Xanthine oxidoreductase activity in perfused hearts of various species, including humans.

Abstract

Oxygen free radicals generated by xanthine oxidase have been implicated in cardiac damage. The activity of xanthine oxidase/reductase in adult rat heart is considerable. Its assay gives controversial results for other species, for example, rabbits and humans. Therefore, we perfused isolated hearts of various species, including explanted human hearts, to measure the conversion of exogenous hypoxanthine to xanthine and urate. We assayed these purines with high-performance liquid chromatography. The apparent xanthine oxidoreductase activities, calculated as release of xanthine plus 2x urate, were (milliunits per gram wet weight, mean +/- SEM) mice 33 +/- 3 (n = 5), rats 28.5 +/- 1.4 (n = 9), guinea pigs 14.4 +/- 1.0 (n = 5), rabbits 0.59 +/- 0.09 (n = 5), pigs less than 0.1 (n = 6), humans 0.31 +/- 0.04 (n = 7), and cows 3.7 +/- 0.8 (n = 4). In rabbit heart the conversion of hypoxanthine to xanthine was slow, and that of xanthine to urate was even slower. On the other hand, guinea pig and human heart released little xanthine, indicating that xanthine breakdown exceeds its formation. We conclude that isolated perfused mouse, rat, guinea pig, and also bovine hearts show considerable xanthine oxidoreductase activity, contrasting rabbit, porcine, and diseased human hearts.

Kinetics of adenylate metabolism in human and rat myocardium

“…We found a very low activity in perfused diseased human hearts [28], agreeing with the results of others [see, e.g., [29,30]]. In rat heart we deter mined activity [31] and kinetic data for X O D with hypox anthine and xanthine as substrate [24].…”

Chronic xanthine oxidase inhibition prevents myofibrillar protein oxidation and preserves cardiac function in a transgenic mouse model of cardiomyopathy

“…There is significant variability in the reported detection of XO within the myocardium of certain mammalian species, including humans (7,28,35). The observed increase in XO activity in the current study is striking and certainly suggests that oxidative stress occurs in the early stages of heart failure.…”

Uric Acid and Survival in Chronic Heart Failure

“…For example, myocardial XO enzyme activity was found high in the dog 17 and rat 18 but low in the rabbit 19 and pig. 20 In humans, studies report myocardial XO activity to be either high, 21 low, 22 or undetectable. 23,24 Although there is some considerable evidence that suggests that the enzyme XO may indeed be expressed in the human myocardium, [25][26][27] we believe that the effect may be local.…”