An ultracompact, light weight, completely implantable motor-driven ventricular assist device (VAD) having the overall volume and weight of 285 ml and 380 g, respectively has been developed at Yamagata University. This VAD is pusher-plate, driven by a miniature DC brush-less motor combined with a miniature planetary roller-screw. Currently, in vitro performance and endurance tests are being carried out to assess its capability as an implantable VAD prior to animal study. One of the studies which is addressed in this paper is optimization of the motor velocity control waveform. The performance of the VAD subjected to three different control voltage waveforms were; Type I: fast rise time square waveform for both systolic and diastolic phases with zero control voltage toward the end of systolic phase, Type II: Type I control waveform modified to have a ramp increase in the diastolic phase, and Type III: Typel modified to have a ramp increase the systolic phase. The best pump performance with highest pump flow, minimum power, and highest system efficiency was obtained with Type II control voltage waveform. The required power to deliver pump output of 4-5 L/min ranged from 4 to 6 watts with the electrical-to-hydraulic efficiency being 19-21%. The maximum pump putput was 8 L/min with pump rate of 140 BPM, requiring the electrical power of 9 watts. In order to meet requirements of a completely implantable VAD system, efforts have also been expended to obtain components such transcutaneous energy transmission system (TETS), internal battery system, and compliance chamber as well as to incorporate a built-in polyurethane valve in the pump port. The built-in polyurethane valve should minimize the requrgitant flows of Bjork-Shiley valve and improve the pump performance. Endurance study and animal implantation are being scheduled to evaluate its long-term performance both in vitro and in vivo.

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A rechargeable internal backup battery (RIBB) for a totally implantable artificial heart (TIAH) is required as a backup for the transcutaneous energy transmission system (TETS). We have been developing an externally coupled transcutaneous energy transmission system (ECTETS) as a TETS. This paper reports on the use of the ECTETS to simultaneously power a TIAH and Li-ion rechargeable internal backup batteries as a RIBB. A charge-control circuit consisted of a constant-current and constant-voltage circuit created on an experimental basis, and a push-pull circuit was used as the switching circuit for the ECTETS. The energy from the ECTETS was simultaneously supplied to a TIAH consuming a power of 20 W, simulated by an electronic load simulator, and the charger of the RIBB. As a result, it was found that the time required to charge up was 102 minutes, the outnput power and the DC-to-DC energy transmission efficiency of the ECTETS were 22-35 W and 81-84%, respectively, and the efficiency of the charge control circuit was 91-93%. It is concluded that charging was safely, quickly and efficiently performed, and the ECTETS showed a high enough level of performance to simultaneously power the TIAH and the charger.

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When simultaneously charging a rechargeable internal backup battery and driving a totally implantable artificial heart (TIAH), we must transcutaneously transmit a power of more than 40 W from outside of the body. In this paper, the materials, shape, and section area of the ferrite core used in an externally-coupled transcutaneous energy transmission system (ECTETS) were investigat ed with regard to high-power transmission.A material of low energy loss and temperature dependency in the range of 25-36°C was selected for the ferrite core, and this ferrite core was designed to be shaped like a donut from the viewpoint of easy attachment to the body. Three kinds of transformers (section areas of T1: 126 mm2, T2: 189 mm2 and T3: 242 mm2, respectively) were made experimentally, and the DC-to-DC energy transmission efficiency (with a transmission power of 40 W) of the ECTETS with each transformer was measured in an in vitro experiment. As a result, it was found that the efficiencies when using T2 and T3 were improved by more than 15%, and the temperature rises were suppressed by 50% compared with the conventional transformer. Although acute and the 2-week chronic animal experiments were also conducted with goats, there were no noticeable differences in the results compared with the in vitro experiment. In the animal experiments, the temperature on the ferrite core surface was suppressed to less than 42°C.It is concluded that the ferrite core with a section area of more than 189 mm2 can be used as an externally coupled transcutaneous transformer.KEYWO

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This study was designed to reveal the significance of QT dispersion (QTD) and U waves on perioperative electrocardiograms (ECGs) in patients who underwent coronary artery bypass grafting (CABG) supported with intra-aortic balloon pumping (IABP). The perioperative ECGs of 30 patients were examined retrospectively. Increased QTD was found before CABG in 38.4% of 13 patients with preoperative IABP and in 76.4 % of 17 patients with intraoperative IABP. This finding may suggest a suppressing effect of IABP on ventricular arrhythmogenesis. The ECGs immediately after CABG had significantly fewer U waves and a lower QTD than those before the operation. This may suggest protective effects on the myocardium of both CABG and IABP. Ten patients without U waves and QTD on the ECGs immediately after discontinuation of IABP all had improved or unchanged ECGs at discharge in compari son with those before the operation. In 75% of the patients whose ECGs at discharge were more aggravated than the preoperative ECGs, the leads showing U waves after discontinuation of IABP were identical with the leads having the aggravated findings at discharge. In other 25%, QTD was present on the ECGs immediately after discontinuation of IABP. In conclusion, U waves and QTD on perioperative ECGs may be considered as important indicators for evaluating myocardial ischemia in patients undergoing CABG supported with IABP.

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A 15-day-old boy was found to have TGA (I) and underwent the Jatene procedure, but, could not be weaned from CPB. We carried out 40 hours of assisted circulation used a heparin-coated circuit without heparin in this case. Massive pulmonary bleeding during assisted circulation was successfully controlled by heparin neutraliza tion and the use of heparin-coated circuits. Assisted circulation without systemic heparinization was performed for 40 hours without apparent complications, although thrombus was found at the filter and the reservoir.

