Microporous glassy membranes have high resistances to chemicals and heating and can be regenerated repeatedly by rinsing with chemicals. They also have a limited pore diameter distribution. Both filtration fluxes and protein sievings of those glassy membranes for bovine blood are adequate at pore diameters ranging from 1 to 1.5μm, a transmembrane pressure of 25mmHg an a wall shear rate of 2000s^-1 in the clinical point of view. The filtrate flux is proportional to the -1/3 power of the tube length for variable shear rates. The ultrafiltration theory is not appropriate for explaining the dependence of filtrate flux on hematocrit of the bovine blood. Low temperature plasmapheresis is feasible at transmembrane pressure ranging from 25 to 50mmHg and a wall shear rate of 2000s^-1.

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A hydrophilized polyethylene membrane plasma separator (OP-02) has been recently developed and compared with the existing cellulose membrane plasma separator (AP-02) while used for plasma perfusion under Puthan anticoagulation. OP-02 has a better sieving coefficient than AP-02. Moreover, a new polyethylene hollow fiber membrane filter for plasma perfusion, with effective area of 0.07M²and a pore size of 0.2-0.3μm, has been developed. It has both the capacity of a drip chamber to remove air bubbles and the capacity of a filter to remove microparticles. Basic studies of the filter indicated that 3 L of bovine plasma passed through the new filter at the flow rate of 40ml/min below 20mm Hg in perfusion pressure and that an injection of 5ml of air before the filter increased the perfusion pressure up to 50mm Hg; the perfusion, however, remained smooth. The function of removing microparticles or platelets mixed with perfusate showed satisfactory results in vitro and in vivo experiments. The new membrane plasma separator and the new filter contribute greatly to safe, efficient, easy-to-handle, and microembolie-free plasma perfusion.

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We developped a new immunoadsorbent PC-2, preparing from Cross-linked Agarose (Sepharose CL-4B) and hexamethylenediisocyanate. PC-2 can specifically remove IgG, Anti-nuclear Ab., Anti-DNA Ab., Anti-AchR. Ab., Beta-2-Microglobulin, Immune Complex. and IgG-RF. Especialy, PC-2 Showed 100% adsorption until 240pmol/ml. Thus, we should enable to use PC-2 clinically for Myasthenia gravis, Rhematoid arithritis or other autoimmune diseases. We also evaluated adsorption mechanism of PC-2 by FPLC system and it is found to the interaction between PC-2 and IgG are hydrophobic binding and hydric binding.

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An important facet of this study is to develop new polymeric adsorbent with specific affinity toward a particular subpopulations of lymphocytes. Based on our strategy of separating lymphocyte subpopulations through their differential ionic affinity toward solid-phase matrices, a series of poly(2-hydroxyethyl methacrylate)/polyamine graft copolymers (HA copolymers) was prepared. HA copolymer columns were found to show specific adsorption affinity toward B cells out of a mixture of B and T cells. Further, a partially quaternized HA copolymer (HQA) was found to have a capability of resoluting even T cell subsets, indicating its utility as a novel adsorbent for T cell subsets.

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Anti-A or B antibody was removed by applying the immunoadsorption technique in the kidney recipient candidates in the ABO blood-type-incompatible couples before kidney transplantation. A titer of anti-A or/and-B antibody was/were markedly reduced by each immunoadsorption procedure. Twelve out of 13 grafts transplanted showed or have been showing good kidney function for an observation period of 2-11 months even after rejection episode(s).

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We applied various blood pumps for assisted circulation in 19 cases who has undergone cardiac or aortic surgery for last 6 years. Six cases out of 19 had left heart assist. One case out of 19 had right heart assist. Remaining 12 cases had biventricular assist. In this series three could weaned from the all assist blood pumps and two of these three were survived. Pulsatile assist blood pumps and centrifugal blood pumps are both effective in hemodynamics. Compared to the pulsatile pump, centrifugal pump is easy to use as an assist pump from applicavility, availability and economical view points. Its efficacy is comparable with pulsatile assist blood pump especially when applied with IABP though there still exist controversy as for the superiority of pulsatile flow in ventricular assist.

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Eleven adult patients (pts) received left or biventricular support (BVS) with centrifugal pump for weaning from cardiopulmonary bypass (n=9) and postoperative cardiogenic shock due to ventricular arrhythmia (n=2). Out of 11 pts, 8 (73%) could be weaned from LVS or BVS and 6 (55%) including 2 cases of BVS discharged. All three pts who required BVS had preceding elevated CVP and low pump flow, and all were weaned. As complications, 6 pts had bleeding that needed rethoracotomy and 3 pts had cerebral infarction. While the centrifugal pump has some limitation in durability and antithorombogenesity, it seems useful for temporary circulatory support.

