Problems in Treating Experimentally Induced Acute Hepatic Failure by Hemoperfusion or Cross Circulation

Abstract

Acute hepatic failure was induced in rats by galactosamine injection intraperitoneally (1 gm per kg). Twenty-four hours later rats were treated by hemoperfusion (HP) over encapsulated sorbents: cellulose acetate-coated charcoal, polyelectrolyte-coated XAD4, a combination of both, or cross circulation with a healthy donor. Compared with control treatment (prevention of hypoglycemia by glucose infusion), the survival rate was not improved by HP or cross circulation: controls 19% vs. treated animals 0 to 17%. Extension of duration or increased frequency of HP gave the same survival rates. Computer simulation based on zero-order introduction of a possible toxin into a two-compartment model shows that HP up to 5 hr per day is not able to clear the body effectively from the assumed toxin if its partition coefficient exceeds a value of 50.It is generally assumed that hepatic encephalopathy (HE) can be caused by a detrimental negative effect of a changed plasma composition on normal brain function (1).Although progress in the study of objective quantification of brain malfunction certainly will improve our understanding of the pathogenesis of HE in the near future (2), the clinician cannot wait and watch the patient in the mean time. Many different techniques of clearing the blood of possible toxic substances and waste metabolites have been applied, varying from exchange transfusion to hemoperfusion (HP) (3).In 1972, Chang (4) reported recovery of consciousness in Grade IV hepatic coma in man after charcoal HP treatment. Extension of this treatment to 56 patients showed no conclusive evidence of its beneficial effect partly due to the lack of controlled trials (5).In 1981, Chang (6) published survival rates of fulminant hepatic failure in rats with severe galactosamine (Gal-N) hepatitis. During Grade I1 hepatic coma, survival rates improved significantly by HP over albumincoated activated charcoal (ACAC) and by in situ homolReceived November 26, 1982; accepted March 27,1983. Address reprint requests to: Robert A. Further improvement of survival rates could possibly be realized by an increase of the frequency of HP and/ or changing the type of adsorbent (XAD,, a neutral resin with high affinity for fat-soluble compounds or a combination of charcoal and XAD4). Therefore, we decided to study the effect of these different types of HP in rats with severe Gal-N-induced hepatitis. As a reference, cross circulation with a healthy inbred donor rat was applied. MATERIALS AND METHODS ANIMALSMale Wistar rats (TNO, Zeist, The Netherlands), weight 300 to 350 gm, were maintained on an unrestricted commercial diet (Hope-Farms). Twenty-four hours before Gal-N administration, rats were starved for 24 hr.After Gal-N administration, food and liquid (10% glucose) were available ad libitum. If spontaneous drinking stopped, 5% glucose was administered intraperitoneally or subcutaneously (5 to 10 ml per 24 hr). SORBENTS