Summary
For temporary hepatic assistance we used 200 g porcine liver pieces (5×5×5 mm3) which were perfused for 6 h with 11 swine blood.
ATP and energy reserve values reached their maxima 30 min after starting perfusion, remained unchanged for 120 min, and decreased thereafter. Following 30 min of perfusion energy charge values increased from 0.260±0.110 µmol/g to 0.560±0.093 µmol/g (normal value; 0.854 ± 0.022 µmol/g) and thereafter remained unchanged for 6 h. These results suggest that good energy regulation was maintained in the liver pieces. The small liver cubes showed excellent ammonia and phenol detoxication. However, the liver pieces were not found to be able to conjugate serum bilirubin, which might have been caused by a lack of this anatomic pathway in our model.
Levels of hepatic and lytic enzymes in the perfusate increased with the time of perfusion, though they were relatively low as compared to levels in patients with acute hepatic failure. The concentration of free fatty acids in the perfusate, which are known to potentiate hepatic coma, increased slightly. However, methyl mercaptane remained constant during perfusion. Concentrations of nearly all amino acids rose during 6-h perfusion due to damage of hepatic tissues, but the molar ratio of the branched chain amino acid to aromatic amino acid was not changed.
These results suggest that liberated substances from the damaged liver would not potentiate hepatic encephalopathy. We feel that hemoperfusion over small liver pieces could be a useful method for hepatic assistance.
Zusammenfassung
Als temporären Leberersatz verwendeten wir 5×5×5 mm3 große Schweineleberwürfel, von denen jeweils 200g mit 11 frischem Schweineblut über 6h perfundiert wurden.
ATP und Energie-Reserve erreichten schon 30 min nach Perfusionsbeginn ihren Maximalwert, blieben bis zu 120 min konstant und fielen danach langsam ab. Auch das Energiegleichgewicht hatte sich nach 30 min stabilisiert und war über 6 h unverändert, was auf einen guten Energiehaushalt der Leberstückchen hindeutet. Die Leberwürfel zeigten eine ausgezeichnete Entgiftungsfunktion für Ammoniak und Phenol, jedoch konnte keine Bilirubinglucuronisierung festgestellt werden, was u. E. durch die in unserem Modell fehlende Exkretionsbahn für Galle bedingt war. Die Spiegel der Leberenzyme und der lytischen Enzyme stiegen der Perfusionszeit entsprechend langsam an, jedoch waren sie im Vergleich zu denen bei Patienten mit Leberversagen niedrig und zu vernachlässigen.
Die Konzentration der leberkomapotenzierenden freien Fettsäuren stieg in klinisch bedeutungslosem Maße an, die Methylmerkaptanwerte zeigten jedoch keine Änderung während der Perfusion. Obwohl fast alle Aminosäurekonzentrationen durch den Lebergewebezerfall zunahmen, blieb der molare Quotient (verzweigtkettige Aminosäure zu aramotische Aminosäure) im Laufe der 6stündigen Perfusion konstant. Daraus ist ersichtlich, daß die Zerfallsprodukte der Leberstückchen während dieser Zeit ein Leberkoma wahrscheinlich nicht potenzieren werden. Die Leberstückchenperfusion könnte daher in Zukunft zur Behandlung des Leberkomas erfolgreich angewendet werden.
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Lie, T.S., Ukigusa, M., Scherf, F.G. et al. Möglichkeiten und Grenzen des temporären Leberersatzes durch Hämoperfusion mit biologischem Material. Res. Exp. Med. 183, 19–33 (1983). https://doi.org/10.1007/BF01851760
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DOI: https://doi.org/10.1007/BF01851760