A miniature intraventricular axial flow blood pump for left ventricular support are under development. One of the key technologies which requires for them is sealing of the motor shaft. In this study, to prevent the blood from back flowing into the motor side, mechanical seals were developed, and the tribological performance of them was investigated. In the experimental apparatus, the mechanical seal separates the bovine blood on the chamber side from the cooling water on the motor side. A leakage of the blood and a rate of hemolysis were measured. A torque of the shaft was measured by a torque transducer. A rotation speed of the shaft and a contact force of the seal faces were changed in the experiments. In order to estimate the lubrication regimes, the Stribeck Curve, which is a diagram of the coefficient of friction against the bearing characteristics number G, was drawn. As the results of experiments, both the leakage of the blood and the rate of hemolysis were very small. The friction loss was also very small. The condition of lubrication could be clarified by the Stribeck Curve.

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Novacor left ventricular assist device has been used as a bridge to heart transplant world wide. Despite the obstacles using this device for chronic use, we nevertheless implanted Novacor LVAD (wearable type) in a patient with dilated cardiomyopathy. The patient is 29-year-old man and his physical status was significantly improved to NYHA 1. He was discharged to the home 5months after the implantation. During the 7-month of circulatory assist, no serious complications such as a thromboembolism and infection have occurred. Thereafter, the patient received heart transplantation at UCLA, 7 months latex The histology of showed very little changes between pre and post assist circulation. No thrombosis was seen including valve units. Therefore, we concluded that the wider application of Novacor implantation is useful as a bridge to transplant.

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The spiral vortex pump (SV), an innovative, penumatically-driven ventricular assist device, was tested using flow visualization technique and laser Doppler anemometry to study effect of the inlet valve orientation under steady flow condition. The pump was operated in a purposely constructed steady flow circuit aimed at obtaining flow field data both qualitatively and quantitatively. Qualitative information was obtained using flow visualization technique. Slit lighting technique and florescent bees provided clear flow field view at desired location. The flow fields were photographed using 35mm SLR camera and Hi8 type 8mm video camera, clearly capturing vortex nature of the flow field. Quantitative informations in terms of mean velocity and fluctuating velocity profile were obtained using Kanomax single channel FLV system (Fiberoptic Laser Velocitimeter: Nihon Kagaku Kogyo, Model 8801 with Model 8015 Frequency Tracker). Three diametrical traverse locations (immediately downstream; 45° downstream and 90° downstream from the inlet valve) and three vertical locations (5, 10, and 15 mm from the diaphragm at neutral location) were selected for measurements. Both qualitative and quantitative comparison of the records demonstrated vortex nature of the flow field and confirmed relatively high velocity at HD junction (Housing-Diaphram junction). It also showed clear influence of the inlet valve orientation on the flow field inside the pump. Based on the experimental data, the following general conclusions can be made: (i) the SV pump created vortex flow field inside the pump; (ii) the inlet valve orientation sharply influence the flow inside the SV pump; (iii) the minimum flow disturbance was observed when the major orifice of the inlet valve is situated towards upward (pump outlet direction); and (iv) the maximum flow disturbance was observed when the major orifice of the inlet valve is situated towards downward (diaphragm direction).

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A magnetically suspended centrifugal pump (MSCP) has been developed for long term use. The size of the pump is 82×51 mm weighing 420 g. The power required is 15 w. Chronic animal studies were performed in three sheep. The blood was withdrawn from the left ventricular apex, and returned to the descending aorta. The pumps were positioned outside the body in two and inside the body (outside the thoracic wall) in one sheep. The pumping flow was estimated by indirect method using the motor current and rotational speed. The pumping flow was 3.5-6.5 L/min. The free hemoglobin level was less than 25 mg/dl. The duration of animal experiments were 60, 140, and 80 days+(ongoing). The temperature of the pump surface was around 42°C. No thrombus was observed even after 140 days support. In conclusion, the MSCP was promising device for an implantable assist heart.

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In vivo performance of an electrohydraulic total artificial heart (EHTAH) system was evaluated for 10 days in a chronic animal experiment. The system consisting of blood pumps and an energy converter was implanted in a 62 kg calf, and was actuated by an external controller though a percutaneous lead at a fixed rate of 85 bpm. A shunt hole of 4.5 mm in diameter was made in the atrial septum to redistribute imbalanced left and right atrial pressures and volumes. During the experiment, the animal's circulation was stably maintained by the EHTAH with an adequate left-right balance. Oxygen metabolic condition was kept favorable at any time of the experiment. No abnormality was found in major organ functions. Generation and dissipation of heat from the device was also acceptable. There occurred, however, mechanical failures including hydraulic oil leakage detected on the 9th day and bearing breakdown resulting in device malfunction on the 10th day. The device demonstrated good anatomic fit at autopsy, as well as at implantation, without compromising the great vessels and adjacent tissues. It is concluded that the EHTAH system has a sufficient in vivo basic performance, although appropriate measures are to be implemented against the mechanical problems detected in the present study.

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Aiming at a totally implantable type ventricular assist device (VAD), Vibrating flow pump (VFP) was developed in Tohoku University. The transcutaneous energy transmission system (TETS) using the amorphousness fiber was developed to constitute the totally implantable VAD system. Artificial heart works with high frequency compared with a natural heart. It is frequency of 10-50 Hz. In this research, animal experiment was carried out with the healthy adult goats. Blood from left ventricular apex was received, and sent to descending aorta. Enough supporting effect of left heart was provided. In particular, depression effect of left ventricle was obvious. As a result, enough artificial heart flow was provided. For the totally implantable type VAD, left heart bypass of almost 100% may be necessary in some situations. So, apex approaches of the left heart bypass may be desirable. From the anatomical consideration, , an apex of a heart is suitable for the totally implantable VFP. In the left heart bypass with left apical approach, almost 100 % bypass was possible, which is important for natural heart to wait for recovery of enough cardiac function. And it is important that left heart circulation is maintained fully. In summary, VFP was considered to be useful as a totally implable type left ventricular assist device.