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We have been developing a novel integrated heart-lung assist device usable for both emergency and prolonged cardiopulmonary support. The device comprises centrifugal pump and artificial lung components. The lung component, made of a special membrane which precludes plasma leakage in protracted use and enables preprimed setup, is located around the pump component to be a free-of-assembly ultracompact all-in-one system. Heparin is covalently bonded on the device's entire blood-contacting surface to impart good antithrombogenicity. Test lungs consisting of the same membrane preserved sufficient gas-exchange function after 3 months of preprimed storage. Heparin bonded test lungs could be continuously perfused without systemic anticoagulation for as long as 36 days in venoarterial bypass animal study using goats. The prototype device (diameter: 132 mm, height: 54 mm, membrane area: 0.85 m², priming volume: 180 ml) demonstrated a 9 L/min pump output at 400 mmHg pressure head, and 180 ml/min oxygen and 110 ml/min carbon dioxide transfer rates at 5 L/min blood flow. We conclude that this device has the potential to become the next generation of cardiopulmonary support systems.

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In order to develop a hybrid artificial liver (HAL) support system, we have established a hollow fiber HAL module with hepatocytes entrapped in collagen gel. Anchoring hepatocytes to the three-dimensional hollow fiber module with collagen gel has allowed us to realize the highest cell-density culture ever. Intending it for human use, we prepared a large HAL module containing 5.4×10⁹ porcine hepatocytes and then evaluated the module in the acute liver failure model in pigs. During the HAL treatment, the elevation of serum ammonia level was significantly suppressed. The mean survival time of the HAL treatment group was 31.2±3.1 hours, which was significantly longer than those of the sham and the control groups. Improvement of the prothrombin time in response to the HAL treatment was not significant, although the bleeding tendency was suppressed. Even after 12 hr of treatment, the hepatocytes in the HAL module were still viable under light microscopy. Our HAL support system provides adequate liver functions to support acute liver failure in pigs.

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We studied P wave amplitude (PWA) histograms in the patients with implanted DDDR pacemakers. The pacemakers detect PWA automatically every 6 minutes and data are expressed on histograms by eight bins. The subjects were 29 patients (71.7+10.2 ‹SD› years old). There were significant positive correlation between the routine single assessment of the PWA and the peak of the PWA histogram (r=0.601, p<0.001), and between the peak of the first PWA histogram and that of the second (r=0.880, p<0.001). Atrial sensing failures can be estimated by the pattern of PWA histograms. In conclusion, PWA histogram is a useful technique for determining adequate atrial sensitivity; thus atrial undersensing can be avoided.

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A Posture monitoring algorithm using a 3 axis acceleration sensor. Detection of change in the posture of a patient with an implanted pacemaker provides a useful means for diagnosing and treating fainting caused by hemodynamic changes relating to patients' postures. We conducted a study using a 3-axis acceleration sensor, built into a pacemaker. To obtain the variation and detect the change of posture, we twice integrated the absolute values of the vector of the acceleration generated by a movement. But this algorithm easily produces error caused by the integration of even a small noise or offset of the sensor. This resulted in a low detection rate. Therefore we modified this algorithm along more practical lines so as to detect the postural changes. We subtracted the gravity component using a filter rather than constant value. We limited the integration interval to a period of body movement and compensated for kinetic acceleration using centrifugal force from the rotating motion of the body that accompanies posture change. We recorded acceleration during posture changes from sitting to standing and standing to sitting in 13 subjects. The algorithm detected posture changes by the double integration of acceleration signal with a 92% recognition rate from a total of 474 postural changes. This algorithm generated stable detection.

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Reliability of the Atrial Tachyarrhythmia Monitoring Function of the Dual Chamber Pacemaker Atrial tachyarrhythmias are often observed after pacemaker implantation in patients with sick sinus syndrome. The reliability of the atrial tachyarrhythmia monitoring function of the dual chamber pacemaker Thera DRR (Medtronic inc., Minneapolis, USA) was evaluated in nine patients (mean age 67 years±10 ‹SD›) with sick sinus syndrome after pacemaker implantation. Twenty four hour Holter monitoring and atrial tachyarrhythmia monitoring of the pacemaker were recorded simultaneously. Incidence and the total duration of the atrial tachyarrhythmia were measured. There was a significant positive correlation between the total duration of the atrial tachyarrhythmias recorded by Holter monitor ing and by the monitoring function of the pacemaker (r =1.0, p<0.001). There was also a significant positive correlation between the incidence of the atrial tachyarrhythmias recorded by Holter monitoring and by the monitoring function of the pacemaker (r=0.85, p<0.001). In conclusion, the monitoring function of Thera DR ^® is reliable for detecting atrial tachyarrhythmias.

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It is well known that electromag netic interference (EMI) generated from various sources can interfere with normal implantable cardiac pacemaker function. However, no data are available for the pacemakers currently encountered in the market place. In the present study we examined the influence of EMI on in vivo and in vitro pacemakers, with an emphasis on the ambient magnetic field and electric field measurements. Eleven pacemakers from nine manufacturers were evaluated in as close to physiological circumstances as possible. The measured magnetic field strengths from several interference sources encountered in daily life, in the working process, and in medical practice were too low to result in device inactivation, except in medical diathermy and in mobile phone use. Medical diathermy produced a noise response in all devices except Medtronic KAPPA^TM DR and Vitatron DIAMOND^TM II. No pacemaker function changes were seen due to electrical interference. During diathermy exposure, high levels of electrical fields were measured at a distance of up to 50 cm. There were no cross-programming of interaction between pacemakers and inappropriate programmers (different manufacturers). Among the different exogenous interference sources, no pacemaker currently distributed was found to be influenced in a detrimental way, ie: oversensing or no output. Despite our results, EMI cannot be ignored entirely because EMI of increasing variety and complexity are more frequently encountered today.

