title: Defining the Salvage Time Window for the Use of Ischemic Postconditioning in Skeletal Muscle Ischemia Reperfusion Injury.
abstract: BACKGROUND
  The aim of this study was to determine the optimal salvage time window within which ischemic postconditioning can be used to ameliorate ischemia/reperfusion (I/R) injury in skeletal muscle.
  
  
  METHODS
  A total of 48 Sprague-Dawley rats were divided into two groups: I/R only (control) and I/R with postconditioning. Subgroups were divided by duration of ischemia (2, 4, 6, and 8 hours). A pedicled gracilis muscle model was used. The postconditioning protocol consisted of six cycles of 15 seconds of reperfusion followed by 15 seconds of ischemia (total time = 3 minutes). Muscles were harvested 24 hours after I/R injury to examine tissue viability, histology, myeloperoxidase activity, and protective gene expression.
  
  
  RESULTS
  Postconditioning groups showed improved muscle viability after 4 and 6 hours of ischemia time as compared with controls (p < 0.05). Higher expression of mitochondrial complexes I, II, III, endothelial nitric oxide synthase, inducible nitric oxide synthase, and Bcl-2 were observed in the postconditioning group after 4 and 6 hours of ischemia (p < 0.05). Lower expression of tumor necrosis factor-α and caspase 3 was observed in the postconditioning group at 4 hours (p < 0.05). Myeloperoxidase activity was similar in both groups at all-time points except 8 hours ischemia, where the control group had higher activity (p < 0.05).
  
  
  CONCLUSIONS
  Results of this study demonstrate that the effective time window within which postconditioning is most effective for the salvage of skeletal muscle is between 4 and 6 hours of ischemia. Postconditioning offered improved mitochondrial and vascular function with decreased inflammation and cell death. This may be clinically useful as a postinjury salvage technique to attenuate I/R injury after 4 to 6 hours of ischemia.
authors.affiliation: The Institute for Plastic Surgery, Southern Illinois University School of Medicine, Springfield, Illinois.
authors.forename: Ryan W
authors.initials: RW
authors.lastname: Schmucker
authors.affiliation: The Institute for Plastic Surgery, Southern Illinois University School of Medicine, Springfield, Illinois.
authors.forename: Shaun D
authors.initials: SD
authors.lastname: Mendenhall
authors.affiliation: The Institute for Plastic Surgery, Southern Illinois University School of Medicine, Springfield, Illinois.
authors.forename: Joel D
authors.initials: JD
authors.lastname: Reichensperger
authors.affiliation: The Institute for Plastic Surgery, Southern Illinois University School of Medicine, Springfield, Illinois.
authors.forename: Mei
authors.initials: M
authors.lastname: Yang
authors.affiliation: The Institute for Plastic Surgery, Southern Illinois University School of Medicine, Springfield, Illinois.
authors.forename: Michael W
authors.initials: MW
authors.lastname: Neumeister
mesh_terms: D000818:Animals; D001707:Biopsy, Needle; D004195:Disease Models, Animal; D007150:Immunohistochemistry; D007511:Ischemia / Q000628:therapy*; D057775:Ischemic Postconditioning / Q000379:methods*; D008297:Male; D018482:Muscle, Skeletal / Q000098:blood supply* / Q000473:pathology / Q000601:surgery; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000517:prevention & control*; D018570:Risk Assessment; D016879:Salvage Therapy / Q000379:methods*; D013997:Time Factors; D016896:Treatment Outcome