期刊
JOURNAL OF ELECTROCARDIOLOGY
卷 50, 期 4, 页码 437-443出版社
CHURCHILL LIVINGSTONE INC MEDICAL PUBLISHERS
DOI: 10.1016/j.jelectrocard.2017.03.007
关键词
Ischemia/reperfusion; Arrhythmia; I-Kr current; QT interval; Vitamin E
资金
- Major Science and Technology Projects, Bureau of Science, Technology & Information, Guangzhou City [2013 (164), 201,300,000,051]
- Science and Technology Planning Project of Guangdong Province, China [2012(104), 2012B011000050]
- National Natural Science Foundation of China [31,300,940]
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-Kr) channel plays an important role in I/R-induced QT interval prolongation. We observed a marked attenuation of I-Kr and a significant prolongation of action potential duration (APD) in a simulated I/R system with sodium dithionite (Na2S2O4) in ventricular myocytes of guinea pigs. The I-Kr current density was inhibited by 64% and APD increased by 87% respectively. Moreover, the inhibition of I-Kr is primarily ascribed to overproduction of reactive oxygen species (ROS) by I/R, which can be partly reversed by antioxidant vitamin E (100 mu mol/L). The value of I-Kr 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-Kr 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. (C) 2017 Elsevier Inc. All rights reserved.
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