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From July 1997 through September 1998, 17 patients underwent primary isolated aortic valve replacement (AVR) through an upper partial sternotomy at our hospital. To demonstrate the effect of a modified cardiopulmonary bypass system in minimally invasive cardiac surgery, we compared isolated AVR using an upper partial sternotomy (group M) with a conventional sternotomy (group F). Aspiration to the reservoir was required to actively drain the right side of the heart in the group M. However, lactic dehydrogenase and total bilirubin in group M were not significantly higher. The mean duration of operation, cardiopulmonary bypass, or aortic crossclamp time in group M were not prolonged. There was no operative mortality, stroke, aortic dissection, or perivalvular leaks due to technical factors. The incidence of major morbidity and postoperative factors, excluding the postoperative intubation period, was not significantly different between both groups, although mean flow rate in group M during cardiopulmonary bypass was significantly lower. We concluded that our minimal access incision for isolated AVR does not compromise the quality of operation and reduces surgical trauma.

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To avoid prolonged extracorporeal circulation, we have introduced selective visceral shunting instead of selective visceral perfusion for organ protection during thoracoabdominal aortic operation, and described our shunt circuit and clinical results. Among 47 patients who underwent thoracoabdominal aortic operation between 1991 and September 1998, 40 required reconstruction of the abdominal branches. Of these patients, 18 underwent selective visceral perfusion, 6 underwent selective visceral shunting, and perfusion was converted to the shunt in 4 additional patients. The shunt circuit consists of a 10 mm heparin-bound tube with four independent 6 mm side branches, and provides a free flow of 280 ml/min at 80 mmHg when a 12 Fr balloon catheter is connected. Extracorporeal circulation was terminated after completion of intercostal reconstruction, and the shunt was established and heparin was partially neutralized. A branch of the aortic prosthesis was used as an inflow. No complications related to the use of shunt were noticed. Postoperative hepatic and renal function was satisfactory, as compared with that provided by selective visceral perfusion, which was performed at a rate of 175±35 ml/min/branch under partial cardiopulmonary bypass. Despite the flow limit dependent on hemodynamics, the clinical results of organ protection provided by selective visceral shunting were satisfactory.

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We investigated the effect of hemodilution on cerebral oxygen metabolism during mild hypothermic cardiopulmonary bypass (CPB) Methods: Seventeen adults scheduled for cardiac operations with CPB were studied. The percentage of oxygenated hemoglobin (% Oxy-Hb) measured by near-infrared spectroscopy and jugular bulb oxygen saturation (SJO2) were obtained at six points during CPB. Both parameters in low hematocrit points (group L: Ht<20) were compared with those in high hematocrit points (group H: Ht≥20). The influence of operative management parameters on cerebral oxygenation was calculated by regression analysis. Results: In group H and in group L, the % Oxy-Hb was 54.1±10.9 and 63.8±13.8, respectively and Sj0₂ was 66.9+15.3 and 74.5±16.7, respectively. Both parameters were higher in group H than in group L (p < 0.05). There were significant correlations between the % Oxy-Hb and Ht (r=0.53), PaCO₂ (r=0.32) and Sj0₂ (r=0.54). It was observed that eighty five percent of the % Oxy-Hb over 60% in group L was maintained more than 35 mmHg in PaCO₂, which suggested that although hemodilution had a detrimental effect on cerebral oxygen metabolism, impaired cerebral oxygenation during marked hemodilution was attenuated by high PaCO₂.

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The long-term results of using Hancock porcine bioprostheses in 209 patients were evaluated. Forty patients underwent aortic valve replacement (AVR), 116 mitral valve replacement (MVR), 43 combined valve replacemet (CVR), and 10 valve replacement on the right side of the heart (RVR). The mean duration of the follow-up was 10.5 years (maximum, 20.5 years), and the cumulative follow-up totaled 2147.0 patient-years (PY). The linearized rate of thromboembolism was 0.5%/PY for AVR, 1.7%/PY for MVR, 1.8%/PY for CVR, and 0%/PY for RVR. Freedom from valve-related mortality at 19 years was 81% for AVR, 85% for MVR, 48% for CVR, and 100% for RVR. Freedom from structural valvular deterioration at 20 years was 0% for AVR, 3% for MVR, and 50% for RVR. We conclude that the durability of the Hancock porcine bioprosthesis at 20 years' follow-up is better on the right side of the heart than the left side.

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An investigation was carried out to determine whether or not the tissue factor (TF), a blood coagulation factor, which has recently come within the reach of measurement is useful for monitoring of anticoagulant therapy. The subjects of investigation consisted of 44 patients (22 AVR patients, 22 MVR patients) who were followed after valve replacement and 5 patients (2 AVR patients, 3 MVR patients) in the early postoperative phase (the former and the latter patients are subsequently referred to as groups A and B, respectively). The measurements made were TF, Thrombotest, PT-INR, TAT and D-dimer. The TF of group A was 118-411pg/ml (mean 252.5±64.8pg/ml), and the TF of group B was increased from 177±43.0pg/ml pre-operation to 181±30.5pg/ml 4-7 days after operation. In group A, the TF varied and had no correlation with Thrombotest or PT-INR. In group B the TF remained unchanged in contrast to other tests which showed significant changes. The results of this investigation suggest that TF can hardly provide a tool for monitoring of anticoagulat therapy.

