CORE
🇺🇦
make metadata, not war
Services
Services overview
Explore all CORE services
Access to raw data
API
Dataset
FastSync
Content discovery
Recommender
Discovery
OAI identifiers
OAI Resolver
Managing content
Dashboard
Bespoke contracts
Consultancy services
Support us
Support us
Membership
Sponsorship
Community governance
Advisory Board
Board of supporters
Research network
About
About us
Our mission
Team
Blog
FAQs
Contact us
research
Factors determining short- and long-term survival after orthotopic liver homotransplantation in the dog
Authors
TD Faris
TJ Herrmann
+6 more
CJ Hlad
TL Marchioro
KA Porter
TE Starzl
PD Taylor
WR Waddell
Publication date
1 January 1965
Publisher
View
on
PubMed
Abstract
Without azathioprine therapy, the operative risk with orthotopic liver transplantation is small. Twenty-two of 23 animals survived 2 days or more, and 19 for 6 days or longer. All eventually died of rejection within 10 days. Changes in homograft histology and function were similar to those previously reported, with cellular infiltration and hepatocyte necrosis which was heavily concentrated in the centrilobular areas. In individual experiments, there was little evidence of immunologically induced segmental hepatic arterial or portal venous occlusion; hepatocyte loss was homogeneous, and fibrinoid vascular lesions were uncommon. There was, however, some evidence of damage to the sinusoidal endothelium by adherent mononuclear cells. The changing character of the mononuclear infiltration of the homograft was reflected by widespread proliferation of similar cells in the host lymphoid tissue. Specific changes in other host organs were not noted. Some of the biochemical and histologic alterations caused by unmodified rejection can also be produced by azathioprine. In 18 nontransplanted dogs, acute rises in SGOT, SGPT, and alkaline phosphatase, unaccompanied by hyperbilirubinemia, were noted within a few days after beginning administration of this agent. Although these abnormalities tended to regress within the 40 day period of observation, more than two thirds of the livers showed histologic evidence of centrilobular hepatocyte damage or necrosis-often with intrahepatic cholestasis, but always without mononuclear cell infiltration. The hepatotoxicity was not prevented by methionine. Weight loss and progressive anemia also occurred. Lymphoid tissue was depleted. The mortality from the toxicity study was 33 percent. The use of azathioprine to mitigate rejection increased the early mortality after homotransplantation, 32 of 116 dogs dying within the first week (28 percent), most commonly of pulmonary complications. The 84 animals living longer than 7 days had a greatly potentiated homograft survival, exceeding 25 days in 44 dogs, and 50 days in 24. Fifteen animals are still alive from 62 to 324 days postoperatively. Six dogs had all drugs stopped after 116 to 123 days. Only 1 has had a clinically evident late rejection and 5 are still alive from 63 to 204 days later. Three of these animals had repeat biopsies 77 to 182 days after cessation of therapy; one homograft which was normal at 4 months remained so 6 months later, another had an improved histologic appearance, and the third had deteriorated. The longest mean survival was in those animals receiving adjuvant therapy with L-methionine or S35-methionine, but the variability of the results was so great that a statistically significant advantage of these agents could not be demonstrated. Soon after operation red cell survival was decreased, but in chronic survivors there was no evidence of a grafthost reaction. There was great variability in the vigor of rejection, ranging from the uncontrollable (29 percent) to the clinically undetectable (23 percent). Most of the animals (49 percent) had some biochemical evidence of rejection which proved to be spontaneously reversible, to a greater or lesser degree, since intensification of immunosuppressive therapy was not required. These findings correlate well with the histologic studies. In virtually all animals, azathioprine delayed the onset of rejection but in those dying in the second and third postoperative weeks, the pathologic stigmas of rejection were very similar to the untreated controls. As in the untreated animals, the number of proliferating large pyroninophilic cells in the host's lymphoid tissues was roughly proportional to the number of mononuclear cells invading the homograft liver. After this time, the predominant histologic features in most animals were those of repair and regeneration, with either absent or relatively minor degrees or continuing destruction. Since the major rejection damage was centrizonal, the healing was most prominent in these areas with interconecting fibrosis around the central veins, centrilobular bile canalicular dilatation and cholestasis, and pseudolobule formation. In some of the homografts, increased connective tissue was also present in the portal tracts, but in others including the longest survivor there were no residual abnormalities whatever. In azathioprine-treated animals, damage to the vessels in the homograft portal tracts was found in only one liver. With electron microscopy there was some evidence of damage to the sinusoidal endothelium by adherent mononuclear cells, a finding which could be analogous to that described by Kountz and co-workers11 in the peritubular capillaries of renal homografts. If immunologically mediated hemodynamic alterations play an important role in liver homograft rejection by interrupting the blood supply to the hepatocytes, it seems most likely that they occur at this intrasinusoidal capillary level rather than in the larger vessels. © 1965
Similar works
Full text
Open in the Core reader
Download PDF
Available Versions
Name not available
See this paper in CORE
Go to the repository landing page
Download from data provider
oai:d-scholarship.pitt.edu:348...
Last time updated on 15/12/2016
Name not available
See this paper in CORE
Go to the repository landing page
Download from data provider
oai:d-scholarship.pitt.edu:348...
Last time updated on 23/11/2016
D-Scholarship@Pitt
See this paper in CORE
Go to the repository landing page
Download from data provider
oai:d-scholarship.pitt.edu:348...
Last time updated on 19/07/2013