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A total artificial heart (TAH) goat survived for 360 days on the new automatic control method (1/R control), in which the cardiac output of the TAH can be controlled through the cardiovascular center by making it function by reflecting the beta-adrenergic reaction in peripheral vascular resistance. This is thought to be the only long-term, real-time, measurable parameter by which information on the activity of the cardiovascular center can be received directly by the TAH system. In this goat, the hemodynamic parameters (RAP, AoP, and so forth) were kept within physiologic limits when control was stable, and the cardiac output was automatically increased in response to exercise, not unlike that in the natural heart. There were no abnormal blood chemical or hormone data except at end stage. Based on these results 1/R can be considered a physiologic control method for a TAH.

Chronic study of the peripheral circulation and metabolism is very important in evaluation of artificial organ performance. However, there has been no way to observe the microcirculation in situ, chronically and continuously, without restriction. In this study, the authors developed a new apparatus that could be implanted and connected to an artificial organ that would allow continuous observation of the microcirculation while the subject is awake. The apparatus uses a charge coupled device (CCD) under a new principle: thin living tissue, such as mesentery, is put directly on a highly integrated CCD and transilluminated with a light emitting diode (LED). The vascular nets in the tissue are projected onto the CCD like a contact photograph, which is sent to a television screen and can be analyzed for motion and function. A 0.5 inch CCD with 25K pixels was used in this study. The cover glass of the CCD was removed so the tissue would be able to directly contact the CCD surface. The CCD, as well as LED, were molded with hard polyurethane as electrical insulation. The apparatus is 35 mm in diameter and 10 mm high with a micro stand for lighting with the LED, which is easy to implant in a goat or calf. The resolution of this apparatus was tested by putting a micro scale on the CCD surface. Several tenths of micrometers could be seen. In an animal experiment with a rabbit, configurations of arterioles and venules and their motions could be observed continuously for a night until the electrical insulation was broken. This method might be a strong weapon in artificial organs research.

Of 77 University of Tokyo ventricular assist devices used in a total of 70 patients at 21 institutions, 13 pumps were found to have macroscopic thrombus formations. Because 19 devices that were used for less than 24 hours showed no thrombus deposition, they were considered not to have been sufficiently exposed to the thrombogenic environment for macroscopic thrombus deposition and were removed from the subsequent multivariate study. A total of eight potential risk factors were assessed in relation to thrombosis. Prevalences of thrombus formation were compared between two groups with or without each of the risk factors. In a univariate analysis, the following categoric variables were demonstrated to be significantly associated with complications, in descending order of significance: use of gabexate mesilate (protease inhibitor) as an anticoagulant (p = 0.005), normal platelet count (p = 0.010), duration of support (p = 0.038), leukocytosis (p = 0.042), and minimum pumping flow (p = 0.042). Use of heparin and the consequent increase in activated clotting time showed no relationship. Multivariate discriminant analysis, which was done to identify risk factors rejecting cross correlation between each variable, demonstrated platelet count (p = 0.006), use of gabexate mesilate (p = 0.007), and minimum flow (p = 0.008) to have significant and independent risks. These results indicate the importance of maintaining pumping flow above a certain minimum level, addition of antiplatelet drugs to the antithrombogenic regimen, and nonuse of gabexate mesitate.

For the purpose of future total implantation, a new pulsatile total artificial heart, a flow transformed pulsatile total artificial heart (FTPTAH), in which the continuous flow from a single centrifugal pump (CFP) was converted to pulsatile flow by switching two three-way valves that could alternately perfuse the systemic and pulmonary circulation, was proposed, and the data from the prototype model were reported. As the next step, the second model, in which a CFP and a spool valve (SV) driven with a solenoid were fabricated in one piece, was made and tested in a mock circulatory system. The system could send 4.7 L/min of pulsatile output alternately to the pulmonary artery and aorta, with 30 and 100 mmHg afterload, respectively, at 3000 rpm CFP. However, three problems were encountered: the output was not enough, mixture or inversion of venous and arterial blood in the CFP would occur, and heat generation at the solenoid was very severe. To solve these problems, a third model was designed in the current study. To increase pump output, hydrodynamic analysis was performed. The SV was divided into inlet and outlet to control the blood mixture or inversion. To suppress heat generation, each SV was driven back and forth by two solenoids, one on each side of the SV. The model revealed satisfactory results in a mock circulatory system.

