title: Modifying the vessel walls in porcine kidneys during machine perfusion.
abstract: BACKGROUND
  Endothelial glycocalyx regulates the endothelial function and plays an active role in maintaining vascular homeostasis. During ischema and reperfusion, the glycocalyx is rapidly shed into the blood stream. A Corline heparin conjugate (CHC; Corline systems AB, Uppsala, Sweden) consists of 70 heparin molecules that have the capacity to adhere strongly to biological tissues expressing heparin affinity. We hypothesized that CHC could be used to restore disrupted glycocalyx in vivo in kidneys from brain-dead pigs.
  
  
  METHODS
  Brain death was induced in male landrace pigs (n = 6) by inflating a balloon catheter in the epidural space until obtaining negative cerebral perfusion. The recovered kidneys (n = 5 + 5) were perfused by hypothermic machine perfusion using two Lifeport kidney transporters (Organ Recovery Systems, Chicago, IL). CHC (50 mg) (including 25 mg biotinylated CHC) or 50 mg unfractionated heparin (control) was added to the perfusion fluid in the respective machines. In one case, the kidneys were used only for dose escalation of CHC with the same procedure.
  
  
  RESULTS
  CHC was detected by immunofluorescence and confocal microscopy in the inner surface of the vessel walls. The binding of CHC in the kidney was confirmed indirectly by consumption of CHC from the perfusion fluid.
  
  
  CONCLUSIONS
  In this first attempt, we show that CHC maybe used to coat the vessel walls of perfused kidneys during hypothermic machine perfusion, an approach that could become useful in restoring endothelial glycocalyx of kidneys recovered from deceased donors to protect vascular endothelium and possibly ameliorate ischemia and reperfusion injuries.
authors.affiliation: Department of Surgical Sciences, Section of Transplantation Surgery, Uppsala University, Uppsala, Sweden. Electronic address: amir.sedigh@surgsci.uu.se.
authors.forename: Amir
authors.initials: A
authors.lastname: Sedigh
authors.affiliation: Department of Immunology, Genetics and Pathology, Section of Clinical Immunology, Uppsala University, Uppsala, Sweden.
authors.forename: Rolf
authors.initials: R
authors.lastname: Larsson
authors.affiliation: Department of Immunology, Genetics and Pathology, Section of Clinical Immunology, Uppsala University, Uppsala, Sweden.
authors.forename: Johan
authors.initials: J
authors.lastname: Brännström
authors.affiliation: Department of Immunology, Genetics and Pathology, Section of Clinical Immunology, Uppsala University, Uppsala, Sweden.
authors.forename: Peetra
authors.initials: P
authors.lastname: Magnusson
authors.affiliation: Department of Immunology, Genetics and Pathology, Section of Clinical Pathology and Cytology, Uppsala University, Uppsala, Sweden.
authors.forename: Erik
authors.initials: E
authors.lastname: Larsson
authors.affiliation: Department of Surgical Sciences, Section of Transplantation Surgery, Uppsala University, Uppsala, Sweden.
authors.forename: Gunnar
authors.initials: G
authors.lastname: Tufveson
authors.affiliation: Department of Surgical Sciences, Section of Transplantation Surgery, Uppsala University, Uppsala, Sweden.
authors.forename: Tomas
authors.initials: T
authors.lastname: Lorant
mesh_terms: D000818:Animals; D003094:Collagen / Q000378:metabolism; D005263:Femoral Artery / Q000378:metabolism; D019276:Glycocalyx / Q000502:physiology*; D006493:Heparin / Q000378:metabolism*; D007668:Kidney / Q000098:blood supply*; D008297:Male; D018613:Microscopy, Confocal; D009926:Organ Preservation; D010477:Perfusion / Q000379:methods; D015427:Reperfusion Injury / Q000517:prevention & control; D013552:Swine
chemical_list: D006493:Heparin; D003094:Collagen
keywords: Brain death; Endothelial glycocalyx; Ischemia/reperfusion injuries; Machine perfusion; Organ preservation and procurement