Circulation, Vol 80, 1115-1127, Copyright © 1989 by American Heart Association
RA Kloner, K Przyklenk and P Whittaker
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.
ARTICLES
Deleterious effects of oxygen radicals in ischemia/reperfusion. Resolved and unresolved issues
Heart Institute, Hospital of the Good Samaritan, Los Angeles 90017.
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