Oxygen free radicals are known to be generated during periods of
ischemia followed by reperfusion. There is still some controversy, however, concerning the use of electron paramagnetic resonance spectroscopy to accurately detect and identify the
free radical species that are formed. There is no doubt that
oxygen radicals are deleterious to the myocardium;
free radicals cause
left ventricular dysfunction and structural damage to myocytes and endothelial cells in both in vitro and in vivo preparations. Potential sources of these cytotoxic
oxygen species include the
xanthine oxidase pathway, activated neutrophils, mitochondria, and arachidonate metabolism, yet the crucial source of
free radicals in the setting of
ischemia and reperfusion is unresolved. There is little doubt that
oxygen radicals play a role in the phenomenon of
stunned myocardium induced by brief periods of
ischemia followed by reperfusion; numerous studies have consistently observed that pretreatment with
free radical scavengers and
antioxidants enhances contractile function of stunned, postischemic tissue. Whether
oxygen free radical scavengers administered only during reperfusion enhance recovery of
stunned myocardium in models of brief
ischemia remains to be determined. In models of prolonged
ischemia (2 hours) followed by reperfusion, we have not observed a beneficial effect of scavengers on
stunned myocardium. The issue of whether
oxygen free radical scavengers are capable of reducing so-called irreversible or lethal
reperfusion injury remains, in our opinion, unresolved. Although some studies have observed that agents such as
superoxide dismutase and
catalase reduce
infarct size in
ischemia and reperfusion models, many others have reported negative results. Additional studies will be needed to resolve this ongoing controversy.
Oxygen free radicals may also contribute to reperfusion-induced arrhythmias in rodent heart preparations; however, less data are available in other animal models. The concept of
reperfusion injury should not be considered a deterrent to reperfusion for the treatment of acute
myocardial infarcts in the clinical setting.
Thrombolytic therapy reduces
myocardial infarct size, enhances recovery of left ventricular function, and improves survival. Whether incremental beneficial effects on these parameters will be obtained when
oxygen radical-scavenging agents are used as adjuvant
therapy to thrombolysis in patients remains to be determined.