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Treprostinil, a prostacyclin analog, ameliorates ischemia-reperfusion injury in rat orthotopic liver transplantation

Ghonem, N and Yoshida, J and Stolz, DB and Humar, A and Starzl, TE and Murase, N and Venkataramanan, R (2011) Treprostinil, a prostacyclin analog, ameliorates ischemia-reperfusion injury in rat orthotopic liver transplantation. American Journal of Transplantation, 11 (11). 2508 - 2516. ISSN 1600-6135

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Abstract

Prostaglandins have been evaluated for their ability to reduce IRI after liver transplantation; however, poor stability, side effects and the inability to show a significant difference in primary endpoint have limited their clinical application. Treprostinil, a prostacyclin (PGI 2) analog, has a higher potency and longer elimination half-life than other commercially available PGI2 analogs. We examined the efficacy of treprostinil to prevent IRI during OLT. OLT was performed in syngeneic Lewis rats after 18 h of cold preservation (4°C) in the UW solution. IRI significantly increased serum ALT and AST levels, neutrophil infiltration, hepatic necrosis and mRNA levels of proinflammatory cytokines post-OLT, while treatment with treprostinil decreased all the parameters. Cold storage of liver grafts significantly reduced ATP levels and treprostinil restored energy levels in liver grafts early postreperfusion. In addition, treprostinil preserved the sinusoidal endothelial cell lining and reduced platelet deposition early post-transplantation compared to placebo. Hepatic tissue blood flow was significantly compromised in the placebo group, whereas treprostinil maintained bloodflow similar to normal levels. Treprostinil protected the liver graft against IRI during OLT. Treprostinil has the potential to serve as a therapeutic option to protect the liver graft against I/R injury in patients undergoing OLT. © Copyright 2011 The American Society of Transplantation.


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Details

Item Type: Article
Status: Published
Creators/Authors:
CreatorsEmailPitt UsernameORCID
Ghonem, N
Yoshida, J
Stolz, DB
Humar, A
Starzl, TEtes11@pitt.eduTES11
Murase, N
Venkataramanan, Rrv@pitt.eduRV
Centers: Other Centers, Institutes, or Units > Thomas E. Starzl Transplantation Institute
Date: 1 November 2011
Date Type: Publication
Journal or Publication Title: American Journal of Transplantation
Volume: 11
Number: 11
Page Range: 2508 - 2516
DOI or Unique Handle: 10.1111/j.1600-6143.2011.03568.x
Schools and Programs: School of Medicine > Surgery
Refereed: Yes
ISSN: 1600-6135
MeSH Headings: Adenosine Triphosphate--metabolism; Animals; Cold Ischemia; Epoprostenol--analogs & derivatives; Epoprostenol--therapeutic use; Interferon-gamma--biosynthesis; Liver Circulation--drug effects; Liver Transplantation--adverse effects; Liver Transplantation--physiology; Male; Neutrophil Infiltration--drug effects; Rats; Rats, Inbred Lew; Reperfusion Injury--prevention & control; Tumor Necrosis Factor-alpha--biosynthesis
PubMed ID: 21668631
Date Deposited: 05 Dec 2012 21:58
Last Modified: 03 Feb 2019 03:55
URI: http://d-scholarship.pitt.edu/id/eprint/16176

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