uu.seUppsala University Publications
Change search
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf
Modifying the vessel walls in porcine kidneys during machine perfusion
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Transplantation Surgery.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical Immunology.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical Immunology.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical Immunology.
Show others and affiliations
2014 (English)In: Journal of Surgical Research, ISSN 0022-4804, E-ISSN 1095-8673, Vol. 191, no 2, 455-462 p.Article in journal (Refereed) Published
Abstract [en]

Background: Endothelial glycocalyx regulates the endothelial function and plays an active role in maintaining vascular homeostasis. During ischemia/reperfusion, the glycocalyx is rapidly shed into the blood stream. A 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.

Materials and 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 (HMP) using two Lifeport kidney transporters (Organ Recovery Systems, Chicago, IL, USA). 50 mg CHC (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 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 may be used to coat the vessel walls of perfused kidneys during HMP, an approach that could become useful in restoring endothelial glycocalyx of kidneys recovered from deceased donors to protect vascular endothelium and possibly ameliorate ischemia/reperfusion injuries.

Place, publisher, year, edition, pages
2014. Vol. 191, no 2, 455-462 p.
National Category
Surgery
Identifiers
URN: urn:nbn:se:uu:diva-221875DOI: 10.1016/j.jss.2014.04.006ISI: 000341358100027PubMedID: 24819743OAI: oai:DiVA.org:uu-221875DiVA: diva2:710524
Available from: 2014-04-07 Created: 2014-04-06 Last updated: 2017-12-05Bibliographically approved
In thesis
1. Management of Ischemia and Brain Death-Associated Injuries in Porcine Kidney Grafts
Open this publication in new window or tab >>Management of Ischemia and Brain Death-Associated Injuries in Porcine Kidney Grafts
2014 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Organs from deceased donors after brain death (BD) remain the major source of organs for transplantation. The catastrophic event of BD and the inevitable consequences of ischemia reperfusion injury (IRI) are linked to impaired graft quality and transplantation outcome. The aim of this thesis was to create a BD model in pigs to assess early effects on IRI in kidneys preserved with an oxygenated solution and to evaluate the protective effects of coating the renal vessel walls with a heparin conjugate during hypothermic machine perfusion (HMP).

Brain death was achieved by raising the intracranial pressure (ICP) through stepwise increasing the volume of an epidurally placed balloon to the point of exceeding the mean arterial pressure (MAP) creating a negative cerebral perfusion pressure (CPP). This reproducible, clinically relevant experimental model makes evaluation of potential targeted methods to protect the organs possible. Kidneys retrieved from brain-dead pigs were preserved either in an oxygenated emulsion composed of 75% histidine-tryptophan-ketoglutarate (HTK) and 25% perfluorohexyloctane F6H8 or HTK alone. After 18h of cold storage the kidneys were transplanted into allogeneic pigs. F6H8 was associated with replenishment of adenosine triphosphate and lower gene expression of hypoxia inducible factor (HIF)-1a, vascular endothelial growth factor (VEGF), interleukin (IL)-1α and tumour necrosis factor (TNF)-α. F6H8 reduced early IRI at both the cellular and molecular level.

Kidneys from BD pigs were evaluated for the feasibility of coating the vessel walls with the heparin conjugate CHC (Corline Systems AB, Uppsala, Sweden) to restore glycocalyx. Porcine kidneys were preserved by HMP for 20h with 50 mg biotinylated CHC added to the perfusion solution. CHC was detected on the inner surface of the kidney vessels by immunofluorescence, and its uptake in kidneys was confirmed by reduced content in the perfusate. An ex vivo normothermic perfusion circuit was developed to assess kidney function. Perfusion with CHC during HMP was associated with lower creatinine levels, increased urine volume and reduced tubular injury. Modifying renal vessels walls using CHC during HMP improved early graft function. Preservation with the oxygenated F6H8 solution or CHC could be used to improve graft quality and ameliorate IRI in kidneys retrieved from deceased donors.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2014. 77 p.
Series
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 1651-6206 ; 993
National Category
Surgery
Identifiers
urn:nbn:se:uu:diva-222020 (URN)978-91-554-8939-7 (ISBN)
Public defence
2014-05-31, Gustavianum Auditorium Minus, Akademigatan 3, uppsala, 09:15 (Swedish)
Opponent
Supervisors
Available from: 2014-05-08 Created: 2014-04-07 Last updated: 2014-06-30

Open Access in DiVA

No full text

Other links

Publisher's full textPubMed

Authority records BETA

Sedigh, AmirLarsson, RolfBrännström, JohanMagnusson, PeetraLarsson, ErikTufveson, GunnarLorant, Tomas

Search in DiVA

By author/editor
Sedigh, AmirLarsson, RolfBrännström, JohanMagnusson, PeetraLarsson, ErikTufveson, GunnarLorant, Tomas
By organisation
Transplantation SurgeryClinical ImmunologyDepartment of Immunology, Genetics and Pathology
In the same journal
Journal of Surgical Research
Surgery

Search outside of DiVA

GoogleGoogle Scholar

doi
pubmed
urn-nbn

Altmetric score

doi
pubmed
urn-nbn
Total: 1047 hits
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf