Remote ischemic preconditioning activates adenosine A1 receptor and attenuates mitochondrial damage during myocardial reperfusion

PAEZ D; MARCHINI T; GELPI RJ; GARCES M; EVELSON P; DONATO M; GOYENECHE MA

Mar del Plata

Congreso; LXI Reunión Científica Anual de la Sociedad Argentina de Investigación Clínica (SAIC).; 2016

Sociedad Argentina de Investigación Clínica (SAIC).

Introduction: Remote ischemic preconditioning (rIPC) reduces infarct size through the activation of pre-ischemic muscarinic pathway. However, the mechanism activated during reperfusión remains unclear.Objective The first aim was to evaluate whether A1 adenosine receptor is part of the rIPC cardioprotective mechanism during early reperfusion. A second objective was to evaluate the effect of rIPC on ischemia/reperfusion mitochondrial damage.Methods: Isolated rat hearts were subjected to 30 minutes of global ischemia and 60 minutes of reperfusión (I/R, n=9). In a second (n=10) group, before the isolation of the heart, a rIPC protocol (three cycles of left femoral artery ischemia/reperfusion) was performed, followed by I/R protocol. In a third group (n=5), the above protocol was repeated but, during the first 5 min of reperfusion, an adenosine A1 receptor blocker was administered (DPCPX). We evaluated infarct size using triphenyl tetrazolium chloride staining and oxidative damage to macromolecules by TBARS and carbonylated proteins. Additionally, we measured mitochondrial respiration and H202 production rate in freshly isolated mitochondria.Results: rIPC significantly decreased infarct size (50,33±2,74 vs 31,29±2,52 %, p< 0,05 Vs I/R) and this effect was abolished by DPCPX administration (55,74±6,41 %). rIPC significantly decreased carbonylated proteins without any modification in TBARS content. Finally, 30 min of global ischemia followed by 60 min of reperfusion induced an impairment of mitochondrial respiration and decreased H2O2 production rate, which was attenuated in the rIPC group.Conclusions: rIPC reduces infarct size by activation of adenosine A1 receptors at reperfusion, and attenuates oxidative stress, preserving mitochondrial function.