Adaptability between the artificial organ and the human body is discussed citing the prosthetic heart valve (PHV). The first point is the adaptability of PHV to the heart. Requirements of PHV for clinical use are the design and material to obtain good hemodynamics, low incidence of thromboembolism and durability. Through the history of PHVs, both mechanical and bioprosthetic valves, there have been no ideal PHVs, and try and error has been repeated on their development. Today, pyrolitic carbon as the material of the mechanical valve and the new preservation method of the bioprosthetic valve are expecting. The second point is the adaptability of indication of the heart to PHVs. That is, how to use available PHVs effectively and safely for the diseased heart is an important problem irk practice. The author discuss this thema citing enlargement of the small aortic ring for aortic valve replacement and modified mitral valve replacement with preservation of posterior leaflet, chordae and papillary muscles in order to maintain contracting function of the left ventricle.

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Segmented polyurethanes (SPUs) have been enjoying the first-class reputation as a basic material for blood pumps. Our experiences with SPUs showed that 1) long-term antithrombogenicity of hydrophobic SPU was controlled by newly-proposed hypothesis (multilayerd protein passivation mechanism), 2)hydrophilic SPU exhibited lesser degree of biological responses in vitro and short-term ex vivo, associated with hydrogel-like structure, and 3) enhanced hemocompatibility of hydrophilic SPUs can be easily incorporated with controlled release characteristics of anticoagulant.

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Our hypothesis for an antithrombogenic material is to generate the surface structure which minimizes the attachment of blood components. This requirement is expected to be met by creating a thin layer with a very high water content onto the material surface. We call it the diffuse layer. Such a novel surface can be produced either by the graft coupling of water-soluble macromolecules or by graft copolymerization of water-soluble monomers onto the base material. It has been found that the grafted surface strongly refuses both protein adsorption and platelet adhesion in vitro and thrombus formation in vivo, if the amount of grafted polymers is in an adequate range.

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Important factors related with the blood-compatibility of two kinds of synthetic hydrogels were reported. First example is polymeric hydrogels combined with heparin by ionic bond. It is important for preventing the thrombus formation that a minimum effective concentration of heparin is kept in the stagnant layer of the blood flow on the surface of the hydrogel. Second example is polymeric hydrogels without heparin composed of methacrylate having polyethyleneglycol side chains. It is suggested that both the molecular mobility of the side chain and the dynamic structure of water in the hydrogel correlate with excellent blood-compatibility of the hydrogel.

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A plasminogen activator, Urokinase (UK) was covalently immobilized on different kinds of polymer surfaces to provide antithrambogenic materials. The activity of the UK on each material maintained for more than 2 years at the room tatperature. The UK-immobilized tubes were clinically applied as drainage tubings and as intravascular catheters. They all worked well and patency of the UK-treated tubes was superior to that of non-treated tubes. Deposit of neither fibrin nor fibronectin was observed on the surfaces of clinically applied UK-immobilized tubes.

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By the technique of tissue culture, delayed seeding of the cultured canine endothelial cells, which were derived enzymatically from the vein, was applied to dacron graft. The seeded graft was implanted to the femoropopliteal system of the same animal. Microscopically monolayer pattern of the seeded endothelial cells were found on the flow surface.

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Plasma exchange combined with hemodialysis has been currently used for reliable and practical hepatic support. In order to improve our hepatic support system, a surfactant-free polyolefine membrane plasma separator has been developed and evaluated to be better than conventional ones in both efficiency and biocompatibility. And also, a new module of Ionex, saturated completely with heparine, has been developed for safe and efficient adsorbent, which selectively adsorb bilirubin and bile acids.

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Hepatic assists were performed in 69 patients with acute liver failure. The survival rates are 18 percent in Charcoal Hemoperfusion, 17 percent in PAN-Membrane Hemodialysis, and 17 percent in Plasmapheresis, respectively. The features of clinical datas in survived patients were below 15mg per deciliter in serum bilirubin value, and below 150mg per deciliter in plasma total aminoacids concentration. The occurence rates of the cerbral edema were over 50 percent of all the patients. We think the cerebral edema might be influenced on the severity of alkalosis in arteral pH of the patient.