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In cases where a cardiac assist device becomes urgerntly necessary in the ICU, time loss occurs in setting up the extracorporeal circulation by the air driving LVAD. We have experienced two long survived cases through an assist device using a Bio-pump after cardiac resuscitation in the ICU. And consequently, these were all with heparinization. This time, we developed an all nonthrombogenic circuit and centrifugal pump free heparinization. We have utilized this system for cardiogenic shock in 4 patients. At the post-used examination, clots were not seen in the suface of the these parts. This simple, effective system provides for patient support. The parts of non-pulsatile LVAD were separated by (1) centrifugal pump (Bio-Medicus), (2)flow meter, (3) percutanous arterial infusion cannula, (4) left atrial drainage cannula and (5) connecting tube. (1) and (2) were coated by Carmeda Bioactive surface and (4) and (5) were coated by Toray Co. (Japan) with heparin-coating.

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Since 1987, 13 patients with profound heart failure after cardiotomy were supported with the mechanical circulatory assist by a roller pump system using heparin-coated tube. Left heart bypass was performed in seven, right heart bypass in one, biventricular assist in two, and venoarterial bypass without oxygenation was done in three patients. The flow rate ranged from 0.8 to 3.2L/min, and duration of the mechanical support ranged from 5 hours to 21 days. In all patients, no anticoagulation was used during the first three days. There were no significant complications such as stroke, hemolysis, or sepsis. Eight were weaned from the support, and six were discharged from the hospital.

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We have used our automatic VAS in 20 patients (pts) with post-cardiotomy profound heart failure. Twelve of 20 pts were weaned and 3 were discharged from the hospital. We reviewed these pts to clarify the problems in clinical application of VAS. (1) Delayed application of VAS developed multiple organ failure. (2) In our series, LVAS could maintain the circulation with volume loading and catecholamines even if right ventricular failure was coexisted. (3) Evaluation of natural heart (NH) function by echocardiography, automatic level control on left atrial pressure (LAP) and flow, and a composite driving system for LVAS and IABP were practical and effective in hemodynamic control and weaning process from LVAS. (4) LV thrombus were detected in the pts with severely depressed NH function. Intra-LV heparinization was effective to prevent thrombus formation in LV. (5) Possibility of recovery of NH could be predicted from corrected ejection time/LAP. In conclusion, timely application and careful management are important to save the VAS pts.

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We evaluated the hemostatic alteration in patients who were supported by left ventricular assist device (LVAD) because of postcardiotomy heart failure. The coagulation and the fibrinolytic system were strongly activated during prolonged cardiopulmonary bypass. In patients with LVAD, fibrinopeptide A and thrombin-antithrombin III complex increased markedly after the 3rd or 4th day during LVAD. And also fibrinogen/fibrin degradation product and α 2plasmin inhibitor-plasmin complex were markedly increased over entire course of LVAD. It suggests that the anticoagulant therapy including the protease inhibitor are required at least from 3rd and 4th day of LVAD to avoid the thromboembolic or bleeding complica-tions.

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A left ventricular assist device (LVAD) was used for five patients who could not be weaned from cardiopulmonary bypass(CPB) even when intraaortic balloon pumping (IABP)was employed. The LVAD were removed after surgery in 4 patients. One of the four patients from whom the LVAD was removed died in the hospital on the 39th day after surgery because of multiple organ failure. Postoperative course in the remaining three was relatively good and they were discharged in good condition. Two patients are still enjoying their daily life at 46 and 29 months after surgery respectively.

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Temporary circulatory support with a variety of mechanical ventricular assists including IABP, ECMO, VAD with pneumatic pump and centrifugal pump had been undertaken in a total of 123 cases which were associated with severe postoperative cardiogenic shock in 1978-1989 at our institute. This paper describes their perioperative and long-term results. The IABP have been used in 78 patients(pts) and 790 of them could be weaned off the support and 51% survived and discharged from the hospital. The weaning and discharge ratio of the pneumatic VAD were 46% and 23% respectively and 22% and 11% for centrifugal pump. Long term follow up study of IABP cases demonstrated actuarial survival ratio of 82% at 5 years and 51% at 10 years, which were singnificantly low compared to the controlled group. Three survivors of LVAD have been observed for 1.5 to 5 postoperative years. A case after CABG for AMI demonstrated depressed left ventricular contractions with EF of 0.32. Other two cases showed satisfactory cardiac function.

