|Budget Amount *help
¥2,100,000 (Direct Cost : ¥2,100,000)
Fiscal Year 1990 : ¥1,000,000 (Direct Cost : ¥1,000,000)
Fiscal Year 1989 : ¥1,100,000 (Direct Cost : ¥1,100,000)
Ischemia/reperfusion injury observed in many ischemic diseases and organ transplantation is accompanied by the formation of reactive oxygen species (ROS). The purpose of the present study is to investigate the mechanism and prevention of this type injury using suitable skin flap models. During ischemia, ATP is broken down to hypoxanthine, a substrate of xanthine oxidase, and xanthine dehydrogenase is converted to oxidase by calpain, a calcium activated neutral proteinase. When the tissue is reoxygenated, a burst of superoxide and hydrogen peroxide occurs with resultant tissue damage. Two kinds of skin flaps, island and random, were lifted in rats, and the blood flow, cutaneous superoxide dismutase (SOD) activity, survival rates were measured after injection of liposomal SOD (L-SOD), E-64-c (specific inhibitor of cysteine proteinases including calpain) or allopurinol (xanthine oxidase inhibitor). Improved survival of island skin flaps after 10hr ligation was observed by these three agents. Remarkably reduced blood flow and SOD activity were confirmed. However, only L-SOD, but not E-64-c or allopurinol, improved the survival length in random skin flaps. These findings suggest the significant contribution of ROS generated in xanthine oxidase system to ischemia/reperfusionn injury. Also the discrepant results using three agents indicate the involvement of different mechanisms presumably linking to neutrophil-dependent inflammation in these two models. Our simple and quantitati ve skin flap models are useful in pharmacological evaluation and screening of any possible agent for the treatment of ischemic heart and cerebrovascular diseases as well as organ transplantation.