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Plasma exchange using cellulose acetate hollow fiber has been applied to patients with hepatic failure. 8 out of 43 patients with fulminant hepatic failure and all 8 patients with acute fatty liver of pregnancy were survived.
Even in fatal cases of fulminant hepatic failure, the prolongation of survival time was shown to be possible by daily repeated plasma exchange. These clinical results indicated that plasma exchange was effective in treatment of hepatic failure. Elevation of APP in serum indicated to be cured.

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Chronic long-term plasma exchange treatment has been safely carried out in two cases with postoperative biliary cirrhosis. Of 4 cirrhotic patients who acutely fell into hepatic failure postoperatively, only one could survive. Of. 7 patients without cirrhosis, 3 who did not have any complications could survive. In patients alive, increases of serum bilirubin after surgery were gradual and the abnormality of plasma amino acids before treatment were moderate, compared with those in patients died.
In postoperative liver failure, not only plasma exchange but combined modality therapy for in fection must be necessary.

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The present study was undertaken to investigate the indication and the limitation of plasma exchange in the treatment of hepatic failure. All the patients, whose arterial ketone body ratio was less than 0.2 or whose serum osmolality gap was not normalized by the plasma exchange, were nonsurvivors. Furthermore, there were no survivors among the hepatic failure patients secondary to liver cirrhosis. These results indicate that the plasma exchange for the hepatic failure has its limitation and that the indication of this treatment should be considered very cautiously.

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There were eleven patients with fulminant hepatitis undergoing plasma exchange therapy (PEx) from 1974 to 1985 in our hospital. The present study was designed to clarify the adequacy and limitation of PEx to fulminant hepatic failure. (1) The patients who suffered from more than four complications were died, and most of them had commonly the combination of acute renal failure, infection and DIC. (2) Bilirubin kinetics can be explained with one compartment model in the short time related to the therapy. These results lead to the assumption formula to determine the exchange-plasma volume necessary to reduce the serum bilirubin concentration to the given level (3) Bilirubin appearance rate advocated by us at the present time might be useful as one of indices to predict the prognosis of the fulminant hepatic failure and control the exchange-plasma volume.

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Infectious complications in maintenance hemodialysis patients will be divided into two categories; (1)those related to pathophysiology of underlying end stage renal diseases which required hemodialysis and (2)those related directly to hemodialysis procedures per se. Maintenance hemodialysis patients are compromised hosts affected by immunological deficiencies most likely due to decreased cellular immunity. This condition is greatly influenced by degrees of chronic anemia, malnutrition and metabolic abnormalities.Clinical data reveal that maintenance hemodialysis patients show a high incidence of infection and most common type of infections are those related to the blood access devices, pulmonary and urinary tracts, which often result in the cause of death.

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Seventy-one cases were studied regarding peritonitis (P). Overall incidence of P was one episode every 20.1 patients month (PM). The incidence of P in the group continuing CAPD was remarkably lower (one episode per 27.5 PM) than that of the withdrawn (one episode per 11.6 PM). P occupied the half of the causes of withdrawal. Patients on CAPD showed no significant difference in serum IgG levels, granulocyte count and T-cell function.

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The ability of a host defence in chronic hemodialysis patients was investigated, by studying the function of immunocompetent cells and the influence of the reactions, which may occur during hemodialysis (HD), on their functions. The impaired activities of polymorphnuclear cell, T cell, natural killer cell Sand killer cell were observed, and these functional impairment can not be always recovered by the blood purifications inclusive of HD and hemoperfusion. The cause of these incomplete recovery from the functional impairment may be partly related to the protein-binding inhibitor. The activations of the compliment system, arachidonic acid cascade and other reactions, which may occur during HD, can play some roles in functional impairment of the immunocompetent cells, and the elucidation of whole interrelationships between activation of these reactions and immune response needs further investigation.

