title: Characterization of systemic and histologic injury after crush syndrome and intervals of reperfusion in a small animal model.
abstract: BACKGROUND
  Prolonged compression of limb muscles and subsequent decompression are important in the development of crush syndrome (CS). We applied a simple rubber tourniquet to rat hind limbs to create a CS model.
  
  
  METHODS
  Anesthetized rats were subjected to bilateral hind limb compression for 5 hours followed by decompression and reperfusion for 0 hour, 1 hour, 3 hours, and 24 hours under monitoring of arterial blood pressure and electrocardiography. Blood and tissue samples were collected for histology, biochemical analysis, and tissue myeloperoxidase activity assessment.
  
  
  RESULTS
  The survival rates of the CS-model groups remained at 100% until 3 hours, however, dropped to 25% at 24 hours after reperfusion mainly because of hyperkalemia and consequent hypotension observed at 1 hour and deteriorated at 3 hours after reperfusion. Rhabdomyolysis evaluated by circulating and histologic markers of injury was found as early as 1 hour and more marked at 3 hours, resulting in impaired renal function 24 hours after reperfusion. Myeloperoxidase activities increased with incremental periods after reperfusion not only in injured limb muscles but also in kidney and lung, suggesting an abnormal interaction between the vascular endothelium and circulating leukocytes after rhabdomyolysis, possibly causing subsequent multiple organ dysfunction frequently encountered in CS.
  
  
  CONCLUSIONS
  The findings from this study demonstrate the feasibility of a novel small animal model of extremity crush injury. By using this model, the impact of incremental periods of reperfusion on mortality and remote organ dysfunctions can be characterized. Future studies are necessary to better define a threshold for this injury pattern and the impact of other factors underlying this syndrome.
authors.affiliation: Division of Pathophysiology, Department of Clinical Dietetics and Human Nutrition, Faculty of Pharmaceutical Science, Josai University, Saitama, Japan.
authors.forename: Isamu
authors.initials: I
authors.lastname: Murata
authors.forename: Kazuya
authors.initials: K
authors.lastname: Ooi
authors.forename: Hiromi
authors.initials: H
authors.lastname: Sasaki
authors.forename: Soichiro
authors.initials: S
authors.lastname: Kimura
authors.forename: Kazuo
authors.initials: K
authors.lastname: Ohtake
authors.forename: Hideo
authors.initials: H
authors.lastname: Ueda
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Uchida
authors.forename: Norikiyo
authors.initials: N
authors.lastname: Yasui
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Tsutsui
authors.forename: Naoya
authors.initials: N
authors.lastname: Yoshizawa
authors.forename: Ichiro
authors.initials: I
authors.lastname: Hirotsu
authors.forename: Yasunori
authors.initials: Y
authors.lastname: Morimoto
authors.forename: Jun
authors.initials: J
authors.lastname: Kobayashi
mesh_terms: D000818:Animals; D003444:Crush Syndrome / Q000473:pathology / Q000503:physiopathology*; D004195:Disease Models, Animal; D004562:Electrocardiography; D005240:Feasibility Studies; D006614:Hindlimb / Q000098:blood supply; D007677:Kidney Function Tests; D008297:Male; D009195:Peroxidase / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D015424:Reperfusion; D015427:Reperfusion Injury / Q000473:pathology / Q000503:physiopathology; D012206:Rhabdomyolysis / Q000473:pathology / Q000503:physiopathology; D015996:Survival Rate; D014111:Tourniquets
chemical_list: D009195:Peroxidase