When using a rechargeable battery for an energy source outside the body, it is necessary to reduce the input voltage of the ECTE TS (Externally coupled transcutaneous energy transmission system). Three types of ferrite cores, that were toroidal, “O” and “θ” -shaped, were made on an experimental basis, and the attachability of the transcutaneous transformer to the body surface was also investigated. As a result, it was found that in an in vitro experiment, the input voltage to the ECTETS with a Push-pull type converter was reduced from 61.3 V to 28.7 V for a transmission power of 20 W and from 73.4 V to 32.0 V for that of 40 W, in addition, the DC-DC energy transmission efficiency was 76.9-86.5% at an output power of 5-40 W. The results obtained from the in vivo experiment were almost equivalent to those from the in vitro experiment, in addition, the ECTETS performed stably in the chronic experiment, and had no problems related to viewpoint of rises in temperatures. Further, an EHTAH (Electrohydraulic total artificial heart) was driven by the ECTETS. As a result, we found that a left ventricular output flow of 4.8-7.9l/min (heart rate of 60-90 bpm) could be obtained. The attachability of the “O” and “θ”-shaped ferrite cores were favorable in comparison with the toroidal core.

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This paper reports on the measurement and evaluation of electromagnetic disturbance for a transcutaneous energy transmission system. Radiated emissions from two types of transcutaneous transformers, referred to as coreless and externally coupled, respectively, were measured by a probe for near magnetic field, and these measured near magnetic fields were converted into electromagnetic fields according to a regulation of VDE-0871. The coreless transformer showed radiated emissions of 71.0d BμV/m, while the emissions of the externally coupled transformer were 53.4d BμV/m, the former emission exceeded the regulation of VDE-0871 by 0.9d BμV/m. The radiated emissions from the latter with a current resonance-type inverter were suppressed by 13.8d BμV/m at the third harmonic wave and by 11.8d BμV/m at the fifth harmonic wave compared with the non-resonance-type inverter. Although the conducted emissions from each of the two transformers were suppressed by using the noise filter and the ferrite beads, the emissions from the coreless transformer exceeded the regulation of VDE-0871 by 17.4d BμV at the fundamental wave, and were increased at frequencies larger than 10MHz by off-resonance caused by body motion. It is concluded that the externally coupled transcutaneous energy transmission system performs well in terms of electromagnetic compatibility.

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We have been developing an externally-coupled transcutaneous energy transmission system (ECTETS) for a totally implantable total artificial heart (TITAH) When a patient takes a bath or if some emergency of transcutaneous energy transmission occurs, the energy backup system must switch the energy source from the ECTETS to a rechargeable internal backup battery (RIBB). Then when the transcutaneous energy transmission has been restarted, the energy backup system must switch the energy source from the rechargeable battery to the ECTETS in order to drive TITAH and charge the RIBB. In this study, an energy backup system that can automatically switch energy sources without any discontinuity of the energy supply, was designed and manufactured on an experimental basis. Further, the performance of the energy backup system was evaluated in an in vivo experiment by implanting the secondary coil of the transcutaneous transformer and the RIBB (consisting of a series connection of seven Li⁺ rechargeable batteries) enclosed in a titanous canister in the goat body. As a result, it was found that the switch from the ECTETS to the RIBB requires 100ms and from the RIBB to the ECTETS 50ms. The total efficiency of the ECTETS with the energy backup system was 73-97%, and the temperatures of the implanted devices were less than 40.5°C. It is concluded that the ECTETS with an energy backup system performs adequately.

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The transcutaneous energy transmission (TET) system under development for the electrohydraulic total artificial heart system was evaluated in a chronic animal experiment. The internal coil of the TET system was implanted in the left chest wall of a goat weighing 39 kg. An energy of 20 W for 23 hours and an energy of 40 W for 1 hour a day were transferred continuously through the skin with the TET system. The surface temperatures of the external coil and the internal coil, and the energy transmission efficiency were measured. The results show that an energy-transfer efficiency of 82-85% was successfully maintained for more than 4 months, and the rise in temperature in the implanted parts was within acceptable limits. In conclusion, our TET system has sufficient practicality in terms of its stability and durability.

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Implantable lithium-ion rechargeable batteries that are used for a rechargeable internal backup battery (RIBB) for a totally implantable artificial heart were manufactured on a n experimental basis and encapsulated in a titanous canister. The electrical characteristics and the temperature rises of the RIBB in charging and discharging processes were evaluated in in vitro and in vivo experiments. The in vivo experiment was carried out in the body of the goat in which the RIBB was implanted. As a result, the electrical characteristics of the RIBB in charging and discharging processes differed little between the in vitro and in vivo experiments. Although the temperatures of the canister surface in the in vitro experiment rose to 43.4°C during the charging process and 43.2°C during the discharging process, those in the in vivo experiment were suppressed less than 40.0°C during the charging process and 39.7°C during the discharging process. It seems that the in vivo temperature rises were suppressed by the cooling effect of the blood flow. Further, in the in vivo experiment, the temperatures of the RIBB were measured in a 4-cycle continuously repeating process of charging and discharging. By this method, it was found that the temperatures rose to 39.6°C in charging and 39.8°C in discharging, which is within the permissible temperature limits for the body. It is concluded that the Lithium ion rechargeable batteries manufac tured on an experimental basis for use in this study are suitable for use in an RIBB.