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Infections of permanent pacemakers were studied in 505 cases. Mean follow-up period was 5.6 years (2832 patients years). Twenty cases had infected pacemakers. In 13 cases, infection. which was considered to be related to operation was observed in 6 months after the previous operation. The other 7 cases showed exposed pacemaker in more than 1 year after the last operation. Exposure of pacemaker had disappeared by the use of lithium pacemaker of small size. Strictly aseptic managemant in operation was thought to be necessary to diminish pacemaker infection.

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Among 1918 openheart cases from 1981 to September 1985, 328 cases required assisted circulation (17.1%). IABP in 319 cases (97.2%), V-A bypass in 26 cases (7.9%), LV bypass in 6 cases (1.8%) and LVAD in 1 case (0.3%). Its longevity depends on the prevention of infective complications. Reduction of blood access in assist devices seemed to be important. Prosthetic valve endocarditis is the severest complication and translocation of artificial aortic valve from infected focus was introduced.

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Thirty-eight consecutive patients with prosthetic valve endocarditis (PVE) between 1964 and 1985 were reviewed. Twenty-four patients had aortic (A) PVE, 10 had mitral (M) PVE and 4 had A+M PVE. Sixteen patients had early PVE, and 22 had late PVE. 15 (39.5%) had positive blood culture. Twenty-six patients were treated with medical therapy and 5 patients eventually survived. Twelve patients consisting of 5 early and 7 late PVE had combined medical and surgical. therapies. The indication for surgery were congestive heart failure, systemic emboli and persistent sepsis. Surgical techniques were excision of infected valve, debridement of infected tissue and replacement of cardiac valve prosthesis. Three patients with aortic root abscess (ARA) had translocation of the aortic valve. Four patients (33.3%) died postoperatively. Three patients had re-operation for perivalvular leakage and 3 died in the late postoperative period. Surgical timing and surgical technique for active PVE with ARA are still unsolved problems.

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Clinical application of partial artificial heart (PAH) for 3 patients associated with profound postoperative ventricular failure was reported. PAH's were applied for left heart in, 2 cases and for right heart in one case. Duration of cardiac assistance were 7 days in 2 cases and 70 days in one case. Of the three, 2 cases weaned f ran PAH and one case became the first longterm survival in Japan. Installation technique of PAH along with problems and care during postoperative period were discussed.

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[in Japanese]

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Automatic LVAD system consisting of an automatic level control (ALC) system for LAP and total flow (IF) has been used in 7 patients. At the beginning the bypass flow (BF) stayed high to keep LAP at 0-5 mmHg and to maintain IF at 3.0-3.5 L/min/m . During the recovery stage, the preset level of LAP was gradually raised. ALC of LAP worked and subsequently BF decreased. The patients' entire circulation was well maintained during the period of 3-15 days. Appropriate, safe and automatic circulation control during profound heart failure and subsequent recovery were achieved by our automatic LVAD system. However, the patients eventually died of multiple organ failure which developed during prolonged ischemia prior to LVAD assistance. Timely use of LVAD by right judgment is important.

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Thirty-four calves and five sheep were operated for total. artificial heart replacement since February of 1980. Two different sized Thomasu hearts were used for these experiments. We are still confronted by two major problems of durability and thrombus formation.

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In August, 1982, after completion of our ventricular assist device, we are using these devices for three patients at present. Two of them have been weaned off the devices successfully, while the remaining one depended. Although long-term survival was not obtained, dramatic effect were observed in all three cases. We pointed out about problems of the ventricular assist device--clinical application, pump, adjustment of the device and multiple organ failure.

