The effect of allopurinol on interstitial purine metabolism and tissue damage in skeletal muscle I-R injury.
OBJECTIVE
Many studies show that allopurinol can reduce skeletal muscle I-R (ischemia-reperfusion) injury, but the mechanism of the effect is still unclear and some studies suspect the effect. In this study, we determined whether allopurinol really reaches to reperfused muscle and reduces tissue injury by inhibiting xanthine oxidase or not.


METHODS
In this study, microdialysis method combined with HPLC (high performance liquid chromatography) were employed and purines, MDA (malondialdehyde), allopurinol in gracilis muscle were measured continuously in I-R injury model of canine gracilis muscle. The effect was compared between Group N (no treatment: n=8), Group P (pre-ischemic treatment: n=8) and Group R (pre-reperfusion treatment: n=8).


RESULTS
Allopurinol reduced the increase of xanthine, uric acid, MDA in the muscle and CPK in blood effluent from gracilis muscle after reperfusion. Tissue protecting effect of allopurinol was more effective in group R than in group P.


CONCLUSIONS
By continuous measurement of purines, allopurinol and MDA in canine gracilis muscle during 5 hr ischemia and 2 hr reperfusion, it was proved that allopurinol was delivered to reperfused skeletal muscle and reduced I-R injury by inhibiting xanthine oxidase.
Asami
A
A
Department of Surgery, School of Medicine, Keio University, Tokyo, Japan.
Orii
M
M
Shirasugi
N
N
Yamazaki
M
M
Akiyama
Y
Y
Kitajima
M
M
D000493:Allopurinol / Q000627:therapeutic use*; D000818:Animals; D002851:Chromatography, High Pressure Liquid; D003402:Creatine Kinase / Q000378:metabolism; D004285:Dogs; D004791:Enzyme Inhibitors / Q000627:therapeutic use*; D005110:Extracellular Space / Q000378:metabolism; D005260:Female; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D017551:Microdialysis; D018482:Muscle, Skeletal / Q000098:blood supply* / Q000378:metabolism; D011687:Purines / Q000378:metabolism*; D015427:Reperfusion Injury / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D013997:Time Factors; D014969:Xanthine Oxidase / Q000037:antagonists & inhibitors*
D004791:Enzyme Inhibitors; D011687:Purines; D008315:Malondialdehyde; D000493:Allopurinol; D014969:Xanthine Oxidase; D003402:Creatine Kinase