Role of neutrophil depletion and elastase inhibition in modifying skeletal muscle reperfusion injury.
This study investigated the effect of neutrophil depletion and neutrophil elastase inhibition on the severity of skeletal muscle reperfusion injury. In a rodent model, indices (experimental/normal limb) of gastrocnemius muscle viability (histochemical staining), oedema (wet:dry weight ratio) and myeloperoxidase content (neutrophil recruitment) were assessed in normal (no ischaemia), ischaemic (6-h unilateral hindlimb ischaemia), control (6-h ischaemia and 4-h reperfusion), neutrophil-depleted rats (given antineutrophil serum) and rats receiving the neutrophil elastase inhibitor Elafin. Neutrophil recruitment muscle infarction and oedema did not occur in normal limbs, or in those subjected to ischaemia without reperfusion. In contrast increased muscle myeloperoxidase levels (P < 0.001), muscle infarction (P < 0.01) and oedema (P < 0.001) all occurred in the reperfused limbs of control animals compared with those of normal and ischaemic rats. Antineutrophil serum and Elafin both reduced neutrophil recruitment during reperfusion (P < 0.001 and P < 0.01 respectively) and muscle viability was preserved. Reperfusion oedema still occurred however, suggesting that altered endothelial permeability is mediated by factors other than neutrophils.
Vascular Surgical Unit, General Infirmary at Leeds, UK.
J N
JN
Crinnion
S
S
Homer-Vanniasinkam
R
R
Hatton
S M
SM
Parkin
M J
MJ
Gough
D000208:Acute Disease; D000818:Animals; D004195:Disease Models, Animal; D004487:Edema / Q000201:enzymology / Q000209:etiology; D006614:Hindlimb / Q000098:blood supply; D007106:Immune Sera / Q000008:administration & dosage; D007511:Ischemia / Q000150:complications / Q000201:enzymology; D019272:Leukocyte Elastase / Q000037:antagonists & inhibitors*; D008297:Male; D018482:Muscle, Skeletal / Q000098:blood supply* / Q000201:enzymology; D009503:Neutropenia / Q000150:complications* / Q000201:enzymology; D009504:Neutrophils / Q000201:enzymology* / Q000276:immunology; D010196:Pancreatic Elastase / Q000037:antagonists & inhibitors*; D009195:Peroxidase / Q000378:metabolism; D053491:Proteinase Inhibitory Proteins, Secretory; D011506:Proteins; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000201:enzymology / Q000209:etiology*; D015842:Serine Proteinase Inhibitors / Q000008:administration & dosage; D013997:Time Factors
D007106:Immune Sera; D053491:Proteinase Inhibitory Proteins, Secretory; D011506:Proteins; D015842:Serine Proteinase Inhibitors; D009195:Peroxidase; D010196:Pancreatic Elastase; D019272:Leukocyte Elastase