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Ten-years clinical experiences with vascular surgery for arterial and venous reconstructions by using prosthetic vascular graft were reviewed. The study includes 240 cases of arterial reconstruction and 35 cases of venous reconstruction. As prosthetic vascular grafts, crimped Dacron graft. Sauvage double velour Dacron graft and e-PTFE graft, ranging 6 to 24mm in size, were used. A 3-year graft patency rate is 97% in aorto-ilio-femoral bypass with Sauvage graft and 80% in axillo-femoral bypass with same graft. Graft patency in e-PTFE graft used for venous reconstruction was also encouraging, with 1-month patency rate of 73%. A case of Budd-Chiari, treated by bypassing the obstructed IVC with 16mm e-PTFE graft, is doing well 4 years 7 months after operation, showing patent bypass graft. Problems to be solved in future for prosthetic vascular graft would be a development of new graft for reconstruction of small artery and peripheral vein.

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Though the use of autosaphenous vein has generally been accepted as the first choice of graft for the reconstruction of small caliber arteries, it is limited in term of supply, size and breakdown. Therefor, vascular prostheses.for a small caliber artery is now needed, and EPTFE, human umbilical vein and Davcon EXS prostheses have been used clinically. Recently newer vascular prostheses are under development, by means of more anti-thrombogenic materials, tissue culture technique and complianced polymeric materials.

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From our surgical experience upon vascular grafts, currently available vascular prostheses are satisfactory in the reconstruction of aorta or large artery. On the other hand, there are still many problems to be overcome in clinical application of vascular prosthesis to vena cava and small sized artery.

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Reconstruction of the aorta and its major branches using fabric vascular prostheses are now done with almost satisfactory results. The main complications, such as graft infection, aneurysm formation at the sites of anastomosis and delayed graft bleeding are markedly diminished by modification and improvement of the graft material as well as operative procedure. On the other hand, the operative results using vascular prostheses in the region of small caliber artery are still far from that of autovein. Relatively favourable results are obtained in the group of prostheses with smooth inner surface such as Biograft and PTFE. But the incidence of anastomotic intimal hyperplasia causing late graft occlusion seems to be characteristically high in this group. It is essential to investigate the preventive method for anastomotic intimal hyperplasia together with searching for highly blood-compatible material in order to improve the operative results. The advent of PTFE and modified umbilical vein homograft make a surgeon to be easy of access to venous reconstruction.

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Some problems of vascular grafts used in clinic were reported. Many investigations of the development of new vascular grafts were introduced and interpreted. High porous vascular prostheses made of knitted dacron have a good ability of the neointimal healing, however, their most serious demerit was the bleeding from the graft wall even after enough preclotting, because of the f ibrinolysis of the host. Low porous one indicated no bleeding, however, the neointima healed poorly. As for the new technique to give an antithrombogenicity to the vascular grafts, the heparinization method and the anticoagulant effect of segmented polyurethanes were explaitied, The characteristics of the future grafts were also discussed, for example, a graft which has a strong resistance against micro organisms, a growabl e graft, a venous graft with valve, etc.

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Ex vivo and in vivo studies on continuous arteriovenous hemofiltration (CAVH) were carried out using two different hemofilters: Diafilter-20 (Amicon, Mass, USA) and PAN-50P (Asahi Medical, Tokyo, Japan). The ultrafiltration rate (UFR) and sieving coefficient (SC) were obtained from dogs in which uremia was induced by bilateral ureteral ligation. UFR was entirely dependent on blood flow (Qb) and the pressure difference between hydrostatic transmembrane pressure (TMP^H) and protein oncotic pressure, and it inversely correlated with hematocrit. SC for urea, creatinine and electrolytes was 1.0, and that for inulin was 0.8. No deterioration of UFR or SC for inulin wass observed with operation under spontaneous pressure difference. When CAVH, slow continuous ultrafiltration (SUF) and continuous hemofiltration (CHF) were applied to patients with overhydration who were resistant to conventional therapies and to those with multiorgan failure including acute renal failure, the clinical effectiveness was excellent in the patients with intractable overhydration and cardiac failure. Although mortality of the patients with multiorgan failure was still more than 75%, the control of these patients was better with CAVH and CHF. Therefore, these methods have better therapeutic potential in controlling multiorgan failure including acute renal failure.

