Chen Yaoxu, Yin Chunxia, Yang Yingying, Fan Zhuo, Shang Jinling, Tan Wen
School of Bioscience and Bioengineering, South China University of Technology, Guangzhou, China.
School of Bioscience and Bioengineering, South China University of Technology, Guangzhou, China; Cardiac Electrophysiology Research Lab, The second affiliated hospital of Guangzhou University of Chinese Medicine, Guangzhou, China.
J Electrocardiol. 2017 Jul-Aug;50(4):437-443. doi: 10.1016/j.jelectrocard.2017.03.007. Epub 2017 Mar 14.
Ischemia/reperfusion (I/R) induces prolongation of QT interval and action potential duration (APD), which is a major cardiac electrical disorder in patients with arrhythmias. However, the mechanism of QT interval prolongation induced by I/R remains unclear. In the present study, we hypothesized that the rapid component of delayed rectifier potassium (I) channel plays an important role in I/R-induced QT interval prolongation. We observed a marked attenuation of I and a significant prolongation of action potential duration (APD) in a simulated I/R system with sodium dithionite (NaSO) in ventricular myocytes of guinea pigs. The I current density was inhibited by 64% and APD increased by 87% respectively. Moreover, the inhibition of I is primarily ascribed to overproduction of reactive oxygen species (ROS) by I/R, which can be partly reversed by antioxidant vitamin E (100μmol/L). The value of I tail current density increased from 0.516±0.040 pA/pF in I/R to 0.939±0.091 pA/pF when treated with vitamin E. Moreover, we also demonstrated that QTc interval was increased by I/R and reversed by Vitamin E in isolated guinea pig hearts. In conclusion, the inhibition of I is one of the underlying mechanisms of prolongation of QT interval and APD in I/R. Vitamin E might have a benefit in coronary reperfusion therapy.
缺血/再灌注（I/R）可导致QT间期和动作电位时程（APD）延长，这是心律失常患者的一种主要心脏电紊乱。然而，I/R诱导QT间期延长的机制仍不清楚。在本研究中，我们假设延迟整流钾（I）通道的快速成分在I/R诱导的QT间期延长中起重要作用。我们在豚鼠心室肌细胞中用连二亚硫酸钠（NaSO）模拟I/R系统，观察到I显著衰减和动作电位时程（APD）显著延长。I电流密度分别被抑制64%，APD增加87%。此外，I的抑制主要归因于I/R产生的活性氧（ROS）过量，抗氧化剂维生素E（100μmol/L）可部分逆转这种情况。I尾电流密度值从I/R时的0.516±0.040 pA/pF增加到用维生素E处理时的0.939±0.091 pA/pF。此外，我们还证明在离体豚鼠心脏中，I/R使QTc间期增加，而维生素E使其逆转。总之，I的抑制是I/R中QT间期和APD延长的潜在机制之一。维生素E可能对冠状动脉再灌注治疗有益。
