A comparative study of the effects of insulin/glucagon infusions, parenteral amino acids and high dose corticosteroids on survival in a rabbit model of acute fulminant hepatitis

Authors

  • Gerald Y. Minuk.M.D.,

    Corresponding author
    1. Division of Gastroenterology, Department of Medicine, University of Calgary, Calgary, Alberta, Canada
    • Assistant Professor, F.R.C.P.(C), Department of Medicine, University of Calgary, Health Science Centre, 3330 Hospital Drive, N.W., Calgary, Alberta T2N 4N1, Canada
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    • Recipient of an Alberta Heritage Foundation Medical Research Scholarship Award.

  • Thomas A. Sherman,

    1. Division of Gastroenterology, Department of Medicine, University of Calgary, Calgary, Alberta, Canada
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  • Eldon A. Shaffer,

    1. Division of Gastroenterology, Department of Medicine, University of Calgary, Calgary, Alberta, Canada
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  • Seamus K. Kelly

    1. Division of Gastroenterology, Department of Medicine, University of Calgary, Calgary, Alberta, Canada
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Abstract

Acute fulminant hepatitis was induced in 55 healthy adult male rabbits with the potent hepatotoxin galactosamine hydrochloride (3.75 mmoles per kg i.v.). Control rabbits (n = 27) were divided into three groups: Group I (n = 10) underwent sham surgery for placement of an indwelling central venous catheter; Group II (n = 9) received 5% dextrose and water via an indwelling central venous catheter, and Group III (n = 8) received daily intramuscular injections of 0.9% sodium chloride. Treated rabbits (n = 28) also consisted of three groups: Group IV (n = 9) received 12-hr intravenous infusions of insulin (0.029 units per kg per hr) and glucagon (2.86 μg per kg per hr) daily; Group V (n = 10) received a continuous infusion of parenteral amino acids (Travasol), and Group VI (n = 9) received daily intramuscular methylprednisolone (0.69 mg per kg). In each case, treatment was initiated 16 hr following galactosamine injection. Serum aminotransferase activity was determined on Days 0, 1, 4 and 10 of the 10-day study. Liver histology was obtained immediately after death and graded under code on a scale of 1 to 4 for severity of hepatitis. Rabbits surviving 10 days were sacrificed on Day 10 for histologic examination.

The extent of galactosamine-induced hepatic injury was similar in all six groups as manifest by peak mean SGPT(range: 2,662 to 3,568 IU per liter), SGOT (range: 4,435 to 5,625 IU per liter) levels and hepatic histologic findings. The overall survival rate in controls was 6/27 (22%); in insulin/glucagon-treated animals 2/9 (22%), and in the amino acid-treated group 2/10 (20%). The corticosteroid-treated group, however, had significantly improved survival: 6/9 (67%, p < 0.05, Fisher's exact test). No difference between groups was observed in the mean survival times of animals dying prior to Day 10 (range: 30.7 ± 2.7 — 55.5 ± 13.0 hr, mean ± S.E., p > 0.05). In conclusion, the results of this study indicate that in this animal model of acute fulminant hepatitis and withthese doses, insulin/glucagon infusions and parenteral amino acids have no beneficial effect, while high dose corticosteroids significantly enhance survival. On the basis of these results, a reappraisal of the use of high dose corticosteroidsin the treatment of nonviral forms of acute fulminant heptitis in humans would appear to be indicated.

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