Premium
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
Author(s) -
Minuk.M.D. Gerald Y.,
Sherman Thomas A.,
Shaffer Eldon A.,
Kelly Seamus K.
Publication year - 1986
Publication title -
hepatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.488
H-Index - 361
eISSN - 1527-3350
pISSN - 0270-9139
DOI - 10.1002/hep.1840060114
Subject(s) - medicine , fulminant hepatic failure , liter , insulin , gastroenterology , galactosamine , anesthesia , surgery , transplantation , liver transplantation , chemistry , organic chemistry , glucosamine
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.