The distribution of adsorbed plasma proteins (albumin, IgG, and fibrinogen) on 10 artificial heart blood pumps coated with 2 segmented polyurethanes was evaluated quantitatively after long-term in vivo experiments with goats to determine how the adsorption of plasma proteins on the pumps was affected by the kinds of biomaterials used, and by the pumping duration. The adsorbed plasma proteins on the materials were determined quantitatively using the iodine-125 conjugated antibody method. Microscopically, the adsorbed plasma proteins were marked by the gold colloid conjugated antibody method, and analyzed using a field emission scanning electron microscope. The macroscopic results showed that: 1) the adsorbed plasma proteins on KP-13 were more evenly and finely distributed than those on Cardiothane; 2) with KP-13, the adsorption of IgG and albumin at the center of the pumps was significantly less than in the peripheral areas, and the adsorbed IgG and albumin decreased significantly as the pumping duration increased; 3) in contrast, the adsorbed fibrinogen increased significantly with time; and 4) with Cardiothane, the tendencies for adsorbed IgG and albumin to decrease, and for adsorbed fibrinogen to increase, were less significant than with KP-13. Microscopically, the gold colloids marking plasma proteins were found to not cover the whole of the surface, but were found scattered randomly or in clusters, with no relationship observed between the distributions of the three plasma proteins.(ABSTRACT TRUNCATED AT 250 WORDS)

For a valve to be fabricated seamlessly into an artificial heart (AH) blood pump, a jellyfish valve has been developed, in which a thin membrane is fixed at the center of a valve seat having several spokes to protect against prolapse of the membrane. The valve is superior in performances to a Björk-Shiley valve, and reveals good blood compatibility. The valve would be very useful not only for AH animal study, but for future clinical use in infants to adults. Several institutions are already trying the valve. In this paper, the fabrication of the jellyfish valve is introduced, and in vitro and in vivo results summarized. A computer aided design (CAD) system was developed to cut a male wax mold of the valve seat. The input parameters to the CAD are diameter, height, thickness of rim, number of spokes, width and thickness of spokes, etc. Jellyfish valves with diameters of 4 to 27 mm have already been fabricated for many types of AHs and assist pumps.

To realize a totally implantable total artificial heart (TAH), a new pulsatile TAH, the flow-transformed pulsatile TAH (FTPTAH), was developed. The system was composed of a single centrifugal pump (CFP) and two three-way valves. One port of each three-way valve was connected to the inlet and outlet of a CFP. The other two ports of each valve were connected to the right and left atrium, and the pulmonary artery and aorta. The CFP can perfuse the pulmonary and systemic circulation alternately with pulsatile flow by switching the two three-way valves. A prototype and the secondary model in which the solenoid valves and a spool valve were included, respectively, were connected to a mock circulatory unit with the results that a pulsatile TAH with physiological flow wave form could be obtained from a single CFP, about 5 L/min of pulsatile output could be obtained alternately on the right and left side by switching the solenoid valves or a spool valve, and flow balance between the right and left could be easily controlled by the switching duration. The system is feasible for a totally implantable TAH because it does not need a compliance chamber and can be miniaturized.

What are the most essential technologies for developing the implantable artificial heart in future? The first is the development of autonomic and dispersed micro actuators for acting as sarcomeres of the heart muscle. An electric motor driven artificial heart transmitted the power with belts had been developed as a preliminary mechanism. A micro actuation using noise energy has been developed for simulating the structure and the function of striate-muscle sarcomeres. The chemical energy conversion mechanism must be applied instead of the conventional electro-mechanical mechanisms, when we implant the total artificial heart permanently. As a implantable assisted artificial heart using tentatively, we have developed an axial flow pump system. The pump system acts as a systemic and a pulmonary pump produced pulsatile flow switching an axial pump output. The second is the search of biocompatible materials, which do not only mean blood compatibility but also tissue compatibility. The great masses in chest cavity have inevitably occurred infection. The autonomic and dispersed control system is the third item. We have developed a jellyfish valve with low fluid dynamical resistances for improving the pump dynamic characteristics.

Atrial natriuretic peptide (ANP) was administered intravenously to three goats at a dose of 0.1 micrograms/kg/min for 40 min both before total artificial heart (TAH) placement and at 1, 7, and 14 postoperative weeks to determine whether exogenous ANP exhibits the same effect on animals with TAHs as it does on normal animals. No significant changes in the increases in plasma levels of ANP and cyclic guanosine monophosphate (c-GMP) were observed during ANP administration after TAH insertion. In preoperative animals, urine volume and urinary sodium excretion increased greatly during ANP administration, but this natriuretic effect was strongly suppressed in TAH animals. The changes in the decreases in arterial pressure and in central venous pressure (CVP) or right atrial pressure that occurred during the administration of ANP were not significant either pre- or post-operatively. Thus, only the natriuretic effect of ANP on the kidney was significantly suppressed in TAH animals, which might be due to some down-regulation of ANP receptors in the kidney, the production of some antagonists of ANP, sympathetic hypertonicity, or the elevation of CVP.

