Remote ischaemic pre‐ and delayed postconditioning – similar degree of cardioprotection but distinct mechanisms

Abstract

Myocardial ischaemia–reperfusion injury can be significantly reduced by an episode(s) of ischaemia–reperfusion applied prior to or during myocardial ischaemia (MI) to peripheral tissue located at a distance from the heart; this phenomenon is called remote ischaemic conditioning (RIc). Here, we compared the efficacy of RIc in protecting the heart when the RIc stimulus is applied prior to, during and at different time points after MI. A rat model of myocardial ischaemia–reperfusion injury involved 30 min of left coronary artery occlusion followed by 120 min of reperfusion. Remote ischaemic conditioning was induced by 15 min occlusion of femoral arteries and conferred a similar degree of cardioprotection when applied 25 min prior to MI, 10 or 25 min after the onset of MI, or starting 10 min after the onset of reperfusion. These RIc stimuli reduced infarct size by 54, 56, 56 and 48% (all P < 0.001), respectively. Remote ischaemic conditioning applied 30 min into the reperfusion period was ineffective. Activation of sensory nerves by application of capsaicin was effective in establishing cardioprotection only when elicited prior to MI. Vagotomy or denervation of the peripheral ischaemic tissue both completely abolished cardioprotection induced by RIc applied prior to MI. Cardioprotection conferred by delayed remote postconditioning was not affected by either vagotomy or peripheral denervation. These results indicate that RIc confers potent cardioprotection even if applied with a significant delay after the onset of myocardial reperfusion. Cardioprotection by remote preconditioning is critically dependent on afferent innervation of the remote organ and intact parasympathetic activity, while delayed remote postconditioning appears to rely on a different signalling pathway(s).

Molecular Basis of Cardioprotection

“…The activation of the peripheral sensory fibers involves activation of the PKCγ isoform. 439 In some studies, activation of the autonomic nervous system through spinal and supraspinal reflexes [435][436][437]442 was mandatory to reduce IS in the ischemic/reperfused myocardium, 32,92,434,435,437,443 in others it was not. 432,444 Of importance, humoral transfer of protection with plasma or dialysate obtained after the peripheral preconditioning cycles to another individual or individual heart, even across species, is possible and highlights the functional importance of the humoral transfer signal.…”

Interaction of Risk Factors, Comorbidities, and Comedications with Ischemia/Reperfusion Injury and Cardioprotection by Preconditioning, Postconditioning, and Remote Conditioning

“…It can be applied before myocardial ischemia (remote ischemic preconditioning) (Przyklenk et al, 1993); after the onset of myocardial ischemia but before reperfusion (remote ischemic perconditioning) (Schmidt et al, 2007); at the onset of myocardial reperfusion (remote ischemic postconditioning) (Andreka et al, 2007); and even after 15 minutes of reperfusion has elapsed (remote ischemic delayed postconditioning) (Basalay et al, 2012). Remote conditioning interventions thereby lend themselves to application in a number of different clinical settings of acute ischemia/reperfusion injury (see section III).…”

Trials, tribulations and speculation! Report from the 7th Biennial Hatter Cardiovascular Institute Workshop

“…Recent data has also inferred the presence of a delayed postconditioning phenomenon, [13,14] and further exploration and characterisation of this phenomenon is required which may represent a later onset of inflammation and neutrophil infiltration. In terms of future targets for cardioprotection, the interaction between endothelium, neutrophils and platelets were discussed in terms of attenuating microvascular obstruction and post-infarction inflammation.…”