Pathophysiological vs biochemical ischaemia: a key to transition from reversible to irreversible damage

'Myocardial ischaemia' is defined as an imbalance between fractional uptake of oxygen and the rate of cellular oxidation in the heart. This condition may have several potential outcomes: (1) when ischaemia is brief, a transie nt post-ischaemic ventricular dysfunction occurs on reperfusion, a conditio n named 'stunned myocardium'; (2) when it is prolonged and severe, irrevers ible damage occurs, with no recovery in contractile function upon reperfusi on; (3) when ischaemia is less severe, but still prolonged, the myocytes ma y remain viable but exhibit depressed contractile function. Under this cond ition, named 'hibernating myocardium', the reperfusion is able to restore c ontractility. During these different ischaemic conditions, many biochemical changes occur : initially they represent a defensive and protective reaction against isch aemia such as cellular acidosis and increase of inorganic phosphate levels that rapidly abolish the contractile activity. But with the prolongation of ischaemia and restoration of the coronary flow, alterations in ions and ov erall Ca2+ homeostasis occur, together with an oxidative stress mediated by oxygen free radicals, not adequately counteracted by the cellular antioxid ant defences. The mitochondria are likely to play a central role in these e vents which leads to membrane damage and irreversible deterioration of cont ractile function. The issue of reperfusion injury, however, is not unanimou sly accepted. Many, but not all, cardiologists are of the opinion that some components of reperfusion may be detrimental and able to inflict injury ov er and above that attributable to ischaemia. This article defines the seque nce of events occurring during the transition from angina to infarction. (C ) 2001 The European Society of Cardiology.