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In order to improve the antithrombogenicity of a blood pump of total artificial heart, the flow characteristics inside the blood pump of TAH were investigated. Flow pattern in the blood pump was changed by varying the major orifice direction of inflow and outflow Bjork-Shiley valves, and was analyzed by following two flow visualization techniques; The tracer method was used for quantitative analysis of flow velocity and direction on a Laser light sheet plane. A new flow visualization technique based on paint erosion has been developed to estimate the wall shear stress related to washout effect. In this method, on the assumption that the wall shear stress was reflected by the change of paint thickness, poor washout field was depicted as a paint residual place. The results were as follows; 1)The circulating flow was observed in every model which has different valve orientation., 2) Washout effect was dramatically influenced by the direction of circulating flow and a horizontally circulating flow parallel with the Diaphragm-Housing junction was of most significance for good wash-out. 3) The center of circulating flow to be at the center of the blood pump was important for even washout effect.

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Thirty animal studies in calves were performed between September '93 and April '97. All calves underwent implantation of the completely implantable electric total artificial heart (ETAH) system developed at The Pennsylvania State University. Sixteen of 30 calves died prior to POD 14 (short term survivors: STS), and 14 animals survived for over 2 weeks (long term survivors: LTS). The causes of death of STS were surgery related complications (n=5), pulmonary complications (n=9), and device failure (DF: n=2), while the causes of death of LTS were DF (n=8), infections (INF: n=3), outgrowth (OG: n=2) and scheduled termination (n=1). Six animals survived for over 3 months, with the longest surviving 160 days. The cause of death of these animals were DF (n=2), INF (n=2) and OG (n=2). Cardiac output was almost 8 L/min at approximately 140 bpm. CVP was kept under 15 mmHg for about 3 months after surgery. This in vivo study shows the high potential of the Penn State completely implantable ETAH system.

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Externally-coupled transcutaneous energy transmission system(ECTETS) which has DC to DC energy transmission efficiency of more than 86% in in vitro experiment is very useful for a totally implantable artificial heart. In in vivo experiment of the ECTETS with the internal coil and the rectifier circuit implanted under the skin of a living goat, the DC to DC energy transmission efficiencies were measured using electronic load simulator(ELS) and implantable electrohydraulic total artificial heart(EHTAH) as a load, respectively. As a result, the DC to DC energy transmission efficiency of the ECTETS with the ELS was 81.4% in operation at the output power of 19.2W. It was found that the lowering of the efficiency compared with that in in vitro experiment was caused by the increase in stray capacitance between the windings of the external coil by applying liquid to that surface for sterilization. In driving the EHTAH at the heart rate of 70bpm, the driving power was 20.7W, the pump output flow was 6.2L/min, the DC to DC energy transmission efficiency was 82.1%, and the surface temperature of the internal circuit was less than 40.5°C. In conclusion, the ECTETS had good performance in in vivo experiment.

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The biocompatibilty and practicality of the transcutaneous energy transmission unit(PEI) for the totally implantable artificial heart system were evaluated m in vitro and in vivo experiments. The distribution of the surface temperature on an internal rectifier circuit was investigated by using a thermography camera in the air. We studied thermal characteristics and energy transfer efficiency of the implanted TET system with a goat weighing of 44kg. An energy of 24W was transferred through skin with the TET system. The surface temperature of the rectifier circuit the external coil, and the energy transmission efficiency were measured for one month. A treadmill exercise best at a speed of 2km/h was carried out to investigate the influence of the body movement on the energy transmission efficiency of the TET system. Abnormal high temperature spot on the TET system was not observed, and the temperature on the implanted system slid not rise and stayed with the same level of the body temperature. The energy transfer efficiency was 80-85% and no change of the efficiency was observed on the treadmill exercise test. As a result sufficient practicality and biocompatibilty of the TET stem were confirmed.

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To supply the electric power for driving a total artificial heart (TAR), a transcutaneous enegy transmission (TET) system is advantageous. For a TET system with aircore-type coils, it is generally said that the electric energy can be effectively trasnmitted in the case that resonant frequencies of the serial LCR (coil-capacitor-resistor) circuits of both sides are the same as a driving frequency, but it is dangerous that a short circuit occur when a primary coil is away from a secondary coil and/or a secondary LCR circuit is open because of unloaded. In this study, a secondary resonant frequency is chosen to be higher than a primary one and a driving frequency is chosen to be higher than a secondary one, then it is able to keep away from a short circuit and keep energy transmission and its efficiency stable. The electric power of 40W can be transmitted to a dummy load with a resistance of 20ω at sufficiently high efficiency.

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In the totally implantable artificial heart system now being developed by the authors, seven lithium-ion secondary batteries connected in series were used as the backup secondary battery. In this paper are reported the results of investigations made on the charging and discharging characteristics of four kinds of lithium-ion secondary batteries using different cathode active materials and electrolytes. It was found that, of the four kinds of batteries under examination, one that uses LiNi_0.8Co_0.2O₂ as cathode active material and electrolyte B, called Ni-B, was most suitable, because with this battery the charging time of 75.8 minutes was shortest and the temperature of 43.1°C at the time of discharging was least. A totally implantable electrohydraulic artificial heart was driven by the Ni-B secondary batteries put in the housing manufactured for the implantation, which was placed in a constant incubator kept at 39.0°C for simulating inside body. As a result, the system was capable of continuous operation for about 60 minutes with a pump output flow 5.8-6.4L/min and the temperature of the battery housing surface was 40.4°C at the end of discharging. In conclusion, the Ni-B secondary battery has sufficient performance for an implantable backup battery.

