Past and present course of cardioprotection against ischemia-reperfusion injury.

Despite tremendous advances in cardiovascular research and clinical therapy, ischemic heart disease remains the leading cause of serious morbidity and mortality in western society and is growing in developing countries. For the past 5 decades, many scientists have studied the pathophysiology of myocardial ischemia-reperfusion (I/R) injury leading to infarction. With the exception of reperfusion therapy, attempts to salvage the myocardium during an acute myocardial infarction showed disappointing results in directly decreasing infarct size. Nevertheless, the phenomena of ischemic preconditioning and ischemic postconditioning show a consistent and robust cardioprotective effect in every used experimental animal model. As a result, many studies have focused on the intracellular protective signaling pathways that are involved in preconditioning and postconditioning. More recently, it has been suggested that components of the reperfusion injury salvage kinases pathway, protein kinase B, and the extracellular signal-regulated kinases can induce cardioprotection against I/R injury when they are activated during the postischemic reperfusion period. In addition, inhibition of mitochondrial permeability transition during postischemic reperfusion also shows a strong cardioprotective effect against I/R injury. The present mini-review highlights a short summary of the historical and present course of research into cardioprotection against myocardial I/R injury.

Myocardial protection in cardiac surgery: a historical review from the beginning to the current topics.

Myocardial protection has become an essential adjunctive measure in cardiac surgery for a couple of decades, because since the 1950s, the methods of cardioprotection (cardioplegic solutions and related procedures) have been improved by the mechanism of myocardial ischemia/reperfusion-induced damage being unveiled through the untiring efforts of researchers and clinicians. The concept of myocardial protection in cardiac surgery was proposed along with introduction of hypothermic crystalloid potassium cardioplegia in the beginning and has been diversified by pharmacological additives, blood cardioplegia, temperature modulation (warm; tepid), retrograde cardioplegia, controlled reperfusion, integrated cardioplegia, and pre-and postconditioning. This historical review summarized experimental and clinical studies dealing with the methods and results of myocardial protection in cardiac surgery, introducing the newly developed concepts for the last decade and the current topics.

Genesis of remote conditioning: action at a distance--'hypotheses non fingo'?

Remote ischemic preconditioning is the phenomenon whereby brief episodes of ischemia-reperfusion applied in a distant organ or tissue render the myocardium resistant to infarction. The discovery of remote conditioning was not a serendipitous finding, but, rather, was predicted by mathematical modeling. In the current review, we describe how the hypothesis for remote conditioning was formulated and tested, how the paradigm has expanded to encompass a spectrum of remote triggers, and summarize the progress that has been made in elucidating the mechanisms responsible for this intriguing form of cardioprotection.

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 huge-it has allowed a change of paradigm in the understanding of ischaemia-reperfusion 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.