The Effects of Cannabinoid Receptor Antagonists AM251 and AM630 on Ischemia/Reperfusion-Induced Arrhythmias in Anesthetized Rats

Abstract

Aim: The aim of this study is to investigate the effects of AM251 (cannabinoid-1 receptor antagonist) and AM630 (cannabinoid-2 receptor antagonist) on ischemia/reperfusion (I/R)-induced arrhythmias in anesthetized rats.

Materials and Methods: Wistar Albino male rats were divided into 3 groups: I) Control (n = 13), II) AM251 (n = 17) and III) AM630 (n = 17). AM251 and AM630 were administered intravenously at 1 mg / kg dose 10 minutes prior to ligation. In the anesthetized rats with urethan, the left main coronary artery was ligated to perform the ischemia for 6 minutes, the occluded artery was loosened and reperfusion was performed for 10 minutes.Ventricular arrhythmia durations, QRS, Q-T and P-R intervals in ECG recordings, heart rate and mean arterial blood pressure were calculated in ischemia and reperfusion period in all in all groups of rats.

Results: The AM251 significantly increased mortality, the incidence of ventricular tachycardia and ventricular fibrillation, the duration of total arrhythmia and the ventricular fibrillation and the arrhythmia scores compared to the control group (p<0.05).

Conclusion: The cannabinoid-1 receptor antagonist AM251 increased I/R-induced arrhythmias. The cannabinoid-2 receptor antagonist AM630 did not show any effect. These results demonstrate that endogenous cannabinoids may have a role in the reducing the generatiom of ventricular arrhythmias via KB1 receptor activation.

Kannabinoid Reseptör Antagonistleri AM251 ve AM630’un Anestezi Altındaki Sıçanlarda İskemi/Reperfüzyon ile Uyarılan Aritmiler Üzerine Etkileri

Abstract

Amaç: Bu çalışmanın amacı AM251(kannabinoid-1 reseptör antagonisti) ve AM630’un (kannabinoid-2 reseptör antagonisti) anestezi altındaki sıçanlarda iskemi/reperfüzyon (I/R) ile uyarılan aritmiler üzerine etkilerini araştırmaktır.

Gereç ve Yöntemler: Wistar Albino türü erkek sıçanlar 3 gruba ayrıldı: I) Kontrol (n=13), II) AM251 (n=17) ve III) AM630 (n=17). AM251 ve AM630 1mg/kg dozda intravenöz yolla ligasyondan 10 dakika önce verildi. Üretan ile anestezi edilen sıçanlarda sol ana koroner arter bağlanarak 6 dakika iskemi, tıkanan damar gevşetilerek 10 dakika reperfüzyon yapıldı. Tüm gruplardaki deneklerde iskemi ve reperfüzyon periyotlarında ventriküler aritmi süreleri, EKG’de QRS, Q-T ve P-R aralıkları, kalp atımı ve ortalama arteriyal kan basıncı hesaplandı.

Bulgular: AM251 reperfüzyon periyodunda ölüm oranını, ventriküler taşikardi ve ventriküler fibrilasyonun görülme sıklığını, ventriküler fibrilasyon süresi, toplam aritmi süresi ve aritmi skorunu kontrol grubuna göre istatistiksel olarak anlamlı bir şekilde artırdı (p<0.05).

Sonuç: Kannabinoid-1 reseptör antagonisti AM251 I/R ile uyarılan aritmileri arttırdı. Kannabinoid-2 reseptör antagonisti AM630 ise herhangi bir etki göstermedi. Bu sonuçlar endojen kannabinoidlerin KB1 reseptör aktivasyonu yoluyla ventriküler aritmilerin oluşumunu azaltıcı bir role sahip olabileceğini göstermektedir.

Keywords

• AM251,AM630,Kannabinoidler,İskemi/reperfüzyon aritmileri

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