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In this study, an ultracompact, lightweight, completely implantable pulsatile ventricular assist device (VAD) intended for 50-60kg-size patients was developed. The overall volume and weight of this VAD are 285ml and 380g, respectively. The in vitro tests were carried out to assess the device's capabilities. The mean pump output of 4-5l/min could be obtained with the pump rate of 80-100 BPM against the mean afterload of 100mmHg. The tri-leaflet valves made of polyurethane were used for inflow and outflow valves of VAD after comparing three types of artificial valve. Currently we have completed improvement on the device, and the development of a completely implantable VAD system including a transcutaneous energy transmission system (TETS), internal battery system, and a compliance chamber have been advancing. In an experimental using Ni-MH battery, increasing the number of batteries was found to extend the drive time of VAD but the efficiency decrease due to the increase in the input power. In addition regulating the input voltage of batteries to the 15-16V optimum drive voltage of VAD could drive VAD with high efficiency of 23-24% for 2.5h.

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The integrity of the shaft seal is a critical factor in the success of an implantable centrifugal blood pump. A precision mechanical seal has been developed to address this requirement. The seal incorporates a recirculating cooling water system to provide lubrication and prevent deposition of blood elements. The objective of the current study was to experimentally evaluate the sealing properties of this mechanical seal in vivo. The leakage rate of plasma into the cooling water through the mechanical seal was measured by monitoring the infiltration of sodium ions from bovine blood. Measurement of the concentration of sodium ions was performed using inductively coupled plasma light emission analysis. The leakage rate of the cooling water into the blood through the mechanical seal was measured by monitoring the volume of the cooling water in the reservoir. Over a period of 153 days, the leakage rate of plasma was 0.022ml/day and the leakage rate of the cooling water was 0.497ml/day. In conclusion, the mechanical seal performed acceptably well to support its use in a centrifugal blood pump for chronic application.

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Although the left ventricular assist device (LVAD) is an effective method of treating the severe heart failure, some people require a biventricular assist during the early phase. As common ventricular assist devices consist of a pulsatile pump, control methods for the biventricular assist device (BVAD) with continuous flow pumps are rarely reported. Using 5 piglets, we set a BVAD with continuous flow pumps via left thoracotomy. Global ischemia was induced for 30min by clamping the base of the ascending aorta. After unclamping the aorta, the analysis of pumping performance was evaluated every an hour for over 6 h reperfusion. To detect ventricular collapse without any specific sensor, we calculated the index of current amplitude (ICA) from motor current waveforms and simultaneous mean current values, and applied these data when controlling the BVAD. The RVAD speed was determined by setting the target LVAD flow and target ICA value. Using the LVAD target ICA value, we could set the RVAD flow rate to match cardiac function. Using the known pump flow or the pump-flow estimation can be one method of controlling BVAD with continuous flow pumps.

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To estimate the performance of skeletal muscle ventricles in terms of long-term safety, a simple system of measurement was developed that employed Boyle's method and avoided the need for a flowmeter or cable. The accuracy of this system was tested by constructing skeletal muscle ventricles from the latissimus dorsi muscle of adult dogs. The performance at afterloads of 30mmHg and 80mmHg was measured by a simple method using Boyle's law and also by a control method using a transit-time ultrasonic flowmeter and a pressure-volume loop. With the simple method, a 6.0% and 7.3% underestimation was observed in the measured stroke volume. A 28.0% and 18.7% overestimation was observed in calculated stroke work at afterloads of 30mmHg and 80mmHg, respectively. It is important to take care when estimating the performance of skeletal muscle ventricles with the simple method because of the significant overestimation of the stroke work.

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We have developed a dilatable cannula to reduce the inflow resistance of a bloodcircuit and increase the efficiency of assistance during left ventricular bypass. The inner diameter of the cannula is controlled by using shape memory alloy (SMA). A single wire of SMA, the diameter of which is 0.28 mm, is knit a tubular shape. The dilated shape of the tube is “ memorized ” when it is heated. Afterword, the diameter of the tube of SMA is decreased by hand. Finally, the SMA tube is covered with silastic rubber. Heating the cannula allowed dilation of its diameter to 175% that obtained at the room temperature. The effect the cannula's dilation on decreasing its flow resistance was examined. The pressure difference between the inlet and outlet of the cannula decreased to one-half that of a nondilated cannula at the same flow rate.

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In the roller-pump-driven cardiopulmonary bypass system, inadvertent kinking or bending of the blood stream tube may cause abrupt changes in circuit pressure and produce fatal damage to the system and/or a patient. To avoid this type of hazard, we invented equipment with which CPB circuit pressure could be used to regulate the rotation cycle of the roller pump. After checking its efficacy in vitro, we investigated its clinical usefulness and safety in 598 cardiovascular surgical CPB cases. In 596 of them, our equipment was used as a safety guard both in the inlet and outlet circuit of the CPB system, and in the remaining two as a constant flow modulator. For the former purpose, our equipment worked promptly and immediately produced an appropriate alarm. No harmful changes in circuit pressure were observed. The restoration of the CPB system was also prompt and smooth after resolving any kinks or bends in the tubes. In the latter cases, satisfactory constant blood flow could be maintained. In conclusion, our pressure-feedback regulator equipment could offer safe and effective management of CPB. Furthermore, it can be useful in the further automation of the CPB system.

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As an artificial material comes in contact with blood during extracorporeal circulation, it will rapidly adsorb protein onto its surface. This adsorbed protein layer will determine all further events, namely, the activation of contact phase, coagulation systems, platelets, leukocy-tes, and complements. In a previous report we discussed Poly2methoxyethylacrylate (PMEA). PMEA suppresses the adsorption and denaturation of plasma protein. In the present study, a PMEA-coated oxyge-nator (Group P) was compared to a heparin-coated oxy-genator (Group H) and a non-coated oxygenator (Group N) under conditions of in vitro circulation using human blood. The results of this study indicated that in comparison to Group N, Group P allowed retention of a significantly larger percentage of white blood cells and platelets in blood and production of a significantly smaller amount of Bradykinin, TAT, β-TG, and PMN-elastase. There were no significant differences between Group P and Group H. After 6 h, circulation adsorbed protein on the oxygenator was extracted and analyzed by immunoblotting. It was considered that the adsorbed amount of fibrinogen on the Group P membranes was smaller than that of Group N. Group P showed biocompatibility equal to that of Group H. It was co-nsidered that the biocompatibility of Group P was mainly due to lower level of protein adsorpton, as well as being a result of the lower degree of denaturation.