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Three patients were successfully separated from VAS support (2 LVAS & 1 RYAS) and long-survival for 16-29 months were obtained in the Saitama Medical School during past five years. To evaluate the recovery of cardiac function in the late postoperative period, we studied ECG, chest X-ray, echocardiogram, RI angiogram, Holter ECG, and stress ECG with Ergometer (one patient) or Treadmill (two patients) and almost satisfactory results were obtained, although some limitations exist in their daily activities. All patients have returned their previous work. In conclusion, survivors from VAS support have a good chance of resuming active lives and long life-span.

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In order to develop an artificial lung(AL) for prolonged use, versatile approaches are under way in our institute. We established a method for evaluating a long-term performance of an AL by interposing it in the outlet conduit of a right ventricular assist device system implanted in chronic experimental animals. Two types of specially designed microporous gas-exchange membranes with thin dense layer and one novel membrane made of silicone-polyurethane block copolymer were newly developed. Prototype artificial lungs using these membranes were evaluated and all proved to be potential candidates for long-term use. We are also developing two unique devices for long-term gas-exchange, a blood-liquid oxygenator (BLO) and an artificial heart-lung device (ARID). The BLO, in which blood layer was placed between upper silicone oil layer and lower fluorocarbon layer, showed a sufficient gas-exchange ability and an excellent antithrombogenicity. The AHLD, an AL with thrombo-resistant hollow fibers between two pusher-plate type artificial hearts, is promising in preventing blood stagnation, improving gas-exchange efficiency and minimizing the size of total system. We suppose that all of these various approaches, relating one another, are necessary for developing an AL for prolonged use.

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Prolonged extracorporeal lung assist, ECLA, with an artificial lung, requires special expertise. A membrane lung suitable for open heart surgery is not necessarily appropriate for prolonged ECLA. The present status of ECLA and other extracorporeal life support systems with an artificial lung in Japan and abroad is reviewed. For prolonged ECLA, a lung made of non-porous dense membrane hollow-fibers with an external perfusion system is preferable. The lung must be durable for a long period of time with better affinity to the blood, and should not have stagnation in the circuit. An intravenous lung also deserves study for the future. A unique idea to facilitate the intravenous insertion of this lung is introduced.

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A new develolped membrane oxygenator consists of silicone hollow fiber membrane oxygenator, heat exchanger and arterial blood reservoir. As outside flow type is employed in this oxygenator, gas transfer is realized by gravity venous drainage. Animal experiments using 10 sheep were carried out, in normothermic CPB for 8 hours (high flow group 4.7±0.5L /min, low flow group 1L/min). Performances of this oxygenator were evaluated in gas transfer capability and hematological exatnination. Blood gas was maintained with high PO₂ and acceptable PCO₂ levels throughout CPB. Plasma free hemoglobin was significanty low compared with polypropylene hollow fiber oxygenator. Consumption of platelet and fibrinogen was also maintained within physiological levels. These results suggest that this oxygenator has high performance of gas exchange with least blood cell trauma and also useful for pulsatile and/or separating CPB because of arterial blood reservoir.

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Oxygen transfer rate of oxygenators composed of bundles of 1 to 6 and 24 hollow-fibers was compared in O₂-water experiments. The parts where hollow-fibers are in contact with each other do not work for gas exchange. A single hollow-fiber oxygenator had the best oxygen transfer rate, because the hollow-fibers in the single hollow-fiber oxygenator do not contact with each other. By X-ray computed tomography showing blood flow patterns of the 1, 3 and 6 hollow-fiber oxygenators, higher flow rates at the center of oxygenators causing lowering of oxygen transfer rate are observable for the 3 and 6 hollow-fiber oxygenators than that for the single hollow-fiber one. By pulse-response experiments made for flow pattern observation, the single hollow-fiber oxygenator had only one peak in the flow velocity distribution curve, showing no channeling flow exists.

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Veno-venous extracorporeal membrane oxygenation(ECMO) was performed without systemic heparinization using heparin-coated circuits in dogs. ECMO system consisted of a hollow-fiber membrane oxygenator, pediatric centrifugal pump, conventional cannulae and connectors. Reservoir was not used. In group-1(n=6), all systems but centrifugal pumps were coated with heparin using a covalent heparin binding method and ECMO was performed for 12 hours without systemic heparinization. In group-2(n=4), the system without heparin-coating was used under systemic heparinization. There were no apparent macroscopic thrombus formation in both groups. This heparincoated simplified ECMO system showed efficient gas exchange and anti-thrombogenisity without systemic heparinization.

