Reperfusion injury includes a spectrum of events, such as reperfusion arrhythmias, vascular damage and no-reflow, and myocardial functional stunning. The concept of
reperfusion injury remains controversial with many proposed mechanisms when applied to humans, whereas in animal models, there are two main proposed mechanisms:
calcium over-load and formation of
oxygen free radicals. To prove that
reperfusion injury is specifically caused by reperfusion would require evidence that an intervention given at the time of reperfusion can diminish or abolish the injury as in the case of arrhythmias, which are thought to be mediated by excess recycling of cytosolic
calcium with delayed afterdepolarizations and ventricular automaticity. In the case of
myocardial stunning, the phenomenon may be mediated, at least in part, by a burst of
free radicals formed within the first minute of reperfusion and improved by
free radical scavengers given at the time of reperfusion. The alternate hypothesis is that cytosolic
calcium overload damages mechanisms for normal intracellular
calcium regulation so that the
stunned myocardium responds to agents that are thought to increase intracellular cytosolic
calcium, such as beta-receptor agonists. A further component of
reperfusion injury, under active investigation, is microvascular damage with alterations at the level of platelets, leukocytes, and endothelial integrity. From the therapeutic point of view, the divergent results of experimental interventions and the possibility that the abrupt onset of reperfusion in animals differs from the situation in humans with thrombolysis means that the best way currently available to limit
reperfusion injury is by minimizing the ischemic period by early reperfusion and by optimizing the metabolic status of the ischemic myocardium at the end of the ischemic period.