left untreated for 8 min. Biphasic defibrillation of 50 J was increased by 50-J increments as necessary. Defibrillation-energy requirements were defined as the lowest energy required to achieve defibrillation. Electrocardiographic values were obtained before and after the administration of agents. Western blot and immunofluorescence analyses were performed on ventricular myocardial samples. All but one pig survived. The ZP123 treatment did not alter electrocardiographic variables. In the ZP123 group, the average required defibrillation energy was lower than that in the control group (327.28±269.6 vs 610±192.64 J; P=0.015), and the cumulative percentage of successful defibrillation at upper energy levels was higher (P<0.05). Supraventricular rhythm occurred more often in the ZP123 group than in the control group (72.7% vs 50%, P=0.042). Western-blot and immunofluorescence results showed that ZP123 did not alter the total amount of connexin43 but did prevent its dephosphorylation. We conclude that ZP123 can reduce defibrillation-energy requirements by preventing connexin43 remodeling during prolonged ventricular fibrillation.
在心室颤动中，缝隙连接的解偶联会减慢传导速度并增加动作电位离散度，从而减缓并削弱除颤效果。我们研究了缝隙连接增强肽ZP123如何降低活猪心室颤动期间的除颤能量需求。我们将33头猪随机分为3组：ZP123组（接受1μg/kg的ZP123推注和10μg/kg/小时的ZP123输注）、对照组（接受生理盐水）和假手术组（接受假手术）。给药30分钟后，诱发心室颤动并任其持续8分钟。必要时，以50J的增幅增加50J的双相除颤。除颤能量需求定义为实现除颤所需的最低能量。在给药前后获取心电图值。对心室心肌样本进行蛋白质印迹和免疫荧光分析。除1头猪外，所有猪均存活。ZP123治疗未改变心电图变量。在ZP123组中，平均所需除颤能量低于对照组（327.28±269.6 vs 610±192.64J；P = 0.015），且较高能量水平下成功除颤的累积百分比更高（P<0.05）。ZP123组室上性心律的发生频率高于对照组（72.7% vs 50%，P = 0.042）。蛋白质印迹和免疫荧光结果显示，ZP123未改变连接蛋白43的总量，但确实阻止了其去磷酸化。我们得出结论，ZP123可通过在长时间心室颤动期间防止连接蛋白43重塑来降低除颤能量需求。
