| Thrombolytic therapy and coronary artery intervention(CAI) are established managements of acute myocardial infraction. However, rapid restoration of blood and oxygen flow to ischemic myocardium further results in ischemia/reperfusion(I/R) injury. It’s reported that I/R could induce QT interval prolongation and increase the risk of arrhythmias. However, the electrophysiologic mechanism of QT interval prolongation induced by I/R remains unclear. In the present experiments, we study the mechanism of I/R-induced prolongation of QT interval in isolated guinea pig heart by langendorff perfusion system and a simulated I/R system with sodium dithionite(Na2S2O4) in ventricular myocytes of guinea pigs. Besides, we also study the protective effect and mechanism of STVNa and vitamin E on I/R injury in the simulated I/R system. The research contents are as follows:(1) We observed that QT interval prolonged by langendorff perfusion system after I/R, the QT interval prolonged from 191.27 ± 8.49 ms to 230.56 ± 9.59 ms. In addition, QT interval dispersion and RR interval dispersion were also increased by I/R. All of these changes can be partly reversed by Vitamin E.(2) In the simulated I/R system of ventricular myocytes, we observed a significant attenuation of IKr and a significant prolongation of action potential duration(APD). The IKr current density decreased from 1.44 ± 0.06 p A·p F-1 to 0.52 ± 0.04 p A·p F-1, and APD90 increased from 324.75 ± 41.21 ms to 603.94 ± 65.53 ms after I/R. Moreover, the inhibition of IKr can be partly reversed by antioxidant vitamin E(100 mmol/L) and mitochondrial reactive oxygen species scavenger Mito-tempo.(3) In the simulated I/R system of ventricular myocytes, we observed that STVNa partly reversed I/R-induced prolongation of action potential duration. We also observed that I/R-induced decrease of resting potential and inhibition of IKr current could be partly reversed by STVNa.(4) We studied h ERG channel block-related cardiotoxicity of STVNa on HEK293 cell and guinea pig ventricular myocytes, and observed that STVNa has no effect on both h ERG current and IKr current.Conclusions:(1) IKr current was inhibited during I/R by overproduction of reactive species oxygen, which is one of the underlying mechanisms of QT interval prolongation.(2) Vitamin E could reverse I/R-induced QT interval prolongation.(3) STVNa reversed I/R induced IKr current inhibition and prolongation of APD by scavenging reactive oxygen species.(4) STVNa has no h ERG channel block-related cardiotoxicity. |
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