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In its true sense of the word, CAPD cannot be defined as an artificial organ, for the process utilizes bilogical peritoneum as a dialysis membrane. When the ability to maintain the life of uremic patients is considered, however, it should be included in the family of artificial organs in a broad sense. Some characteristic aspects of CAPD as an artificial organ include (1) artificial vessel in view of the possibility to be performed in patients without blood access, (2) artificial pancreas in view of a favourable administration route of insulin in the patients of insulin-dependent diabetes induced chronic renal failure, (3) artificial endocrine organ in view of the ability to prevent delay of catch-up growth in pediatric uremic patients. Needless to say, the most important role is (4) artificial kidney.
The most remarkable characteristic of CAPD in comparison with dialysis, Hype artificial kidney is (1)low efficiency of diffusion and ultrafiltration, (2) continuous and persistency of the treatment mode and (3)biocompatibility. These merits of CAPD have resulted in the simplification of the modality and safety, bringing about lack of dysequilibrium syndrome, stability of cardiovascular system, easily obtainable high UFR, allowance. for liberal intake of food and water for patients.
The target of reserch and developement in the field of dialysis type artificial kidhas hitherto been high efficiency associated with complex mechanical apparatus and monitors. CAPD uncurtained some blind spots which is worth being incorporated into R-and-D of artificial organs. This paper intends to review those productive blind spots.

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High efficiency dialysis is needed for short time dialysis. Therefore, it is important to increase blood flow rate, to use hemodiafiltration and to prevent disequilibrium syndrome. Short time dialysis (3 hours x 3 times a week) was performed with Push/Pull HDH. The blood flow rate was 300ml/min. High sodium bicarbonate dialysate and the oral administration of L-carnitine were used to prevent disequilibrium syndrome. For the two hours dialysis, 500ml/min of blood flow rate is necessary. Therefore, short time dialysis for three hours three times a week is the most practical method.

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CAPD and CHF are our kinds of portable artificial kidney, but they have such a weak point as infection, or restrict of activity. So we are developing the wearable artificial kidney, which contain some kinds of adsoebent in order to regenerate for the dialysate. This new artificial kidney has some problems. 1) There was no adsorbent which adsorb urea directly. 2) Alumina, which is used for adsorbent of phosphate, has side effect such as bone or brain disorder. 3) It is very difficult to make a light wearable artificial kidney because of too much of adsorbents. In order to solve such problems we are developing new urea and phosphate adsorbents and new type container of adsorbents, which can be changed easily. But still now, more effective adsorbents are expected to make more small wearable artificial kidney.

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Several characterization parameters have been introduced for performance evaluation in hemopurification systems. In this paper, validity of these parameters were elucidated during in vivo and in vitro experiments. Whole blood clearance could be applied for U. N. but not for creatinine and U. A. by a comparative analysis for mass transfer rate between blood and dialysate sides. Although several sieving coefficient (SC) derived from different definitions have been already presented, real SC was obtained as the intercept of the ordinate by a relation between the reciprocal of inlet flow rate and apparent SC.

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This study was conducted to make clear the advantages and disadvantages of elimination of large molecules by using a dialyzer of higher cut-off point than that of conventional one. A dialyzer with a higher cut-off point, known as a KF-101-12C dialyzer, was compared with a conventional Cuprophan membrane dialyzer AM-10 for removal of low molecular weight proteins. Nine low molecular weight proteins were removed with hemodialysis by the KF-101-12C dialyzer that were undetectable by the AM-10 dialyzer. A cross-over study on 27 long term dialysis patients with the KF and AM-10 dialyzers was made. The erythrocyte count, hematocrit, and hemoglobin levels significantly increased with the KF-101-12C dialyzer. However, together with the β₂-microglobulin decreased, and the plasma total cholesterol, triglyceride, and HDL-cholesterol increased on the KF-101-12C dialyzer. It is clear that a new membrane has to developed that would have a sharply increased rejection rate for substances larger than albumin.