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As a means of sending signals from the interior of a living body to the exterior, or vice versa, we have proposed a transcutaneous optical telemetry system (TOTS). As there is the skin between the transmitter and the receiver, light will be attenuated in it and the signal will be deteriorated. Therefore, careful examinations are necessary on the performances of the transcutaneous optical coupler, wavelength of the light used, directivities of the light-emitting device and light-receiving device. In this study, each of a light emitting diode (LED) and a laser diode (LD) is used as the light-emitting device, and PINPD as the light-receiving device. Transcutaneous transmission characteristics of these optical couplers are measured and compared. As a result, it is found that, in the transcutaneous telemetry system used, the LD as a light-emitting device shows better transmission characteristics in the light-emitting efficiency and the permissible deviation caused by body motion, and also found that there is a optimum separation between the emitting device and the receiving device for the permissible deviation to be maximum

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The goal of this study is to develop a percutaneous insertable intra-pericardial balloon and to evaluate its hemodynamic effects. New device consists of the pre-wrapped balloon, the drive line and the sheath (15Fr) for insertion. The balloon is air-driven and inserted directly for good positioning (anterior of the LV free wall and RV free wall). We use mongrel dogs under general anethesia, and intra-pericardial balloon (volume 20cc) is inserted by Seldinger technique or mini-thoracotomy or median sternotomy. Heart failure was induced by propranolol (2mg/kg, iv and 50-100%mu;g/kg/min, div). The balloon was synchronously driven with ECG (2:1). We measured hemodynamic parameters (aortic pressure, aortic flow, right atrial pressure, pulmonary arterial pressure and cardiac output) during off-on test and compare the effect of two positions. The balloon (20cc) increased cardiac output by 7.7% under profound heart failure after administration of propranolol. Conclusion: This simple and quick insertable Intra-Pericardial Balloon is very promising as a bridge to other powerful mechanical assist devices for profound heart failure.

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Small sized (1ml/kg BW) and intrathoracically positioned skeletal muscle ventricles (SMVs) were constructed from electrically conditioned canine latissimus dorsi muscle. Our hypothesis is that the smaller pump size would give sufficient ejection fraction (EF) and pressure resistance during circulatory assist. The stroke work (SW) and EF of SMVS were studied with a mock circulation device. EF reached 43.6% and 31.5%, SW reached 42.3mJ and 46.0mJ, which is estimated as 247% of canine RV-SW, and 54% of LV-SW, at afterloads of 30 mmHg and 80 mmHg, respectively. The EF seems higher than previous reported larger SMVs. Future studies are needed to investigate the effect of down sizing of SMVS on muscle tissue preservation or rupture prevention and antithrombogenesity.

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The long-term evaluation of a heparin bonded artificial lung (AL) was performed with chronic animal experiments. The AL developed in our institution was made with polyolefin hollow fiber membrane where micropores are blind-ended to prevent serum leakage. The blood contacting surface is treated with newly developed covalently heparin-bonding technique to provide good antithrombogenicity. Six goats weighing 50±1.1 kg were perfused with the AL and a pneumatic ventricular assist device in a venoarterial bypass circuit for up to 36 days (17±14 days). Serum leakage was completely prevented in all the devices throughout the experiments. Minimum amounts of heparin (2-3 U/kg/h) were used for systemic anticoagulation. Only in one case the thrombotic complication related to the AL was observed The gas exchange performance was satisfactorily demonstrated for up to 36 days. Blood components and coagulation factors were maintained within acceptable limits. The blood contacting surfaces after the experiment were found almost free of thrombus, while in 3 cases which were perfused more than 2 weeks, thrombus formation was observed mainly on the margin of the inflow side. These results indicate that our AL can be used for prolonged ECMO, although further improvement in thromboresistant properties should be achieved.

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An outside blood flow membrane oxygenator (OFMO) currently available in clinical treatments was developed by the try-and-error method where much time and cost were spent. The objective of the present study is to simulate the blood flow and oxygen transfer rate of the OFMO. The Darcy's law for fluid flow through porous media and the enhancement factor for the mass transfer with chemical reaction were used for evaluation of the blood flow and oxygen transfer rate of the OFMO, respectively. The governing differential equations were numerically solved by the finite element method. Simulation analysis of the blood flow found that channeling occurred depending on fiber arrangement. These results agree well with visual observations previously obtained in our laboratory by X-ray computed tomography. Simulation analysis of the oxygen transfer rate of the OFMO, where the liquid side mass transfer coefficient for blood k_LB, estimated using the dimensionless equations of mass transfer coefficient in fluid flow outside a tube, was used, is capable of theoretically predicting the oxygen transfer performance of the OFMO. We conclude that the simulation analysis using both Darcy's law and enhancement factor is useful for evaluation of the blood flow and oxygen transfer rate of the OFMO.

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We evaluated the effect in unloading of the left ventricle with transaortic catheter venting(TACV) during venoarterial bypass(VAB). The preload recruitable stroke work(PRSW) in VAB with TACV decreased significantly than VAB only. the LV pressure-volume area (PVA) in VAB with TACV decreased significantly comparing with VAB and baseline. The potential energy (PE)/PVA, the index of the energetic charge in VAB with TACV increased significantly than baseline.So TACV was suggested to be the effectiveness of the assist device with PCPS for severe left heart failure.

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Percutaneuos cardioplumonary support (PCPS) using Capiox EBS system (Termo Corp.) or CCS-1 system (Medtronic Carp.), was performed perioperatively in seven cardiovascular patients suffering from low cardiac output syndrome. The patients were divided into two groups; argatroban-treated group (n=4) and heparin. treated group (n=3). Platelet loss was greater and more progressive during PCPS in heparin group than in argatroban group. Plasma levels of fibrinogen decreased in the first postoperative day, and then gradual increase was observed in both groups after the 2nd postoperative day. However, the rate of postoperative increase of fibrinogen was more rapid in argatroban group than in heparin group. Blood loss was progressively increased in heparin group in spite that complete hemostasis had been established intraoperatively. On the other hand, blood loss was significantly decreased in the 3rd postoperative day despite that large amount of blood loss was developed until the 2nd postoperative day, because of two cases of acute aortic dissection included in argatroban group. Argatroban is considered useful for preventing the loss of platelet and fibrinogen without systemic thromboembolization during PCPS.

