Imperfect myocardial protection during prolonged ischaemia results in adverse changes during reperfusion. Clinical studies carried out during cardiac surgery show that: (1) Oxygen free radicals produced during reperfusion can lead to chromosomal damage in leukocytes. However, this effect seems to be prevented by the addition of allopurinol in the cardioplegic solution. (2) Polymorphonuclear leukocytes are directly implicated in situ in the genesis of free radicals responsible for reperfusion injury. (3) Pre-treatment with trimetazidine, an anti-ischaemic drug with antioxidant properties, and addition of the drug to the cardioplegic solution reduced oxygen free radical damage, as shown by a reduced release of malondialdehyde increase and of myosin; moreover, pre-treatment with trimetazidine enabled patients to undergo surgery with improved left ventricular function.