Allopurinol pretreatment improves evoked response recovery following global cerebral ischemia in dogs.
The reperfusion of previously ischemic tissue may lead to the formation of highly reactive free radicals that promote tissue injury. Xanthine oxidase has been implicated as one source of these free radicals. We examined the role of xanthine oxidase in brain injury using a cerebrospinal fluid compression model of global cerebral ischemia with 15 minutes of ischemia and 4 hours of reperfusion. Seven dogs were pretreated with the xanthine oxidase inhibitor allopurinol (50 mg/kg for 5 days). Neurophysiological recovery was monitored with cortical somatosensory evoked potentials. As an attempt to correlate brain recovery with the mechanism of protection, free brain malondialdehyde was measured at the end of reperfusion by high-performance liquid chromatography. Brain water content was measured by wet-dry weights. Compared with seven untreated control dogs, allopurinol pretreatment significantly improved recovery of somatosensory evoked potentials after 4 hours of reperfusion. However, the amount of free malondialdehyde in the allopurinol-treated dogs was 32% greater than that in the controls. Brain water content was similar in the two groups. These results suggest that xanthine oxidase contributes to brain injury after ischemia and reperfusion. However, tissue damage caused by xanthine oxidase may be mediated through mechanisms other than free radical production.
Mink
R B
RB
Diving Medicine Department, Naval Medical Research Institute, Bethesda, Md 20814-5055.
Dutka
A J
AJ
Hallenbeck
J M
JM
D000493:Allopurinol / Q000494:pharmacology* / Q000627:therapeutic use; D000818:Animals; D002545:Brain Ischemia / Q000201:enzymology / Q000378:metabolism* / Q000503:physiopathology; D002560:Cerebrovascular Circulation; D004285:Dogs; D005073:Evoked Potentials, Somatosensory / Q000187:drug effects; D015427:Reperfusion Injury / Q000378:metabolism / Q000517:prevention & control; D014969:Xanthine Oxidase / Q000494:pharmacology*
D000493:Allopurinol; D014969:Xanthine Oxidase