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Hypothermic cerebral perfusion is one of the commonly used methods for cerebral protection in aortic arch surgery. To reduce the adverse effects caused by hypothermia, we used a modified selective cerebral perfusion technique, called cool head-warm body perfusion, during the period from January 1990 to March 1999, for 61 patients with aneurysm of the ascending aorta or aortic arch who underwent aortic repair using selective cerebral perfusion. Three perfusion techniques were used, differentiated by body temperature: deep hypothermia (nasopharyngeal temperature of 20°c, n=14) (DH group), moderate hypothermia (nasopharyngeal temperature of 28°c, n=17) (MH group), cool head-warm body (nasopharyngeal temperature of 25°c and bladder temperature of 32°c, n=30) (CHWB group). The three groups were compared in terms of duration of cardiopulmonary bypass and operation, intraoperative blood loss, and operative outcome. Operation and rewarming time was significantly shorter in the CHWB group than in the other groups. Cardiopulmonary bypass time was significantly shorter in the CHWB group than in the DH group. Blood loss was significantly less in the CHWB group than in the DH group. Postoperative awakening time was significantly shorter in the CHWB group than in the other groups, and postoperative intubation time was significantly shorter in the CHWB group than in the DH group. Hospital mortality was 14% in the DH group, 12% in the MH group, and 7% in the CHWB group. Stroke occurred in one patient in each group (7% for DH, 6% for MH, 3% for CHWB). No difference was observed in the rate of hospital mortality or stroke. These data suggest that cool head-warm body perfusion in aortic surgery is a useful and safe technique.

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Selective cerebral perfusion (SCP), , used for brain protection in aortic arch aneurysm surgery, has been improved by the introduction of the cannulation technique. From 1991 to 1994, arterial cannulas were inserted into the bilateral axillary arteries and the left common carotid artery through each stab wound (Group A, n=12). From 1995, arterial cannulas were inserted through the ostia of the three arch vessels after incision of the aneurysm (Group D, n=27). Cerebral perfusion flow, pressures and cerebral complications were examined in these two groups. The total cerebral perfusion flow in group D was significantly higher than that in group A. The cerebral perfusion pressure in the left common carotid artery in group D was significantly lower than that in the left temporal artery in group A. Permanent brain damage occurred in one patient of group A (8.3%), and in three patients of group D (11.1%). Temporary brain damage was diagnoesd in one patient of group A (8.3%), and in three of group D (11.1%). In conclusion, in group D, anesthetic induction time became shorter and the procedure of SCP could be simplified. No significant differences were observed in incidence of cerebral complications between the two groups.

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Cerebral blood flow during mild hypothermic cardiopulmonary bypass (CPB) was investigated by measuring the blood flow velocity of the medial cerebral artery (MCAV), ophthalmic artery (OAV), and common carotid artery (CAV), and the regional cerebral oxygen saturation (rSO²), in 5 adult patients who underwent cardiac surgery. Maximal blood flow velocity in the medial cerebral artery (MCAVmax), ophthalmic artery (OAVmax), and common carotid artery (CAVmax) were measured with Doppler ultrasonography. MCAVmax, OAVmax, and CAVmax before CPB were 25.9±3.6cm/s, 28.3±14.5cm/s, 62.5±28.8cm/s, respectively. When CPB pump flow was varied 2.4 to 2.0l/min/m², the parameters during and after CPB changed as follows: MCAVmax, 93.2%, 83.8%, 131%; OAVmax, 47.6%, 46.7%, 161%; and CAVmax, 69.3%, 70.7%, 213%. rSO ₂ was 72.4±3.7% before CPB, 70.4% and 68.5% during CPB, and 71.8% after CPB. Because MCAVmax was maintained during CPB and less increased after CPB compared with OAVmax and CAVmax, autoregulation was thought to be preserved during mild hypothermic cardiopulmonary bypass. It was determined that 2.0l/min/m ² of CPB pump flow in mild hypothermic cardiopulmonary bypass was adequate, based on changes in rSO ₂.

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Embolization due to gas bubbles is one of the potential hazards associated with extracorporeal circulation during cardiac surgery. To decrease this risk, an arterial line filter was used as an additional safeguard against the release of gas bubbles. On the other hand, use of a hollow fiber membrane-type oxygenator is also very common in the clinical application. The hollow fibers of these oxygenators are cross-wound, or woven together. These fiber structures function as a bubble filter like arterial line filter. In this study, we suggested a new measurement method of bubble trap performance and investigated the trap performance of a membrane oxygenator. In the in vitro experiments, we measured the air trap performance (AirTP) and the bubble trap performance (Bubble TP) using a microbubble detector. Our results showed that the SPIRALGOLD oxygenator was found to perform better as a BubbleTP than did the AF1040 filter. Moreover, the BubbleTP was considered a valid parameter for assessing filtration function. The feature of the membrane oxygenator and its trap performance suggested the possibility of using smaller extracorporeal circuit without an arterial line filter. In the future, we can use the Bubble Trap Performance test to design an optimal model, test its application, and thereby contribute to the development and effectiveness of the membrane oxygenator.