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The beneficial effect of platelet-leukocyte plasmapheresis on postbypass pulmonary function was evaluated in a prospective, randomized manner. The study involved 25 patients undergoing coronary artery bypass surgery with harvest of platelet concentrate (Pcon) and a control group of 25 patients without harvest of Peon. Pcon was harvested before systemic heparinization and was reinfused after cardiopulmonary bypass. Both oxygenation index and Aa-DO₂ on ICU arrival and extubat ion were significantly better in the Peon group than in the control group. Leukocyte counts on the 1st and 2nd postoperative day were significantly lower in the Peon group than in the control group. These data suggest that platelet and leukocyte protection by Peon technique results in preservation of pulmonary function after cardiopulmonary bypass.

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We evaluated changes in platelet function during cardiopulmonary bypass (CPB) and effects of retransfusion of autologous platelets collected before CPB, by percent shortening of activated coagulation time (clot ratio) resulting from addition of platelet activating factor (PAF) using hemoSTATUS. Changes during CPB were evaluated in nine adult patients who underwent heart surgery under mild hypothermia. Patients' age was 61±11 years and CPB time was 145±22 minutes. Clot ratio to 150nM of PAF significantly decreased to 81±12% five minutes after the onset of CPB and subsequently recovered 30 minutes after the onset of CPB (p<0.05). Effects of autologous platelet retransfusion were evaluated in 10 adult patients. Two aortic operations under profound hypothermia were included. Patients' age was 62±14 years and CPB time was 190±90 minutes. Collection of 8.2±3.0 units of platelets resulted in a significant decrease in platelet count (from 18.5±3.3 to 12.3±3.9, p<0.01) but no change in the clot ratio. Retransfusion of the autologous platelets resulted in a significant recovery of the clot ratio (from 90±23% to 110±20%, p<0.01). Results of the hemoSTATUS platelet function test suggest the beneficial effects of retransfusion of autologous platelets.

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Heparin/protamine titration for the measurement of heparin levels (Heparin: MedtronicHemotec) is a promising device. In this study we evaluated efficacy of Hepcon system and compared. Twentry-four patieents subjected to cardiopulmonary bypass were divided into two groups. For the control group, the anticoagulation and reversal protocol consisted of an initial fixed dose of 300U/Kg of heparin. The initial protamin dose for reversal consisted of a fixed dose of 1ml protamine per 1ml total hepar in administered. For the Hepcon group, a heparin doseresponse assay is automatically directed the initial dose of heparin. After the discontinuation of CPB, Hepcon was queried to determine that dose of protamine. (1)Initial dose of heparin was not statistically different. (2)A strong correlation was observed between plasma and a whole blood concentration of heparin. However, the both heparin levels were not correlate with ACT valuse in any of time point. (3)For the Hepcon group, the dose of protamine determined by the titration of protamine to heparin was significantly less. The amount of blood transfusion and bleeding was not different between two groups. In conclusion, whole blood heparin measurements obtained by Hepcon correlated well with plasma concentration. Minimizing the dose of protamine decreased the chance of adverse reactions. However, initial and additional dose of heparin indicated by Hepcon requirement might resulted in overdose, especially if the duration of CPB prolonged.

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Roller pump has been used as a standard flow-generator in various extracorporeal circulation (ECC) systems, however, it has a critical problem that a sudden stenosis or occlusion of a blood-stream line can result in an excessive high or negative pressure in the circuit. To avoid this hazardous accident, we've developed a device which regulates the rotation of a roller pump according to the blood circuit pressure. We designed this device to use with CAPS Roller Pump type 10-10-00 (Stoeckert instrumente GmbH., Munich, Germany), which has an auxiliary signal input port to regulate the rotation of a pump. Our device has four beneficial features: no alteration is necessary for a roller pump itself; two pressure points where the device begins to regulate the rotation of a pump (pressure ‘S’) and stops it completely can be freely set; between these two pressure points (range ‘W’), the rotation of a pump is inversely regulated to the blood circuit pressure; the device can also respond to the negative pressure in the blood circuit. We evaluated our device using a model ECC circuit. The pump charactericity of the ECC system with our device until the circuit pressure reached the pressure ‘S’ was mimic to that of the ordinary roller pump system, whereas, during the range ‘W’, to that of a centrifugal pump system. In conclusion, our device can provide a safe management of ECC without any critical sharp fluctuation in the blood circuit pressure.

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Toevaluatebiooompatibility anddinical usefulnessof heparin-coated cardiopulmonary bypass (CPB) on patients treated with aprotinin and steroid during open heart surgery, we conducted a clinical study for 15 patients sufferingfrom ischemic heart disease or valvular heart disease. The patients were assigned randomly to two groups, heparin-ooated group (group C, n=7) and non-coated group (group NC, n=8). Plasma concentration of XIIa was significantly lower in group C than NC. Scanning electron microscopy demonstrated fewer deposition of blood componenton the surfaces of heparin-coated tube, artificial lung, and arterial filter than that of non-coated circuit Those results indicate that combined use of heparin-coated circuits approtinin and steroid suppress coagulation system and inflammatory reactionduring CPB.

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We analyzed the effects of a heparin-coated cardiopulmonary bypass (CPB) circuit on coagulation-fibrinolysis system and platelet, especially platelet surface glycopro-teins, in 18 adult patients. The patients were divided into two groups according to the circuit used; group D (n=10, Duraflo II heparin-coated) and group N (n=8, non-coated). Age, gender, operative procedures, aortic cross-clamping time and CPB time were not significantly different between groups. Heparin dosage was 3mg/kg and pericardial blood was recirculated in both groups. Blood samples were obtained before and after heparin administration, five and 30 minutes after CPB initiation, just before CPB termination and after protamine administration. During CPB, platelet count and fibrinogen concentration decreased with time in the group N, while they remained unchanged in the group D. Consequently, there were significant differences between two groups before CPB termination. Platelet surface glycoprotein IIbIIIa increased after CPB initiation, and TAT, PIC and D-dimer increased with time during CPB. There was no difference between groups. A heparin-coated circuit preserves platelet count and fibrinogen during CPB. Suppression of the activated platelet-surface interaction in the low-shear environment is likely to explain this effect.

