Timing of coronary recanalization. Paradigms, paradoxes, and pertinence.

In hearts of experimental animals, irreversible myocardial injury occurs when perfusion is interrupted completely for intervals as brief as 20-60 minutes.45 The failure of reperfusion to salvage irreversibly injured tissue has been documented rigorously. For example, Reimer et a14 ligated coronary arteries in dogs for selected intervals and assessed necrosis morphologically. In contrast to the 55% of ischemic myocardium that remained viable when reperfusion was implemented after 40 minutes, less than 17% remained viable when reperfusion was implemented only after 6 hours (Figure 1). Similarly, in dogs with experimentally induced thrombotic coronary artery occlusion and subsequent thrombolysis induced with streptokinase, reperfusion within 2 hours salvaged approximately 50% of jeopardized myocardium as judged from positron emission tomograms.5 In contrast, late reperfusion (implemented after 6 hours) resulted in no significant salvage (Figure 2). Despite the consistency of these results, extrapolation to human hearts is neither straightforward nor necessarily justified. In patients, the impact of thrombotic occlusion will be conditioned by the severity and extent of underlying atherosclerotic coronary artery disease and variable contributions of collateral flow to protection of myocardium.6 In addition, some favorable consequences of reperfusion may depend on mechanisms independent of salvage of jeopardized myocardium, as discussed below. Nevertheless, results of several con-