The microcirculation is the key site involved in the pathophysiology of reperfusion injury. The microvasculature is an important site of nitric oxide (NO) production as well as of superoxide formation. Moreover, it is a primary location for leukocyte–endothelial cell interaction, which is the hallmark of reperfusion injury. Reperfusion injury is initiated within minutes of reperfusion by the generation of superoxide radicals that inactivate NO. The reduced bioavailability of NO triggers an endothelial dysfunction that promotes neutrophil adherence and concomitant injury to the ischemic-reperfused tissue. This neutrophil amplification stage is the primary mechanism of reperfusion injury to the heart or other organs subjected to ischemia and reperfusion...