gms | German Medical Science

128. Kongress der Deutschen Gesellschaft für Chirurgie

Deutsche Gesellschaft für Chirurgie

03.05. - 06.05.2011, München

Tetrahydrobiopterin as a novel therapeutic Agent in the Prevention of Chronic Allograft Vasculopathy

Meeting Abstract

  • Rupert Oberhuber - Medical University Innsbruck, Austria, Center of Operative Medicine, Department of Visceral, Transplant and Thoracic Surgery, Innsbruck
  • David Bernhard - Medical University Vienna, Austria, Department of Cardiac and Thoracic Surgery, Wien
  • Barbara Messner - Medical University Vienna, Austria, Department of Cardiac and Thoracic Surgery, Wien
  • Benno Cardini - Medical University Innsbruck, Austria, Center of Operative Medicine, Department of Visceral, Transplant and Thoracic Surgery, Innsbruck
  • Gregor Riede - Medical University Innsbruck, Austria, Center of Operative Medicine, Department of Visceral, Transplant and Thoracic Surgery, Innsbruck
  • Walter Mark - Medical University Innsbruck, Austria, Center of Operative Medicine, Department of Visceral, Transplant and Thoracic Surgery, Innsbruck
  • Christina Steger - Medical University Innsbruck, Austria, Center of Operative Medicine, Department of Heart Surgery, Innsbruck
  • Gerald Brandacher - Medical University Innsbruck, Austria, Center of Operative Medicine, Department of Visceral, Transplant and Thoracic Surgery, Innsbruck
  • Johann Pratschke - Medical University Innsbruck, Austria, Center of Operative Medicine, Department of Visceral, Transplant and Thoracic Surgery, Innsbruck
  • Katrin Watschinger - Medical University Innsbruck, Austria, Division of Biological Chemistry, Biocenter, Innsbruck
  • Werner Ernst - Medical University Innsbruck, Austria, Division of Biological Chemistry, Biocenter, Innsbruck
  • Manuel Maglione - Medical University Innsbruck, Austria, Center of Operative Medicine, Department of Visceral, Transplant and Thoracic Surgery, Innsbruck

Deutsche Gesellschaft für Chirurgie. 128. Kongress der Deutschen Gesellschaft für Chirurgie. München, 03.-06.05.2011. Düsseldorf: German Medical Science GMS Publishing House; 2011. Doc11dgch718

DOI: 10.3205/11dgch718, URN: urn:nbn:de:0183-11dgch7185

Published: May 20, 2011

© 2011 Oberhuber et al.
This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by-nc-nd/3.0/deed.en). You are free: to Share – to copy, distribute and transmit the work, provided the original author and source are credited.


Outline

Text

Introduction: Chronic rejection characterized by allograft vasculopathy is still a major obstacle to long term graft survival. Among different triggers the outstanding non-immunologic factor associated with chronic allograft vasculopathy (CAV) is ischemia reperfusion injury. Recently we were able to show that tetrahydrobiopterin (H4B), the essential cofactor for nitric oxide synthases significantly reduces ischemia reperfusion injury (IRI). Herein we analyzed whether H4B supplementation may also attenuate CAV by prevention of IRI.

Materials and methods: A fully MHC mismatched (Balbc to C57bl6) mouse heterotopic cervical aortic transplantation model was used. Transplanted grafts were subjected to 24h prolonged cold ischemia time (CIT) and to 45min warm ischemia time. Donor animals received either H4B (50mg/kg/BW) prior to organ retrieval or saline. Naive aortas served as controls. Aortic grafts were retrieved for further analysis 10h and 4 weeks following reperfusion, respectively. Glutathion (GSH) tissue level measurements as well as HSP-70 western blot were performed to assess IRI-related tissue damage (10h following reperfusion). Quantification of intimal hyperplasia as CAV-indicator was done by histology (hematoxylin and eosin) 4 weeks following reperfusion.

Results: Prolonged CIT resulted in a significant reduction of GSH tissue levels when compared to control animals (p<0.05). In parallel HSP-70 expression was elevated (p<0.05). Furthermore, supplementation of H4B resulted in significant restoration of GSH tissue levels, as well as in a reduction of HSP-70 expression (p<0.05). Histopathology at 4 weeks after transplantation revealed CAV characterized by prominent intimal hyperplasia in the untreated group. In contrast pretreatment with H4B lead to a significant reduction of intimal hyperplasia (p<0.001).

Conclusion: These data suggest that the degree of IRI strongly correlates with CAV development and that donor pre-treatment with H4B might therefore represent a novel agent in transplantation to attenuate CAV