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Oxygen transfer in the curved tube with periodically varying curvature and woven tubes was measured under steady and pulsatile blood flow conditions to evaluate the design features which most effectively augment gas transfer. Under steady and pulsatile blood flow conditions, a wide range of geometrical parameters could be combined to enhance gas transfer performance. As a result an effective design of compact artificial lung becomes feasible.

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We report that high density cell inoculation can be achieved by forcing endothelial cell (EC) suspension through ultrafine polyester fabrics (Filtration method). The purpose of this report is histological evaluation of the efficacy of this method. In addition, we will report here the preliminary results of mixed-seeding of smooth muscle cells (SMCs) and ECs with this method. Canine ECs and SMCs were enzymatically harvested from jugular vein and cultured. These cells were seeded on 7 mm ID low porosity velour woven graft made of ultrafine polyester fiber with filtration method. On 11 grafts, only ECs were inoculated and on another 2 grafts ECs and SMCs were seeded using mixed cell suspension. The proximal portions of these grafts were kept unseeded for the control. After 3-day incubation period, these grafts were interposed into the abdominal aorta of the dog from which ECs and SMCs had been harvested. EC-seeded grafts were harvested 2 to 14 days after implantation. Mixed-seeded grafts were harvested at 7th-postoperative day. In the control portion, only limited EC ingrowth was observed at the border to the seeded part or at the anastomosis. In the EC-seeded part, wide-range endothelialization was observed after three days. Many microvessel formations were observed under EC monolayer. In the Mixed seeded area, EC-like cell monolayer was observed on the wide range but under the monolayer, SMCs-multilayer structure which mainly oriented circumferentially and microvascular formation were also observed. In conclusion, cells inoculated in this method could tolerate to the arterial flow and promote cellular rearrangement including early endothelialization, microvascular formation and multilayer of SMCs.

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Rapid endothelialization by transplantation of autologous tissue fragments into the fabric vascular prosthesis wall was developed. It was applied in a small diameter fabric vascular prosthesis. Ten grafts (4 mm ID and 6 cm in length) impregnated with autologous venous tissue fragments were implanted into the both carotid arteries of S dogs. Four out of 10 grafts were occluded by the graft infection and fresh thrombus within 7 days after implantation. Remaining 6 grafts kept their patency with smooth neointima. Endothelialization in the entire inner surface was noticed at 46 days after implantation. The grafts were thrombogenic, since the tissue fragments contained collagen fibers. Therefore, with powerful anticoagulant therapy, the graft treated with this method will be applicable as a small diameter vascular graft.

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Autologous connective tissue is probably one of ideal materials for vascular substitutes. Animal experiments demonstrated that numerous capillaries, which newly developed in the connective tissue tube wall, opened onto the luminal surface of the grafts and pro-vided colonies of endothelial cells after the implantation to vascular system. This paper introduces the characteristics of an autologous connective tissue tube as a small diameter vascular substitute we have developed. The major properties are as follows: 1) The application of ultrafine polyester fibers (UFPF) for a framework of connective tissue tube: UFPF has high cell-affinity which makes the rapid construc-tion of connective tissue possible. 2) The attainment of temporary antithrombogenici-ty of the graft: This in situ heparinization technique can prevent the early-stage thrombosis of the graft effectively. The results of our studies suggest that autolo-gous connective tissue tube with temporary antithrombogenicity may be applicable to clinical use of a small diameter vascular substitute.

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To evaluate the biological compatibility of GAUV, GAUV grafts were implanted to the aortas of 59 dogs and the specimens were obtained at a period of time from 1 hour to 35 months after implantation. Thrombus free areas were sporadically seen on the luminal surface of the grafts 1 hour after implantation and coincided with areas covered by a thin membrane which was preserved at the time of initial procurement of the GAUV. The human umbilical vein has a well-developed TEL. In 3 of 44 grafts implanted for more than 1 month the luminal surfaces showed no adhered thrombus and the intima at the anastomotic sites was fixed firmly. These grafts have continued to function without anastomotic stenosis even under the conditions of low blood flow rates. To clarify this favourable biological compatibility observed in certain GAUVs, additional 5 GAUVs were also implanted to the aortas of 5 dogs. These grafts were tanned with GA just after delivery in order to preserve the TEL as sound as possible. All grafts were completely free from thrombus adhesion and have continued to have good patency without any stenosis due to anastomotic intimal hyperplasia (All) at an implantation period of up to 4 months. We conclude that the perfectly preserved TEL shows exellent blood compatibility and has the potential capacity to prevent AIH.