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There are many problems to be solved to perform hemodialysis without using any anticoagulant. The purpose of this report is to review these problems and compare chemical changes in blood of long-term nonanticoagulant hemodialysis patients with the blood coagulation and platelet functions of heparinized hemodialysis patients.

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Various types of membranes with different pore structure have been applied for various methods of blood purification, such as plasma separation, plasma fractionation, hemofiltration and hemodialysis. Filtration characteristics of different types of membranes i n blood filtration were discussed. Filtration flux and sulute sieving closely relates to membrane types and membrane properties. Optimal operating condition for each membrane type and selection of membrane types must be considered in various methods of blood purification.

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We injected [C]-phosphatidylcholine (PC) -labelled lipo-heparin into rats to investigate the prolonged effect of lipo-heparin in vivo.The radioactivity of [C]-PC in plasma was cleared very rapidly from the circulation (about 5% of the injected dose at 5min) whereas the anticoagulant activity of heparin remained until 90min. The degradation of [C]-PC in plasma was not detected by TLC. However, almost all radioactivity was taken up in 10min by liver and spleen suggesting that the prolonged effect of lipo-heparin may be due to the gradual release of heparin from liposomes entrapped in those organs.

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A new method to heparinize the biological materials was developed. The materials can be given a cationic group by the covalent bondwith glycidyl trimethyl ammonium chloride (GTMAC). GTMAC has two special groups, i. e., the epoxide group and the quaternary ammonium group. The epoxide group of GTMAC can react easily with the amino groups, hydroxyl groups, and the carboxyl groups of the biological materials. The quaternary ammonium group has positive charge, so that it can retain a strong ionical complex with a negative charged substance. Therefore, heparin can bind ionically to GTMAC which has bound to the biological materials already. In vitro experiment, we reported the both the content and the distribution of heparin in the materials can be controlled exactly with those of GTMAC binding to the materials. The heparin contents in the materials was in the ranges of 30 to 60units/cm². The other in vitro experiment of the release behavior of heparin from the materials showed that about 50% of the original heparin in the material released into PBS solution 1 week after the implantation, and 60%, after 3 weeks. While, in vivo experiments, a vascular grafts of 3mm in internal diameter was heparinized and implanted into the femoral and carotid arteries of the experimental dogs. The grafts showed perfect antithrombogenicity as a small caliber graft. The other in vivo experiment of the heparinized collagen suture inserted into the peripheral veins also showed excellent antithrombogenicity of this heparinization method in the venous system. From these results, this new method was approved as 2 effective and simple method to give an antithrombogenic property to the biological materials.

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There are two methods of V-V bypasses during anhepatic phase. The one is the forced circulation method (Group I) and the other is the circulation without pump using heparin coating tubes (Group II). In this report we studied the differences between these two methods. And the results were as follows: 1) In the Group I, the hemodynamics were kept in stable during bypass. 2) In the Group II, the hemodynamics were markedly unstable and they showed the cardiac failure. Therefore, it was suggested that the venous return was disturbed in the Group II. We conclude that the forced circulation method using pump may be the better way in the V-V bypass method during anhepatic phase of the orthotopic liver transplantation.

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A venous bypass method using Anthron® catheter that does not require the use of systemic anticoagulation or pump is used during anhepatic phase of experimental liver transplantation. The safety and efficiency of this bypass-method were proved by the studies of systemic hemodynamics, and blood coagulation and fibrinolysis.

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Hemostatic effect of collagen sponge to which protamine is covalently bonded with hexamethylene diisocyanate was tested for hemostatic effect at bleeding site of dong's spleen. Hemostatic time of the sponge decreased proportionally to protamine content up to 5% (W/W), it showed constant minumum time in protamine content over 5%. Collagen sponge containing 5% protamine indicated hemostasis time as quick as a quarter of regular collagen hemostatic sponge without protamine.

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