Process of ischemic and reoxygenation injuries in organs

点击翻译按钮获取中文摘要

In an attempt to clarify the process of ischemic or anoxic injury, we studied mechanisms involved in the dysfunction of mitochondria and disruption of cytoskelton system during anoxia, making focus on the homeostasis and variation in the intracellular level of calcium.Results obtained from the prigment study are as follows : (1) The leakage of cytosolic enzymes from anoxic heart or liver is due to disruption of blebs which have been formed during anoxia by mechanical stress of blood flow or contraction of muscles. (2) Application of a newly-developed spectrofluorophotometer combined with fiber to the perfused heart enabled to make a real-time measurement of variation of intracellular calcium in response to muscle contraction, and to directly observe changes in the calcium level during anoxia and reoxygenation. (3) In the perfused liver and heart, matrix enzymes were leaked out during reoxygenation, mechanism of which was considered to be different from that of leakage of cytosolic enzymes. (4) Reoxygenation of isolated mitochondria caused leakage of matrix'enzymes, simultaneously with the generation of hydrogen peroxide. This was not due to activation of phospholipase A2, but was a calcium-dependent phenomenon which is strongly inhibited by ATP or cyclosporin A. This non-specific increase in permeability of the inner membrane was considered to be the main cause of reoxygenation injury of mitochondria.