[The possible limits of thrombolysis: reocclusion and reperfusion damage]

The availability of safe and potent thrombolytic drugs has made reperfusion within the initial few hours the treatment of choice in a vast number of patients with acute myocardial infarction. However, there remain several problems which may substantially reduce the possible beneficial effects of timely reperfusion of ischemic hearts. One important aspect is represented by the possible reocclusion of the infarct-related vessel. Many clinical studies have documented that in a relatively large proportion of patients, the infarct-related vessel may reocclude within few hours after discontinuation of thrombolytic therapy. This phenomenon would obviously hamper the results of thrombolysis in these patients. Investigation on the mechanisms responsible for this early reocclusion represents an area of active research. The results of several large clinical trials have shown that this phenomenon occurs despite full anticoagulation therapy, and it is apparently unrelated to the specific thrombolytic agent employed. On the other hand, experiments performed with animal models which reproduce the setting of a thrombogenic stimulus in the presence of a coronary artery stenosis have indicated that platelet activation plays a key role in the process of intracoronary thrombus formation, suggesting that antiplatelet interventions may be of benefit in this setting. Another potential problem which might partly offset the benefits of thrombolytic therapy is represented by the occurrence of a form of myocardial injury specifically associated with reperfusion. Several experimental studies have now demonstrated that a large amount of toxic oxygen metabolites (oxygen radicals) can be generated at the time of postischemic reperfusion, and that interventions with agents which can inactivate oxygen radicals, or prevent their formation, can significantly improve recovery of contractility and reduce infarct size in reperfused hearts. Although the actual incidence of this phenomenon is still debated, this issue has received considerable attention, because of the possibility of further expanding the benefits of thrombolysis should reperfusion injury be preventable in man.