Comment utiliser le paradigme de préconditionnement ischémique pour protéger le myocarde ?

Abstract

Le préconditionnement ischémique est un concept né il y a une quinzaine d’années. Dans cet article, nous présentons les généralités sur la protection anti-ischémique qui en découle ainsi que la part du mécanisme qui a pu être éclaircie à ce jour. Nous discutons l’application clinique de ce phénomène et envisageons comment l’évolution récente du concept ainsi que les derniers travaux laissent entrevoir d’importants développements dans un avenir proche.

Ischemic preconditioning affords the most powerful protection to a heart submitted to a prolonged ischemia-reperfusion. During the past decade, a huge amount of work allowed to better understand the features of this protective effect as well as the molecular mechanisms. Ischemic preconditioning reduces infarct size and improves functional recovery; its effects on arrhythmias remain debated. Triggering of the protection involves cell surface receptors that activate pro-survival pathways including protein kinase C, PI3-kinase, possibly Akt and ERK1/2, whose downstream targets remain to be determined. Much attention has been recently focused on the role of mitochondrial K+ ATP channels and the permeability transition pore that seem to play a major role in the progression toward irreversible cellular injury. Based on these experimental studies attempts have been made to transfer preconditioning from bench to bedside. Human experimental models of ischemic preconditioning have been set up, including cardiac surgery, coronary angioplasty or treadmill exercise, to perform pathophysiological studies. Yet, protecting the heart of CAD (coronary artery disease) patients requires a pharmacological approach. The IONA trial has been an example of the clinical utility of preconditioning. It helped to demonstrate that chronic administration of nicorandil, a K+ ATP opener that mimicks ischemic preconditioning in experimental preparations, improves the cardiovascular prognosis in CAD patients. Recent experimental studies appear further encouraging. It appears that “postconditioning” the heart (i.e. performing brief episodes of ischemiareperfusion at the time of reperfusion) is as protective as preconditioning. In other words, a therapeutic intervention performed as late as at the time of reflow can still significantly limit infarct size. Further work is needed to determine whether this may be transfered to the clinical practice.