title: Ischemia/reperfusion injury of porcine limbs after extracorporeal perfusion.
abstract: BACKGROUND
  Revascularization of amputated extremities after prolonged ischemia is complicated by reperfusion injury. We assessed ischemia/reperfusion (I/R) injury of porcine extremities after prolonged preservation using extracorporeal circulation (ECC).
  
  
  METHODS
  Forelimbs of 32 pigs were divided into four groups based on ischemia times: group I: 6 h, group II: 12 h, group III: 0 h plus replantation, and group IV: 6 h plus replantation. Limbs were perfused with autologous blood using ECC for 12 h except group II with only 5 h perfusion. Limbs from groups III and IV were heterotopically replanted with a 7-d follow-up. Contralateral limbs served as controls in all groups. Tissue, plasma, and serum were analyzed for the extent of I/R injury.
  
  
  RESULTS
  No significant differences in tissue wet/dry ratios were found within or between groups. This finding was confirmed by histology, except for an increased damage in group IV muscles compared with baseline (P = 0.016). Complement C3 deposition was only increased in group IV muscle (P = 0.031), group II nerves (P = 0.046), and group II vessels (P = 0.037). Group IV muscle and nerve tissues were the only ones with significant IgM antibody deposition (P = 0.031) at end of perfusion. Values were normal again after replantation. Reduced complement activity and elevated IL-6, IL-8, MCP-1, VEGF, PDGF-bb, bFGF, and complement split products were found during perfusion but were normal again after replantation. Staining for heparin sulfate proteoglycans and von Willebrand factor confirmed minimal activation of endothelial cells.
  
  
  CONCLUSIONS
  The results demonstrate that prolonged limb preservation using ECC has minimal impact on I/R-induced tissue injury. Extracorporeal perfusion is a potential limb-preserving technique encouraging further studies for use in limb revascularization.
authors: Department of Plastic, Reconstructive and Hand Surgery, Bern University Hospital, Inselspital, Bern, Switzerland.
authors: Sabine
authors: S
authors: Müller
authors: Mihai A
authors: MA
authors: Constantinescu
authors: David M
authors: DM
authors: Kiermeir
authors: Thusitha
authors: T
authors: Gajanayake
authors: Anjan K
authors: AK
authors: Bongoni
authors: Felix H
authors: FH
authors: Vollbach
authors: Martino
authors: M
authors: Meoli
authors: Jan
authors: J
authors: Plock
authors: Hansjörg
authors: H
authors: Jenni
authors: Andrej
authors: A
authors: Banic
authors: Robert
authors: R
authors: Rieben
authors: Esther
authors: E
authors: Vögelin
mesh_terms: D000818:Animals; D003167:Complement Activation; D016207:Cytokines / Q000097:blood; D042783:Endothelial Cells / Q000502:physiology; D005112:Extracorporeal Circulation; D005121:Extremities / Q000098:blood supply*; D005260:Female; D036341:Intercellular Signaling Peptides and Proteins / Q000097:blood; D008297:Male; D015427:Reperfusion Injury / Q000209:etiology*; D013552:Swine
chemical_list: D016207:Cytokines; D036341:Intercellular Signaling Peptides and Proteins