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One of the important purposes of apheresis in immune diseases is to remove EDA (+) fibronectin, which becomes elevated in the plasma of patients with serious rheumatoid arthritis, SLE, and rejection of kidney graft. We developed EDA (+) fibronectin adsorbent (OHC-10), but as described previously, it adsorbed not only EDA (+) fibronectin but also AT III and lipids. We recently developed a new adsorbent (OHC-20) which dose not adsorb AT III. Using 1 ml of OHC-20, a single pass test of 40ml blood was performed in 3 volunteers. Reduction rates were calculated for EDA (+) fibronectin, AT III, fibrinogen, cholesterol, triglyceride, and platelets. The reduction rate of EDA (+) fibronectin was more than 40%. One ml of OHC-20 could adsorb EDA (+) fibronectin in more than 40ml of blood. The reduction rate of AT III was less than 10%. Cholesterol and triglyceride were adsorbed to only a small degree. OHC-20 might be practical for the reduction of EDA (+) fibronectin.

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A novel concept different from the traditional artificial kidney is disclosed to cure chronic renal disease, particularly SLE (systemic lupus erythematosus) which is caused by the existence of an excessive amount of immune complex in the kidney. In this study, a full-length of human tonsil CR1 cDNA was transfected into cultured normal rat glomerular epithelial cells to enable CR1 expression over the long term. After preparing the pathogenic immune complex (IC) of DNA/anti DNA antibody, the binding effect of the constructed cells was examined. As compared with the control cells, the CR1-expressed cells showed a higher binding effect to IC in long period, and the binding effect was demonstrated to be mediated by a complement of serum. Anti-CR1 antibody blocking the binding effect indicates that CR1 plays an important role in the removal of IC. Microscopic observation showing that the CR1 expressed cells enhanced the phagocytosis, may suggest that the mechanism of removal of IC involves the ligand-receptor binding and phagocytosis of the constructed cells. This mechanism may be applicable to patients with SLE in removing the excess IC in vivo.

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In order to enhance the solute removal efficiency of a dialyzer, several types of IFEHD have been introduced for clinical applications. In this paper, the effectiveness of IFEHD was examined during an analytical and an experimental study. As a result of the analytical study, the maximum internal filtration flow rate was increased in a dialyzer with a smaller fiber diameter (D), a larger fiber length (L_eff) and a larger fiber density ratio (FDR). The results of an in vitro evaluation using myoglobin solution showed the same tendencies as those of the analytical study. Development of a dialyzer for IFEHD, however, should take into account the patient's safety.

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Continuous hemodiafiltration (CHDF) is regarded as an effective treatment for fulminant hepatitis and acute hepatic failure. We evaluated the efficacy of maintenance hemodiafiltration (MHDF) in five end-stage renal failure (ESRF) patients with liver cirrhosis. MHDF was effective in improving the hepatic encephalopathy and general condition. After MHDF therapy, blood NH3 levels decreased, blood albumin levels increased and were kept above 3.5g/dl, and Fisher's molar ratio increased. From these results, it is suggested that MHDF for ESRF patients with liver cirrhosis is an effective therapy for not only for prolonging survival periods but also for improving the quality of life.

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«BIOREX AM-BC-X» is a new cellulosic membrane with a symmetrical gradient morphology in pore size distribution in the membrane wall. The pore radius surrounding the middle part of the membrane wall is larger than that of the «BIOREX AM-BC-F». The inner surface is as smooth as that of the «AM-BC-F». «BIOREX AM-BC-X» has some advantages required for hemodialysis membranes, (1) reduced mass transfer resistance, (2) reduced backfiltration of pyrogens from dialysate side into blood side, (3) reduced albumin penetration and adhesion onto membrane wall, (4) adequate mechanical strength, compared with symmetrical, gradient, reversed gradient pore structure membranes, respectively. These characteristic advantages are brought about by the symmetrical gradient pore structure.

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We applied intravascular ultrasound imaging (IVUS) to pre and post intervention therapy of blood access 9 timesfor 8 cases. After sumcient dilation was observed by angiography, IVUS was applied. The shapes that appeared-circular, Dharma, lacerated, confetti-suggested that they were not always sumciently dilated, IVUS isuseful not only in deciding the end point of interventional treatment but also in helping to investigate the cause of recurrence of vascular stenosis.

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Between January l996 and December 1997, 80HDS^® vascular access grafts were implanted in end stage renal failure patients (male/female: 33/47, average age of 59years, diabetes mellitus in39%). The mean duration of hemodialysis at the time of implantation was 3.8 years, and the mean number of previous vascular access procedures was 2.8. Eight grafts were implanted in the forearm, 14 in the form of antecubital jump bypass, 57 in the up Perarm, and l between the brachial artery and the axillary vein. Thirty four grafts were cannulated within 1 week after implantation. The hemostasis after cessation of cannulation was carried out with in 15 minutes in almost all cases. Thrombosis occurred 18 times in 15 grafts, venous stenosis 9 times in 7 grafts, infection 6 times in 6 grafts, graft exposure 8 times in 5 grafts, and seroma 3 times in 2 grafts. The primary patency rates were 63.8% at l year and 53.3% at 2 years. These ondary patency rates were 81.3% at 1 year and 78.3% at 2 years. We conclude that early cannulation of the HDS^® graft can be performed safely, and also that the medium term patency rate of the graft is satisfacto.

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Effects of dissolved oxygen concentration in culture medium on metabolic functions of hepatocytes cultured in a packed-bed reactor. To enable the high-density culture of hepatocytes for use as a bioartificial liver, a packed-bed reactor using reticulated polyvinyl formal (PVF) resin was applied to a primary culture of hepatocytes. Cubic PVF resins (2×2×2mm, mean pore size: 250μm) were used as supporting substrates to immobilize the hepatocytes. By controlling the oxygen concentration at a relatively high level (260-460μM), both viability and metabolic activity of cultured hepatocytes were improved. The highest density of immobilized hepatocytes in the PVF resin reached 2×10⁷cells/cm³-PVF. It is concluded that a packed-bed reactor using PVF resin is a promising means for developing a bioartificial liver.

