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Inhibition of free radical generation and improved survival by protection of the hepatic microvascular endothelium by targeted erythrocytes in orthotopic rat liver transplantation

Rao, PN and Walsh, TR and Makowka, L and Liu, T and Demetris, AJ and Rubin, RS and Snyder, JT and Mischinger, HJ and Starzl, TE (1990) Inhibition of free radical generation and improved survival by protection of the hepatic microvascular endothelium by targeted erythrocytes in orthotopic rat liver transplantation. Transplantation, 49 (6). 1055 - 1059. ISSN 0041-1337

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Abstract

The capacity of specifically targeted erythrocytes to inhibit free radical—mediated injury to the endothelial cell after cold preservation, and improve liver function was studied in two experimental models: An isolated perfused rat liver (IPRL) system and syngeneic orthotopic rat liver transplantation. In the IPRL model, livers were preserved in University of Wisconsin solution for 24 h at 4°C. At the end of the preservation period, livers were flushed with lactated Ringer’s (control), immu- noerythrocytes (IES), or blank intact erythrocytes prior to warm reperfusion for 2 h using an assanguinous Krebs-Henseleit buffer. Production of superoxide (O < inf > 2 < /inf > < sup > - < /sup > ) anion during warm reperfusion in the IES-treated liver was reduced by 65% as compared with controls (P < 0.001) and by 74% (P < 0.001) when compared with blank erythrocyte—treated livers. Endothelial cell preservation, as assessed by levels of purine nucleoside phos- phorylase (PNP), was much better in the IES-treated group (P < 0.001) when compared with untreated livers. Hepatocellular preservation was markedly improved in the IES-treated livers. In the syngeneic liver transplantation model, livers were preserved in UW solution for 24 h at 4°C. Prior to implantation, livers were flushed with 5 ml of cold lactated Ringer’s or immunoerythrocytes. Survival after three weeks was 60% in the IES-treated group and 30% in the untreated group. Survival in the IES-treated group was not significantly different from a control (no preservation) group. IES-treated livers in both models demonstrated better endothelial cell integrity and ultimate liver function. IES treatment therefore appears to protect the hepatic microvascular endothelial cell from reperfusion injury and could prove to be an easy reproducible method of donor organ preparation after cold preservation. © 1990 by Williams & Wilkins.


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Details

Item Type: Article
Status: Published
Creators/Authors:
CreatorsEmailPitt UsernameORCID
Rao, PN
Walsh, TR
Makowka, L
Liu, T
Demetris, AJ
Rubin, RS
Snyder, JT
Mischinger, HJ
Starzl, TEtes11@pitt.eduTES11
Centers: Other Centers, Institutes, or Units > Thomas E. Starzl Transplantation Institute
Date: 1 January 1990
Date Type: Publication
Journal or Publication Title: Transplantation
Volume: 49
Number: 6
Page Range: 1055 - 1059
Institution: University of Pittsburgh
Refereed: Yes
ISSN: 0041-1337
Other ID: uls-drl:31735062116797, Starzl CV No. 1126
Date Deposited: 08 Apr 2010 17:19
Last Modified: 13 Oct 2017 21:57
URI: http://d-scholarship.pitt.edu/id/eprint/4512

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