The acute combined effect of Pinacidil and Glimepiride on ischemia and reperfusion induced arrhythmia, “The Role of ATP- Dependent Potassium Channel”

Year 2024, Volume: 7 Issue: 2, 54 - 62, 30.08.2024

Mariam Daher Khatıb , Ömer Bozdoğan , Şevval Özdemir

https://doi.org/10.56150/tjhsl.1297218

Abstract

Aim: In previous studies, it was shown that both Pinacidil and Glimepiride have antiarrhythmic action in their pretreatment before ischemia. But there was no study found about their combined effect on the arrhythmia in the acute stage of ischemia and reperfusion. That is why in this study the combined acute effect of these two drugs on these arrhythmias was aimed to be researched. Main Method: 26 Anesthetized male Sprague-Dawley rats aged 6-7 years have been used in this study. Ischemia was performed for 6 min. by the ligation of left main coronary artery reperfusion by releasing the silk thread on the artery. Results: 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, and the expected protective results against I/R induced arrhythmia were not observed. Conclusion: The result of this study showed that combination of KATP channel opener and blocker given in different time during ischemia and reperfusion period do not have synergic effect to decrease the arrhythmia. This might be increasing heterogeneity in action potential duration in ischemic or normal myocardium.

Keywords

myocardial ischemia, reperfusion, arrhythmia, pinacidil, glimepiride, combination

Supporting Institution

Research fund grant from Abant Izzet Baysal University

Project Number

Grant No: 2022.03.01.1547

Pinasidil ve Glimepirid'in birlikte iskemi ve reperfüzyon ile uyarılan aritmiler üzerine akut etkisi, “ATP Bağımlı Potasyum Kanalının Rolü”

Abstract

Bu çalışmada, akut iskemi-reperfüzyon ile uyarılan aritmiler sırasında, K-ATP kanal açıcı olarak Pinasidil ve kanal bloker olarak Glimepirid uygulaması ile, ATP bağımlı potasyum kanalının rolünü vurgulamak amaçlanmıştır. Çalışmada 4 grup olarak 6-7 aylık 58 adet erkek Sprague-Dawley türü sıçan kullanılmıştır. Cerrahi işleme trakeostomi ile başlanmıştır, ardından operasyon sırasında kan basıncını ölçmek için, sağ femoral arterden kanülasyon yapılmıştır. İpek iplikle koroner arter bağlanmıştır ve bu şekilde 6 dakika kadar iskemi oluşturulmuştur, bu ip gevşetilerek 6 dakika reperfüzyon yapılmıştır. Kontrol grubunda, iskeminin ikinci dakikasında ve reperfüzyon başlangıcında sadece ilaç çözücüleri uygulanmıştır. Gruplar arasında ilaç uygulama zamanı değiştirilmemiştir. Pinasidil grubunda, Pinasidil ilacı Glimepirid solventi ile uygulanmıştır ve aynı şekilde Glimepirid grubunda Pinasidil solventi uygulandı. Kombinasyon grubunda hem Pinasidil hem de Glimepirid ilaçları birlikte verilmiştir. Aritmi tipleri, süreleri ve aritmi skoru, tek yönlü ANOVA ve bağımsız t-testi kullanılarak yapılmıştır. Pinasidil tek başına reperfüzyon döneminde antiaritmik etki göstermiş, ama Glimepirid proaritmik etkili olmuştur. Kombinasyon durumunda Pinasidil'in koruyucu etkisi Glimepirid ile ortadan kalkmıştır. Sonuç olarak, kanal açıcı ve bloker kullanımı birlikte aritmiye karşı beklenen koruyucu etkiyi göstermemiştir. Bunun nedeninin iki ilacın aksiyon potansiyeli süresindeki farklı etkisiyle, normal ve iskemik hücreler arasındaki heterojenliğin artmasından kaynaklanabileceği düşünülmüştür. Pinasidilin tek başına aritmiye azaltıcı etkisi, ilacın hipotansif etkisiyle değil, onun aksiyon potansiyeli üzerine etkisiyle olabilir.

Keywords

miyokardiyal iskemi, reperfüzyon, aritmi, Pinacidil, Glimepride, kombinasyon

Project Number

Grant No: 2022.03.01.1547

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