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Intra-and inter-dialysis serum TNF-α were evaluated in 34 hemodialysis(HD) patients by newly developed, highly sensitive ELISA method. Pre-HD TNF-α rose significantly in HD patients than in healthy controls, and they nega-tively correlated to the HD period. Dialysate buffer (bicarbonate or acetate) and/or membrane species (cellulose or synthetic, low or high flux) did not affected the pre-HD TNF-α levels. TNF-a did not change during either intra- or inter-HD inde-pendently of the dialysate buffers or membranes. Inter-HD concentration of serum endotoxin increased transiently within normal range, however serum TNF-α did not change. These results indicate that in vivo HD does not provide the increase in serum TNF-α, and the possibility that endocrine action of TNF-α would be induced by in vivo HD may be excluded.

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In the present study we panned to clarify the interaction of dialysis membrane and plasma factor in the production of (OFR) from neutrophils during hemodialysis. Production of OFR were monitored by means of fluorocytometry using 2, 7-dichlorofluororescin diacetate and luminol-enhanced chemiluminescence. It was demonstrated that whole blood containing neutrophils taken from arterial side at time 15 min and/or 30 min after the start of hemodialysis using conventional cellulose acetate (CA), but not cellulose tri-acetate (CTA), membrane genera remarkable amount of OFR. However, Isolated neutrophils floating in the Krebs Henseleit buffer, synthetic plasma, did not showed any evidences of generation of OFR. Moreover, isolated neutrophils stimulated with both of CA and C5a reveled marked response in the production of OFR compared to CA or CSa alone. From these results, it is conclusive that hemodialysis induces generation of OFR depending on membrane materials, and dialysis patients are continuously exposed to OFR stress, which may lead to lipid peroxidation of cell membrane, circula-tory disturbance and so on. It might be necessary to check a production of OFR in case of developing new membrane.

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The membrane-specific adsorption of the uremic plasma solutes is to be considered as one of the aspects of the biointerface between the artificial materials and the blood. In vitro incubation tests of the membrane materials in the uremic plasma revealed the membrane-specific strong affinities for glucagon, PTH, B2-microglobulin, ribonuclease, lysozyme, myoglobin, as well as retinol binding protein. FUT-175, a protease inhibitor, used as the anticoagulant agent, was also discovered the strong affinity for PMMA(B-2) and PAN membrane. The adsorptive eliminations of the plasma solutes or drugs on the artificial materials are to be investigated further more.

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The antithrombogenicity of newly developed heparinized polyurethane(H-PU) coated PVC tube was evaluated by 4hrs temporary A-A bypass in 5 dogs. With the limited shear rate(24.8+5/sec), the H-PU coated PVC tubes exhibited significantly less morphologic change of adhered plateletes in SEM finding compared with pellethane(PU) coated PVC tubes(n=6) and uncoated PVC tubes(n=6). And, it had shown only little spotted thrombus deposited in the four H-PU coated PVC tubes and no thrombus in one. The result of ACT and heparin concentration during bypass within three groups revealed there might be no release of heparin from the new H-PU coated tubes. In conclusion, this study indicated that the new H-PU coated PVC tube probably offered excel-lent antithrombogenicity at the low shunt blood flow.

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The substrate dependency of neoendothelialization was evaluated using an in vitro culture model with bovine aortic endothelial cells. The materials used were glass coated with four types of segmented polyurethanes and three kinds of proteins. The quantitative analysis of cellular behaviors including adhesion, spread-ing, proliferation and migration (velocity and directionality) defined determinant factors for in vitro endothelialization as follows: 1) Substrates with poor adhesive, spreading and proliferative responses resulted in immature endothelialization regard-less of migratory response. 2) The substrate with profound cellular responses in the every process was found to be best-suited for enhancement of endothelialization. Thus, endothelialization is determined by concerted processes of cellular behaviors, each of which largely depends on type of substrate and kind of proteins. This concept may be a logical basis of the development of biomaterial for vascular system.

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The antithrombogenicity was tested by the superior vena cava indwelling method, using Ga-67-fibrinogen and In-111-tropo-lone-platelets. Ga-67-fibrinogen facilitated greater accuracy in the assessment of thrombus formation on the test sample than did In-111-tropolone-platelets. The accumulation of platelets and fibrinogen in the major organs was always to increase as a results of indwelling foreign material. These results showed that it is important to inves-tigate the thrombus formed both on the specimens and major organs.

