Absence of xanthine oxidoreductase activity in human myocardium.
OBJECTIVE
The aim was to examine whether or not xanthine oxidase activity may be a significant source of oxygen derived free radicals in the human heart.


METHODS
Xanthine oxidoreductase activity of human myocardium was assayed in vitro. In addition, tests were performed to assess whether or not endogenous inhibitors of the enzyme were present in myocardial homogenates. The enzyme assay was based on high performance liquid chromatography with electrochemical and/or radiochemical detection of hypoxanthine, xanthine, and urate.


METHODS
Measurements were done on (a) isolated perfused rat myocardia and (b) left ventricular needle biopsies and papillary muscles obtained during elective cardiac surgery (chiefly aortic and/or mitral valve replacement and aortocoronary bypass) (n = 105 patients).


RESULTS
Homogenisation of human papillary muscles in buffer caused significant accumulation of hypoxanthine but not xanthine or urate. In addition, during incubation of crude myocardial homogenates with exogenous xanthine or hypoxanthine in the presence of NAD+ and/or O2 no production of urate was detected. Likewise, following aerobic incubation of papillary muscle homogenates with 14C-hypoxanthine neither 14C-xanthine nor 14C-urate were formed. Absence of xanthine oxidising activity was also observed with human papillary muscle extracts that were subjected to either ultrafiltration or gel filtration. In contrast, the rat heart was found to contain abundant xanthine oxidoreductase activity. The rat heart enzyme was inhibited by both allopurinol and oxypurinol but remained active when mixed with human papillary muscle homogenates.


CONCLUSIONS
These findings show absence of xanthine oxidase and xanthine dehydrogenase activities in human myocardium, indicating that xanthine oxidase is not a source of oxygen derived free radicals in the human heart.
Podzuweit
T
T
Max Planck Institute for Physiological and Clinical Research, Bad Nauheim, Germany.
Beck
H
H
Müller
A
A
Bader
R
R
Görlach
G
G
Scheld
H H
HH
D000293:Adolescent; D000328:Adult; D000368:Aged; D002648:Child; D002675:Child, Preschool; D002850:Chromatography, Gel; D002851:Chromatography, High Pressure Liquid; D005260:Female; D005609:Free Radicals; D006801:Humans; D008297:Male; D008875:Middle Aged; D009206:Myocardium / Q000201:enzymology*; D014462:Ultrafiltration; D014968:Xanthine Dehydrogenase / Q000378:metabolism; D014969:Xanthine Oxidase / Q000037:antagonists & inhibitors / Q000378:metabolism*
D005609:Free Radicals; D014968:Xanthine Dehydrogenase; D014969:Xanthine Oxidase