Abstract
1. Reports on pathogenesis of hepatic coma and on the artificial liver up to present are briefly summarized.
2. Artificial liver unit devised by us consists of both blood dialysis and enzyme perfusion circuit. Hollow fiber b/HFO-1 as dialyzer is used. The first step of our studies depends on establishment of physicochemical natures of membranes and possibility of enzymatic elimination of toxic substances, especially of ammonia. In the closed perfusion circuit, mixtures of glutamic dehydrogenase, α-ketoglutaric acid and NADH are enclosed. Ammonia dialyzed through dialysis circuit is trapped and bound with α-ketoglutaric acid with conversion to glutamic acid in the perfusion circuit. NAD thus formed is converted into NADH by another dehydrogenase and reductive form of substrate. The unit is suitable for enzymatic ammonia disposal.
3. The second step is efficacy of unit when it is combined with animals. Liver failure dogs are made by portacaval shunt subsequently with ligation of hepatic artery. They expire within 6-8 hrs with elevation of blood ammonia. Two hrs after portacaval shunt and ligation of hepatic artery, the femoral vessels of liver failure dogs are connected with the artificial liver unit. While perfusion, the elevation of blood ammonia is prevented with corresponding production of glutamic acid.
4. The third step is enzymatic disposal of toxic substances other than ammonia such as amino acids or amines. In addition with enzymatic system of ammonia detoxification, combination of several kinds of enzyme preparations to be enclosed in the perfusion circuit is now attempted and in progress.
