اثرات ضد آريتمي آگونيست انتخابي گيرنده هاي A1 آدنوزيني در دهليز جدا شده خوكچه هندي

The antiarrhythmic effect of A1-selective adenosine agonist in isolated guinea pig atria

Background: Adenosine receptors play an important role in the treatment of paroxysmal supraventricular tachycardia in cardiovascular system. This effect is through interaction with A1 type of G-protein-coupled adenosine receptors. The effect of N6-cyclopentyladenosine (CPA), an A1-selective adenosine agonist, was studied on ouabain-induced toxicity in spontaneously beating isolated guinea pig atria. Methods: The isolated guinea pig atria were mounted on the organ bath containing modified krebs and contractile responses in the four groups (sham, CPA, ouabain, CPAouabain) were measured. Results: CPA significantly increased the time of onset of arrhythmia (toxicity) induced by ouabain (1.2μM) when it was administered 10 min before ouabain was added in organ bath. CPA (2-16nM) produced a dose-dependent decrease in the force of contractions (34%-51%) and in the rate of contractions (22%-48%). Ouabain (1.2μM) alone produced arrhythmia at 7 min and either asystole or standstill at 22 min. CPA alone did not prduce any arrhythmogenic effect but CPA (8nM) increased the time required to produce arrhythmia to 27.5 min and prolonged beating atria to more than 63 min and prevented the occurrence of asystole. Conclusion: CPA produces direct cardiac action, probably due the inhibition of cardiac Ca2+ channel and membrane hyperpolarization of atrium cells in guinea pig atria. Moreover, our results suggest that CPA may reduce the membrane conduction through inhibition of ionic channels, which decrease ouabain- induced toxicity.