Mitochondrial dysfunction in ischaemia-reperfusion
Article first published online: 30 DEC 2008
Copyright © 1995 Acta Anaesthesiol Scand
Acta Anaesthesiologica Scandinavica
Volume 39, Issue Supplement s107, pages 171–176, September 1995
How to Cite
SARIS, N.-E. L. and ERIKSSON, K. O. (1995), Mitochondrial dysfunction in ischaemia-reperfusion. Acta Anaesthesiologica Scandinavica, 39: 171–176. doi: 10.1111/j.1399-6576.1995.tb04353.x
- Issue published online: 30 DEC 2008
- Article first published online: 30 DEC 2008
- mitochondrial permeability transition;
- tissue damage;
The mitochondrial dysfunction in ischaemia-reperfusion is shortly reviewed. During ischaemia the ATP level and pH drops, phospholipids are degraded, membrane permeabilities increased and the cytosolic levels of Na+ and Ca2+ raised. During the following reperfusion the Ca2+ levels may further increase while pH is raised. The oxidative phosphorylation is resumed and the ATP used for membrane repair and ion pumping. The mitochondrial Ca2+ handling is important in removing Ca2+ from the cytosol since the mitochondria are able to take up substantial amounts of Ca2*. However, if a certain threshold is exceeded, mitochondria undergo a so-called permeability transition (MPT), release their Ca2+, undergo swelling and become uncoupled. MPT has been shown to be due to the opening of large pore allowing passage of substances with a M8 <1500. Data are presented showing by electron microscopy swelling of mitochondria in cells in perfused liver before other gross morphological changes have taken place.
There are a number of factors lowering the threshold for Ca2+ in inducing the MPT: inorganic phosphate, prooxidants that oxidize membrane SH-groups, oxidation of NAD(P)H and GSH, while a protective effect is exerted by Mg2+, ADP (and ATP), some antioxidants, carnitine, decrease in pH, and cyclosporin A that binds to cyclophilin. The potential benefit of these in minimizing reperfusion-induced tissue damage is discussed.