Salvage of postischemic skeletal muscle by monoclonal antibody blockade of neutrophil adhesion molecule CD18.
Reperfusion of ischemic skeletal muscle is associated with neutrophil (PMN) adherence to damaged endothelium and PMN-mediated tissue destruction. Neutrophils may attach to endothelium through surface adhesive molecules, such as CD18. The purpose of this study was to determine whether monoclonal antibody blockade of CD18 would reduce skeletal muscle necrosis associated with ischemia and reperfusion. In rabbits, an entire hindlimb was rendered ischemic for 4 hr, followed by 48 hr of in vivo reperfusion. Animals were allocated to one of five treatment groups: ischemia/reperfusion without treatment (I/R controls), I/R plus treatment with the anti-CD18 antibody IB4 (end-ischemic 2 mg/kg dose), I/R plus treatment with an identical dose of isotype-matched control Ig, I/R plus anterior compartment fasciotomy, or I/R plus both IB4 and fasciotomy. After 48 hr of reperfusion anterior tibial muscle necrosis was assessed (by tetrazolium staining and computerized planimetry), wet:dry muscle weights (W:D) were determined, and muscle PMN sequestration was measured by myeloperoxidase (MPO) activity. IB4-treated animals exhibited markedly reduced muscle MPO activity, compared to untreated animals. Although all interventions reduced edema formation (W:D ratios), none did so significantly. IB4 treatment reduced muscle necrosis when used alone (to 28 +/- 7%, vs. 48% +/- 6% in untreated controls), however this was not statistically significant (P = 0.06).2+ Fasciotomy significantly reduced necrosis (to 22 +/- 2%, P < 0.05); however, the addition of IB4 to fasciotomy resulted in necrosis that was significantly lower than that after fasciotomy alone (12 +/- 4%, P < 0.05 vs fasciotomy group) and the least necrosis of any group.(ABSTRACT TRUNCATED AT 250 WORDS)
Petrasek
P F
PF
R. Fraser Elliot Vascular Surgery Research Laboratory, University of Toronto, Ontario, Canada.
Liauw
S
S
Romaschin
A D
AD
Walker
P M
PM
D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D015703:Antigens, CD / Q000276:immunology / Q000502:physiology*; D018821:CD18 Antigens; D005260:Female; D007511:Ischemia; D009132:Muscles / Q000098:blood supply* / Q000473:pathology; D009336:Necrosis; D009504:Neutrophils / Q000502:physiology; D009929:Organ Size; D009195:Peroxidase / Q000378:metabolism; D011817:Rabbits; D015427:Reperfusion Injury / Q000517:prevention & control*
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D018821:CD18 Antigens; D009195:Peroxidase