AIMS: Remote 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 METHODS: Two 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 FINDINGS: The 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 30min of ischaemia and 120min reperfusion. Of the specific receptor antagonists, only that specific for the mu receptor subtype, and not delta or kappa receptor, block the protective response. SIGNIFICANCE: These 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.
AIMS: Remote 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 METHODS: Two 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 FINDINGS: The 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 30min of ischaemia and 120min reperfusion. Of the specific receptor antagonists, only that specific for the mu receptor subtype, and not delta or kappa receptor, block the protective response. SIGNIFICANCE: These 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.
Authors: Louise E See Hoe; Jan M Schilling; Emiri Tarbit; Can J Kiessling; Anna R Busija; Ingrid R Niesman; Eugene Du Toit; Kevin J Ashton; David M Roth; John P Headrick; Hemal H Patel; Jason N Peart Journal: Am J Physiol Heart Circ Physiol Date: 2014-07-25 Impact factor: 4.733
Authors: Gerd Heusch; Hans Erik Bøtker; Karin Przyklenk; Andrew Redington; Derek Yellon Journal: J Am Coll Cardiol Date: 2015-01-20 Impact factor: 24.094
Authors: Derek J Hausenloy; Hans Erik Bøtker; Peter Ferdinandy; Gerd Heusch; G André Ng; Andrew Redington; David Garcia-Dorado Journal: Cardiovasc Res Date: 2019-06-01 Impact factor: 10.787