Ischaemia-reperfusion injury in mouse skeletal muscle is reduced by N omega-nitro-L-arginine methyl ester and dexamethasone.
We have developed a model of ischaemia-reperfusion injury in C57BL/6 mice involving ischaemia for 0.5 to 2.5 h with an elastic tourniquet on one hind limb and reperfusion for 24 h, analogous to a well-established model of ischaemia-reperfusion injury in the rat. Viability was assessed in tissue homogenates of the gastrocnemius muscles from the affected and contralateral control limb by a triphenyl tetrazolium chloride dye reaction, measuring the activity of the oxidative mitochondrial enzymes. After 1.5 h ischaemia and 24 h reperfusion, viability in the ischaemic-reperfused limb was 13%, with the control muscle regarded as 100% viable. Significant improvements in viability to 86% (P < 0.05) and 56% (P < 0.05) were achieved, with administration 30 min prior to tourniquet release, of the nitric oxide (NO) synthase inhibitor nitro-L-arginine methyl ester (L-NAME, 30 mg/kg) and the anti-inflammatory glucocorticoid dexamethasone (2.5 mg/kg) respectively, with similar findings in the rat tourniquet model.
Knight
K R
KR
Bernard O'Brien Institute of Microsurgery, St. Vincent's Hospital, Fitzroy, Melbourne, Australia. knightkr@mail2.svhm.org.au
Zhang
B
B
Morrison
W A
WA
Stewart
A G
AG
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology / Q000627:therapeutic use*; D002470:Cell Survival / Q000187:drug effects; D003907:Dexamethasone / Q000494:pharmacology / Q000627:therapeutic use*; D004487:Edema / Q000503:physiopathology / Q000517:prevention & control; D004791:Enzyme Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018482:Muscle, Skeletal / Q000187:drug effects / Q000201:enzymology / Q000503:physiopathology*; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology / Q000627:therapeutic use*; D009580:Nitroblue Tetrazolium; D010085:Oxidative Phosphorylation / Q000187:drug effects; D009195:Peroxidase / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000503:physiopathology / Q000517:prevention & control*; D013778:Tetrazolium Salts
D000893:Anti-Inflammatory Agents; D004791:Enzyme Inhibitors; D013778:Tetrazolium Salts; D009580:Nitroblue Tetrazolium; C009591:triphenyltetrazolium; D003907:Dexamethasone; D009195:Peroxidase; D019331:NG-Nitroarginine Methyl Ester