The pathophysiology of myocardial reperfusion: a pathologist’s perspective

Coronary artery thrombosis, caused either by fissuring or erosion of atherosclerotic plaques, is the usual cause of acute myocardial infarction.1 If a coronary occlusion persists for more than 30 minutes, irreversible damage to the myocardium occurs. Persistent coronary occlusion results in a progressive increase of the infarct size with a wave-front transmural extension from the endocardium towards the epicardium.2,3 Although reperfusion can occur spontaneously, thrombotic coronary artery occlusion persists in the majority of patients suffering an acute myocardial infarction. Thus, timely coronary artery recanalisation and myocardial reperfusion, either by thrombolytic therapy or primary angioplasty and/or stenting, represents the most effective way of restoring the balance between myocardial oxygen supply and demand. Prevention of myocardial cell necrosis by the restoration of blood flow depends on the severity and duration of pre-existing myocardial ischaemia. Experimental and clinical data indicate that the recovery of systolic and diastolic function and the reduction in overall mortality are more favourably influenced by early coronary blood flow restoration. Collateral coronary vessels also appear to play an additional role, providing sufficient blood flow to the myocardium as to reduce the extent of myocyte irreversible injury.3 However, although beneficial in terms of myocardial salvage, the process of reperfusion may itself elicit pathologic consequences and the term “reperfusion injury” has been introduced.4–6 With this term, we normally refer to causal events associated with reperfusion that had not occurred during the preceding ischaemic period. Although ischaemia–reperfusion injury is now a well accepted phenomenon in the research experimental setting, its clinical relevance remains to be proven.7 The main difficulty is in differentiating between the pre-existing ischaemic damage and any subsequent damage occurring during the reperfusion phase. As summarised by Kloner,5 four types of reperfusion injury have been observed in experimental animals (table 1) and …