ANTIARRHYTHMIC EFFECTS OF BN-063, A NEWLY SYNTHESIZED ADENOSINE A(1) AGONIST, ON MYOCARDIAL-ISCHEMIA IN RATS

1 It has been shown that adenosine is able to reduce the severity of a rrhythmias induced by myocardial ischaemia. In isolated preparations, the antiarrhythmic effect of adenosine on ventricular myocardium is kn own to antagonize the catecholamine-induced stimulation of intracellul ar cyclic AMP production, an effect mediated via adenosine A(1) recept ors. 2 The aim of this study was to evaluate the antiarrhythmic effect of BN-063 (1-cyclopropylisoguanosine), a newly synthesized selective adenosine A(1) agonist, on ventricular arrhythmias in rats. 3 Arrhythm ias were induced by left coronary artery ligation or by administration of isoprenaline (7 mg kg(-1)) subcutaneously. Pretreatment with BN-06 3 (0.25, 0.5 and 1.0 mg kg(-1)) 10 min prior to occlusion significantl y delayed the onset of ventricular arrhythmias, reduced the total numb er of ventricular premature contraction (VPC) and ventricular tachycar dia (VT), decreased the incidence of VT and ventricular fibrillation ( VF) and mortality during the first 30 min following left coronary arte ry ligation. In contrast, pretreatment with 8-cyclopentyl-1,3-dipropyl xanthine (DPCPX), an adenosine A(1) antagonist, was arrhythmogenic dur ing the ischaemic period. The rate-pressure product, an index for indi rect measurement of myocardial oxygen consumption, was also significan tly reduced by BN-063 during ligation time. 4 The incidence of VT, VF and mortality was also significantly reduced when BN-063 was administe red after left coronary artery ligation. 5 BN-063 converted the VF ind uced by isoprenaline to normal sinus rhythm and improved the survival rate. 6 It is concluded that, through activation of adenosine A(1) rec eptors, BN-063 can suppress ventricular arrhythmias induced by myocard ial ischaemia and catecholamines. The antiarrhythmic actions of BN-063 may be mediated by reducing heart rate and antagonizing the stimulato ry effects of catecholamine in myocardial ischaemia.