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Purpose: A new membrane oxygenator consisting of microporous polypropylene hollow fibers coated with an ultra-thin layer of silicone was developed, we have already reported that this new oxygenator maintains good gas transfer and shows good durability in animal models. We studied the biocompatablity and clinical usefulness of this ultra-thin silicone-coated polypropylene hollow fiber oxygenator. Materials and methods: To evaluate clinical usefulness of the new oxygenator, 22 patients underwent cardiopulmonary bypass(CPB) with the silicone-coated oxygenator. Plasma free Hb, platelet count, thrombin-antithrombin III complex(TAT), α 2 plasmin inhibitor-plasmin complex(PIC), and granulocyte elastase were investigated during CPB in 10 patients(Group S) compared with those in 10 patients managed with a standerd heparin-coated oxygenator(Group H). Results: Blood gas analyses revealed that high PO₂ and acceptable PCO₂ levels were maintained during CPB. Air could be vented through the silicone-coated hollow fibers and the circuits were easy to prime. There were ho significant differences between Group S and Group H in plasma free Hb, platelet count, TAT, PIC, or granulocyte elastase levels. Conclusions: These results suggest that this new oxygenator maintains good gas transfer and shows good biocompatibility under clinical conditions.

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The purpose of this study was to develop a circulatory-assist system for use during hypothermic circulatory arrest (CA) and to evaluate the brain damage caused by CA during prolonged periods of deep hypothermia. Seven dogs were divided into two groups: those in group C (n=3) were kept hypothermic (15°C, tympanic temperature) for 90 minutes without CA, and those in group T (n=4) were subjected to 90 minutes of induced CA at 15°C, with cooling and rewarming (37°C) performed by cardiopulmonary bypass using the femoral artery and vein, and external jugular vein cannulation. Seventy-two hours after surgery, the brains were perfusion fixed and examined by light and electron microscopy. All of the dogs were successfully resuscitated after surgery. No morphologic changes were observed in any areas of the cerebrum of group C dogs. However, the nuclei of many cells of the CA1 pyramidal cell layer of the hippocampus of the group T dogs were shrunken, and dense chromatin masses were detected in the nuclei of these neurons. These results demonstrate the occurrence of cerebral morphological damage after 90 minutes of deep hypothermic CA.

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A new catheter for retrograde cerebral perfusion (RCP), which can (1) deliver blood directly into the internal jugular vein (IJV) even in a case with the competent venous valves at the jugular subclavian junction, (2) prevent blood from draining into the lower half of the body, and (3) allow aortic arch replacement via median sternatomy as well as lateral thoracotomy, was developed. This catheter can be inserted into the W via a standard puncture technique. A balloon for occlusion of superior vena cava (SVC) is installed at thee catheter tip. Side holes, through which blood is delivered into the UV, are located 95 mm from the catheter tip. RCP by use of this catheter was performed in seven cases of aortic arch replacement. Venography showed that the inflated balloon successfully occluded SVC, and contrast media preferentially flowed from IJV into the head. The mean flow rate was 327 mL/min for maintenance of the pressure of the UV pressure at around 20 mmHg. Since all procedures were controlled from outside of the operative field, RCP by use of this catheter could be useful in distal arch replacement via left lateral thoracotomy.

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We evaluated the effecton cerebral oxygen metabolism of various perfusion temperature during cardiopulmonary bypass(CPB). A randomizedtrial comparing among warm (36°C), tepid (33°C) andcold (30°C) perfusion was done in 21 patients With the use of the near-infraredspectroscopy, we monitored the change of oxyhemoglobin (oxyllb) and oxidation lebel of cytochrome oxidase (cyt. aa3). In additionjugular bulb saturation (Sj02), cerebral circulatory index(CCI), lactate extraction ratio and lactate-pyruvate ratio were measured. None hadany neurological complication in this study. During CPB, the oxylb and cyt. aa3 droppedin all groups, while SjO2 aal CCI elevatedin tepid and cold groups. In cold group all parameters indicateddesaturation during rewarming period. Anearobic metabolism representedby change of lactate metabolism deterioratedparallel to operative course, in which we found out no differencesamong groups. These findings suggested that although hypothermia was benefical to cerebral oxygen metabolism, care should be taken to avoid the collapse of oxygen supply /demandrelationship during rewarming.

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We studied the influence of perfusion temperature during extracorporeal circulation (ECC). 44 adult consecutive patients who underwent CABO were divided into two groups. One group received 35°Csystemic perfusion (35°C group, n=22) and another group received 32°C systemic perfusion (32°C group, n=22). There were no differences between both groups in the preoperative data. There were no hospital death and cerebral complications in both groups. ECC time and aortic cross-clamp time were not different between both groups. Blood loss after operation was not different between both groups. 35°C group needed significantly lower dose of dopamine at 1CU admission than 32 °C group. Postoperative cardiac index, mean arterial pressure and systemic vascular resistance were not different between both groups. PaO₂ at ICU admission in group 35°C tended to he higher than that in group 32°C . Serum CK and OPT levels at ICU admission were significantly lower in 35 °C group. WBC counts at l and 2POD were also significantly lower in 35°C group. We concluded that normothermic(35°C) ECC was safe and useful management.

