Reducing the impact of myocardial ischaemia/reperfusion injury

It seems surprising that more than five decades of intense biochemical and molecular research on a leading cause of death and disability globally—ischaemic myocardial injury/myocardial infarction—and the spending of huge sums of money have achieved relatively little in the prevention of cell death secondary to ischaemia. The greatest progress has been made in methods to mechanically or chemically re-open acutely occluded coronary arteries and in increasingly better logistics of pre-hospital treatment and patient transport to hospitals providing this kind of therapy. This has resulted in a very important reduction in mortality among patients with acute myocardial infarction. The understanding of the pathological mechanism of ischaemic cell injury in the heart has also grown impressively, but much of this knowledge concerns the initiation of cell injury as a result of oxygen and energy deprivation, accumulating cellular ion imbalance, proteolytic activation, cell swelling, and similar mechanisms. The effects on ischaemic cell injury of a very effective protective regimen that is provided by the procedure of preconditioning applied prior to ischaemia are also impressive. But apart from the limited applicability of this therapeutic wisdom in cardiac surgery, nothing practical has come out of this knowledge as the much more frequent clinical situation is the one in which cardiac ischaemia is already manifest at the time the patient seeks medical help. There is encouraging preliminary evidence that ischaemic and pharmacological conditioning at the time of reperfusion may also be protective, but the impact of these approaches on clinical practice is negligible.Having made this point, we think it is fortunate that researchers have not given up early on analysing the cellular and subcellular changes in ischaemic myocardial cells. As it turned out, many different mechanisms play a role in cardiomyocyte injury when the ischaemic tissue is reperfused. This is not a trivial finding, since …