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A new method for countering the number of adhered platelets on polymer surfaces to evaluate their nonthrombogenicity was developed by using the assay of their adenines in the adhered platelets. This method is simple with high sensitivity and good reproducibility. Moreover, the method is applicable for a wide range of polymers with various properties and shapes. The platelets adhered on the biocompatible copolymers having 2-methacryloyloxyethyl phosphorylcholine (MPC) moiety were compared with those on the conventional materials by this method. It was reconfirmed that the MPC copolymers suppressed effectively the adhesion and activation of platelets.

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We applied the IL-2 mini-pellet to cancer immunotherapy and investigated the antitumor effect of it in 6 hepatocellurar carcinoma patients. The IL-2 mini-pellet was developed on a conception of slow delivery system and it contains 4×10⁶ J. R. U. IL-2. The IL-2 mini pellet was administered into the hepatic artery associating TAE or hepatic arterial infusion chemotherapy. We obtained 1 PR case and 1 MR case after this treatment. Serum AFP decreased in 4 cases. We also performed immunological monitoring of NK, LAK activity and lymphocyte subsets of peripheral blood.

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Catheter-related sepsis (CRS) is a major complication of long-term parenteral nutrition. To prevent a CRS, especially to block a microbial entering from catheter insertion point, we developed a intravenous catheter with percutaneous device made of dense sintered hydroxyapatite(HAp-PD). We tried it 32 times for 28 patients. Catheterization period ranged from 5 to 211 days, and mean catheterization period (76.ldays) is longer than that of conventional catheter (20.8 days)(P<0.01). Catheter sepsis frequency index (CSFI, CRS/1000 catheterization days) is 1.23, also lower than that of conventional catheter(5.69)(P<0.01). HAp-PD fitted to skin tightly without disinfecting treatment, and patients enjoyed taking a bath. This trial proved a clinical usefullness of a catheter with HAp-PD.

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“On-off” regulation of drug permeation through membranes in response to external temperature change has already been achieved using thermosensitive copolymers of N-isopropyl acrylamide (IPAAm) with butyl methacrylate (BMA). It was clarified that increasing temperature induced formation of a dehydrated polymeric surface skin layer that stopped drug permeation. In this study, to control “on-off” permeability of a drug, the polymer surface shrinking process was regulated by changing the length of alkyl side chain of the copolymer methacrylate component. Permeation experiments with indomethacin were performed in response to step-wise temperature change between 20°C and 30°C with copolymers of IPAAm with BMA, hexyl methacrylate (HMA), and lauryl methacrylate (LMA). Burst permeation was found at the initial stage of the second “on” period for IPAAm-co-HMA or IPAAm-co-LMA. These results suggest that drug diffuses to change the concentration profile in the polymer gel during “off” periods. Polymer surface skin formation maintains a localized high water content inside the polymer gel even if drug permeation stops. The length of the alkyl side chain is an important parameter to control “on-off” permeability of drug.

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Design of substrata for cell attachment is very important for the development of biosimu-lator as well as hybrid organ. In this study, we mainly focused ionic interaction between hepatocytes and substrata. We synthesized poly-L-lysine(PLL) derivatives as a cationic polymers and examined behavior of hepatocyte attachment on the polymer. Suitable ratio of cationic group of the polymer for cultured hepatocyte was between 10 and 18 mol% in PLL derivative examined. It was also suggested that there are multiple interactions on hepatocyte attachment to the polymers, which can change depending on culture medium(divalent cation), temperature, time, and so on.

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Five kinds of copolymers containing strene(St) and aminomethyl styrene (AMSt) in various component ratios (AM-10, 30, 50, 70, 90, 100:number suggested AMSt contents in feed) and 4 kinds of blanched copolymers having aminoacyl groups at the side chain (AM-10-III, V, VII, X: number suggested alkyl carbon number in side chains) were prepared by radical polymerization in solution. They are casted on glass plate to get films and investigated wetting characteristics, hepatocytes attaching and growth on their surfaces. The value of surface tention suggested the formation of specific structure on AM-90 and AM-10-III film surfaces against the anticipation that the values of these parameter changed according to the compositions of AMSt in copolymers. AM-10-III showed hydrophilic and AM-90 most hydrophobic. AM-90 surface with FCS and AM-10-III without FCS showed excellent performances on canine hepatocytes attaching, growth and ureogenesis. These functions were well identical to those established in the primary cultured hepatocytes monolayer on collagen coated glass plates with FCS.

