Ischaemic preconditioning

Abstract

Is myocardial ischaemia always harmful? Research is proving that it is not. Traditionally it was thought that myocardium sublethally injured by a brief period of ischaemia would become more sensitive to subsequent ischaemia and that repeated brief ischaemic insults might cumulatively cause infarction. This is not the case. In 1986 Murry and colleagues described the results of a series of experiments on canine hearts, which examined the metabolic consequences of repeated brief episodes of ischaemia with intervening reperfusion (reviewed by Reimer and Jennings1). Although myocardial ATP concentrations fell during the first brief coronary artery occlusion, these concentrations were preserved during further identical occlusions and no necrosis occurred. Murry and colleagues then found that pretreatment with similar repeated brief periods of ischaemia also triggered adaptive changes that protected the myocardium from the effects of a subsequent, prolonged ischaemic insult.1 Compared with that in controls the size of myocardial infarction fell by three quarters. Inducing tolerance to ischaemia in this way is now known as “ischaemic preconditioning.” Ischaemic preconditioning is the most powerful and reproducible method of delaying ischaemic injury described. It protects against every consequence of ischaemia, and despite extensive investigation by many independent laboratories there are no reports of “failure to precondition” in any species. To predict the circumstances in which preconditioning may occur, an understanding of the essential features of the phenomenon is important. A single brief period of ischaemia of as little as three minutes is sufficient to induce preconditioning, and this must be followed by at least one minute of reperfusion.2,3 If this period of reperfusion exceeds 120 …