Guo Rui, Gao Xing-Ya, Wang Wei, Wang Han-Jun, Zhang Feng, Zhang Ying, Zhu Guo-Qing
Department of Physiology, Nanjing Medical University, 140 Hanzhong Road, Nanjing 210029, China.
Pharmacol Res. 2005 Aug;52(2):192-8. doi: 10.1016/j.phrs.2005.03.001.
The generation of reactive oxygen species (ROS) contributes to reperfusion-induced arrhythmias. In the present study, the antiarrhythmic effects of tempol and tiron, two membrane-permeable radical scavengers, on reperfusion-induced arrhythmias in rats in vivo were investigated. The anaesthetized rats were subjected to 5 min of left descending coronary artery (LAD) occlusion followed by 30 min of reperfusion. All rats pretreated with saline developed ventricular tachycardia (VT) and ventricular fibrillation (VF) at the onset of reperfusion, and most of the rats died from irreversible VF at the end of reperfusion. However, pretreatment with tempol (30 or 100 mg kg(-1)) 5 min before reperfusion reduced mortality, arrhythmia score and the incidence and duration of VT and VF. In the rats pretreated with high dose of tempol (100 mg kg(-1)), no VF happened and all rats were alive at the end of the experiment. The arrhythmia score was also significantly decreased compared with that of rats pretreated with saline (0.80 +/- 0.4 versus 5.6 +/- 0.4, P < 0.01). Tiron also provided nearly complete protection against reperfusion-induced arrhythmias when given 2 min before reperfusion. On the other hand, intravenous administration of tempol induced decreases in mean arterial pressure (MAP), heart rate (HR) and pressure rate index (PRI), a relative indicator of myocardial oxygen consumption. In order to determine whether the antiarrhythmic effects of tempol were secondary to the reduction of myocardial oxygen consumption, continuous electrical stimulation of the aortic depressor nerve (3 V, 10 ms and 10 Hz) was carried out in a group of rats to induce decreases in MAP, HR and PRI similar to those in the high dose of Tempol group. However, these rats did not show significant changes in the severity of reperfusion-induced arrhythmias. We conclude that both tempol and tiron significantly reduce reperfusion-induced arrhythmias in rats, and this protective action is independent of hemodynamic effects.
活性氧（ROS）的产生会导致再灌注诱导的心律失常。在本研究中，研究了两种可透过细胞膜的自由基清除剂tempol和tiron对大鼠体内再灌注诱导的心律失常的抗心律失常作用。将麻醉后的大鼠左冠状动脉前降支（LAD）闭塞5分钟，然后再灌注30分钟。所有用生理盐水预处理的大鼠在再灌注开始时均出现室性心动过速（VT）和心室颤动（VF），并且大多数大鼠在再灌注结束时死于不可逆的VF。然而，在再灌注前5分钟用tempol（30或100 mg·kg⁻¹）预处理可降低死亡率、心律失常评分以及VT和VF的发生率和持续时间。在用高剂量tempol（100 mg·kg⁻¹）预处理的大鼠中，未发生VF，并且在实验结束时所有大鼠均存活。与用生理盐水预处理的大鼠相比，心律失常评分也显著降低（0.80±0.4对5.6±0.4，P<0.01）。Tiron在再灌注前2分钟给予时也能几乎完全保护免受再灌注诱导的心律失常。另一方面，静脉注射tempol会导致平均动脉压（MAP）、心率（HR）和压力心率指数（PRI，心肌耗氧量的相对指标）降低。为了确定tempol的抗心律失常作用是否继发于心肌耗氧量的降低，对一组大鼠进行主动脉减压神经的连续电刺激（3 V，10 ms和10 Hz）以诱导MAP、HR和PRI降低，类似于高剂量tempol组。然而，这些大鼠在再灌注诱导的心律失常严重程度方面未显示出显著变化。我们得出结论，tempol和tiron均能显著降低大鼠再灌注诱导的心律失常，并且这种保护作用与血流动力学效应无关。