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The artificial arm, which was anatomically resembled by two joints and a hand, assembling newly developed artificial muscle using the Shape Memmory Alloy for the gripper (artificial hand), was described in this paper. Firstly, as a result, newly devloped cubic form artificial muscle for the gripper showed both 5mm shortening in length and 58% reduction in volume. Secondly, in stead of moving angle limitation, increasing of the degree of freedom was obtained by the gripper. The third result showed the maximum elevating power of the artificial arm was 4.9N and that of the gripper was 6.5N. From the fourth it could be concluded that this artificial arm will be used actually by lightening the weight by means of internalizing the framework. Final result revealed the fatigue of the SMA artificial muscle was enormously elongated its lifetime by changing heating design.

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Segmented polyurethane films purified by the extraction with methanol were subcutaneously implanted in the back of rats for 21 months. The surface characteristics, mechanical properties and intrinsic viscosity of the retrieved polyurethane films were examined. The opecification appeared on the film surface after 12 weeks of implantation and then developed gradually. However, any apparent fragmentation or damage was not observed during implantation. The ATR-FTIR analyses of the film surface revealed spectral changes characteristic of degradation of polyurethane. Reduction of the bands due to polyether, appearance of ester carbonyl band and reduction of non hydrogen bonded urethane carbonyl band suggested that hydrolytic and oxidative deterioration occurred on surfaces. It is considered that the degradation progressed gradually from the surface to the bulk of film after implantation, since the tensile strength decreased with time and the elongation at failure diminished definitely after 10 months.

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A new heparinization method has been developed to obtain anti-thrombogenic polymers of which anti-thrombogenicity is based on the pharmaceutical effect of heparin. Heparinized polyurethane(H-Pu) was synthesized with this new method, then its anti-thrombogenicity along with the study of behaviors of the heparin in the material was evaluated. At first, several polymerizable cationic surfactants which have a methacrylate group are synthesized. These monomers yield noble complexes which are soluble in some organic solvents to make sonically equivalent bonding with the heparin. Using one of these complexes derived from the quaternary vinyl monomers and heparin, radical polymerization with hydrophilic co-monomer is carried out in dimethylformamide. The Lee-White test revealed an excellent anti-thrombogenicity of the H-Pu. Furthermore, the study of mechanisms of the anti-thrombogenicity using a chromogenic and a prothrombin time method has made it clear that the property is attributed to the effect of retained heparin on the surface of the H-Pu, not of the released one.

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This paper reports development of a solution-castable polymer which can chemically bind proteins. Vinyl copolymers with activated ester groups in side chains were obtained from radical copolymerization of N-acryloxysuccinimide(AOSu) with styrene(ST). The ESCA measurement showed that surface enrichment of ST was observed at lower content of AOSu. However, at higher content of AOSu, anisotropic effect on surface chemical composition was much reduced. The fibronectin-bound surface was found to be cell-adhesive, whereas albumin-bound surface was non-adhesive. Little desorption and exchange of proteins on surfaces were observed for chemically fixed proteins, which was in a marked contrast with those of physically adsorped proteins.

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The purpose of this report is to evaluate an artificial dermis (AD) composed of fibrillar and heat-denatured collagen composites which is dehydrothermally crosslinked in a short time. Three groups of rats were “grafted” the AD on the full thick-ness skin defect, and then secondarily, 0, 1 or 2 weeks after, overlayed auto thin split thickness skin (S.T.S.) on the AD. As a result, each S.T.S, survival rate was 50%, 60%, 90%, respectively, i.e. owing to the appropriate time lag, S.T.S, became survive easily. When the S.T.S, were taken, it showed good cosmetic results with little contracture. Histologically, S.T.S, attached itself on the AD formed pseudo-dermis spontaneously. These findings suggest that this new therapeutic modality by combining AD with S.T.S. graft, provides permanent re-construction for full thickness skin defect.

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CMC/silicone membrane is composed of CMC non-woven fabric lami-nated with silicone membrane, provides better flexibility, permeably, and biocompatibility, and is the high performance material for wound dressing. The following is the description of animall studies, using wistar rats, of the efficacy of a CMC/silicone membrane dressing in superficial skin wound treatment. A superficial skin wound which was treated with the dressing and showed rapid epi-thelization by the 3rd day after surgery. By the 14th day after surgery, the skin wound, that was treated with this dressing, showed no hyperplacia epithlization and little inflammatory cell infilt-ration in granulation tissue. In case of the wounds dressing, using CMC/silicone membrane, resulted in good because this dressing facilitated the moist wound healing condition.

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All (13 pairs) of the rib bones were obtained from 4 mongrel dogs weighting 10-14kg just after sacrificing. The breaking tests using three point bending method were carried out and stress strain diagram were obtained. The breaking strength and Young's modules of each bone were determined. 3reaking strength was 23.9 (±6.6) kgf. Bending Young's modules 185.8 (±107)kgf/mm². The cross head speed influenced to the strength, which suggested that the rib bone has viscoelastisity under the condition of stress.

