Influence of postischemic administration of oxyradical antagonists on ischemic injury to rabbit skeletal muscle.
The aim of this study was to determine whether the administration of free radical antagonists, immediately before and during the early minutes of reperfusion, improves muscle survival 24 hr after a period of ischemia. Rabbit rectus femoris muscles were isolated, made ischemic for 3 1/2 hr and treated with either desferrioxamine (DFX), an Fe3+ chelator, superoxide dismutase and catalase (SOD & CAT), which quench superoxide and hydrogen peroxide, or allopurinol, an inhibitor of xanthine oxidase (XO). After 24 hr reperfusion, muscle viability (+/-s.e.m.), measured by the nitro blue tetrazolium (NBT) vital staining technique, was 41.6 +/- 11.3% for saline-treated ischemic controls, 30.6 +/- 7.6% for DFX-treated, 46.7 +/- 10.3% for SOD & CAT-treated, and 43.3 +/- 9.5% for allopurinol-treated muscles. None of the treated groups differed significantly from the ischemic control group. Tissue myeloperoxidase, ATP and reduced glutathione levels, and plasma lactate dehydrogenase (LDH) and aspartate transaminase (AST) levels were increased by ischemia and reperfusion in all groups, but the changes did not differ between the treatment groups. Levels of XO in the rabbit muscle were determined and found to be very low in both normal and postischemic muscle. As XO is the target enzyme of allopurinol, its absence provides a basis for the lack of effect of this agent. However, it is not clear why DFX and SOD & CAT had no protective effect.
Hickey
M J
MJ
Bernard O'Brien Institute of Microsurgery, St. Vincent's Hospital, Fitzroy, Victoria, Australia.
Knight
K R
KR
Lepore
D A
DA
Hurley
J V
JV
Morrison
W A
WA
D000493:Allopurinol / Q000627:therapeutic use; D000818:Animals; D002374:Catalase / Q000627:therapeutic use; D003676:Deferoxamine / Q000627:therapeutic use; D004791:Enzyme Inhibitors / Q000627:therapeutic use; D005260:Female; D016166:Free Radical Scavengers / Q000627:therapeutic use*; D008297:Male; D018482:Muscle, Skeletal / Q000098:blood supply* / Q000378:metabolism; D011817:Rabbits; D015427:Reperfusion Injury / Q000188:drug therapy* / Q000378:metabolism; D013482:Superoxide Dismutase / Q000627:therapeutic use; D013997:Time Factors; D014969:Xanthine Oxidase / Q000037:antagonists & inhibitors
D004791:Enzyme Inhibitors; D016166:Free Radical Scavengers; D000493:Allopurinol; D002374:Catalase; D013482:Superoxide Dismutase; D014969:Xanthine Oxidase; D003676:Deferoxamine