Assessment of blood interactions with the Therapore Apheresis System.

Biocompatibility evaluations are a complex issue involving not only classical toxicity and animal testing but also the interactions of biological systems. The evaluations of the Therapore Primary System are reported for three model systems: (1) in vitro human blood, (2) a baboon (Papio anubis) animal model, and (3) normal human volunteer apheresis. Measurements of both complement (C3a) and platelet (BTG and TXB2) activation products during the apheresis procedures are given as a sensitive indicator of biocompatibility. No statistically significant elevations of these activation products were observed. Thus, the Therapore System was found to have negligible perturbations of the interacting biological systems evaluated even with the highly sensitive RIA procedures employed. These observations and methods establish a solid foundation for comprehensive biocompatibility evaluations of future extracorporeal devices.

Filtration plasmapheresis in vivo.

A continuous-flow filtration plasmapheresis system has been developed as an alternative to conventional techniques for conducting plasmapheresis from blood donors. The system was tested in two stages, nonreinfusion and continuous reinfusion. Donor safety, separation efficiency, and plasma quality were examined. These studies indicate that membrane plasmapheresis is feasible, safe to the donor, and yields sufficient plasma for either therapeutic or component therapy use.

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.