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In-Vitro evaluation of various kinds of clinically available coronary stents has been performed in order to establish a standard test methodology. First, a silicone tube with an internal diameter of 3 mm was fabricated as a model for the coronary artery. The model provides an equivalent Young's modulus to the natural vessel. Then, changes in the ratio of the stent diameter (elastic recoil) were measured after deflation of an inserted balloon. Radial changes caused by external pressure on the tube were also measured (radial strength). As a result, elastic recoil remained within 6% at the maximum, and radial strength decreased linearly with a range of 0-200mmHg. The maximum of radial strength was 5% at 200mmHg. Secondly, an artificial coronary circuit was developed and installed into a pulsatile flow-type mock circulatory system, where arterial pressure and flow waveforms could be reproduced that were similar to those of the human coronary arteries. The pulsatile flow test revealed that a subsequent change in stent diameter was achieved by a change in a pulsatile coronary flow. However, the maximum change amounted to only 1.5% in the radial direction.

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The purpose of this study is to evaluate the early results of the use of the Carbo-Seal^® composite graft for aortic root replacement. Between June 1997 and January 1998, 5 patients underwent aortic root replacement using either the with open technique (n=4) or Ross procedure (n=1) concomitant with right ventricular outflow tract reconstruction (RVOTR) using Carbo-Seal. Three patients had undergone previous aortic valve replacement, two had Marfan syndrome, and one had active Behcet disease. There were no operative deaths nor postoperative complications related to the use of Carbo-Seal. During the follow-up period, one patient died of traumatic cerebral hemorrhage. The remaining patients were well and free of conduit related complications at a mean follow-up of 22 (range: 19-27) months. Carbo-Seal is a reliable composite graft in an aortic root replacement or RVOTR during the Ross procedure.

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Protein C (PC) deficiency or protein S (PS) deficiency is known as thrombophilia. It sometimes causes coumarin necrosis. We experienced aortic valve replacement of two cases with PC deficiency and one with PS deficiency. The three cases showed 50 to 63% PC or PS activity and had a positive family history. They must be heterozygotes of those disease. We compared perioperative changes in coagulation system and later courses in outpatient clinic between these three cases and other 17 patients without thrombophilia who underwent single cardiac valve replacement. On the first postoperative day, the average PC and PS activity of the normal 17 patients was 81.4% and 60.0%, respectively. The PC activity of the two patients with PC deficiency was 50% and 53%, and PS activity of the case with PS deficiency was 49%. There were no other hematologically significant differences between the two groups. At the outpatient clinic, we prescribed warfarin to all the cases until the level' of thrombotest was lowered to 20±5%. The PC or PS activity of the three cases with thrombophilia was observed to be 20% or more. No episodes of bleeding or thromboembolism were observed in any of the 20 cases. A patient with PC deficiency encountered a peripheral aneurysm 5 years after the AVR. The mycotic aneurys was thrombosed 4 days after the suspension of warfarin in this case. PC and PS are dependent on vitamin K. Heparin is effective in these cases, so we can safely use the conventional cardiopulmonary bypass with heparin. In the late phase of treatment of the outpatient clinic, careful prescription of warfarin appears to be also effective in stabilizing the coagulation system, even in patients with PC or PS deficiency.

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Oral anticoagulant therapy is most commonly monitored by the PT-INR and thrombotest, but bleeding and thromboembolism sometimes still occur in patients with value within the therapeutic range. An investigation was carried out to determine whether or not the Carinactivase-1 (CA-1) method, which has recently become feasible for laboratory use, is an useful monitoring of anticoagulant therapy. The subjects inctuded in the investigation consisted of 7patients in Group A (3AVR, 4MVR) who were in the early postoperative course and 105 patients in Group B (57AVR, 45MVR, 3AVR +MVR) involved in long-term postoperative follow-up care. CA-1 (the normal prothrombin level, CA-1) remained unchanged, similar to PT-INR and thrombotest, at the beginning of treatment with warfarin in Group A. CA-1, normally within the range of 115.2μg/ml, decresed to 50.8μg/ml in Group B. In conclusion, the results of this investigation suggest that the CA-1 is a potentially useful method for monitoring anticoagulant therapy.

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The Jyros valve, the leaflets of which can be rotated in an orifice ring by spiral flow, was also shown to have the unique characteristic of less energy loss than that of other types of valves. This study was carried out to further examine precise hydrodynamic characteristics of the valve. The Jyros valve was placed at the aortic position of a spiral vortex pump (SV pump) fixed in a mock circuit. Pressure gradient at the valve was measured with pressure transducers. Another experiment was conducted under the same conditions, in which we fixed its leaflets in place so that they could not rotate within the ring (fixed Jyros). In addition, the movement of the valve was analyzed with a high speed video camera. The results from these experiments were as follows: (1) The valve leaflet rotation occurs at the late systolic phase, when the valve begins closing, and (2) during this phase, pressure gradient at the valve was lower by 3 mmHg compared to the fixed valve under usual drive conditions. Based on the above results, the valve rotation is shown to reduce flow resistance under the rotational flow condition.

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We investigated the correlation of atrial dipole position and the ability to pace the atrium. We performed electron beam tomography (EBT) in ten patients implanted with a single-pass lead for permanent VDD pacing (Medico Phymos 830-s lead). The distance from the proximal electrode to the atrial free wall was measured. Simultaneous with the EBT, we evaluated atrial pacing thresholds. The mean atrial thresholds at 12months of follow-up were 0.3±0.2 ms at 5 V in 4 patients (low threshold group; LTH) and 1. 3±0.5ms at 5 V in the remaining patients (high threshold group; HTH). In the LTG, the mean distance to the free wall of the right atrium from the proximal electrode was 3.8±0.7mm and that of the HTH was 7.4±2.6mm. In conclusion, single-pass lead DDD pacing by a Medico 830-s lead enabled effective and reliable atrial pacing clinically if the proximal electrode was positioned within 4mm of the atrial free wall. Thus, atrial pacing was achieved when the proximal electrode was in direct contact or very close proximally to the free wall of the right atrium, while single-pass lead DDD pacing was extremely difficult under the condition that the proximal electrode was free floating.

