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A dog model for acetaminophen-induced fulminant hepatic failure.

Francavilla, A and Makowka, L and Polimeno, L and Barone, M and Demetris, J and Prelich, J and Van Thiel, DH and Starzl, TE (1989) A dog model for acetaminophen-induced fulminant hepatic failure. Gastroenterology, 96 (2 Pt 1). 470 - 478. ISSN 0016-5085

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Abstract

The development of a large animal model of fulminant hepatic failure produced with acetaminophen that should be useful in the development and evaluation of potential medical therapies for the important clinical problem of fulminant hepatic failure is described. Acetaminophen in dimethyl sulfoxide (600 mg/ml) given as three subcutaneous injections, with the first dose (750 mg/kg body wt) being given at noon, the second dose (200 mg/kg body wt) being given 9 h later, and the third dose (200 mg/kg body wt) being given 24 h after the initial dose consistently produces fulminant hepatic failure in dogs. The dimethyl sulfoxide vehicle, injected intramuscularly, does not influence either animal survival or hepatic function in control-treated dogs. No deaths occur within the first 36 h. By 72 h after initial drug administration, the mortality is 90%. Histopathological and biochemical investigations demonstrate a high degree of hepatocellular necrosis in nonsurviving animals without appreciable damage to the kidneys, lungs, or heart. The drug schedule and preparation outlined avoids the administration of large volumes of vehicle and results in prolonged high levels of acetaminophen in the blood sufficient to induce severe hepatic injury. Ranitidine (120 mg/kg body wt i.m.) given 30 min before each acetaminophen dose significantly reduces the mortality and hepatic necrosis produced using this model. This model satisfies all criteria established by Miller et al. for the production of a suitable large animal model of fulminant acute hepatic failure.

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Details

Item Type: Article
Status: Published
Creators/Authors:
CreatorsEmailPitt UsernameORCID
Francavilla, A
Makowka, L
Polimeno, L
Barone, M
Demetris, J
Prelich, J
Van Thiel, DH
Starzl, TEtes11@pitt.eduTES11
Centers: Other Centers, Institutes, Offices, or Units > Thomas E. Starzl Transplantation Institute
Date: February 1989
Date Type: Publication
Journal or Publication Title: Gastroenterology
Volume: 96
Number: 2 Pt 1
Page Range: 470 - 478
DOI or Unique Handle: 10.1016/0016-5085(89)91573-4
Institution: University of Pittsburgh
Refereed: Yes
Uncontrolled Keywords: Acetaminophen, Animals, Blood Chemical Analysis, Chemical and Drug Induced Liver Injury, Disease Models, Animal, Dogs, Hematologic Tests, Liver, Liver Diseases, Male
ISSN: 0016-5085
Funders: NIDDK NIH HHS (R01 DK029961-19), NIADDK NIH HHS (AM-31577), NIADDK NIH HHS (AM-30001), NIADDK NIH HHS (AM-29961)
Other ID: uls-drl:31735062130947, Starzl CV No. 945
Date Deposited: 08 Apr 2010 17:16
Last Modified: 16 Jul 2019 15:55
URI: http://d-scholarship.pitt.edu/id/eprint/4331

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