Premium
Antiarrhythmic effects of BN‐063, a newly synthesized adenosine A 1 agonist, on myocardial ischaemia in rats
Author(s) -
Lee YenMei,
Chern JiWang,
Yen MaoHsiung
Publication year - 1994
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1994.tb13186.x
Subject(s) - adenosine , medicine , ventricular fibrillation , isoprenaline , cardiology , agonist , ventricular tachycardia , ligation , adenosine receptor , heart rate , stimulation , anesthesia , receptor , blood pressure
1 It has been shown that adenosine is able to reduce the severity of arrhythmias induced by myocardial ischaemia. In isolated preparations, the antiarrhythmic effect of adenosine on ventricular myocardium is known to antagonize the catecholamine‐induced stimulation of intracellular cyclic AMP production, an effect mediated via adenosine A 1 receptors. 2 The aim of this study was to evaluate the antiarrhythmic effect of BN‐063 (1‐cyclo‐propylisoguanosine), a newly synthesized selective adenosine A 1 agonist, on ventricular arrhythmias in rats. 3 Arrhythmias were induced by left coronary artery ligation or by administration of isoprenaline (7 mg kg −1 ) subcutaneously. Pretreatment with BN‐063 (0.25, 0.5 and 1.0 mg kg −1 ) 10 min prior to occlusion significantly delayed the onset of ventricular arrhythmias, reduced the total number of ventricular premature contraction (VPC) and ventricular tachycardia (VT), decreased the incidence of VT and ventricular fibrillation (VF) and mortality during the first 30 min following left coronary artery ligation. In contrast, pretreatment with 8‐cyclopentyl‐1,3‐dipropylxanthine (DPCPX), an adenosine A 1 antagonist, was arrhythmogenic during the ischaemic period. The rate‐pressure product, an index for indirect measurement of myocardial oxygen consumption, was also significantly reduced by BN‐063 during ligation time. 4 The incidence of VT, VF and mortality was also significantly reduced when BN‐063 was administered after left coronary artery ligation. 5 BN‐063 converted the VF induced by isoprenaline to normal sinus rhythm and improved the survival rate. 6 It is concluded that, through activation of adenosine A 1 receptors, BN‐063 can suppress ventricular arrhythmias induced by myocardial ischaemia and catecholamines. The antiarrhythmic actions of BN‐063 may be mediated by reducing heart rate and antagonizing the stimulatory effects of catecholamine in myocardial ischaemia.