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Frequent cracking occurring on the surface of segmented polyurethane has called for a revival of the silicone elastomer (SE) as pacemaker lead. SE has suffisient biocompatibility, but is diffisult to handle and its durability needs to be improved. Given that a diamond-like carbon coating on SE was expected to improve these aspects, we examined the efficacy of DLC. A DLC-coated SE (DLC) tube was compared with non coated SE (SE) tube. The friction resistance of DLC was less than 25% that of SE. Intravascular placement of either material in the rabbit jugular vein yielded equal tissue compatibility. Concussion-and-dipping test showed that DLC was inferior to SE in terms of platelets and β-TG, but no significant difference as of TAT or C3a. DLC activated platelets but almost equal in term of TAT and complement-fixation reaction. DLC coating seems to improve the physical properties of SE without compromising its tissue compatibility or antithrombotic character, when used to cover the suface of pacemaker lead.

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From January 1989 to December 1998, 212 permanent pacemakers were implanted by our clinic (146 new implants and 66 replacements). Pacemaker infection was recognized in 5 cases. The overall incidence of infection was 2.3%, and its rate in new implants and in replacement implants was 1.4 and 4.5% respectively. Early infection (within 3 months) was identified in 2 cases. Staphylococcus aureus was present in three cases. One patient had the system removed and a new unit implanted. One patient underwent explantation of the generator. Three patients received intravenous antibiotics with relocation of the generators or local irrigation, but two of them required the removal of the system.

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Clinical trial of the PPS (the prospective payment system) has begun in Japan. Our hospital (National Saitama Hospital) is a model hospital participating in this trial. Before this trial was introduced, we were attempting to shorten the length of the hospital inpatient stay after pacemaker implantation. Since screw-in leads tend to dislodge less often than tined leads, we have used them with confidence, especially in fast-track cases. Twenty-eight cases of screw-in leads and 23 cases of tined leads were compared. There were no significant differences in pacing threshold nor in sensitivity, with the exception of the operative day's pacing thresholds under a pulse width of 0.4mS. Therefore, screw-in leads were not shown to be inferior to tined leads as regards pacing characteristics. Overall, 14 patients were discharged on the first post-operative day, and 27 patients discharged within the first post-operative week thrived without post-discharge dislodgment. Also, our experience showed that the shorter hospital stay of the pacemaker implantation patients was strongly related to less expensive patient costs under the previous payment system.

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The continuous measurement of hematocrit value using CLIT-LINE has been reported to be useful stabilizing the clinical symptoms during hemodialysis, and in controlling dry-weight in patients with ESRD. In addition, CLIT-LINE is theoretically available to catch the information of sequential change of the fluid transfer between inter-cellular and extra-cellular space. In this study, we evaluated the accuracy of hematocrit value measured by CLIT-LINE, monitored continuous plasma refilling rate (PRR) during hemodialysis, and subsquently evaluated the efficacy of an original ultrafiltration system synchronized with the change in hematocrit value in 50 patients with ESRD. Their primary disease were CGN (27), DM (10), NS (5), SLE (4), PKD (3), and unknown (1).In vitro, we compared hematocrit values as measured by CLIT-LINE with those of conventional measurements under as different temperature conditions (26, 36, and 46°C) or blood flow rates (100 or 200ml/min) using blood samples from healthy subjects. In addision, we continuously monitored the PRR using our originally developed system connected with single patient dialysis machine (SDS-30) to CLIT-LINE, and evaluated whether PRR is correlated with the change in total blood volume. Total blood volume was then hypothesized to be 8%. ratio by body weight in vivo. Both blood temperature and blood flow affected the hematocrit values measured by CLIT-LINE. The PRR determined by CLIT-LINE correlated well with the changes in total blood volume induced by the ultrafiltration. Furthermore, our ultrafiltration system synchronized with hematocrit value was effective in preventing the hypotension following the removal of target fluid during hemodialysis in 80%. of the patients, but was not-effective in 20% of the patients, especially in patients with ischellLic heart disease. In conclusion, our ultrafiltration system sequentially synchronized with changes in hematocrit value using CLIT-LINE is effective in stabilizing clinical symptoms during hemodialysis in patients with ischemic heart disease.

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Wet-type dialyzers are much more common in Japan than dry-type ones, partly due to the ease with which a wet-type dialyzer, due to rapid air expulsion, can be primed. The polysulfone membrane dialyzer (Fresenius, PS-F) is treated with newly developed in-line steam sterilization. Because this sterilization supplies continuous high-pressure steam to the fibers, the PS-F, though it is a dry-type dialyzer, is considered easy to prime. We examined the F7OS (Fresenius, PS-F) and the PS-1. 6UW, which is a wet-type dialyzer with a similar membrane, and compared these dialyzers clinically. We found that F70S offered superior rapid air expulsion and less polyvinylpiroridon during priming. The in-line steam sterilization technique is considered to be useful for dialyzers.

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The purification of dialysate has been widely discussed. It is necessary to reduce endotoxin concentration first, and essential to measure endotoxin concentration continuously in order to prevent endotoxin contamination. We have developed a system for inline monitoring of endotoxin. In the previous study, it was possible to measure endotoxin concentrations above 40EU/l at a reaction time of 30min. However, the sensitivity was insufficient for purposes of endotoxin monitoring. In the present study, we developed a inline measuring system based on flow injection and using a 6-position rotary valve to control dispersion and prevent contamination. The absorbance of the reaction product was linearly related to endotoxin concentrations ranging from 0 to 125EU/l at a reaction time of 20min. These results demonstrate that it is possible to control endotoxin concentration using this new system, which could make a vital contribution to safe and comfortable dialysis treatments.

