Adenosine deaminase inhibition attenuates reperfusion low flow and improves graft survival after rat liver transplantation

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Publication Details

Author list: Sckell A
Publisher: Lippincott, Williams & Wilkins
Publication year: 2000
Volume number: 69
Issue number: 11
Start page: 2277
End page: 2281
Number of pages: 5
ISSN: 0041-1337
Languages: English-Great Britain (EN-GB)


Abstract

Background: Low flow or no flow is a prefinal step after reperfusion of
hepatic allografts. Adenosine is an intrinsic key regulator of
physiological and pathological hepatic blood flow. Methods. In a model
of rat liver transplantation, the effect of donor pretreatment with
adenosine deaminase inhibitors (0, 0.1, 1, 10 μmol
erythro-9-[2-hydroxy-3-nonyl]adenine) was studied on hepatic
interstitial adenosine concentrations, microcirculatory flow, leukocyte
adhesion, and graft survival by means of microdialysis sampling,
intravital video microscopy, and laser Doppler flowmetry. Results. Donor
pretreatment with 1 μmol erythro-9[2-hydroxy-3-nonyl]adenine increased
interstitial adenosine concentrations 5- to 10-fold, for more than 24 hr
of cold storage. In LDF studies, mean donor blood flow was increased
from 420±42 perfusion units (PU) to 832±52 PU and from 475±79 to 720±81
PU after reperfusion, and in intravital video microscopy studies from
247±24 to 281±39 pl/sec. There was no difference in the number of
leukocytes sticking, but a significantly lower percentage of leukocytes
rolling (26.1±1.9 vs. 36.5±7.5%) along the endothelial wall in the
treatment group. Transplant survival after 44 hr cold storage in UW
solution was 8/10 in the treatment group and 1/13 in the control group.
Conclusions. Donor pretreatment with
erythro-9-[2-hydroxy-3-nonyl]adenine increases survival of critically
injured liver grafts. Donor or recipient treatment rather than addition
of protectants to cold storage solutions are successful strategies to
overcome preservation injury and possibly adverse donor factors.


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Last updated on 2019-10-08 at 00:30