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Biocompatibility is important to assuring a mild body reaction to and long-term stability and functionality of an implanted device. In diabetes research, subcutaneously implanted glucose-monitoring systems need biocompatible surfaces for the long-term application. The biocompatibility of 2-methacryloyloxyethyl phosphorylcholine (MPC), a material similar to the phospholipid layer of a cell membrane was compared in vivo to Cuprophane (CUP). Hollow- fiber probes used for microdialysis were implanted subcutaneously in 5 rats and 7 healthy volunteers. At set intervals, the implants and, in the case of the rats, also the surrounding tissue were removed and characterized by light and electron microscopy. MPC-coated hollow-fiber probes showed smooth and thin deposits in flat layers, whereas the surface deposits on CUP hollow-fiber probes appeared as rough, irregular, and dense attachments of aggregated cells, proteins and fibroblasts. This study confirmed the results of earlier in vitro tests by showing the biocompatibility and reliability of MPC. Even though the number of proteins and cells attached to the MPC surface was not as low as expected from in vitro experiments, the biocompatibility and long-term stability of the implanted devices were superior to CUP.

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A newly developed novel method for controlling blood glucose is compared with the model predictive controller under continuous glucose infusion. (Method) Continu ous intravenous glucose infusion at rates of 50, 100, and 200mg/kg/h was conducted on pancreatectomized dogs. A new blood glucose control method using a combination of the proportional controller in the initial stage and the model predictive controller in the later stage was compared with the model predictive controller. The parameters of the novel controller were determined from identification of individual responses to the infused insulin during the first 60 min. The parameter of the proportional controller was changed at 60, 90, and 120min, so as to reflect the response to infused insulin. (Results) The model predictive controller could reach the target level in the usual manner at the low infusion rate of glucose. However, under glucose infusion rates of 100mg/kg/h and more, it was difficult to reach the target level within 8 hours. In contrast, the novel controller could reach the target level in 5 to 8 hours. (Conclusion) Addition of the modified proportional controller to the model predictive controller can stabilize the blood glucose control under continuous glucose infusion.

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This paper describes a study of flow analysis in a membrane oxygenator using a CFD (Computational Fluid Dynamics). Extracapillary flow type oxygenators have a structure in which blood can flow freely outside of hollow fibers, therefore, an oxygenator has a complex flow pattern. Gas transfer performance is influenced by the behavior of the blood flow patterns. A slight alteration of the shape of an oxygenator results in different blood flow. In the past, these problems of design have been considered by a trial and error method. Our investigaion has centered on the adaptability of the CFD in the analysis of flow patterns in artificial organs especially for the design of membrane oxygenators. In this study, we simulated the flow-speed and the pressure drop in an oxygenator, and observed how hollow fibers are treated as porous materials. The results show that the CFD was able to visualize the flow patterns in the oxygenator. The pressure drop and the flow pattern were almost the same as these of the in-vitro experimen tal results. Thus, fluid analysis with CFD helps to reveal the flow pattern in the oxygenator and therefore may have an important role in the use of artificial organs.

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In order to measure blood hematocrit inside a magnetically suspended centrifugal pump, we have performed forward light scattering measurement using an optical cell. Backward light scattering measurement was performed with specially designed hybrid optical sensor. In the forward scattering measurement, near-infrared light at 780nm was radiated into a 250μm gap region, the light that scattered forward in the gap region was measured using a photo-diode. Light intensity decreased exponentially with an increase in hematocrit. However, it is theoretically and experimentally possible that the scattered forward light suffered at hematocrit levels around 25-45% due to diffusion effects. In the back scattering measurement, LED light at 830nm was radiated into blood layers of 2cm, the diffuse reflectivity was measured with a photo-diode. As a result, better sensitivity in terms of hematocrit change from 10-50% was obtained, these results correlated well with the hypothesis. A linear regression equation was obtained from the experimental data. The correlation coefficient was 0.9522 (r²) and the RMS error in estimation of Hct was 2.45%.

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We examined the relationship between an autologous platelet con-centrated (Pcon) and the early graft patency in patients undergoing coronary artery bypass grafting (CABG). 42 CABG patients were divided into two groups: In group P (Gr-P: n=18), Pcon was harvested immediately prior to cardiopulmonary bypass and was returned to the patient after heparin neutralization. In group C (Gr-C: n=24), Pcon was not harvested. Both platelet count and aggregation were significantly improved in Gr-P compared to Gr-C after heparin neutralization to two postoperative days. The amount of intra-operative and postoperative bleeding was also smaller in Gr-P than in Gr-C. Post-operative coronary arteriogram revealed that early patency of bypass graft was similar in both groups (90% in Gr-P vs 97% in Gr-C). Pcon has useful effects in terms of blood preservation and the platelet function, and dose not have any harmful effect on early graft patency in CABG patients.

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A novel and simple autoblood transfusion system We have developed a novel roller pump-driven, closed circuit autoblood transfusion system to minimize intraoperative blood loss and transfusion volume. Using a powerful roller pump and a potent in-line blood filter (Auto Vent SV^TM, Pall Biomedical Limited, New York), our system is able to promptly restore and transfuse a large amount of blood in an operative field. A side-line fluid container was used both for priming the circuit and for storing the blood from intraoperative bleeding. To evaluate the potency of our system, we examined its capacity for air venting and its flow-pressure relationship with a mock circuit and 30% glycerin solution. In the circuit flow ranging from 10ml/min to 2, 000ml/min, each air bubble was completely removed from the mock circuit by the blood filter. The flow-pressure relation ship of the system revealed that maximal flow maintained under 300mmHg of the circuit pressure was 270ml/min. Opening the fluid container to the circuit enabled the circuit flow to increase up to 750ml/min for a few minutes. We concluded that our system was safe and efficient for autoblood transfusion. Thus, this system is applicable for both elective vascular surgery and also for emergent cases or unexpected bleeding.

