Effect of allopurinol on the survival of experimental pig flaps.
Allopurinol has been reported to improve cell survival in a variety of conditions, including the ischemia-reperfusion injury occurring in skin flaps. It has been suggested that the beneficial effect of allopurinol on rat skin flaps is through blockage of xanthine oxidase-generated oxygen-derived free radicals. We have previously reported on the lack of xanthine oxidase activity in the skin of humans and pigs as compared with that of rats. This current study attempts to improve skin and myocutaneous flap survival in pigs in two separate experiments using allopurinol. In the first experiment, a suspension of 50 mg/kg (N = 12) allopurinol resulted in no significant difference in the survival of control and treated flaps. Because of the negative results in the first experiment, a second experiment was designed making several changes. The length of the global ischemic insult was reduced from 8 to 6 hours, and allopurinol was administered as a solution of 300 mg/kg (N = 14). This higher dose is expected to produce complete inhibition of xanthine oxidase in this animal model. These changes resulted in three operative deaths, no improvement in skin-flap survival, and a decrease in myocutaneous flap survival. Allopurinol's therapeutic effectiveness and its mechanism of action in an ischemia-reperfusion injury model lacking xanthine oxidase activity are discussed.
Picard-Ami
L A
LA
Microsurgical Research Laboratory, Royal Victoria Hospital, Montreal, P.Q., Canada.
MacKay
A
A
Kerrigan
C L
CL
D000493:Allopurinol / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology*; D000818:Animals; D005260:Female; D006085:Graft Survival / Q000187:drug effects*; D009336:Necrosis; D011897:Random Allocation; D015427:Reperfusion Injury / Q000201:enzymology; D013524:Surgical Flaps / Q000473:pathology / Q000502:physiology*; D013552:Swine; D014969:Xanthine Oxidase / Q000037:antagonists & inhibitors / Q000378:metabolism
D000493:Allopurinol; D014969:Xanthine Oxidase