Twenty-five years of preconditioning: Are we ready for ischaemia? from coronary occlusion to systems biology and back

It was 25 years ago that the phenomenon of ischaemic preconditioning was first described. The protection afforded by preconditioning was found to be exceptionally robust and aroused immediate interest amongst the scientific community. During the last quarter century, a large research effort has been made to elucidate its molecular mechanisms with the final aim of using this knowledge to develop new cardioprotective treatments. The scientific impact of the discovery of ischaemic preconditioning has been hugeit has allowed a change of paradigm in the understanding of ischaemiareperfusion injury, from being a mere consequence of energy deprivation to being a complex, active process taking place to a large extent during the reperfusion phase. However, the clinical impact has been small, and some have anticipated a loss of interest in preconditioning unless this changes in the near future. We propose that the failure to develop clinical applications from ischaemic preconditioning is due in part to the incomplete understanding of its mechanisms and that a new integrative scientific approach should be used to resolve the complex networks of preconditioning protection signalling. © The Author 2011.