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This paper describes an intracapillary membrane oxygenator for long-term lung assistance. A membrane oxygenator has been used for extracorporeal circulation as an ECMO. However, the major oxygenators, that have microporous membrane, cause plasma leakage that deteriorates performances for long-term circulation. The authors have developed a fine silicone hollow fiber, that is twice the mechanical strength of conventional fibers, with a small diameter and thin wall thickness. The fine silicone hollow fiber has almost the same transfer performance as microporous hollow fiber when it used in extracapillary flow type. However, extracapillary flow type can cause partiality and stagnancy of flow, possibility causing thrombus and reduction in gas-transfer performance. On the other hand, an intracapillary flow type oxygenator can make laminar flow possible in the hollow fibers. It is able to keep gas-transfer performance stable for long-term circulation without thrombus. One of the disadvantages of intracapillary flow type, however, is the large pressure drop. Therefore, the authors have designed and manufactured an oxygenator that has an expanded inlet using the softness of the silicone material and a large number of short fibers for decreasing pressure drop. This intracapillary oxygenator consists of 25000 silicone hollow fibers wth a length of 80mm inserted in the housing. The surface area of the membrane is 3.0m². The priming volume is 390mL. Gastransfer performance of the oxygenator was evaluated by in vitro experiments. Oxygen and carbon dioxide transfer rate were 93mL/min and 87mL/min, and pressure drop was 53mmHg at a blood flow rate 3L/min. The oxygenator developed in this study can be used for extended duration in such application as extracorporeal membrane oxygenator.

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Study of the EDA (+) fibronectin recognition structure on heparin. We carried out research into an absorber to remove EDA (+) fibronectin (EDA (+) FN) from the blood by using heparin. The elucidation of the EDA (+) FN recognition structure of the heparin is necessary for the development of the effective material. In this study, the examination of recognition structure for EDA (+) FN was carried out by using desulfate heparin and the heparin oligomer. The association constant (KA) of EDA (+) FN and the heparin decreased gradually (1.0E+8→1.0E+7M^-1) with desulfate treatment. There was hardly the change in KA with the decline of the molecular weight. As for the EDA (+) FN recognition structure of the heparin, our results showed that it was a low molecular weight level (less than MW=1.0E+3). We also found that the peculiar arrangement structure was not necessary.

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Nonthrombogenic evaluation of the ventricular assist devices coated with 2-methacryloyloxyethyl phosphorylcholine (MPC) copolymer. The nonthrombogenicity of 2-methacryloyloxyethyl phosphorylcholine (MPC) copolymer coated on ventricular assist devices (VAD) was evaluated. The MPC copolymer having a urethane bond in its side chain was coated on a pulsatile pump made of polyurethane. The MPC copolymer-coated pumps were evaluated using a sheep chronic VAD model. After retrieval, the blood contacting surfaces were analyzed by SEM. Very few thrombi were observed on the MPC copolymer-coated pumps, but a significant number of thrombi were observed on the controls at or near the valves. The adhesion of blood components on the MPC copolymer-coated pump was less than that observed on the controls. Staining of the pump with Kossa solution was negative, and calcium and phosphorus atoms were not detected by XPS analysis, indicating that there was no calcification of the diaphragm of the MPC copolymer-coated pump. The blood components adsorbed on the diaphragm of the pump were extracted with a SDS solution, and the protein concentration in the extract was quantified. The amount of adsorbed protein on the MPC copolymer was less than that on the control. The extract was analyzed by SDS-PAGE and immunoblotting method. Fibrinogen was recognized in the extract of both the MPC copolymer coated-pumps and the controls, but the amounts were not equal. These results show that MPC copolymer clearly inhibits thrombus formation even in in vivo long term implantation.

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Development of Bioresorbable Films for Prevention of Retrosternal Adhesions. The purpose of this study was to test the efficacy of three kinds of bioresorbable films of polyethylene glycol (EO) and polylactic acid (LA) (EO/LA =1.5, 2.5 & 3.0) in the prevention of adhesion formation between the epicardium and the sternum in a rabbit model. Retrosternal adhesions were generated by sternotomy, pericardiotomy and abrasion of the epicardium.The adhesion barrier film was placed between the epicardium and the sternum and sutured to the edge of the pericardium. Epicardial adhesions were evaluated 14 days later by assessing area of adhesion. In the control rabbits, tenacious adhesions were observed between sternum and epicardium. When a bioresorbable film was placed over the pericardium, adhesion formation of the epicardium could be prevented. At this site, the area of adhesion formation in the treated groups were 0% (EO/LA=1.5), 8.4±2.8% (EO/LA=2.5) and 5.6±4.7% (EO/LA = 3.0), significantly less than that of the control group (area 78.0±5.8%; p<0.01). The film was completely resorbed at the time of necropsy in group EO/LA= 2.5 & 3.0.The small peaces of resorbable film were observed in group EO/LA=1.5, but they would be absorbed within one month.In conclusion, the bioresorbable films was efficacious in the prevention of retrosternal adhesions to the epicardium.

