Myocardial release of hypoxanthine and urate during angioplasty
Oxygen free radicals have been implicated in ageing, oncogenesis and atherogenesis , One potential source is xanthine oxidase, the oxyradical-producing form of xanthine oxidoreductase. This enzyme catabolizes the high-energy-phosphate metabolites hypoxanthine and xanthine to urate (Fig. 1). Ischemia converts the native form of the enzyme, xanthine reductase, to xanthine oxidase . During reperfusion oxygen is available for the production of superoxide and hydroxyl radicals [3, 4], both of which are strongly suspected to cause tissue damage [3, 5–7]. Xanthine oxidoreductase activity is present in the myocardium of a number of species , but its presence in human heart is controversial. In autopsy material several authors measured high xanthine oxidoreductase activity [9, 10]. Using histochemical techniques, Jarasch and coworkers found large amounts of the enzyme in human heart endothelium . On the other hand, several authors reported very low to undetectable xanthine oxidoreductase activity in human heart [12–14]. We present evidence that the heart of (a number of) cardiac patients produces significant amounts of urate. Thus xanthine oxidoreductase may be active in the human heart in vivo.
KeywordsLeave Anterior Descend Xanthine Oxidase Human Heart Xanthine Dehydrogenase Urate Concentration
Unable to display preview. Download preview PDF.
- 1.Hearse DJ, Manning AS, Downey JM, Yellon DM (1986) Xanthine oxidase: a critical mediator of myocardial injury during ischemia and reperfusion? Acta Physiol Scand 548 (Suppl): 65 - 78.Google Scholar
- 2.McCord JM (1984) Are free radicals a major culprit? In: Hearse DJ, Yellon DM (eds) Therapeutic Approaches to Myocardial Infarct Size Limitation, pp. 209 - 218 New York: Raven PressGoogle Scholar
- 5.England MD, Cavarocchi NC, O’Brien JF, Sollis V, Pluth JR, Orszulak TA, Kaye MP, Schaff HV (1986) Influence of antioxidants (mannitol and allopurinol) on oxygen free radical generation during and after cardiopulmonary bypass. Circulation 74 (Suppl 3): 134 - 137Google Scholar
- 10.Wajner M, Harkness RA (1988) Distribution of xanthine dehydrogenase and oxidase activities in human and rabbit tissues. Biochem Soc Trans 16: 358 - 359Google Scholar
- 11.Jarasch ED, Bruder G, Heid HW (1986) Significance of xanthine oxidase in capillary endothelial cells. Acta Physiol Scand 548 (Suppl): 39 - 46Google Scholar
- 15.Nelson JA, McDaniel HG, Maurer BJ, Hill WA, James TN (1977) Apparent uptake of purines by the human heart ( Letter to the ed ). N Eng J Med 296: 115Google Scholar
- 17.Scheibe B, Bernt E, Bergmeyer H-U (1974) Uric acid. In: Bergmeyer H-U (ed) Methods of Enzymatic Analysis, pp. 1951 - 1958 New York: Academic PressGoogle Scholar
- 19.Edlund A, Berglund B, Van Dorne D, Kaijser L, Nowak J, Patrono C, Sollevi A, Wennmalm A (1985) Coronary flow regulation in patients with ischemic heart disease: release of purines and prostacyclin and the effect of inhibitors of prostaglandin formation. Circulation 71: 1113 - 1120PubMedCrossRefGoogle Scholar
- 21.Downey JM, Chambers DE, Miura T, Yellon DM, Jones D (1986) Allopurinol fails to limit infarct size in a xanthine oxidase deficient species (abstr). Circulation 74 (Suppl 2): 372Google Scholar
- 22.Podzuweit T, Braun W, Müller A, Schaper W (1986) Arrhythmias and infarction in the ischemic pig heart are not mediated by xanthine oxidase-derived free oxygen radicals (abstr). Circulation 74 (Suppl 2): 346Google Scholar