Circulation, Vol 74, 1424-1433, Copyright © 1986 by American Heart Association
G Ambrosio, LC Becker, GM Hutchins, HF Weisman and ML Weisfeldt
To determine the importance of reperfusion injury and the ability of the
free-radical scavenger recombinant human superoxide dismutase (h- SOD) to
prevent it, open-chest dogs underwent 90 min of proximal circumflex
coronary artery occlusion, and only at the moment of reperfusion received
either h-SOD (400,000 IU bolus into the left atrium followed by a 300,000
IU iv infusion over 1 hr) or saline. After 48 hr the surviving animals were
killed and measurements were made of the risk region (by postmortem
angiography) and infarct size (by gross pathology). All measurements were
made by investigators blinded to treatment given, and the code was broken
only at the end of the study. Hemodynamic variables and collateral flow
during ischemia were similar in the two groups. Infarct size in control
animals (n = 8) averaged 22.4 +/- 3.1% of the left ventricle and 52.2 +/-
7.1% of the risk region, compared with 13.3 +/- 0.8% of the left ventricle
and 33.6 +/- 2.1% of the risk region in h-SOD-treated dogs (n = 8) (p less
than .05). Infarcts in treated animals were not only smaller, but also
exhibited a distinctive "patchiness," suggesting protection along vascular
distributions. Furthermore, analysis of the relationship between infarct
size and collateral flow measured during ischemia in the two groups
indicated that protection by h-SOD was greatest in animals with the lowest
collateral flows. This study supports the concept that reperfusion of
ischemic myocardium results in a separate component of cell damage,
presumably linked to the generation of oxygen free radicals on reflow.
Since the h-SOD preventable reperfusion component of injury was most
pronounced in hearts with the most severe ischemia, scavenging of oxygen
radicals at the time of reflow may offer a novel and particularly promising
therapeutic approach for the protection of ischemic myocardium.
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Reduction in experimental infarct size by recombinant human superoxide dismutase: insights into the pathophysiology of reperfusion injury
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