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In order to minimize Endtoxin (ET) contamination due to stasis in Reverse Osmosis (RO) equipment and supply lines, a new water treatment system was developed which employs an around-the-clock recirculating method to continually prevent stasis in RO water treatment processes. The new system was continually operated for 18 consecutive months continuously, after which ET concentration and durability were assessed. In section of the system following the RO module, the ET concentration was found to be below 5EU/l at the RO tank and supply line inlet to the dialysis room. However, at the supply entr-ance to the dialysis equipment, the ET concentration was 6EU/l after 15 months of operation. The RO water volume was 20±1.0l, the RO module pressure was 4.8±0.9kg/cm², and the conductivity at the RO outlet was 2.0±0.3μS/cm, with those parameters remaining constant during the observation period. The consumption of electricity was increased by 48% and consumption of water by 0.6%, while sterilizing solution was not used and ET cut filter consumption was reduced by half. This full-time recirculating water treatment system could maintain lower concentrations of ET over a long period without draining the initial water or performing a sterilization procedure, while being effective for reducing ET.

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Therehave been various reports on the effects of the vitamin E-modified dialyzer CL-EE. These effects include a decrease in the amount of oxidized LDL and cytokines. We investigated variations in the antioxidative activity of vitamin E during extracorporeal circulation in vitro experiments and we studied the influences of vitamin E on erythrocyte membrane lipids and production of advanced glycation end products (AGEs). The antioxidative properties of vitamin E were evaluated by measuring of the amount of plasma lipid peroxide production after proteins were adsorbed into dialysis membranes of a CL-EE minimodule that was circulating human blood. Variations were not observed, either before or after the adsorption of protein and that showed vitamin E inhibited the production of lipid peroxides. It was revealed vitamin E-modified dialyzer CL-EE inhibited the production of erythrocyte membrane lipid peroxides and AGEs. As mentioned above, CL-EE inhibits not only the production of plasma lipid peroxides, but also the production of erythrocyte membrane lipid peroxides and AGEs. Furthermore, CL-EE is expected to reduce prolonged complications.

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It is well known that the retention of porphyrins might be the cause of secondary porphyria cutanea tarda (PCT) in uremic patients. In recent years, however, the prevalence of PCT in uremic patients has decreased partly due to the use of high-performance dialysis membranes, as well as to the administration of recombinant erythropoietin. Previously, we reported that high-performance dialysis membranes efficiently remove porphyrins in hemodialyzed patients. In the present study, we measured plasma porphyrin concentrations by HPLC analysis and examined the correlation between porphyrin concentration and red blood cell count parameters during the correction of renal anemia in hemodialyzed patients. In eight anuric maintenance hemodialyzed patients examined for 12 months, changes in plasma coproporphyrin concentrations negatively correlated with MCHC changes, suggesting the utilization of porphyrin during erythropoiesis. However, six patients newly introduced to hemodialysis were examined during the first month of treatment; changes in their plasma coproporphyrin concentrations positively correlated with RBC, Hb, and Ht. The reason for the latter results might be ascribed to the concomitant improvement in nutritional conditions favoring the production of porphyrin. The results obtained in the present study suggest that the measurement of plasma porphyrin levels may be useful in the clinical evaluation of the treatment of renal anemia in hemodialyzed patients.

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We intend to develop a bio-artificial kidney using tubular epithelial cells and artificial membranes, and to evaluate the reabsorptive function of the confluent layers. Madin Darby canine kidney (MDCK) cells were selected for use in this study. We cultured cells onto an extracellular matrix coated with either fibronectin, laminin, or a non-coated polycarbonate membrane, and then found changes in the morphology and electrical properties of MDCK during a long culture period under confluent conditions. The results were as follows. (1) Ouabain-sensitive Na⁺ active transport declined at three to four weeks after confluence in each matrix. (2) The localization of Na⁺/K⁺ ATPase indicated diffusion and disappearance in the cell membrane three-four weeks after confluence.(3) Prolongation of the culture period increased the formation of an upheaving cell mass after the formation of the confluent monolayer. (4) Scanning electron microscopy revealed fewer microvilli and more flat cells after three to four weeks of confluency. We concluded that the decline of Na⁺ active transport in the MDCK cells was due to both the formation of multilayers and a decline of cell function throughout the long period of culture following the formation of the confluent monolayers.

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This paper describes our results from an in vitro evaluation by batch perfusion on a newly developed LDL adsorbent (DL-adsorbent) for direct hemoperfusion (DHP) use. This adsorbent has almost the same chemical structure as Liposorber adsorbent, but a larger particle size. The adsorption characteristics of DL-adsorbent were almost the same as those of Liposorber adsorbent showing a selective LDL adsorption ability from whole blood, and no influence induced by anticoagulant. Further, the characteristics of DL-adsorbent are very similar to those of Liposorber adsorbent in terms of adsorption not only of lipoproteins but of other major components. As a result of calculations simulating the treatment of a DL-adsorbent column by DHP, we estimated that DL-adsorbent shows a good adsorption performance of LDL. In conclusion, we considered that the adsorption ability of DL-adsorbent makes it a practical and useful LDL adsorbent.

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This paper describes our results from an in vitro evaluation by mini-column perfusion of a newly developed LDL adsorbent (DL-adsorbent) for direct hemoperfusion (DHP). This adsorbent has almost the same chemical structure as Liposorber adsorbent, but a larger particle size. Blood compatibility tests of DL-adsorbent were performed by single-pass hemoperfusion using human whole blood anticoagulated with ACD-A. The passage rate of each blood cell remained at nearly 100%. Leukocyte and platelet functions did not change at all, and the concentrations of polymorphonuclear-elastase (PMN-E), myeroperoxidase (MPO), β-thromboglobulin (βTG), platelet factor-4 (PF4), and anaphylatoxin C3a were decreased by passing through DL-adsorbent. Hemolysis and coagulation were not observed. Further, no compression of the DL-adsorbent was observed in perfusion of bovine blood at velocity equal to that of clinical use. In conclusion, our investigation has proved that DL-adsorbent has good blood compatibility and sufficient strength for clinical use, and could be clinically applied as a LDL adsorber for DHP use.