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Postoperative alterations of systemic metabolism and acid-base balance following cardiopulmonary bypass (CPB) were observed in patients who underwent hypothermic CPB (n=13) and normothermic CPB (n=13). The average rectal temperature during CPB was 29.2±1.4°C in the hypothermic group and 33.5±0.6°C in the normothermic group. The pump flow rate was maintained at 2.4±0.1 Umin/m₂ in the hypothermic group and 3.0±0.2 Ilmin/m₂ in the normothermic group. In the normothermic group, the operation time and the CPB time were significantly shorter than those of the hypothermic group, then the postoperative oxygen extraction rate, the arterial-venous carbon dioxide tension difference, and the arterial-venous pH difference were kept within physiological ranges. In the hypothermic group, the body temperature fell again, the systemic vascular resistance was extremely high, and the recovery of the cardiac output delayed after operation. In conclusion, normothermic CPB is superior to hypothermic CPB regarding the recovery from metabolic impairment occurring during CPB.

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Hemodynamic performance and valve related complications of the 19mm St. Jude Medical-HP valve in small aortic annulus: Comparison with the 21mm St. Jude Medical standard valve. We compared hemodynamic performance and valve-related complications of the 19mm St. Jude Medical-HP valve(19HP) with those of the 21mm St. Jude Medical standard valve(21S). In the last 3 years, 46patients received these small aortic valves(19HP;n=16, 21S;n=30). By means of Doppler ultrasonic cardiography, average of peak pressure gradient was 34±20mmHg in the 19HP group and 28±14mmHg in the 21S group(N.S.). Valve-related complications such as thrombosed valve, prosthetic valve endocarditis, paravalvular leak, hemolysis, pannus were not detected in both groups. In the early postoperative period, serum lactic dehydrogenase(LDH) activity was elevated to 1081±54311/1 in 19HP and 1014±5361U/l in 21S, but it gradually decreased to the normal range in the late postoperative period. There was no significant difference of the LDH level between both groups in the entire postoperative period. From the results of the present study, hemodynamic performance of both types of the SJM valve was good and incidence of the valve-related complications was low in both groups. But we must be careful in the selection of the 19HP for small aortic annulus in view of pressure gradient.

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Between November 1996 and August 1997, 8 patients had aortic valve replacement with the ATS Advanced Performance (AP) series valve. One patient had aortic regurgitation, 2 had aortic stenosis, and 3 had steno-regurgitation. The mean age of the patients was 53±8 (range 43-64) years; one was a man and 7 women. AP 18 mm was used for 5 patients and AP 20 mm for 3. No patients died in hospital. One patient with coronary spastic angina needed percutaneous cardiopulmonary support (PCPS) and intra-aortic balloon pumping (IABP) soon after the operation. One patient who had simultaneous mitral valve replacement, had an embolic attack with atrial fibrillation on the day after operation. No other serious events were observed. Peak transprosthetic pressure gradient with the ATS AP 18mm valve was 28.0±1.2 mmHg (n=5) and there was no significant difference compared to that with the standard St. Jude Medical (SJM) 21mm valve (n=8, 25.1±3.9 mmHg). LDH value with the ATS AP 18 mm valve was 517±48 u/l (n=5) and there was no significant difference compared to that with the standard SJM 21mm valve (n=6, 497±132 u/l). Early experience suggests that the ATS AP series valve had excellent hemodynamic characteristics in the aortic valve replacement.

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From December 1994 to March 1997, 21 patients with atrioventricular block were implanted with Medtronic model 5032 leads. These patients were classified into two groups: 11.5cm leads of atrioventricle distance were used in S group (15 cases, 74.9±5.9 years) and 13.5 cm leads were used in L group (6 cases, 79.8±12.5 years). Our standard for choosing the leads is: 13.5 cm leads must be considered for patients with preoperative chest roentgenographs at inspiratory phase in supine position showing a heart size larger than 16 cm or for those having both a heart size larger than 15 cm and being more than 145 cm tall, whereas 11.5 cm leads are appropriate for other patients. P wave at implant was 3.23±1.92 mV in S group and 2.68±0.85 mV in L group. P wave was 1.93±1.42 mV in S group and 1.61±1.07 mV in L group 3 months postoperatively. Under these results, our standard is considered very reasonable for choosing the single lead in VDD system.

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We investigated the possibility of single lead DDD sensing/pacing on the basis of the results using an original double balloon bipolar lead having variable dipole spacing. In the present study, on the selective detection of atrial p-waves, it was shown that the best results came from the narrow dipole spacing, small electrode surface area, and the electrode positioning at the high right atrium. In terms of atrial stimulation, it was shown that for floating electrodes a smaller electrode surface area yielded a lower stimulation threshold and the optimal dipole spacing was dependent on the distance between the atrial wall and the stimulating electrodes. However, in all cases the stimulation threshold of the floating electrodes was higher than that of conventional non-floating electrodes. Additionally, the optimal stimulation point in the right atrium could not be determined. Based on these results, we concluded that an adequate stimulation threshold could not be obtained with the floating atrial electrodes. Further studies, including biphasic stimulation, will be necessary to realize the single lead DDD.

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Lymphocytapheresis is a useful treatment for immunological diseases and immunological modulation. However, this treatment is not easy and the cost is high. In this study, we examined a new lymphocytapheresis using non woven polyester for transfusion. One treatment was arteriovenous circulation, and the other was venous-venous transfusion bag system. Lymphocytes were reduced to 50%. T-cells and B-cells were detected about 50% from blood. The activated T-cells were adsorbed and their number was 50%. The VV method was superior to the AV method in effectiveness, safety and easy treatment. The VV transfusion bag method should be considered with other treatments such as the immunoadsorbtion system. Lymphocytapheresis using Finecell will be a very useful treatment for immunological diseases and extra-corporeal immunomodulation.

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An attempt to observe the radical scavenging effect on the various hollow fibers for artificial kidney has been carried out. That is, it was observed that the scavenging effect against radicals generated from redox catalyt on the hollow fibers was able to estimate by the absorbance changes at λ max, at 250nm of UV spectra of ascorbic acid used as the indicater. The order of radical scavenging effect of hollow fibers is as follow. EVAL≥CE ·VE>CE>PSU≥CEt-Ac. It is guessed that the radical scavenging effect of hollow fibrers depends on the chemical structure of the fibers.

