Adenosine A1-receptor induced late preconditioning and myocardial infarction: reperfusion duration is critical

Abstract

We investigated the influence of coronary artery reperfusion (CAR) duration on the infarct-limiting properties of adenosine A1-receptor stimulation-induced delayed preconditioning (A1-DPC) compared with ischemia-induced delayed preconditioning (I-DPC). Sixty-one chronically instrumented conscious rabbits successfully underwent the following protocol. On day 1, rabbits were randomly divided into four groups: control (saline, iv), I-DPC (six 4-min coronary artery occlusion/4-min reperfusion cycles), A1-DPC100( N 6-cyclopentyladenosine, 100 μg/kg iv), and A1-DPC400( N 6-cyclopentyladenosine, 400 μg/kg iv). On day 2 (i.e., 24 h later), rabbits underwent a 30-min coronary artery occlusion after which CAR was started and maintained for either 3 or 72 h. Infarct size (percentage of the area at risk) was determined by triphenyltetrazolium chloride staining. After 3 h of CAR, I-DPC, A1-DPC100, and A1-DPC400 significantly decreased infarct size (36 ± 5, 41 ± 4, 38 ± 5%, respectively) compared with control (55 ± 3%). After 72 h of CAR, infarct sizes were not significantly different among the four groups. This result was confirmed by histologic analysis. Thus A1-DPC at the two investigated doses, as well as I-DPC, decreased infarct size after 3 h but not 72 h of CAR.