title: Use of dextran sulfate in tourniquet-induced skeletal muscle reperfusion injury.
abstract: BACKGROUND
  Lower extremity ischemia-reperfusion injury (IRI)-prolonged ischemia and the subsequent restoration of circulation-may result from thrombotic occlusion, embolism, trauma, or tourniquet application in surgery. The aim of this study was to assess the effect of low-molecular-weight dextran sulfate (DXS) on skeletal muscle IRI.
  
  
  METHODS
  Rats were subjected to 3 h of ischemia and 2 or 24 h of reperfusion. To induce ischemia the femoral artery was clamped and a tourniquet placed under the maintenance of the venous return. DXS was injected systemically 10 min before reperfusion. Muscle and lung tissue samples were analyzed for deposition of immunoglobulin M (IgM), IgG, C1q, C3b/c, fibrin, and expression of vascular endothelial-cadherin and bradykinin receptors b1 and b2.
  
  
  RESULTS
  Antibody deposition in reperfused legs was reduced by DXS after 2 h (P < 0.001, IgM and IgG) and 24 h (P < 0.001, IgM), C3b/c deposition was reduced in muscle and lung tissue (P < 0.001), whereas C1q deposition was reduced only in muscle (P < 0.05). DXS reduced fibrin deposits in contralateral legs after 24 h of reperfusion but did not reduce edema in muscle and lung tissue or improve muscle viability. Bradykinin receptor b1 and vascular endothelial-cadherin expression were increased in lung tissue after 24 h of reperfusion in DXS-treated and non-treated rats but bradykinin receptor b2 was not affected by IRI.
  
  
  CONCLUSIONS
  In contrast to studies in myocardial infarction, DXS did not reduce IRI in this model. Neither edema formation nor viability was improved, whereas deposition of complement and coagulation components was significantly reduced. Our data suggest that skeletal muscle IRI may not be caused by the complement or coagulation alone, but the kinin system may play an important role.
authors.affiliation: Department of Clinical Research, University of Bern, Switzerland; Graduate School for Cellular and Biomedical Sciences, University of Bern, Switzerland.
authors.forename: Claudia
authors.initials: C
authors.lastname: Duehrkop
authors.affiliation: Department of Clinical Research, University of Bern, Switzerland.
authors.forename: Julie
authors.initials: J
authors.lastname: Denoyelle
authors.affiliation: Department of Clinical Research, University of Bern, Switzerland.
authors.forename: Sidney
authors.initials: S
authors.lastname: Shaw
authors.affiliation: Department of Clinical Research, University of Bern, Switzerland. Electronic address: robert.rieben@dkf.unibe.ch.
authors.forename: Robert
authors.initials: R
authors.lastname: Rieben
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000378:metabolism; D015820:Cadherins / Q000378:metabolism; D002317:Cardiovascular Agents / Q000494:pharmacology*; D015922:Complement C1q / Q000378:metabolism; D003179:Complement C3b / Q000378:metabolism; D016264:Dextran Sulfate / Q000494:pharmacology*; D004195:Disease Models, Animal; D004487:Edema / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D005263:Femoral Artery; D005337:Fibrin / Q000378:metabolism; D006614:Hindlimb / Q000098:blood supply / Q000473:pathology; D007074:Immunoglobulin G / Q000378:metabolism; D007075:Immunoglobulin M / Q000378:metabolism; D008297:Male; D018482:Muscle, Skeletal / Q000098:blood supply* / Q000378:metabolism / Q000473:pathology; D010446:Peptide Fragments / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D018002:Receptors, Bradykinin / Q000378:metabolism; D015427:Reperfusion Injury / Q000188:drug therapy* / Q000209:etiology / Q000378:metabolism / Q000473:pathology; D014111:Tourniquets / Q000009:adverse effects; D000099152:Cadherin 5
chemical_list: D015703:Antigens, CD; D015820:Cadherins; D002317:Cardiovascular Agents; D015922:Complement C1q; D003179:Complement C3b; D016264:Dextran Sulfate; D005337:Fibrin; D007074:Immunoglobulin G; D007075:Immunoglobulin M; D010446:Peptide Fragments; D018002:Receptors, Bradykinin; D000099152:Cadherin 5; C082625:C3 beta c
keywords: Dextran sulfate; Hind limb; Ischemia–reperfusion injury; Tourniquet