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We have been treating patients with fulminant hepatic failure (FHF) by applying various kinds of apheresis treatment. In this investigation, 29 patients with FHF were treated. The series included 15 cases of the acute type and 14 cases of the sub-acute type. Total number of treatment were as follows. Plasma exchange (PE) was performed 151 times. Cryofiltration (Cryo) was performed 55 times. Hemo-dialysis (HD) and hemo-dia-filtration (HDF) were performed many times as hepatic support. Ten patients survived. The overall survival rate was 34.5% (acute type 40.0%, sub-acute type 28.6%). Cryo was seen to be effective in 2 cases with FHF who showed hyper-bilirubinemia after PE. Liver volume calculated by CT and brain edema were correlated to survival rate. Survival was difficult for patients whose liver volume had decreased to less than 700cm³ and whose brain edema had progressed. HD and/or HDF were very useful for maintaining homeostasis in patients, specifically in terms of water and pH balance. The beneficial effects of PE with HD and/or HDF have been evident in FHF. These treatments should be applied at the appropriate stage in the clinical course of FHF.

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This study describes the development of two novel visible light-induced surface modification methods providing durable layering of hydrophilic polymers on the material of fabricated devices, which are based on the photochemistry of camphorquinone. One is surface graft copolymerization, which occurred via irradiation of polyurethane and poly (vinyl chloride) films impregnated with 1, 12-dodecane end-capped with camphorquinone through the film in an aqueous N, N-dimethylacrylamide (DMAAm) solution. The other is surface hydrogelation, which occurred via coating of the photoreactive polymer, which was radical copolymer of DMAAm and camphorquinonederivatized styrene, on a poly (ethylene terephthalate) film and subsequent irradiation. These were confirmed by X-ray photoelectron spectroscopic analyses and water contact angle measurements. Confocal laser fluorescence microscopic observations after staining with a fluorescence dye showed that thickness of the produced polymer layer increased with irradiation time in graft copolymerization. The treated surfaces extensively prevented blood coagulation. These methods were applied for conferring potent biocompatibility to the inner surface of a fabricated artificial heart.

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We have developed a new system to evaluate platelet adhesion on the surface of biomaterials under a defined flow condition. This system could be applied to the evaluation of blood compatibility of opaque materials such as metal, ceramics, etc., none of which could be examined in our previous system. In this study, we have evaluated pure-Titanium, SUS-316L, Heparin-immobilized pure-Titanium, Heparin-immobilized SUS316L with this EVM system. Heparin-immobilized metal surfaces showed significantly lower platelet adhesional behavior than did the non-treated metal surfaces (<0.05). In contrast, no significant differences were observed between the other metals. These results showed that heparin immobilization was effective in improving the blood compatibility of metal. Further, it was found that this EVM system was reliable as an in vitro screening method for the evaluation of blood compatibility of opaque biomaterials.

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Poly (2-methoxyethylacrylate) (PMEA) surface shows good blood compatibility with respect to the coagulation, complement, and platelet systems when compared with other polymer surfaces. To clarify the reasons for this good compatibility, the amount of the plasma protein adsorbed onto PMEA and its secondary structure were investigated. Poly (2-hydroxyethylmethacrylate) (PHEMA) and polyacrylate analogs were used as references. The amount of protein adsorbed onto PMEA was very small, and close to that adsorbed onto PHEMA. Circular dichroism (CD) spectroscopy revealed that the conformations of the proteins adsorbed onto PHEMA changed considerably, while those of the proteins adsorbed onto PMEA differed only slightly from the native one. Based on the quartz crystal microbalance (QCM) measurement, we estimated the binding constant and association and dissociation rate constants of the proteins adsorbed onto the polymer surfaces. These results suggested that the excellent blood compatibility of PMEA is closely related to the low denaturation and the high dissociation rate constant of the proteins adsorbed onto PMEA. In addition, the structure of water in the hydrated PMEA was investigated using differential scanning calorimetry (DSC). Cold crystallization of water in the heating process was clearly observed at -42°C. This cold crystallization is interpreted as the phase transition from the amorphous ice to the crystal ice that belongs to the freeze-bound water in PMEA. We believe that this feature of the water structure is related to blood compatibility.

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Poly (2-hydroxyethyl methacrylate) (PHEMA)-Polystyrene (PSt)-PHEMA ABA-type block copolymer (HSB) surfaces with lamellar-shaped microdomain structure inhibited necrosis of lymphocytes. In contrast, PSt and PHEMA-PSt random copolymer (HSR) surfaces caused necrosis of lymphocytes. In order to clarify the inhibitory mechanism, sialic acid-removed lymphocytes adhered to and eluted on HSB surfaces were analyzed by scanning (SEM) and transmission electron microscopy (TEM). TEM images of eluted lymphocytes and the mitochondria were evaluated quantitatively by an image processor-analyzer. Neuraminidase was used to remove sialic acid from the glycoproteins of lymphocyte plasma membrane. PSt and PHEMA-PSt random copolymer (HSR) surfaces were used as controls. The interaction between the polymer surfaces and the lymphocytes was carried out by the microsphere column method. The adhered lymphocytes were all observed to be round in all cases. The eluted lymphocytes were all observed to be round keeping cytoplasm well, too. Computerized TEM image analysis did not indicate significant differences in all cases. The results of previous papers (Jpn J Artif Organs 27-2, 495, 1998/28-1, 230, 1999) as well as this study suggest that the microdomain structure surfaces of HSB inhibit the necrosis of the lymphocytes because the surfaces do not have an important effect on the sialic acid of the plasma membrane glycoproteins.

