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Attenuation of ischemic liver injury by augmentation of endogenous adenosine

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

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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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Details

Item Type: Article
Status: Published
Creators/Authors:
CreatorsEmailPitt UsernameORCID
Todo, S
Zhu, Y
Zhang, S
Jin, MB
Ishizaki, N
Tanaka, H
Subbotin, V
Starzl, TEtes11@pitt.eduTES11
Centers: Other Centers, Institutes, 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: 13 Oct 2017 22:59
URI: http://d-scholarship.pitt.edu/id/eprint/5235

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