Tempol Reduces Reperfusion-induced Arrhythmias In Anaesthetized Rats

When the previous ischemic heart was reperfused, serious arrhythmias occurred. The generation of reactive oxygen species (ROS) contributes to these 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), the incidence of ventricular fibrillation (VF) was 88% during reperfusion, and most of the rats died from irreversible VF at the end of the experiment. However, pretreatment with tempol (30 or 100 mg/kg) 5 min before ischemia 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), 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 vs 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 tempolinduced 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 volts, 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 (100 mg/kg). However, these rats did not show significant changes in the severity of reperfusion-induced arrhythmias (4.5 ± 0.6 vs 5.6 ± 0.4, P>0.05). We conclude that both tempol and tiron significantly reduce reperfusion-induced arrhythmias in rats, and this protective action is independent of hemodynamic effects.