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Abstract A sutureless nerve repair method using an alginate sponge was investigated in the present study. Six cats were used in this experiment, in which a 50-mm gap was created in the right sciatic nerve. The gap was then filled with a freeze-dried alginate sponge (n=5) or was left empty, serving as a control (n=1). Electrophysiological evaluation, compound muscle action potential (CMAP), and somatosensory evoked potentials (SEP), showed good restoration in the alginate-implanted group 13 weeks after the operation. Histological examinations, performed 4 months after implantation, revealed many regenerated axons in the nerve segment distal to the gap. No alginate residue was found in the gaps. In the control, no electrophysiological responses were detected and no regenerated axons were observed beyond the gap. The results suggest that the sutureless implantation of an alginate sponge is a promising procedure for peripheral nerve repair.

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Alginate is a polysaccharide extracted from brown seaweed. A novel freeze-dried alginate sponge was developed in our laboratory and has been shown to enhance peripheral nerve regeneration. In this study, we examined spinal cord repair using alginate sponges in infant rats. In rats (postnatal day 8-12, P8-P12), the spinal cord was transversely resected at Th 6-Th 8 to produce a 2-mm gap and alginate sponge was placed in the gap. The recovery of evoked electromyograms 6 weeks after surgery indicated that elongation of axons could establish electrophysiologically, restoration of function through the gap. Histomorphological study 8 weeks after surgery revealed that myelinated and unmyelinated axons, surrounded by a perineural-like structure, elongated across the gap. In conclusion, the findings of the present study indicate that alginate may provide a permissive microenvironment for the regeneration of spinal cord axons. We demonstrated the exciting possibility that an alginate sponge could serve as an artificial nerve guide for the repair of injured spinal cord. The next step is to investigate the possibility that spinal cord repair could be enhanced by means of alginate as a vehicle for the delivery of neurotrophic or growth promoting agents to injured nerve tissues.

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Objective: Primary concerns about currently available pericardial substitutes include their adhesion and possible epicardial reactions. The purpose of this study is to evaluate host reaction to absorbable pericardial substitutes (gelatin seat and L-lactic acid-E-caprolactone copolymer). Methods: 40 recipient dogs from 8 to 27kg (mean 12kg) were divided into the following four groups: Group A (n=10): control (autologous pericardium), Group B (n=10): gelatin seat, Group C (n=10). L-lactic acid-ε-caprolactone (50/50) copolymer seat, and Group D (n=10): expanded-polytetrafluoroethylene (e-PTFE) seat. The in implanted membranes were retrieved at 2 weeks (n=1), 4 weeks (n=3), 12 weeks (n=3), and 24 weeks (n=3) after implantation. Rresults: Overall, the expanded-polytetrafluoroethylene patches produced a more notable inflammatory reaction and severe adhesion to the heart and pleura than did the absorbable pericardial substitutes.The absorbable substitutes were absorbed at 4 weeks after implantation, and were replaced with fibrous membrane. Conclusions: Absorbable pericardial substitutes may involve less adhesion and cause less inflammatory reaction than expanded-polytetrafluoroethylene.

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A multiblock copoly (ester-ether) consisting of poly (L-lactic acid) (PLLA) and poly (oxypropylene-co-oxyethylene) (PN) was prepared and characterized. Preparation was done via the solution polycondensation of a thermal oligocondensate of L-lactic acid, a commercially available telechelic polyether Pluronic-F68^TM(PN), and decanedioic acid which is a carboxyl/hydroxyl adjusting agent. When stannous oxide was used as the catalyst, the molecular weight of the resultant PLLA/PN block copolymers became very high (and even showed a high PN content) under optimized reaction conditions. The copolymers were melt-spun by conventional methods and drawn at 60°C at the given draw ratio. The resultant fiber showed greater tensile strength and more flexibility, both which correlated with the increase in PN contents. In addition, tissue reactions against the multiblock copolymers were milder than those against PLLA homopolymer. These results show that these multiblock copolymers have great potential as biodegradable sutures and as other biomaterials e. g., scaffolds for tissue regeneration.

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We developed a new vascular graft for hemodialysis, which consists of three layers: inner and outer layers made of highly porous membrane to provide for sufficient tissue anchoring, and a middle layer made of non-porous elastomer with strong sealing characteristics. In this study, we examined the graft's kinking, tensile, and burst strengths, and leakage due to puncture holes using the ePTFE graft as a control. In vitro study showed that the new graft efficiently resealed itself after removal of a needle and demonstrated high durability after repeated punctures in comparison with the control graft. In a canine arteriovenous shunt model, the new graft revealed not only the ability to seal needle puncture sites with minimal compression time but the ability to prevent bleeding. These properties showed that this new graft could be a novel alternative to conventional artificial grafts for hemodialysis.

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An Anthron^® bypass catheter was used to allow radical surgery for hepatobiliary and pancreatic cancer. Between July 1981 and June 1998, 156 portal vein resections were performed using this catheter for case of hepatobiliary and pancreatic cancer. Sixty-two cases involved total pancreatectomy combined with portal vein (PV) or superior mesenteric vein (SMV) resection. There were 79 cases of pancreatoduodenectomy (PD) combined with PV or SMV resection. This catheter was most commonly used to bypass the SMV to the femoral vein in order to avoid portal congestion. In cases where the hepatic artery was occluded, the mesenteric venous blood was shunted through the umbilical vein or the hepatic hilar portal vein to avoid hepatic ischemia. The duration of the portal bypass ranged from 40 to 502min and the duration of occlusion ranged from 15 to 302 min. This catheter allows ample time for portal vein resection and reconstruction. This catheter was useful in cases of hepatobiliary and pancreatic cancer surgery combined with portal vein resection.

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