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Novel poly (ethylene glycol) macromers with a well-defined number of ester bonds (1, 3 or 5 bonds) at both ends were prepared (1, 2, 3, respectively). UV irradiation of several tenths of seconds to mixed aqueous solutions of the macromers and benzophenone-derivatized PEG produced hydrogels by radical polymerization initiated by benzophenone. Gel yield increased with an increase in irradiation time. Hydrophilic properties decreased with an increase in irradiation duration. Gel rupture occurred under strains ranging from about 0.6 to 0.8. The elasticity of the gels was enhanced by an increase in number of ester bonds. After 8 weeks of incubation, 10% for macromer (1), 40% for (2) and 60% for (3) had degraded. Histological examination of rat skin implanted with the gels showed that biodegraded gels were encapsulated and revealed no signs of necrosis. The order of in vivo weight loss was (3) > (2) > (1). Four weeks after implantation, 80% of (3) had been degraded. Thus, these macromers may be useful for biodegradable biomedical materials.

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We have developed a novel manufacturing method for surgical materials with a high degree of mechanical. strength. The final materials were made from extracted collagen alone. Using this method, we made three types of surgical membranes. The base membranes were made from freeze-dried collagen solution in a cast. Membrane A was made from this base membrane. Coating procedures with collagen solution were supplemented to both surfaces of a pressed base membrane. Membrane B1: A base membrane is soaked in collagen solution and heat treatment in vacuo and compression was added. Membrane B2: The soaking procedures were carried out twice on a base membrane and it was then pressed. All membranes were heated in vacuo as a final heat treatment. Microstructural observation showed that the surfaces of Membrane A were coated with dense amorphous collagen layers and that B1 and B2 increased in the number of collagen layer piles. Though Membrane B1 did not have strong enough mechanical properties to resist being cut by a suture under wet conditions, Membrane A and B2 did have sufficient strength to resist cutting. Because our manufacturing method is easy and not costly, it is applicable for various surgical materials.

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Aims: We manufactured a new type of spongy hemostat (Oxy-Col) made of oxidized cellulose fibers and atelocol lagen, and hemostatic effects and degradation were examined in in vivo experiments. Methods: A solution of atelocollagen acetate mixed with oxidized cellulose fibers were frozen, and freeze-dried. The dry material was exposed to a dehydrothermal treatment. The splenic capsule was resected in three places, as a bleeding wound models, in five dogs. The hemostatic effects of our new Oxy-Col hemostat, a cotton-like oxidized cellulose hemostat (Oxy) and a cotton-like chemically cross-linked fibrous collagen hemostat (Col) were compared in each bleeding wound. Results: The number of complete hemostatic wounds and the minimum time required for hemostasis were 5 of 5 wounds and 2.8 min for the Oxy-Col hemostat, 5 of 5 wounds and 4.0 min for the Col hemostat, and 3 of 5 wounds and 5.0 min for the Oxy hemostat. Re-bleeding was not observed in the Oxy-Col-treated wounds. Conclusion: Oxy-Col is a suitable hemostat material to apply to bleeding wounds, resulting in a rapid hemostatic effect.

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The application of atelocollagen solution to a lacrimal duct occlusion. Occlusion of the lacrimal duct improves the symptoms of dry-eye syndrome. Currently, temporary occlusion of the duct is carried out through the insertion of a collagen-rod, silicone, or plastic plug. However, these devices often cause an unpleasant foreign-body sensation as well as corneal epithelial injury and accidental dropout. To solve these problems, atelocollagen neutral solution, which forms a gel at body temperature, was tested as a means of occluding the lacrimal duct through its injection into the rabbit duct (n=6). All the cases tested resulted in complete occlusion of the duct, and this effect was maintained for 7 weeks in 3 cases. Since atelocollagen solution can be injected along the lacrimal duct to form an elastic soft gel, regardless of variations in its shape and size among individual cases, this novel device may provide an excellent way of treating patients with dry-eye syndrome with much less foreign-body sensation.

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For evaluating necrosis inhibitory ability of lymphocytes after contact with PHEMA PSt-PHEMA ABA-type block copolymer (HSB) surfaces with a microdomain structure, the mitochondria swelling of the lymphocytes was analyzed quantitatively by computerized transmission electron micro scopic image analysis (CTEMIA). Also, the glycocalyx of the contacted lymphocytes on the HSB surfaces was analyzed by transmission electron microscopy (TEM). The lymphocytes made contact with the PSt, PHEMA-PSt random copolymer and Biomer surfaces were analyzed by TEM. Intact lymphocytes were used as the control. The mitochondria and glycocalyx of the lymphocytes on the control polymer surfaces were not analyzed by CTEMIA and TEM, respectively, because the lymphocytes were disrupted. The mitochondria size and the entire glycocalyx of the contacted lymphocytes on the HSB surfaces were the same as that of the intact lymphocytes. It was found that the HSB surfaces inhibited necrosis of the contacted lymphocytes, in contrast to the response of those on the control polymer surfaces. It was suggested that the microdomain structure surface of the HSB inhibited lymphocyte necrosis by keeping the glycocalyx structure of the lymphocyte. [Abbreviations: PHEMA, poly (2-hydroxyethyl methacrylate); PSt, polystyrene]

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Structural design for artincial organs and tissue engineering: Microporing of elastic mms by excimer laser ablation and evaluation of them echanical properties. Two series of microporous segmented polyurethane films (thickness: 30μm) were prepared using excimer laser microprocessing: one series of films was designed so that the pore diameter was fixed (100μm) but the relative pore area varied (3.1 to 34.9%), and the other series so that the relative area of the pores was flxed (3.1%) but pore size was varied (9 to 100μm). Upon extension of the films, linear stress-strain relationships were observed for nonporous and microporous films up to about 30% of deformation. Young's modulus decreased with increases in the relative pore area, but was almost the same between variations in the pore size. Control of the micropore design (pore size and number) allowed for control of the mechanical properties of an elastomeric film that may be useful as a scafrold substrate for hybrid artificial organs, and for tissue engineering.

