Cardioprotection from remote preconditioning involves spinal opioid receptor activation

AimsRemote preconditioning is a powerful and potentially clinically viable mode of cardioprotection. The mechanisms underlying its transmission process have not been extensively studied. The aim of this study was to test the hypothesis that spinal opioid receptors are involved with signal transmission of remote cardiac preconditioning.Main methodsTwo established models of remote preconditioning were used, one using intermittent ischaemia of the lower limb (remote ischaemic preconditioning, RIPC) and the other by stimulation of cutaneous pain fibres via an abdominal incision (remote preconditioning of trauma, RPOT). Classic ischaemic preconditioning (IPC) was used as positive control. Selective blockade of spinal opioid receptors was achieved through intrathecal injection of naloxone methiodide, a compound not known to cross the blood-brain barrier.Key findingsThe prior introduction of naloxone methiodide abolished the cardioprotective effects of RIPC, RPOT but not IPC, as assessed by infarct size as a percentage of area at risk following 30 min of ischaemia and 120 min reperfusion. Of the specific receptor antagonists, only that specific for the mu receptor subtype, and not delta or kappa receptor, block the protective response.SignificanceThese results suggest that the central nervous system at the spinal cord level is involved with the relaying of signals between the afferent and efferent arms of remote preconditioning.