REPRESSION OF HYPOXIA-REOXYGENATION INJURY IN THE CATALASE-OVEREXPRESSING HEART OF TRANSGENIC MICE

Hypoxia-reoxygenation injury results at least in part from reactive ox ygen free radicals, Catalase is a major enzyme involved in detoxificat ion of hydrogen peroxide, The activity of catalase per gram of tissue in the heart is very low, being only about 2% that of liver in rodents and humans, which may be responsible for the high sensitivity of the heart to hypoxia-reoxygenation injury. The present study was undertake n to determine whether elevation of catalase specifically in the heart of transgenic mice could provide protection against hypoxia-reoxygena tion injury. Transgenic mice with elevated cardiac catalase 60-fold hi gher than normal were selected, and the effects of catalase elevation on hypoxia-reoxygenation induced functional and morphological changes in isolated atria were determined. Catalase overexpression ameliorated reductions in contractile force and heart rate caused by hypoxia-reox ygenation, and eliminated reoxygenation-induced arrhythmia. The catala se-overexpressing transgenic atria were also highly resistant to hypox ia-reoxygenation-induced morphological alterations, as examined by ele ctron microscopy, Use of cardiac catalase-overexpressing transgenic mi ce thus demonstrates that hydrogen peroxide is involved in hypoxia-reo xygenation cardiotoxicity, and that this mouse model provides a useful tool for study of free radical mechanism in the heart damage.