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Therapeutic value of antioxidants for abnormal prolongation of QT interval and the associated arrhythmias in a rabbit model of diabetes
Zhang Yiqiang 1,Sun Xuelin 2,Zhang Ying 3,Wang Jingxiong 4,LV Yanjie 3,Yang Baofeng 4,Wang Zhiguo 5 *
1.Research Center, Montreal Heart Institute
2. Department of Medicine, University of Montreal, Montreal, PQ H3C 3J7 Canada
3.Department of Pharmacology (State-Province Key Laboratory of China), Harbin Medical University, Harbin, Heilongjiang 150086, P. R. China
4. Institute of Cardiovascular Research, Harbin Medical University, Harbin, Heilongjiang 150086, P. R. China
5.Research Center, Montreal Heart Institute, Montreal, PQ H1T 1C8 Canada
*Correspondence author
#Submitted by
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Funding: none
Opened online:22 April 2011
Accepted by: none
Citation: Zhang Yiqiang,Sun Xuelin,Zhang Ying.Therapeutic value of antioxidants for abnormal prolongation of QT interval and the associated arrhythmias in a rabbit model of diabetes[OL]. [22 April 2011] http://en.paper.edu.cn/en_releasepaper/content/4421002
 
 
Abnormal QT prolongation is the major cardiac electrical disorder and a predictor of mortality in diabetic patients. Our previous studies suggest that dysfunction of delayed rectifier K+ current (IKr) is the main cause for the problem. Here we report the potential therapeutic role and mechanisms of vitamin E in the rabbit model of diabetes. The QT interval and action potential duration were considerably prolonged with frequent occurrence of ventricular tachyarrhythmias in diabetic rabbits. Administration of vitamin E corrected the abnormal QT prolongation and abolished the arrhythmic incidence. IKr was found markedly reduced resulting in slowing of cardiac repolarization thereby QT prolongation in diabetic hearts. The diabetic depression of IKr is primarily ascribed to oxidative damages to the cardiac membrane and proteins, as indicated by the overproduction of reactive oxygen species leading to severe lipid peroxidation and protein oxidation. Moreover, IKr depression is most likely due to the dysfunction of HERG K+ channel, the major subunit underlying native IKr, in response to oxidative stress, for peroxide aniongenerating system produced similar depression of HERG channels. Vitamin E restored the depressed IKr and HERG by its antioxidant actions which likely underlie its beneficial effects on diabetic QT prolongation and the associated arrhythmias. The data indicate that an antioxidant is sufficient for reversing the IKr/IHERG dysfunction and the consequent electrical disorders in diabetic hearts. Our study also conceptually simplifies the complex nature of diabetic electrical disorders to primarily oxidative stress, and should stimulate interest in antioxidants as a therapeutic strategy for diabetic QT prolongation.
Keywords:vitamin E; diabetic complications; QT prolongation; rapid delayed rectifier K+ current IKr; HERG; reactive oxygen species
 
 
 

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