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Recently, new synthetic absorbable cuff materials (D L-lactic-glycolie acid (80/20) copolymer) with the same composition as that of absorbable surgical suture have been developed in Japan. In experimental studies, we have found previously that this biodegradable material was suitable for use in venous anastomosis as a cuff material, the cuff layer being completely absorbed within 20 weeks after anastomosis in rats. In this study, one year later, there were no stenotic changes in the vascular lumen and the anastomosed site showed no evidence of infection. End-cephalic vein-to-end of radial artery fistula in wrist were created by the cuff method in 11 patients with end-stage renal disease. Only one patient showed venous maturation failure. Ten of 11 vascular accesses created were sufficiently available for hemodialysis, providing sufficient flow of more than 200 ml/min. According to the venous-fistulographic findings, the fistula diameter dilated gradually with time after A-V anastomosis, becoming more than 70% that of the proximal artery 20 weeks later. This finding suggested that this type of anastomosis using a cuff made of the present synthetic absorbable material has sufficient flexibility.

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It has been discussed whether desmopressin acetate (DDAVP) administration reduces blood loss after cardiac surgery. We inve-stigated the effect of DDAVP administration in a randomized, prospective study including 20 patients undergoing cardiopulmonary bypass (CPB) surgery. Twenty patients were divided into four groups: DDAVP administration using bubble or membrane oxygenater, and placebo using bubble of membrane oxygenatero The amount of blood loss and transfusion within the first 24 hours after operation did not differ significantly in the four groups. The mean levels of von willebrand factor antigen, factor VIII activity and ristocetin cofactor after CPB were increased from base line in the four groups. However, the mean levels of these factors immediately before DDAVP administration and 60 minutes after DDAVP administration were not significantly different. We conclude that the patients who undergo cardiac surgery receive no hemostatic benefit from the use of DDAVP in this study, but further studies should be necessary to make clear the effect of DDAVP in cardiac surgery.

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Determination of cardiac output(CO) measured with Swan-Ganz catheter(SGC) depends on the time constant for heat transfer. Clinically used SGC's have thermistors with variable time constant. As a result, currently employed CO monitoring system is not accurate and use of the Stewart-Hamilton equation may cause marked errors The authors propose a new method of determining CO using SGC's with variable time constants using the Newton's law of cooling for analyzing the thermal dilution data. Blood flow rate calculated by the new method for a bovine blood with a perfectly mixtured tank mimicking a natural heart were insensitive to the time constants under the pulsatile and non-pulsatile flow conditions. Results were consistent regardless volume and temperature of the infused saline even after several tests hadd been performed.

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Silicone membrane emits a yellow fluorescence of wavelength 518nm with a use of ultraviolet light of wavelength 416nm. The fluorescence is quenched in the presence of oxygen, the concentration of which can be calculated by an extended Stern-Volmer relation. However, oxygen sensors currently used do not have rapid response to oxygen in liquid because membranes used in the sensor depress oxygen transport rate. The authors prepared oxygen sensors in which silicone membranes containing alkylated decacyclene was used. The membrane were 46.36 to 2057μm in thickness. The alkylated decacyclene concentration in organic solvent was changed from 0.167 to 33.3mol/m³. Using our sensor, partial pressures of oxygen in the air and/or in water were obtained, in spite of variations in temperature or flow patterns. The half life periods of the fluorescence was 70.3ms at the membrane thickness of 46.36 U m. These data support that a thinner silicone membrane makes it possible to develop a more rapidly sensible oxygen sensor.

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Two-mm internal diameter EPTFE grafts with fibril lengths of 15, 30, 60 and 90μm, the outer wall of which has the ridge structure similar to that of Technograft®, were prepared, and these graft segments of 2cm in length were placed end-to-end in the carotid arteries of normal male rabbits (n=48). Eight weeks after the implantation the grafts were retrieved and examined for degree of endothelial coverage, pseudointimal thickening and transmural tissue ingrowth. Luminal endothelial coverage, which exclusively originated from each anastomosis, was significantly promoted in the grafts of 30μm or longer compared with those of 15μm fibril length. We suggest that the rapid endothelialization is a result of a stable thrombotic coverage of the luminal surface of the EPTFE graft, followed by rapid transmural healing attributable to the longer fibril length. No complications, e.g. perigraft hematoma or seroma formation and decreasing patency rate, were found with increasing fibril length.

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