Circulation, Vol 75, 1237-1248, Copyright © 1987 by American Heart Association
A Uraizee, KA Reimer, CE Murry and RB Jennings
Reactive oxygen species such as the superoxide anion (.O2-) have recently
been implicated as important agents involved in causing cell death in the
setting of myocardial ischemia and reperfusion. When superoxide anion is
involved in ischemic injury the administration of superoxide dismutase
(SOD) may limit infarct size by reducing the level of superoxide anions in
the myocardium. The study described herein was done to determine whether
SOD could limit myocardial infarct size when infarcts were produced in dogs
by a 40 min occlusion of the circumflex coronary artery followed by 4 days
of reperfusion. The animals in the SOD treatment group received a 1 hr
intra-atrial infusion of SOD, at a rate of 250 U/kg/min starting 15 min
after occlusion and ending 35 min after reperfusion; control dogs received
a saline infusion over the same time frame. Infarct size was determined
histologically and expressed as a percentage of the anatomic area at risk
(AAR). Infarct size was similar in the two groups, averaging 26.2 +/- 2.5%
in the control group (n = 10) and 21.1 +/- 4.8% in the SOD group (n = 11)
(p = .40). Hemodynamic variables were not statistically different in the
two groups during the occlusion. The transmural mean collateral blood flow
at 10 min into the 40 min occlusion was 0.13 +/- 0.02 ml/min/g in the
controls and 0.17 +/- 0.03 ml/min/g in the SOD group (p = NS); moreover,
SOD did not alter collateral blood flow. In control dogs, infarct size was
inversely related to collateral blood flow; analysis of covariance showed
that SOD did not shift this relationship. Thus, SOD did not limit infarct
size in this study. The results of the current study are consistent with
our previous study in which allopurinol, a xanthine oxidase inhibitor, did
not limit infarct size in this same experimental preparation. The results
suggest that superoxide anions that are accessible to the infused SOD are
not a major cause of myocyte death caused by 40 min of severe ischemia
followed by reperfusion.
ARTICLES
Failure of superoxide dismutase to limit size of myocardial infarction after 40 minutes of ischemia and 4 days of reperfusion in dogs
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