The role of xanthine oxidase and xanthine dehydrogenase in skin ischemia.
The importance of sequential events which lead to skin necrosis has significant implications in trauma, vascular injury, and wound healing. In this series of experiments, we tested the hypothesis that xanthine oxidase (XO) activity was increased along an ischemic gradient of a skin flap and that the XO enzyme activity correlated with an increase in neutrophils. There were two animal groups in which the skin flaps were raised and assayed at 0, 1, or 6 hr. In the other group, they were created as bipedicle flaps for 7 days, before the distal attachment was divided and the tissue assayed. In the acutely raised flaps, some animals were treated with the XO inhibitor, allopurinol. Xanthine dehydrogenase (XD) and XO activity was measured with a fluorometric pterin assay and neutrophil concentration was measured using a myeloperoxidase marker. In this model, there was consistent skin necrosis in the distal end of the skin flap (48 +/- 8%). The data showed that both XD and XO activity in the distal ends was statistically significantly increased over the sham control or proximal ends of the skin flaps at 1 hr (P < 0.05). XO activity remained elevated in the distal ends at 6 hr. Allopurinol significantly reduced the neutrophil concentrations in the distal ends of the skin flaps when compared to untreated animals (P < 0.05). Moreover, allopurinol reduced skin necrosis to 12 +/- 1%. Preconditioning of the skin flap reduced the XO activity to sham control levels. The observations implicate XO activity as source of free radical injury in skin necrosis seen in random skin flaps.(ABSTRACT TRUNCATED AT 250 WORDS)
Rees
R
R
Department of Surgery, University of Michigan, Ann Arbor 48109.
Smith
D
D
Li
T D
TD
Cashmer
B
B
Garner
W
W
Punch
J
J
Smith
D J
DJ
D000493:Allopurinol / Q000494:pharmacology; D000818:Animals; D004305:Dose-Response Relationship, Drug; D006652:Histological Techniques; D007511:Ischemia / Q000201:enzymology*; D009195:Peroxidase / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012867:Skin / Q000098:blood supply*; D013524:Surgical Flaps; D013997:Time Factors; D014968:Xanthine Dehydrogenase / Q000378:metabolism / Q000502:physiology*; D014969:Xanthine Oxidase / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000502:physiology*
D000493:Allopurinol; D009195:Peroxidase; D014968:Xanthine Dehydrogenase; D014969:Xanthine Oxidase