Myocardial triggers involved in remote ischemic preconditioning activation

New Findings

What is the central question of this study?

Ischemia/reperfusion of peripheral tissues protects the heart from subsequent myocardial ischemia/reperfusion injury, a phenomenon referred to as remote ischemic preconditioning (rIPC). This study evaluated the possible myocardial triggers of rIPC.

What is the main finding and its importance?

rIPC reduces infarct size through a vagal pathway and a mechanism involving Akt and eNOS phosphorylation, opening of mitochondrial K⁺_ATP channels and increasing of mitochondrial H₂O₂ production. All these phenomena occur prior to the myocardial ischemia, therefore they could act as "triggers" of rIPC.

Aims: It has been proposed that remote ischemic preconditioning (rIPC) activates a parasympathetic neural pathway. However, the myocardial rIPC intracellular mechanism remains unclear. Here we characterized some of the intracellular signals participating as rIPC triggers. Methods and Results: Isolated rat hearts were subjected to 30 minutes of global ischemia and 120 minutes of reperfusion (Non-rIPC). In a second group, before the isolation of the heart, a rIPC protocol (3 cycles of hindlimb ischemia/reperfusion) was performed. The infarct size was measured with tetrazolium staining. Akt and eNOS expression/phosphorylation, and mitochondrial H₂O₂ production were evaluated at the end of rIPC protocol, before myocardial ischemia/reperfusion. rIPC significantly decreased the infarct size and induced Akt and eNOS phosphorylation. The protective effect on infarct size was abolished by cervical vagal section (CVS), L-NAME (NO synthesis inhibitor) and 5-HD (mK⁺_ATP channels blocker). Mitochondrial production of H₂O₂ was increased by rIPC while it was abolished by CVS, L-NAME and 5-HD. Conclusions: rIPC activates a parasympathetic vagal pathway and a mechanism involving the Akt and eNOS phosphorylation, the opening of mK⁺_ATP, and the release of H₂O₂ by the mitochondria. These entire phenomena occur prior to the myocardial ischemia, which could act as triggers of rIPC.

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