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Biocompatibility of dialysis membrane has been studied directing our attention to difference in membrane material. To clarify a membrane of thrombus formation, it should be evaluated with respect to not only membrane material but also flow characteristics on membrane surface depending on surface roughness. Platelet adhesion on the membrane surface was measured using 5 dialysis membranes of different surface roughneses. Bovine blood (500ml) added with trisodium citrate dihydrate (approximately 2g) as an anticoagulant was circulated in a test dialyzer at a flow rate of 200ml/min. Pressure drop and flow rate of PMMA (particle diameter: 1μm) suspension in glycerol(Bingham fluid)(glycerol: PMMA=2: 1 by weight ratio) were measured to determine yield stress. The yield stress of the membranes and increased with surface roughness. The amount of platelet adhesion increased with yield stress, indicating that the platelet adhesion depends on surface roughness.

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Clinical effect and significance of the modified cellulose membrane which is fixed with vitamin E (α-tocopherol) on inner surface (CL-EE) have not been clear.
Oxidized LDL(Ox-LDL)was investigated in 64 haemo-dialysis patients. The significant correlation between the high incidence of complication of atherosclerotic diseases and the high elevation rate of Ox-LDL during haemodialysis.
CL-EE was used for 3 months to the 13 patients who's Ox-LDL elevatcd 140% or more during haemodialysis at the screening test. Their post-haemodialysis level and the elevation rate of Ox-LDL reduced dramatically by CL-EE.
These results indicate the possibility of Ox-LDL elevation rate during haemodialysis as indication for CL-EE usage.

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In patients with chronic renal failure, water except for basic metabolism is not necessary after swallowing. Water is absorbed to circulation in the gastrointestinal tract, and accumulates in the body. We developed a new method using super absorbent polymer that could precede intestinal mucosa in absorption of water in the gastrointestinal tract. The powder of super absorbent polymer is transformed to jelly just after contact with water. After administration of polymer to the stomach, it is excreted as soft feces. We made five kinds of polymer(KO-Li, KO-02, KO-03, KO-04 and KO-05), which are made from polyacrylate and are different in effective gel capacity, and administered it via a gastric tube in rats which underwent total kidney resection. In the control group, without polymer, the mean survival time was 65 hours. However, in polymer administration groups, it was prolonged. In KO-Li, KO-02 and KO-03 groups, it reached 82, 87 and 91 hours, respectively. In serum electrolytes, potassium, calcium and magnesium were lower, and phosphorus was higher in KO-Li, KO-02 and KO-03 groups than those in control group. Furthermore, the increase of body weight after nephrectomy was suppressed by administration of polymer. The administration of super absorbent polymer was effective in control of body weight and constipation, and might contribute to quality of life and survival in hemodialysis patients.

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We observed peripheral nerve regeneration across a 25mm gap bridged by polyglycolic acid (PGA) mesh tubes coated with collagen. In five cats (Factor(+)), the tubes were filled with the mixture of NGF, bFGF and laminin. In the other nine cats (Factor(-)), the tubes were left empty. Electron microscopic observations showed that myelinated axons with thick myeline sheaths with Shwann cells and many unmyelinated axons appeared in regenerated nerves. In all cats, sufficient restoration of both somatosensory evoked potentials(SEPs) and electromyograms(EMGs) were attained. In Factor(+) group, 86% of the identified lumbosacral spinal motoneurons were backfired from either peroneal or tibial nerves, and 36% of the identified motoneurons were backfired from both peroneal and tibial nerves. These results indicate that several part of the regenerated motor axon from a single motoneuron reached both peroneal and tibial nerves. In Factor(-) group, they were 74% and 16%, respectively. Restoration of walking functions with ankle joint movement were observed. In this study, it is suggested that our PGA-collagen tube induced peripheral nerve regeneration with functional restoration of motor nerve and that NGF, bFGF and laminin may accerelate functional recovery of motoneurons.

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To evaluate an inhibitory activity of PHEMA-PSt-PHEMA ABA type block copolymer (HSB) surfaces with microdomain spacing of 16nm to rat lymphocyte cell death, ultrastructural changes of the lymphocytes adhered to the HSB surfaces for 3 hours were analyzed by scanning(SEM) and transmission electron microscopy(TEM). The TEM images of the lymphocytes on the HSB surfaces and intact lymphocytes were evaluated quantitatively by image processor-analyzer. PSt, PHEMA-PSt random copolymer and Biomer surfaces were used as control polymers. The lymphocytes adhered to the control polymer surfaces were observed to be noticeable deformed and were in a cell death condition after 3 hours. On the contrary, the lymphocytes adhered to the HS B surfaces retained the ultrastructures of plasma membrane, mitochondoria and nuclear membrane the same as those of intact lymphocytes. The TEM images between the lymphocytes on the HS B surfaces and the intact lymphocytes did not indicate any significant difference in the image analyses. It was found that the microdomain structure surfaces of the HSB have a remarkable effect on lymphocyte cell death, compared to those of the control polymer surfaces. This result suggested that the hydrophilic/hydrophobic microdomain structure surfaces inhibit lymphocyte cell death by regulating the distribution of lymphocyte plasma membrane proteins. [Abbreviations: PHEMA, Poly(2-hydroxyethyl methacrylate); PSt, polystyrene]

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Thermoreversible gelation polymer (TGP), whose aqueous solution at room temperature turned into a hydrogel upon heating to body-temperature, was prepared and was tested as a wound dressing. A saline solution of TGP at a concentration of 10wt% (sol-gel transition temperature; 18°C) was cooled on ice and poured onto a full thickness skin wound (4×4 cm²) of rats. The TGP solution turned into a hydrogel within one minute due to being heated to the temperature of the wound surface. The wound covered with the TGP hydrogel secreted no exudate and healed in 4 weeks. Histopathological examination after one week demonstrated granulation was filled with fibroblasts and capillary vessels regenerated. On the other hand, the wound covered with a commercial hydrocolloid wound dressing (Comfeel®) secreted much exudate and healed in 6 weeks, and a few fibroblasts and a lot of inflamation cells were obsereved. These results suggest that the TGP hydrogel adheres wound surface closely with keeping it wet and prevents the exudate loss, and consequently promotes healing by providing the wound with good healing environment.

