Ischaemic conditioning and targeting reperfusion injury: a 30 year voyage of discovery

Abstract

To commemorate the auspicious occasion of the 30th anniversary of IPC, leading pioneers in the field of cardioprotection gathered in Barcelona in May 2016 to review and discuss the history of IPC, its evolution to IPost and RIC, myocardial reperfusion injury as a therapeutic target, and future targets and strategies for cardioprotection. This article provides an overview of the major topics discussed at this special meeting and underscores the huge importance and impact, the discovery of IPC has made in the field of cardiovascular research.

Repeated Non-Invasive Limb Ischemic Preconditioning Confers Cardioprotection Through PKC-Ԑ/STAT3 Signaling in Diabetic Rats

“…IPC-mediated protection of one organ or tissue (even peripheral muscle) also protects distant organs/tissues (e.g. heart or spinal cord) from ischemic injury through a different signaling pathway [6, 7], and this phenomenon is termed remote ischemic preconditioning (RIPC) [8]. Interestingly, brief cycles of non-invasive limb ischemia and reperfusion (NLIP), a type of RIPC, has been proven to be cardioprotective in experimental settings which is easy to operate [9, 10].…”

Acute Myocardial Injury: A Perspective on Lethal Reperfusion Injury

“…Adenosine receptors (A1 and A2 subtypes) as well as protein kinase C receptors also continue to be targeted [112][113][114][115]; mitogen activated protein kinase blockers have also been evaluated [116,117]. Pharmacologic treatments aimed at the Reperfusion Injury Salvage Kinase (RISK) and Survivor Activating Factor Enhancement (SAFE) pathways that activate pro-survival pathways possibly by inhibiting opening of mPTP at the level of the mitochondria are being studied [111,[118][119][120][121]. In fact, preliminary findings supporting the concept of reperfusion injury have been provided using the mPTP inhibitor, cyclosporine; administration prior to reperfusion by percutaneous coronary intervention (PCI) markedly reduced infarct size in patients [122].…”

“…Several thousand studies reported since have documented the cytoprotective efficacy of conditioning strategies (pre, per, post, remote, etc.) in a host of experimental models [121,[140][141][142]. Low-pressure reperfusion (variant of post-conditioning) at the time of reperfusion also merits consideration for post-ischemic myocyte protection [143].…”

At the crossroads from bench to bedside: luteolin is a promising pharmacological agent against myocardial ischemia reperfusion injury

“…However, none has been translated into clinical practice with the exception of early reperfusion (14)(15)(16). The reasons for the failure to translate pharmacologic conditioning strategies of cardioprotective effects from the bench to bedside have been extensively discussed in the literatures (3,(8)(9)(10)(11)(14)(15)(16)(17)(18)(19). Some experts concluded that the causes of failure can be attributed to inadequacy animal IRI models used in the preclinical cardioprotection studies.…”

“…Some experts concluded that the causes of failure can be attributed to inadequacy animal IRI models used in the preclinical cardioprotection studies. Nonetheless, in the position paper which published in 2013 (3), the experts concluded that the failure was not be due to a shortage of potential cardioprotective strategies discovered in the pre-clinical experimental setting (14), but was be due to the inability to successfully translate these promising therapies into interventions that actually improved the outcomes in patients (3,(8)(9)(10)(11)(14)(15)(16)(17)(18)(19).…”