Ischaemia-Reperfusion

Figure 4.8 Reduction of Na/K ATPase activity in isoiated guinea-pig hearts subjected to ischaemia/reperfusion and its prevention by various agents control non-ischaemic hearts (Nl) guinea-pig hearts subjected to global ischaemia for 2 h and subsequently reperfused for 1 h (IR). In other preparations, superoxide dismutase (SOD) 100 U/ml, catalase (CAT) 150 U/ml, dimethylsulphoxide (DMS) 50 mu, histidine (HIS) 10 mu, vitamin E (TOC)...

Although it is widely accepted that ischaemia/ reperfusion-induced oxidant stress is associated with a reduction of Na/K ATPase activity, it is difficult to determine which features of this process are responsible for this effect. A classical approach to this type of problem has been to determine the effect of the application of selected metabolites or agents on the activity of the enzyme of interest, an approach that has been exploited for the sarcolemmal Na/K ATPase and glutathione (Haddock et al., 1990). The application of GSH (O.l-l.OmM) induces a concentration-dependent increase in the activity of a bovine isolated ventricular Na/K ATPase preparation (determined by the ouabain-sensitive hydrolysis of ATP to release inorganic phosphate). In the presence of 1 mM GSH there was a 38% stimulation of activity compared to untreated control... 

The most extensive evidence that supports a role for free radicals in pathological conditions of the brain is provided by studies on experimental models of cerebral ischaemia/reperfusion. Although a burst of free-radical production occurs during the reperfusion phase after temporary cerebral ischaemia, the contribution of this radical burst to brain cell death can not be directly quantified. Perhaps the best way to quantify the contribution of free radicals to brain damage after ischaemia/ reperfusion is to assess damage after treatment with free-radical scavengers or antioxidants. Numerous studies have been reported where free-radical scavengers/ antioxidants have been used to try to ameliorate brain... 

The importance of iron in ischaemia-reperfusion injury through generation of ODFRs via the Haber-Weiss... 

Although these data provided indirect evidence of iron involvement in ischaemia-reperfusion injury in kidneys and the combined administration of DFX and indomethacin had proved beneficial in actual survival experiments (Gower etal., 1989a), we still felt fhistrated by our inability to generate more direct evidence. At that time, information was just emerging that a small pool of intracellular iron was available in catalytic form as chelates... 

Increased levels of cytosolic calcium could potentiate ischaemia-reperfusion injury in several ways. For example, conversion of xanthine dehydrogenase to xanthine oxidase may be catalysed by a calcium-dependent protease (McCord, 1985). However, because it has been so difficult to demonstrate the presence of xanthine... 

Granger, D.N., Benoit, J.N., Suzuki, M. and Grisham, M.B. (1989). Leukocyte adherence to venular endothefium during ischaemia-reperfusion. Am. J. Physiol. G683-688. 

The theory underlying the pathophysiology of ischaemia-reperfusion injury, and the role of free radicals in this process has been discussed in detail above. The human colon contains relatively little XO (Parks and Granger, 1986) and so the arguments supporting a role for this enzyme in the pathogenesis of small bowel... 

Adkinson, D., Hollwarth, M.E., Benoit, J.N., Parks, D.A., McCord, J.M. and Granger, D.N. (1986). Role of free radicals in ischaemia-reperfusion injury to the liver. Acta Physiol. Scand. 548 (Suppl.), 101-107. 

Jaeschke, H., Farhood, A. and Smith, C.W. (1990). Neutrophils contribute to ischaemia/reperfusion injury in rat liver in vivo. FASEB J. 4, 3355-3359. 

Kitahora, T. and Guth, P.H. (1991). Ischaemia-reperfusion induced gastric mucosal microcirculatory alterations in the rat. Microcirc. Endothel. Lymphatics 7, 133-138. 

Koo, A., Komatsu, H., Tao, G., Inoue, M., Guth, P.H. and Kaplowitz, (1991). Contribution of no-reflow phenomenon to hepatic injury after ischaemia-reperfusion evidence for a role for superoxide anion. Hepatolt, 15, 507-514. 

Murthy, S., Qi, Q-H. (1992). Direct evidence for ischaemia-reperfusion injury (R/1) in the rat proximal colon. Gastroenterology 102, A669. 

Osborne, D.L., Carter, P.R., Aw, T.Y. and Kvietys, P.R. (1992). Attenuation of ischaemia/reperfusion injury by a previous ischaemic insult. Gastroenterology 102, A231. 

Parks, D.A. and Granger, D.N. (1988). Ischaemia-reperfusion injury a radical view. Hepatology 8, 680-682. 

Pitt, R.M., McKelvey, T.G., Saenger, J.S., Shah, A.K., Jones, H.P., Manci, E.A. and Powell, R.W. (1991). A tungsten-supplemented diet delivered by transplacental and breastfeeding routes lowers intestinal xanthine oxidase activity and affords cytoprotection in ischaemia-reperfusion injury to the small intestine. J. Paediatr. Suig. 26, 930-935. 

Stein, H.J., Oosthuizen, M.M., Hinder, R.A. and Lamprechts, H. (1991). Oxygen free radicals and glutathione in hepatic ischaemia/reperfusion injury. J. Surg. Res. 50, 398-402. 

Walker, P.M. (1991). Ischaemia/reperfusion injury in skeletal muscle. Ann. Vase. Surg. 5, 399—402. 

As stated at the beginning of this article, the liver is the most intensively studied animal tissue in biochemistry. In the context of the role of free radicals in human diseases, the liver is not obviously at centre stage, since heart disease and cancer are more important in the industrialized world than, for example, cirrhosis. Free-radical biochemistry of the liver will remain a fertile area of work, however, not least because so many original ideas and techniques are developed there and then applied to the study of other tissues. The increasing use of liver transplantation, following the acceptance of kidney and heart transplants as almost routine, will surely increase the interest in the study of ischaemia-reperfusion injury in... 

Omar, B., McCord, J. and Downey, J. (1991). Ischaemia reperfusion. In Oxidative Stress Oxidants and Antioxidants (ed. H. Sies) pp. 493-528. Academic Press, London. 

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