TY - JOUR
T1 - Reduction in experimental infarct size by recombinant human superoxide dismutase
T2 - Insights into the pathophysiology of reperfusion injury
AU - Ambrosio, G.
AU - Becker, L. C.
AU - Hutchins, G. M.
AU - Weisman, H. F.
AU - Weisfeldt, M. L.
PY - 1986
Y1 - 1986
N2 - 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 < .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.
AB - 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 < .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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U2 - 10.1161/01.CIR.74.6.1424
DO - 10.1161/01.CIR.74.6.1424
M3 - Article
C2 - 3779923
AN - SCOPUS:0022982366
SN - 0009-7322
VL - 74
SP - 1424
EP - 1433
JO - Circulation
JF - Circulation
IS - 6
ER -