A biological extracorporeal metabolic device for hepatic support

The results from OCTOPUS-I indicate that combined metabolic activities could be maintained under the optimal conditions provided for a prolonged period of time, but most effectively up to 14 hrs. The results of OCTOPUS-II and -III are lower than those in OCTOPUS-I. However, the activity in these systems is still higher than those previously reported((18)), which had urea production of 0.47 mg/Gm of liver. As imposed by any mass transfer device rate limitation, 60% efficacy of OCTOPUS-I brought into OCTOPUS-II, calculated by urea level, is acceptable. What is required for further improvement is mainly oriented to device rather than procurement andpreparation stages. The obstacles in the OCTOPUS-II and -III were, 1) the long time consumed for mounting the slices and assembling the devices before initiation of incubation, 2) inadequate control of incubation media, particularly blood, for oxygenation and pH, which was only for a short period of time but in the critical early stage of operation, 3) possible inadequate flow geometry in the device resulting in mass transfer resistance between the medium and the slices, 4) decrease in effective surface area of the slices, especially in OCTOPUS-III in which only one side of the slice faced the blood, and 5) in OCTOPUS-II, sagging of the slices due to the vertical position of the frames, with eventual reduction of effective surface area. Could a hepatic assist device utilizing liver slices be practical? Daily excretion of urea in dogs is 0.3-0.5 Gm/Kg((31)). Should the urea productivity in OCTOPUS-I(7.2 mg/Gm of liver/24 hrs) be successfully incorporated in a system, 600 Gm of slices can produce the amount of urea equivalent to the daily excretion in a 15 Kg dog. This volume of slices should not be considered unrealistic. Even though it is realized that in the practical situation 60% efficiency is expected, substitution of liver functions does not appear impossible. Further exploration for optimal conditions and practical considerations for improvement of devices will bring the goal closer to reality.