AJP - Heart and Circulatory Physiology, Vol 259, Issue 6 1655-H1659, Copyright © 1990 by American Physiological Society
No conversion of xanthine dehydrogenase to oxidase in canine cerebral ischemia
R. B. Mink, A. J. Dutka, K. K. Kumaroo and J. M. Hallenbeck
Diving Medicine Department, Naval Medical Research Institute, Bethesda 20889-5055.
Xanthine oxidase (XO) has been implicated as a source of free radicals
mediating ischemia-reperfusion injury. Conversion of the non-free radical
generating xanthine dehydrogenase (XD) to the free radical producing XO
during ischemia has been demonstrated in several tissues. We examined the
irreversible conversion of XD to XO in the dog brain after ischemia and
after ischemia and reperfusion. Under pentobarbital sodium anesthesia and
by use of a cerebrospinal fluid compression model of global cerebral
ischemia, dogs were subjected to 30 min of ischemia (n = 8) or 30 min of
ischemia and 60 min of reperfusion (n = 8). A cerebral perfusion pressure
of 60 mmHg was maintained during reperfusion. Eight control dogs were not
subjected to ischemia. After the dogs were killed their brains were rapidly
removed and frozen in liquid nitrogen. XO and XD + XO activities were
measured with a radioassay utilizing 8-[14C]hypoxanthine and separating
substrate and products by thin-layer chromatography. Total XD + XO activity
was significantly (P less than 0.05) decreased after ischemia and
reperfusion (35.6 +/- 8.0 vs. 60.8 +/- 20.8 nmol.min-1.g protein-1 in
controls, means +/- SD) but not after ischemia alone (48.2 +/- 20.4).
XO/(XD + XO) was approximately 20% in all three groups. Irreversible XD to
XO conversion is not an important mechanism leading to early tissue injury
in global cerebral ischemia.
