CATALASE-OVEREXPRESSING TRANSGENIC MOUSE HEART IS RESISTANT TO ISCHEMIA-REPERFUSION INJURY

Myocardial ischemia-reperfusion injury is at least partially mediated by oxygen-derived free radicals. Catalase is a major enzyme involved i n the detoxification of hydrogen peroxide. The activity of catalase in the heart is very low, which may be a factor responsible for the high sensitivity of the heart to ischemia-reperfusion injury. The present study was undertaken to determine whether elevation of catalase specif ically in the heart of transgenic mice can provide protection against ischemia-reperfusion injury. Hearts isolated from transgenic mice in w hich catalase in the heart was elevated similar to 60-fold higher than that in nontransgenic heart and from the nontransgenic littermates we re subjected to 50 min of warm (37 degrees C) zero-flow ischemia follo wed by 90 min reflow. Compared with nontransgenic controls, transgenic hearts showed significantly improved recovery of contractile force (7 5 vs. 25% at the end of 90 min reperfusion, P < 0.01). Efflux of creat ine kinase was reduced by similar to 50%, and the zone of myocardial i nfarction as demarcated by triphenyltetrazolium at the end of reperfus ion was reduced by similar to 40% in transgenic hearts compared with n ontransgenic controls. These findings support the view that hydrogen p eroxide is an important cause of ischemia-reperfusion damage and sugge st that protection may be provided by elevation of catalase activity.