The acute combined effect of Pinacidil and Glimepiride on ischemia and reperfusi̇on i̇nduced arrhythmia. "The role of ATP- dependent potassi̇um channel"

This study was aimed to highlight the role of ATP-dependent-potassium channel on ischemia/reperfusion induced arrhythmia during the acute phase, with the application of Pinacidil as KATP channel opener and Glimepiride as a channel blocker. In this study among 4 groups, 58 male Sprague-Dawley rats 6-7 months old were used. The surgical procedure started with tracheostomy, then femoral cannulation was performed to measure blood pressure during the operation. By using silk thread, coronary artery was ligated and 6 min. ischemia had been performed, and following 6 min. for reperfusion produced by removing the silk. In control group just drugs solvents were administrated at 2 min of ischemia and at the beginning of reperfusion Time of drugs administration among groups did not change. In Pinacidil group, Pinacidil drug were given with Glimepiride solvent, and the same were applied in Glimepiride group with Pinacidil solvent. In combined group both Pinacidil and Glimepiride drugs were given. The type of arrhythmia, the incidence and arrhythmic score were statistically comprised between groups using one way-ANOVA and independent t-test. Pinacidil alone was anti-arrhythmic in reperfusion period, while Glimepiride was pro-arrhythmic. The protective effect of Pinacidil was abolished by Glimepiride in combination group. In conclusion, the expected protective results against I/R injury induce arrhythmia through using channel activator and blocker were not observed. This result might be increasing heterogeneity in action potential duration due to the different effect of two modulators on action potential duration. The protection generated by Pinacidil alone might be depend on its effects on action potential duration instead of its hypotensive effect.