The role of free radicals in the ischemic myocardium.

Reperfusion is beyond doubt the most effective way to treat the ischaemic myocardium. Late reperfusion may cause further damage, the extent of which can be modified, although the underlying mechanism is still not understood and is likely to be of multifactorial origin. Myocardial production of oxygen free radicals exceeding the neutralizing capacity of the myocytes may be important cause of reperfusion damage. This possibility, however, has by no means been proven. There is evidence that prolonged ischaemia reduces the natural defence mechanism of the heart against oxygen free radicals. Although each method has its limitations, comparison several different methods provided evidence, albeit preliminary, that the formation of these toxic species is enhanced after ischaemia and particularly after reperfusion. It seems that the presence of blood is not a prerequisite for oxygen free radical formation and that the mitochondria are likely to be an important site of production. Experimental work does indicate that the oxygen free radicals-mediated component of the reperfusion damage can be circumvented, which gives rise to optimism for the pharmacologist. However, several controversies exist regarding the meaning of studies in which agents known to interfere with oxygen free radicals have provided protection and conclusions derived from such studies should be considered with caution. Almost no data are available on the role of oxygen free radicals in reperfusion injury in man. This, in our opinion, is the goal to achieve in the very near future, before antioxidant therapy will be blindly and irrationally combined with thrombolytic therapy in the treatment of acute myocardial infarction in man.