Multiple signaling pathways can be implicated in conferring opioid-mediated cardioprotection against ischemia-reperfusion injury, namely reperfusion injury salvage kinases (RISK) pathway involving the activation of Akt and ERK (extracellular signal-regulated kinase) and survivor activating factor enhancement (SAFE) pathway involving the activation of STAT3 (signal transducer and activator of transcription 3) [1, 6]. Here, STAT3 is linked to ischemia reperfusion injury.