Objective: The aim was to test the hypothesis that adenosine A1 receptor activation triggers the cardioprotective effects of ischaemic preconditioning, by determining whether pretreatment with acadesine (5-amino-4-imidazolecarboxamide riboside), an agent which increases cardiac adenosine level during ischaemia, could alter the threshold for preconditioning.
Methods: A branch of the left coronary artery of rabbit hearts was occluded for 30 min and reperfused for 3 h. Infarct size and risk zone size were determined with tetrazolium and fluorescent particles, respectively. Four groups were studied: untreated controls, a group which was pretreated with acadesine (2.5 mg.kg-1.min-1 for 5 min followed by 0.5 mg.kg-1.min-1 for 30 min ending 10 min prior to ischaemia), a group which was preconditioned with 2 min coronary branch occlusion + 10 min reperfusion, and a group which received pretreatment with acadesine prior to 2 min ischaemic preconditioning.
Results: Percent infarction, normalised as a percentage of the ischaemic zone, in the 2 min preconditioning group was 43.2(SEM 5.1)% which was not different from control [40.2(3.5)%]. Two minutes of preconditioning was not long enough to confer the cardioprotective effect of preconditioning. Acadesine alone had no protective effect on infarct size [38.5(4.5)%], but acadesine + 2 min preconditioning significantly limited infarction [18.1(2.7)%; p < 0.01].
Conclusions: Acadesine lowered the threshold for preconditioning in the rabbit to below 2 min of ischaemia. This observation supports the theory that endogenous adenosine which accumulates during the preconditioning ischaemia mediates the protective effects, and that this response can be augmented by acadesine.