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Molecular Design of Functional Artificial Extracellular Matrix: Thermoresponsive Gelatin Thermoresponsive gelatin, partially grafted with poly (N, N-isopropylacrylamide) (PNIPAM), was molecularly designed for an artificial extracellular matrix. Photo-induced “iniferter” based graft copolymerization of PNIPAM produced thermoresponsive gelatin. The phase transition of dissolution/precipitation occurs at around 34°C. Upon coating of the aqueous solution, cell adhesion and proliferation proceeded at physiological temperature. Cellular detachment and sheet-like tissue delamination occurred at room temperature. A tube-like structure of endothelial cells was formed using a capillary glass tube coated with the thermoresponsive gelatin. The mixed coating of PNIPAM-gelatin and PNIPAM produced cell adhesive matrices with a wide spectrum of cell adhesiveness. This enabled to monoclonal cell harvesting from different cell types, which was demonstrated with bovine endothelial cells and smooth muscle cells.

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In patients with chronic renal failure, volume control of dietary water is essential to daily life. Once the water accumulates in the body, followed by the absorption intake into the circulatory system through the gastrointestinal tract, there are no exceptional methods by which hemodialysis or continuous ambulatory peritoneal dialysis (CAPD) can remove stocked circulatory water. We have developed a new method using a super absorbent polymer that could absorb water in the gastrointestinal tract before absorption by the intestinal mucosa. The super-absorbent polymer comes in the form of a powder but is transformed to jelly just after contact with water. After administration of the polymer to the stomach, it is excreted as soft feces. As described previously, in rats with acute renal failure, this polymer suppresses increases in body weight and constipation, and might contribute to a longer survival time than that of not treated with the polymer. In this study, we evaluated intestinal water absorption using the super-absorbent polymer, which is made from polyacrylate sodium, polyacrylate calcium, and N-vinylacetoamide with different particle diameters, mixed with water, saline, and artificial gastric and intestinal juices. Polyacrylate sodium absorbed the largest amounts of fluid, 640 ml/g in water, and polyacrylate calcium absorbed the least. Nvinylacetoamide had an intermediate absorbent capacity independent of the particle size. When used with human intestinal juices, the same highly reproducible results were obtained in terms of water absorption, and the constitutional components (TP, electrolytes, pH, osmolarity) after absorption were not significantly different in N-vinylacetoamide, but the significant increasing of Na in polyacrylate sodium, calcium in polyacrylate calcium were seen. The super-absorbent polymer might be a useful tool for clinical application in patients with chronic renal failure, and these materials should be further developed and optimized.

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Preparation of hydrogel microbeads using photocurable hydrophilic polymers: Drug immobilization and cell entrapment. Three types of photocurable polymers, including photodimerizable N, N-dimethyl acrylamide (DMAAm) copolymers having cinnamic acid or coumarin groups (1 or 2, respectively), and photo-induced radical producing DMAAm copolymer having dithiocarbamate or benzophenone groups (3 or 4, respectively), and PEG end-capped with benzophenone groups (5) were prepared. Ultraviolet light (UV) irradiation to phosphate-buffered salines of each photoreactive polymer (1-4) or (5) with PEG diacrylate stirred into liquid paraffin produced hydrogel microbeads. On the other hand, UV irradiation to a mixed solution of the photocurable polymers and a bioactive substance such as heparin, Protein G and salicylic acid, and cells, resulted in an immobilization of the bioactive substances into the produced beads. The characteristics of the release of the immobilized substances from the beads were controlled by the irradiation conditions and gel composition. When cells were mixed with the copolymer (2), the beads entrapped the cells and functioned as a matrix for cell growth.

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Albumin-coated grafts (ACG) were implanted into the abdominal aorta in 47 patients between October 1993 and August 1998. The postoperative systemic inflammatory reactions were compared in patients receiving an ACG prosthesis versus preclotted Dacron grafts (Bionit^TM: BN). The indication for surgery for the ACG group was abdominal aortic aneurysm (AAA) in 24 cases, occlusive disease (ASO) in 19, and AAA combined with ASO in 4 cases, and for the BN group was AAA in 1 and ASO in 5 cases. The postoperative systemic inflammatory reaction was evaluated by measuring the body temperature, the WBC counts, and the C reactive protein levels. No significant differences in these parameter were observed. The ACG were easily handled and sutured. One graft for the ACG group was occluded 13 months after surgery due to poor run-off. No complications related to the graft including graft infection and aneurysm formation were observed during the follow-up period. ACG eliminate complicated preclotting procedures and are useful in avoiding major complications during aortic surgery.

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A clinical study of a newly developed prosthesis coating with gelatin was carried out to evaluate its efficiency as a zero-porosity prosthesis. From January 1995 to October 1996 those prostheses were used in 79 patients, of which 20 were for the thoracic aorta, 53 were for the abdominal aorta, and 6 were for the iliac artery. Clinical studies were completed in 66 patients. Therein such factors as suturability, hemorrhage, hemostat and flexibility, and the 6 month patencies of prostheses were evaluated. Changes in the blood cell count, chemistry, and body temperature were also studied. The results indicated that the surgical suitability was excellent and patencies of all prostheses were good except for one iliac artery occlusion. Though the body temperature of all patients was elevated after surgery along with the WBC counts and C-reactive protein values, these elavated values represent an ordinary inflammatory response after surgery. It can therefore be concluded that the new prosthesis has many clinical advantages and shows good performance as an artificial graft.

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