The role of mast cells in ischaemia-reperfusion injury in murine skeletal muscle.
To determine the role of mast cells in ischaemia-reperfusion (IR) injury to skeletal muscle, W(f)/W(f) mast cell-deficient and their corresponding wild-type mice were subjected to 70 min tourniquet ischaemia and 24 h reperfusion. As measured by nitroblue tetrazolium (NBT) staining, muscle viability was 9% in wild-type and 94% in mast cell-deficient animals (p<0.001). Assay of residual lactate dehydrogenase activity within the injured muscle (p<0.05) and histological examination confirmed the greater muscle necrosis in treated wild-type than in treated mast cell-deficient mice. There was no significant difference in the degree of neutrophil infiltration, tissue myeloperoxidase content or water content of IR-injured muscle in the two mouse phenotypes. To determine further the role of mast cells in IR injury, wild-type mice were treated 30 min prior to reperfusion with an intraperitoneal dose of either saline or the mast cell-stabilizing agent lodoxamide trometamol (2.5, 7.5, 25 or 75 mg/kg). Twenty-four hours after removal of the tourniquet, saline-treated gastrocnemius muscle had a mean viability of 14% compared with 28% (p<0.05) and 48% (p<0.01) after 25 mg/kg and 75 mg/kg of lodoxamide treatment, respectively. The ability of lodoxamide to stabilize mast cells was confirmed by histological examination. Ischaemic muscle reperfused for 1 h showed much less degranulation of mast cells in mice pretreated with lodoxamide (50 mg/kg) than in saline-treated controls. These findings suggest that mast cells are a major source of mediators of necrosis in IR injury to skeletal muscle.
Bernard O'Brien Institute of Microsurgery, St Vincent's Hospital Melbourne, 42 Fitzroy Street, Fitzroy, Victoria 3065, Australia.
B
B
Lazarus
A
A
Messina
J E
JE
Barker
J V
JV
Hurley
R
R
Romeo
W A
WA
Morrison
K R
KR
Knight
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000627:therapeutic use; D007202:Indicators and Reagents; D007770:L-Lactate Dehydrogenase / Q000502:physiology; D008407:Mast Cells / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018482:Muscle, Skeletal / Q000503:physiopathology*; D009580:Nitroblue Tetrazolium; D010072:Oxamic Acid / Q000031:analogs & derivatives / Q000627:therapeutic use; D015427:Reperfusion Injury / Q000503:physiopathology*; D014022:Tissue Survival
D000894:Anti-Inflammatory Agents, Non-Steroidal; D007202:Indicators and Reagents; D009580:Nitroblue Tetrazolium; D007770:L-Lactate Dehydrogenase; D010072:Oxamic Acid; C021702:lodoxamide ethyl