Published online Sep 30, 1997.
https://doi.org/10.4070/kcj.1997.27.9.907
Effect of Superoxide Dismutase on Apoptosis in Ischemia-Reperfused Myocardium of Rabbit
Abstract
Background
Recently involvenment of apoptosis, or programmed cell death, has been suggested in myocardial reperfusion injury. Free radicals are one of the inducers of apoptosis, and superoxide dismutase(SOD), a oxygen free radical scavenger, inhibits apoptotic cell death of neurons. Reperfusion of ischemic myocardium results in a burst of oxygen free radical production, however, it has not been defined that oxygen free radicals mediate apoptosis in myocardial reperfusion injury. This study was undertaken to investigate the role of oxygen free radicals by examining the inhibition of apoptosis by SOD.
Method
New Zealand white rabbits(n=16) weighing 1.8-2.0kg underwent 30 minutes of left anterior descending coronary artery occlusion followed by reperfusion for 1 or 4 hours. In control group, bovine serum albumin(5mg/kg) was administered continuously via the left atrial appendage starting 10 minutes before reperfusion and ending simultaneously with reperfusion for 1 hour(n=4) or 4 hours(n=4). In SOD group, bovine erythrocyte SOD(15,000u/kg) was administerd starting 10 minutes before reperfusion and ending simultaneously with reperfusion for 1 hour(n=5) or 4 hours(n=3). Ventricles were excised immediately after intervention. Tissues were fixed in 10% buffered formalin and 2.5% glutaraldehyde. Apoptosis was examined by hematoxylin and eosin(H & E) staining, in situ nick end labeling, and transmission electron microscopy. Number of apoptotic cells was evaluated semiquantitatively on H & E stained section.
Results
Evidence of apoptosis was detected in every ischemia-reperfused myocardium, and apoptotic cells were found in the non-necrotic myocardium near areas of contraction band necrosis. In control group, the average number of apoptotic cells was 1.7(range 1.5-2.0) for 1 hour reperfused myocardium and 1.4(range 0.3-2.5) for 4 hours reperfused myocardium per high power field(×400). In SOD group, the average number of apoptotic cells was was 0.2 (range 0.2-0.3) for 1 hour reperfused myocardium and 0.3(range 0.2-0.4) for 4 hours reperfused myocardium. There was a significant difference in the number of apoptotic cells between control and SOD groups(as a whole group 1.5±0.2 vs 0.3±0.1, p<0.01).
Conclusion
SOD partially, however, significantly inhibits apoptosis, which suggests that oxygen free radicals may induce apoptosis in ischemia-reperfused myocardium of rabbit.
