Remote ischaemic conditioning: cardiac protection from afar

Abstract

For patients with ischaemic heart disease, remote ischaemic conditioning may offer an innovative, non-invasive and virtually cost-free therapy for protecting the myocardium against the detrimental effects of acute ischaemia-reperfusion injury, preserving cardiac function and improving clinical outcomes. The intriguing phenomenon of remote ischaemic conditioning was first discovered over 20 years ago, when it was shown that the heart could be rendered resistant to acute ischaemia-reperfusion injury by applying one or more cycles of brief ischaemia and reperfusion to an organ or tissue away from the heart - initially termed 'cardioprotection at a distance'. Subsequent pre-clinical and then clinical studies made the important discovery that remote ischaemic conditioning could be elicited non-invasively, by inducing brief ischaemia and reperfusion to the upper or lower limb using a cuff. The actual mechanism underlying remote ischaemic conditioning cardioprotection remains unclear, although a neuro-hormonal pathway has been implicated. Since its initial discovery in 1993, the first proof-of-concept clinical studies of remote ischaemic conditioning followed in 2006, and now multicentre clinical outcome studies are underway. In this review article, we explore the potential mechanisms underlying this academic curiosity, and assess the success of its application in the clinical setting.

© 2015 The Authors. Anaesthesia published by John Wiley & Sons Ltd on behalf of Association of Anaesthetists of Great Britain and Ireland.

Figures

Figure 1

Hypothetical model highlighting potential mechanistic pathways underlying remote ischaemic conditioning. It has been proposed that brief non‐lethal periods of ischaemia‐reperfusion applied to the upper or lower limb, using serial inflation/deflations of a cuff, causes the release of local autocoids (such as adenosine, bradykinin, opioids) which then activate sensory afferent neurones in the upper or lower limb that in turn relay the cardioprotective signal to the dorsal motor vagal nucleus (DMVN) in the brainstem. At this point, it is not clear how the cardioprotective signal reaches the heart or other organs. Several hypotheses have been suggested. (1) Activation of nuclei within the DMVN results in increased vagal nerve firing to the heart, which via the release of acetylcholine (Ach), and subsequent activation of muscarinic Ach receptors, induces the cardioprotective phenotype. (2) It is largely agreed that a blood‐borne dialysable cardioprotective factor is released into the systemic circulation, from where it conveys the cardioprotective effect to the heart and other organs. However, the actual source of the blood‐borne cardioprotective factor is not clear, although possibilities include: (i) the conditioned limb itself; (ii) the central nervous system, possibly the brainstem; (iii) pre‐/postganglionic parasympathetic nerve endings within the heart; or (iv) a non‐conditioned remote organ/tissue.