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We developed a new apparatus to evaluate platelet-biomaterial interactions, the initial event of thrombus formation, in real-time with relatively small platelet suspension volumes under shear flow conditions. This is the first report on the observation of platelets adhered to opaque biomaterials in real-time by an apparatus consisting of a modified cone and plate-type viscometer combined with an upright epi-fluorescence microscope. Because no difference was observed between the number of labeled and non-labeled platelets with CFSE (a fluorescent dye) adhered to the materials, it was suggested that CFSE has no affect on platelet adhesion to test materials or platelet activation. Using this apparatus, platelets adhered to the ePTFE which is opaque and used as an artificial vessel under three types of shear flow were clearly visualized in real-time by epi-illuminated light. Our findings show that our cone and plate-type viscometer-based apparatus is a useful instrument for testing and screening biomaterials and provides a precise quantitative evaluation of platelet adhesion.

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To evaluate the endothelial injury which is regarded as a major cause of restenosis after percutaneous transluminal coronary angioplasty (PTCA), a perfusion culture system was constructed. Porcine aortic endothelial cells were cultured on the inner surface of a glass tube (3.0 mm, i. d.), and the tube was placed in a closed perfusion circuit (120 mL/min, steady flow). Compressive force (ca. 2.5 kgf/cm², 1 min).was applied to a monolayer of endothelial cells by inflating a PTCA balloon catheter introduced within the tube, and effects of compressive force on the viability of the endothelial cells were estimated. After the application of a compressive injury, the endothelial monolayer was observed continuously under a video microscope. Thereafter, the effects of conditions of catheter operation on the endothelial injury were studied. The endothelial monolayer exposed to compressive force was found to be injured immediately after the deflation of the catheter, and the number of the intact endothelial cells decreased below 10% of that before the catheter operation. During the observation period of 48 h after the deflation, no apparent growth or repair of endothelial monolayer was observed at the denuded area. While, the endothelial injury was considerably suppressed when the balloon was deflated slowly. This system is thought useful in improving PTCA technology.

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We have analyzed the adsorbed proteins on the heparin-coated cardiopulmonary bypass (CPB) circuit to clarify the relationship between nonthrombogenic materials and adsorbed proteins. The heparin-coated CPB circuits were evaluated in vi tro using a fresh heparinized human blood from healthy volunteers. Before and after circulation, the number of platelets, leukocytes, the concentration of C3a, PMN elastase were measured. It was shown that the activation of platelets, leukocytes, complements were suppressed on the heparin-coated surface. After circulation for 4 hours, the CPB circuits were rinsed by saline. Hollow fibers were retrieved from the CPB circuits, then extracted by the sodium dodecyl sulfate (SDS) solution. SDS-PAGE of the extract of the adsorbed proteins on the heparin-coated fibers showed different patterns of the bands from the nontreated fibers and plasma. From immunoblot analysis of the extract it was shown that anti thrombin III apo E, Clq, factor H, Cl esterase inhibitor (Cl INH), C3a were specifically adsorbed. Clq was the most abundant of all, then its percentage was about 50%. It was suggested that inhibition of coagulation was due to adsorption of ATIII, and inhibition of complement was due to adsorption of factor H and Cl INH.

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A stopped flow type system consisting of a single tube for monitoring endotoxin by the limulus test was developed. In this system sample solution reacted with limulus reagent without contact with outer atmosphere. The objective of the present study is to obtain a sensitive system for monitoring endotoxin concentration ranging under 100 EU/l in a short time. Peak area of absorbance observed as a function of reaction time at 405 nm was similar to absorbance observed with batch reaction. Short time monitoring of endotoxin concentration ranging above 40 EU/l at a reaction time of 20 min and 80 EU/l at 10min was possible.

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In order to develop new types of artificial vessel using native vessel wall element, we investigated the effect of formic acid treatment (which was supposed to degrade collagen and retain elastin) and trypsin treatment (which was supposed to degrade elastin and retain collagen) on vessel constructive elements by pathological staining and scannning electron microscope. The results were as follows. (1) By formic acid treatment: In adventitia and tunica media collagen fibers were removed and elastin fibers were partially untied. By short time treatment, vessel wall was thickened, and the luminal was narrowed. By long time treatment, the wall was thinned. (2) By trypsin treatment: Adventitia remained unchanged. In the middle layer, elasin fibers were expanded, and the fibers' bundles were scatterd. In tunica intima, elastin fibers were thinned, and vessel wall was expanded. (3) By either treatment, endothelium cells, smooth mascie cells and connective tissue were broadly removed. Neither collagen specific degradation nor elastin specific degradation was observed. An important unresolved question is the relation between retained extracellular matrixes and initial physical strength.

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Gelatin-sealed branched knitted Dacron grafts (Gelseal;17 cases) were evaluated in total aortic arch replace mentin comparison to collagen-sealed woven Dacron grafts (Hemashield;13 cases). In Gelseal group, subjects included Stanford type A acute aortic dissection in ten, Stanford type Achronic dissecting aneury smin one, aorticarchaneury smin six patients. In Hemashield group, Stanford type A acute aorticdes section in five, Stan ford type A chronic dissecting aneury smin one, aortic archaneury smin seven cases. Theearly mortality rates for Gelseal and Hemashield were 5.9 % and 30.8%, respectively (N. S.). Gelseal graft was soft, pliable and very useful for repla. cement of the aorticarche specially in emergency cases. However, intensive follow up is necessary because it dilated about 25% in diameter one month after surgery.

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