The rationale for thrombolytic therapy

Substantial progress has been made toward understanding the pathophysiological processes that lead to acute myo-cardial infarction. Research has shown that the mech-anism of infarction is the rupture of an atherosclerotic plaque with a subsequent thrombogenic response from exposed subendothelial tissue, leading to additional or complete obstruction of the vessel. Myocardial cell death then proceeds in a wavefront fashion from the subendo-cardium to the epicardium. Time to myocardial reper-fusion and the extent of collateral flow are the primary determinants of final infarct area. This knowledge led to the development of therapeutic strategies to achieve early and sustained reperfusion of the infarct-related vessel, the presumption being that this would result in increased myocardial salvage and better residual left ventricular function in addition to reductions in infarct expansion and electrical instability. The results of several large thrombolytic trials have sup-ported this model, showing that patients who receive thrombolytic therapy derive a constant relative survival benefit when compared with control patients. The largest comparative thrombolytic trial to date has shown that therapies that result in early, more complete reperfusion are indeed associated with lower mortality; however, these therapies may be associated with higher rate of complica-tions such as intracranial haemorrhage and reocclusion. Future evaluations must include assessment of the benefits relative to the risks of newer, more potent thrombolytic regimens