Tempol reduces reperfusion-induced arrhythmias in anaesthetized rats

Rui Guo, Xing Ya Gao, Wei Wang, Han Jun Wang, Feng Zhang, Ying Zhang, Guo Qing Zhu

Research output: Contribution to journalArticle

14 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)192-198
Number of pages7
JournalPharmacological Research
Volume52
Issue number2
DOIs
StatePublished - Aug 2005

Keywords

  • Arrhythmia
  • Myocardial reperfusion
  • Reactive oxygen species
  • Tempol
  • Tiron

ASJC Scopus subject areas

  • Pharmacology

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