Allopurinol prevents ischaemia-dependent haemorheological changes
Pre-treatment with allopurinol is able markedly to attenuate the deterioration in blood viscosity (BV) and whole blood filterability (WBF) that occurs after ischaemia during exercise. It also reduces the exercise-induced increase in serum oxidase activity, although this action is slightly less effective in peripheral obliterative arterial disease (POAD) patients.
Conversely, allopurinol is completely ineffective in modifying haemorheological parameters in vitro, and it does not affect superoxide anion generation or enzyme release from neutrophils stimulated in vitro with formyl-methionyl-leucyl-phenylalanine (FMLP).
It is suggested that allopurinol may attenuate changes in BV and WBF by affecting xanthine-oxidase-dependent free radical formation in tissues.
Key wordsischaemia haemorheology allopurinol xanthine oxidase blood viscosity free radicals neutrophil enzymes superoxide
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- 1.Babior BM, Curnutte JT, Mc Murrich BJ (1976) The particulate superoxide-forming system from human neutrophils: Properties of the system and further evidence supporting its participation in the respiratory burst. J Clin Invest 58: 989–996Google Scholar
- 2.De Wall RA, Vasko KA, Stanley EC, Kazdi P (1971) Responses of the ischemic myocardium to allopurinol. Am Heart J 82: 362–370Google Scholar
- 3.Dintenfass L (1981) Blood viscosity, red cell rigidity and arterial blood pressure in patients with severe coronary occlusion or chest pain. Effect of submaximal exercise. Clin Haemorheol 1: 121–134Google Scholar
- 4.Di Perri T (1979) Rheological factors in vascular disorders. Angiology 30: 480–486Google Scholar
- 5.Di Perri T, Forconi S (1984) Le sindromi da iperviscosità ematica: fisiologia patologia e clinica. Pozzi L. Edizioni — RomaGoogle Scholar
- 6.Di Perri T, Guerrini M, Laghi Pasini F, Acciavatti A, Pieragalli D, Galigani C, Capecchi PL, Orrico A, Franchi M, Blardi P (1985) Haemorheological factors in the pathophysiology of acute and chronic cerebrovascular disease. Cephalalgia 2 [Suppl]: 71–77Google Scholar
- 7.Dormandy JA, Hoare E, Colley J, Arrowsmith DE, Dormandy TL (1973) Impaired haemodynamic rheological and biochemical findings in 126 patients with intermittent claudication. Br Med J 4: 576–582Google Scholar
- 8.Fantone JC, Ward PA (1982) Role of oxygen-derived free radicals and metabolites in leukocyte-dependent inflammatory reactions. Am J Pathol 107: 397–418Google Scholar
- 9.Forconi S, Biasi G, Guerrini M, Ravelli P, Rossi C, Ferrozzi G, Pecchi S (1979) Arterial and venous blood viscosity in ischemic lower limbs of peripheral obliterative arterial disease patients. J Cardiovasc Surg 20: 379–393Google Scholar
- 10.Forconi S, Guerrini M, Rossi C, Pecchi S (1979) Local increase of blood viscosity during cold induced Raynaud's phenomenon. Vasa 8: 116–120Google Scholar
- 11.Forconi S, Pieragalli D, Acciavatti A, Galigani C, Materazzi M, Ralli L, Franchi M, Laghi Pasini F, Messa GL, Bianciardi A, Rigato M, Blardi P, Cappelli R, Guerrini M, Di Perri T (1986) Blood hyperviscosity syndrome of ischaemizing vascular diseases. Clin Haemorheol 6: 215–227Google Scholar
- 12.Granger DN, McCord JM, Parks DA, Hollwarth ME (1986) Xanthine-oxidase inhibitors attenuate ischaemia-induced vascular permeability changes in the cat intestine. Gastroenterology 90: 80–84Google Scholar
- 13.Jarasch ED, Bruder G, Heid HW (1986) Significance of xanthine-oxidase in capillary endothelial cells. Acta Physiol Scand 548 [Suppl]: 39–46Google Scholar
- 14.Jones HP, Grisham MB, Bose SK, Shannon VA, Scott A, McCord JM (1985) Effect of allopurinol on neutrophil superoxide production, chemotaxis or degranulation. Biochem Pharmacol 34: 3673–3676Google Scholar
- 15.Kathuis RJ, Granger DN, Townsley MI, Taylor AE (1985) The role of oxygen-derived free radicals in ischaemia-induced increases in canine skeletal muscle vascular permeability. Circ Res 57: 599–609Google Scholar
- 16.Lowe GDO, Drummond MM, Lorimer AR, Hutton I, Forbes CD, Prentice CRM, Barbene IJC (1980) Relation between extent of coronary artery disease and blood viscosity. Br Med J 280: 673–673Google Scholar
- 17.Lowe GDO (1986) Blood rheology in arterial disease. Clin Sci 71: 137–146Google Scholar
- 18.McPhail LC, De Chatelet LS, Shirley PS (1976) Further characterization of NADPH oxidase activity of human polymorphonuclear leukocytes. J Clin Invest 58: 774–780Google Scholar
- 19.Manfredi JP, Holmes EW (1985) Purine salvage pathways in myocardium. Ann Rev Physiol 47: 691–705Google Scholar
- 20.Matthews SB, Campbell AK (1984) Neutrophil activation after myocardial infarction. Lancet 2: 756–757Google Scholar
- 21.Nakamura M, Baxter CR, Masters BJ (1981) Simultaneous demonstration of phagocytosis-connected oxygen consumption and corresponding NAD(P)H oxidase activity: direct evidence for NADPH as the predominant electron donor to oxygen in phagocyting neutrophils. Biochem Biophys Res Commun 98: 743–751Google Scholar
- 22.Nakao M (1962) A direct relationship between ATP level and in vivo viability of erythrocytes. Nature 194: 877–878Google Scholar
- 23.Paller MS, Hoidal JR, Ferris TF (1984) Oxygen free radicals in ischaemic acute renal failure in the rat. J Clin Invest 74: 1156–1164Google Scholar
- 24.Reid HL, Dormandy JA, Barnes AJ, Lock PJ, Dormandy TL (1976) Impaired red cell deformability in peripheral vascular disease. Lancet 1: 666–668Google Scholar
- 25.Tubaro E, Lotti B, Santiangeli C, Cavallo G (1980) Xanthine-oxidase: An enzyme playing a role in the killing mechanism of polymorphonuclear leukocytes. Biochem Pharmacol 29: 3018–3020Google Scholar
- 26.Tritsch GL, Niswander PW (1983) Modulation of macrophage superoxide release by purine metabolism. Life Sci 32: 1359–1362Google Scholar
- 27.Werns W, Shea MJ, Mitsos SE, Dysko RC, Fantone JC, Schark MA, Abrams GD, Pitt B, Lucchesi BR (1984) Reduction of the size of infarction by allopurinol in the ischemic-reperfused canine heart. Circulation 73: 518–524Google Scholar