Xanthine oxidase mediates cyclic flow variations in a canine model
of coronary arterial thrombosis.
Kuwano, Kazunori, Hisao Ikeda, Tameo Oda, Hiroshi Nakayama, Yoshinori
Koga, Hironori Toshima, and Tsutomu Imaizumi.
Third Department of Internal Medicine and Medical Center, Kurume
University School of Medicine, Kurume, 830 Japan
APStracts 2:0550H, 1995.
We investigated the hypothesis that xanthine oxidase (XO) mediates
platelet aggregation and cyclic flow variations (CFVs) in stenosed
canine coronary arteries. CFVs were produced by an external
constrictor placed at the site of the coronary artery with the
injured endothelium. The severity of CFVs was evaluated by a pulsed
Doppler flow probe. If CFVs developed, dogs intravenously received
allopurinol, a specific XO inhibitor. The transcardiac gradient
(difference between the coronary vein and left atrium) of purine
metabolites was determined during CFVs and after allopurinol
administration. Allopurinol significantly reduced CFVs (from 8 1 to 1
1 cycles/hour, p<0.01, n=14), whereas saline did not (from 8 1
to 7 1 cycles/hour, n=7). In 7 dogs with CFVs, the transcardiac
gradient of xanthine and uric acid concentrations significantly
increased after the establishment of CFVs and significantly decreased
after the administration of allopurinol. In vitro platelet studies
showed that XO enhanced (from 30.9 2.0 to 47.6 1.5%, p<0.0001,
n=10) and allopurinol inhibited ADP-induced platelet aggregation
(from 48.3 1.3 to 24.8 1.5%, p<0.0001, n=10). Our results
indicate that allopurinol inhibits platelet aggregation in vitro and
provides a protection against CFVs in vivo. Thus, XO may be an
important mediator in this model.
Received 23 October 1995; accepted in final form 28 November 1995
APS Manuscript Number H988-5.
Article publication pending Am. J. Physiol. (Heart Circ. Physiology).
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 8 December 95