Pharmacological delayed preconditioning against ischaemia-induced ventricular arrhythmias: effect of an adenosine A(1)-receptor agonist

1 The goal of this study was to investigate the effects of the delayed phar macological preconditioning produced by an adenosine A(1)-receptor agonist (A(1)-DPC) against ventricular arrhythmias induced by ischaemia and reperfu sion, compared to those of ischaemia-induced delayed preconditioning (I-DPC ). 2 Eighty-nine instrumented conscious rabbits underwent a 2 consecutive days protocol. On day 1, rabbits were randomly divided into four groups: 'Contr ol' (saline, i.v.), 'I-DPC' (six 4-min coronary artery occlusion/4-min repe rfusion cycles), 'A(1)-DPC100' (N-6-cyclopentyladenosine, 100 mug kg(-1), i .v.), and 'A(1)-DPC400' (N-6-cyclopentyladenosine, 400 mug kg(-1), i.v.). O n day 2, i.e., 24 h later, the incidence and severity of ventricular arrhyt hmias during a 30-min coronary artery occlusion and subsequent reperfusion were analysed in all animals, using an arrhythmia score. 3 I-DPC, A(1)-DPC100 and A(1)-DPC400 significantly reduced the infarct size (34+/-5, 42+/-3 and 43+/-7% of the area at risk, respectively) as compared to Control (55+/-3% of the area at risk). 4 During both ischaemia and reperfusion, neither the incidence nor the seve rity of ventricular arrhythmias were altered by A(1)-DPC100, A(1)-DPC400 or I-DPC as compared to Control. 5 Thus, despite reduction of infarct size induced by delayed preconditionin g, A(1)-DPC as well as I-DPC failed to exert any anti-arrhythmic effect in the conscious rabbit model of ischaemia-reperfusion.