Acute liver failure (ALF) is a clinical condition with very high mortality rate. Its pathophysiological background is still poorly understood, which necessitates a search for optimal experimental ALF models with features resembling those of the human disorder. Taking into consideration reproducibility of induction of ALF, adequate animal size, cost of animals, the required time gap between insult and death of animals (“therapeutic window”), potential risk to investigator and other aspects, administration of thioacetamide (TAA) in rats is currently most recommended. However, the fundamental details of this ALF model have not yet been evaluated. This prompted us to investigate, first, the course of ALF as induced by intraperitoneal TAA at doses increasing from 175 to 700 mg/kg BW per day. The animals’ survival rate, plasma alanine and aspartate aminotransferase activities, and bilirubin and ammonia levels were determined over the follow-up period. Second, we examined whether Wistar and Lewis rats exhibit any differences in the course of ALF induced by different TAA doses. We found that the optimal dose for ALF induction in rats is 350 mg.kg-1 i.p., given as a single injection. Wistar rats proved more susceptible to the development of TAA-induced ALF compared with Lewis rats. Collectively, our present findings provide a sound methodological background for experimental studies aimed at evaluation of pathophysiology and development of new approaches in the therapy of ALF.
Background: The aim of the study was to determine the influence of fractionated plasma separation and absorption (FPSA) on intracranial pressure (ICP) in acute liver failure (ALF). Methods: A surgical model of ALF in pigs (35–40 kg) was used. We compared laboratory data and haemodynamic parameters from the ALF control group to the ALF group treated by Prometheus using ANOVA with repeated measures and grouping factors, by calculating the area under the curve, and by the Mann-Whitney rank test. Results: Bilirubin levels differed significantly in favour of the FPSA treatment group: after 6 h 12.81 ± 6.54 versus 29.84 ± 9.99, after 9 h 11.94 ± 4.14 versus 29.95 ± 12.36 (p < 0.01) and after 12 h 13.88 ± 6.31 versus 26.10 ± 12.23 mmol/l (p < 0.05). ICP values differed significantly in favour of the FPSA treatment group: after 9 h 19.1 ± 4.09 versus 24.1 ± 2.85 (p < 0.01), after 10 h 21.9 ± 3.63 versus 25.1 ± 2.19, after 11 h 22.5 ± 3.98 versus 26.3 ± 3.50, and after 12 h 24.0 ± 4.66 versus 29.8 ± 5.88 mm Hg (p < 0.05). Conclusion: The authors demonstrated that a significant decrease in ICP was found in pigs with ALF following treatment by FPSA.
The artificial liver support system FPSA reduced ICP values more effectively than the Performer O. Liver RanD BAL system. Compared with this BAL system, the nonbiological elimination method of FPSA is a simpler application with the advantage that it can be applied in a more continuous way.
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