Todo, S and Zhu, Y and Zhang, S and Jin, MB and Ishizaki, N and Tanaka, H and Subbotin, V and Starzl, TE
(1997)
Attenuation of ischemic liver injury by augmentation of endogenous adenosine.
Transplantation, 63 (2).
217 - 223.
ISSN 0041-1337
Abstract
Hepatic grafts from non-heartbeating donors may alleviate the organ shortage, but they inherently suffer from warm ischemia. In the present study, we tested our hypothesis that augmentation of endogenous adenosine by inhibition of nucleoside transport with R75231 attenuates ischemic liver injury. Adult female beagle dogs underwent 2-hr hepatic vascular exclusion with venovenous bypass. R75231 was given to the animals by continuous intravenous infusion for 30 min before ischemia at a dose of 0.1 mg/kg (Group 2, n=6), 0.05 mg/kg (Group 3, n=6), or 0.025 mg/kg (Group 4, n=6). Nontreated animals were used as the control (Group 1, n= 10). Animal survival, hepatic tissue blood flow, liver function, and histopathology were analyzed. Two- week animal survival was 30% in Group 1, 83% in Group 2, 100% in Group 3, and 100% in Group 4. Postreperfusion hepatic tissue blood flow was markedly improved by the treatment. Treatment significantly attenuated liver enzyme release, lipid peroxidation, and changes in adenine nucleotides and purine catabolites. Structural abnormality of the liver after reperfusion was markedly improved by R75231 treatment, showing better architecture and less neutrophil infiltration. Preischemic administration of a nucleoside transport inhibitor ameliorated ischemic liver injury due to the positive effects of augmented endogenous adenosine, and is applicable clinically when the liver is procured from a controlled non-heartbeating donor.
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Item Type: |
Article
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Status: |
Published |
Creators/Authors: |
Creators | Email | Pitt Username | ORCID |
---|
Todo, S | | | | Zhu, Y | | | | Zhang, S | | | | Jin, MB | | | | Ishizaki, N | | | | Tanaka, H | | | | Subbotin, V | | | | Starzl, TE | tes11@pitt.edu | TES11 | |
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Centers: |
Other Centers, Institutes, Offices, or Units > Thomas E. Starzl Transplantation Institute |
Date: |
27 January 1997 |
Date Type: |
Publication |
Journal or Publication Title: |
Transplantation |
Volume: |
63 |
Number: |
2 |
Page Range: |
217 - 223 |
DOI or Unique Handle: |
10.1097/00007890-199701270-00007 |
Institution: |
University of Pittsburgh |
Refereed: |
Yes |
ISSN: |
0041-1337 |
Other ID: |
uls-drl:31735062133131, Starzl CV No. 1849 |
Date Deposited: |
08 Apr 2010 17:31 |
Last Modified: |
04 Feb 2019 22:55 |
URI: |
http://d-scholarship.pitt.edu/id/eprint/5235 |
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