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78 CRITICAL CARE FOCUS: BLOOD AND BLOOD TRANSFUSION Acknowledgements I am indebted to all the haemoglobin and myoglobin researchers at the University of Essex for their contribution to the work presented in this article, in particular Jackie Dunne, Brandon Reeder, Dimitri Svistunenko, Peter Nicholls and Mike Wilson. References 1 Babcock GT,Wikstrsˇm M. Oxygen activation and the conservation of energy in cell respiration. Nature 1992;356:301–9. 2 Alderton WK, Cooper CE, Knowles RG. Nitric oxide synthases: structure, function and inhibition. Biochem J 2001;357:593–615. 3 Kennedy JG, O’Grady P, McCarthy DR, et al. An investigation into the role of oxygen free radical scavengers in preventing polymethylmethacrylate-induced necrosis in an osteoblast cell culture. Orthopedics 2000;23:481–5. 4 Cooper CE. Ferryl iron and protein free radicals. In: Rice-Evans CA, Burdon RH, eds. Free Radical Damage and its Control. Amsterdam: Elsevier 1994, 65–109. 5 Alayash AI, Patel RP, Cashon RE. Redox reactions of hemoglobin and myoglobin: biological and toxicological implications. Antioxid Redox Signal 2001;3:313–27. 6 Svistunenko DA, Patel RP,Voloshchenko SV,Wilson MT.The globin-based free radical of ferryl hemoglobin is detected in normal human blood. J Biol Chem 1997;272:7114–21. 7 Holt SGR, Moore K. Pathogenesis of renal failure in rhabdomyolysis: the role of myoglobin. Exp Nephrol 2000;8:72–6. 8 Alayash AI. Hemoglobin-based blood substitutes and the hazards of blood radicals. Free Rad Res 2000;33:341–8. 9 Holt SGR. Rhabdomyolysis. In: Galley HF, ed. Critical Care Focus, Volume 1: Renal Failure. London: BMJ Books/Intensive Care Society 1999, 15–20. 10 Moore KP, Holt S, Patel RP, et al. A causative role for redox cycling of myoglobin and its inhibition by alkalinization in the pathogenesis and treatment of rhabdomyolysis-induced renal failure. J Biol Chem 1998;273:31731–7. 11 Holt S, Reeder B,Wilson M, et al. Increased lipid peroxidation in patients with rhabdomyolysis. Lancet 1999;353:1241. 12 Reeder BJ, Wilson MT. The effects of pH on the mechanism of hydrogen peroxide and lipid hydroperoxide consumption by myoglobin: a role for the protonated ferryl species. Free Rad Biol Med 2001;30:1311–18. 13 Sanders KE, Ackers G, Sligar S. Engineering and design of blood substitutes. Curr Opin Struct Biol 1996;6:534–40. 14 Winslow RM. Alpha-alpha-crosslinked hemoglobin: was failure predicted by preclinical testing? Vox Sang 2000;79:1–20. 15 D’Agnillo F, Alayash AI. Site-specific modifications and toxicity of blood substitutes.The case of diaspirin cross-linked hemoglobin. Adv Drug Deliv Rev 2000;40:199–212. 16 Dunne J, Svistunenko DA, Alayash AI, Wilson MT, Cooper CE. Reactions of cross-linked methaemoglobins with hydrogen peroxide. Adv Exp Med Biol 1999;471:9–15. 17 Privalle C, Talarico T, Keng T, DeAngelo J. Pyridoxalated hemoglobin polyoxyethylene: a nitric oxide scavenger with antioxidant activity for the treatment of nitric oxide-induced shock. Free Rad Biol Med 2000;28:1507–17. 79 RADICAL REACTIONS OF HAEM PROTEINS 18 Eich RF, Li TS, Lemon DD, et al. Mechanism of NO-induced oxidation of myoglobin and hemoglobin. Biochemistry 1996;35:6976–83. 19 Gross SS, Lane P. Physiological reactions of nitric oxide and hemoglobin: a radical rethink. Proc Natl Acad Sci USA 1999;96:9967–9. 20 Doherty DH, Doyle MP, Curry SR, et al. Rate of reaction with nitric oxide determines the hypertensive effect of cell-free hemoglobin. Nat Biotechnol 1998;16:672–6. 21 Rioux F, Harvey N, Moisan S, et al. Nonpeptide endothelin receptor antagonists attenuate the pressor effect of diaspirin-crosslinked hemoglobin in rat. Can J Physiol Pharmacol 1999;77:188–94. 22 Fischer SR, Traber DL. L-arginine and endothelin receptor antagonist bosentan counteract hemodynamic effects of modified hemoglobin. Shock 1999;11:283–90. 23 Jia L, Bonaventura C, Bonaventura J, Stamler JS. S-Nitrosohemoglobin – a dynamic activity of blood involved in vascular control. Nature 1996;380:221–6. . Pharmacol 199 9;77:188 94 . 22 Fischer SR, Traber DL. L-arginine and endothelin receptor antagonist bosentan counteract hemodynamic effects of modified hemoglobin. Shock 199 9;11:283 90 . 23 Jia. material 82 INDEX colorectal cancer leucocyte-depleted blood transfusion 17 post-operative infections and transfusion 14–15 tumour recurrence and transfusion 15–16 VEGF and metastases 16–17 complement activation. autologous blood 16 leucocyte-depleted blood 17 infections DIC 28 post-operative 13–14 blood transfusion and 14–15 leucofiltration and 20 see also sepsis inflammation interaction with coagulation 39 40 protein

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