Pathobiology and Clinical Impact of Reperfusion Injury.
Reperfusion injury refers to cellular death or dysfunction caused by restoration of blood flow to previously ischemic tissue. This should be differentiated from the normal reparative processes that follow an ischemic insult. Four types of reperfusion injury have been described in the literature: (1) lethal reperfusion injury, (2) nonlethal reperfusion injury (myocardial stunning), (3) reperfusion arrhythmias, and (4) vascular injury (including the "no-reflow" phenomenon). There is continued debate whether reperfusion itself is capable of killing viable myocytes, which otherwise would have survived the ischemic insult. However, there is firm evidence for the existence of myocardial stunning following various ischemic syndromes, including reperfusion therapy for acute myocardial infarction, unstable angina pectoris, vasospastic angina, effort-induced ischemia, coronary artery bypass surgery, and cardiac transplantation. Reperfusion arrhythmia is more common after short ischemic episodes than after long ischemic periods. Thus, while reperfusion arrhythmias in the setting of acute myocardial infarction are relatively rare, reperfusion arrhythmias may be an important cause of sudden death. The "no-reflow" phenomenon has been described following reperfusion in patients with acute myocardial infarction. Three major components have been proposed as mediators of reperfusion injury: (1) oxygen free radicals, (2) the complement system, and (3) neutrophils. Numerous experimental studies have shown short-term benefit by blocking various stages of the postischemic inflammatory response. Oxygen free radicals scavangers, complement inhibition, leukocyte depletion, and the use of antibodies against various adhesion molecules have shown a reduction of infarct size in many ischemic/reperfusion experimental models. However, many of these agents failed to show a benefit in the clinical setting. Moreover, the long-term benefit of such intervention is still unknown.
Birnbaum
Y
Heart Institute, Good Samaritan Hospital, and the University of Southern California, Los Angeles, California.
Leor
J
Kloner
RA