A new pulsatile total artificial heart (TAH) system, combining a single centrifugal pump (CFP) with two three-way valves, was developed. One port of each three-way valve was connected to the inlet and outlet of a CFP, respectively. The other two ports of each valve ware connected to the right and left atrium, pulmonary artery, and aorta. The CFP can perfuse the pulmonary and systemic circulation alternately with pulsatile flow. A prototype system composed of a Sarns' CFP and solenoid valves was connected to a mock circulatory system resulting in 1) a pulsatile TAH that could be produced with a single CFP, 2) 5 L/min of pulsatile output with a normal flow wave form that can be obtained alternately on the right and left side by switching the solenoid valves, and 3) flow balance between the left and the right that could be controlled easily by the length of switching duration. This new system could be miniaturized and is feasible for a totally implantable TAH.

The blood compatibility of the jellyfish valve was studied. Artificial heart (AH) blood pumps incorporating jellyfish valves were connected to 18 goats as total artificial hearts (TAHs) and pumped for 1 to 125 days without anticoagulant or antiplatelet drugs. No thrombus was formed on the valve membrane or around the valve seat. Scanning electron microscopy showed almost no platelet deposition or microfibrin clot formation on the valve membrane, including its central region; the spokes of the valve seat were also free from platelet and microfibrin clots. No calcification was observed during these tests, and plasma free hemoglobin was between 2 and 7 mg/dl. The jellyfish valve revealed good blood compatibility, even without anticoagulant use.

For percutaneous observation of lesions near the spinal cord and percutaneous spinal laser surgery under the visual field, we studied a method and approach to the spinal cord and intraspinal surgical procedures with laser using a newly developed, small-diameter laser endoscope. The subarachnoid and epidural spaces of a goat were punctured using a 17-gauge epidural needle, and the endoscope (diameter 0.7 mm) was inserted through the needle. The spinal cord and surrounding tissue were observed. Next, an endoscope (diameter 1.5 mm) was inserted into the subarachnoid space, and the quality of the picture and manageability of the endoscope were examined. The Xe:Cl excimer laser was irradiated to a nerve root through a 0.4 mm optical fiber for laser transmission through this endoscope. The spinal cord, nerve roots, and arachnoid were clearly observed through this endoscope. The pulsation of the artery accompanying a root was seen clearly, and the quality of the picture of the endoscope was thought to be sufficient for diagnosis. The nerve root was cut within 30 seconds by excimer laser, and the possibility of laser surgery was demonstrated. Although it was shown that this endoscope could be a useful diagnostic and therapeutic tool, improvement in the manageability of the tip of the endoscope was considered to be important for a clinically usable endoscope.

Since 1986, percutaneous intradiscal laser nucleotomy (PILN) has been studied in the authors' laser laboratory. The purpose of this report is to develop PILN as an alternative to chemonucleolysis and percutaneous discectomy, which are currently applied, and to establish a safe, easy, accurate and short-time therapy method for lumbar disc herniation. After laser irradiation, intradiscal pressures (IDP) decreased and the nucleus pulposus was gradually replaced with cartilaginous fibrous tissue. The evaluation of heat distribution with thermocouples and thermography was done to determine safe optimum irradiating conditions and to develop a new double-lumen needle and a bare quartz fiber. Neodymium-yttrium-aluminum-garnet (Nd-YAG) laser devices have been improved for easy and safe use, and a new tip type pressure transducer has been made for improved therapeutic results using this new method.

An artificial heart (AH) driving system, in which a sac or diaphragm type blood pump is liquid gas driven, is designed. The working mechanism of this system is as follows: 1) liquid gas is used for the driving source; 2) a liquid gas is stored in its liquid state in the circuit; 3) a liquid gas is vaporized, and the vaporizing pressure squeezes the blood pump, causing ejection of blood; 4) vaporized gas is aspirated and compressed by a small compressor to liquefaction through the heat exchanger, then negative pressure is applied to the blood pump and blood is aspirated; and 5) the blood pump is driven in this closed cycle. To demonstrate the mechanism of this system, a prototype was developed using Freon 114 as the liquid gas. In this system, the maximum flow of the AH at a 100 pulse per minute rate, was about 6.9 L/min, using a 90 ml sac type blood pump. The advantages of this AH driving mechanism are as follows: 1) a small system is available because pressure chambers are not necessary; 2) a biventricular system is available, with a single compressor; 3) no compliance chamber is necessary if the system is small enough to be implanted.

A total of 61 VASs developed in Tokyo University were evaluated at 21 institutions in the period 1985-1989 for determination of its reliability and effectiveness. The system is comprised of a pneumatic sack-type pump (Nippon Zeon Co.), and its driving console (Aishin Seiki Co.). The stroke volume of the pump is 40 ml and blood contacting surfaces are coated with Cardiothane. Ages of the patients (pts) ranged from 12-82 yrs (mean 58 yrs). VASs were used in the assist mode of LVAD (54 pts), RVAD (5 pts) and BVAD (2 pts). Most of the cases (58 pts) included postocardiotomy cardiogenic shock after surgery for ischemic (28 pts), valvular (22 pts), both ischemic and valvular (7 pts) and congenital (1 pt) heart diseases. Average duration of the assist ranged from 1 hr-20 days (mean 5.6 dys). The VADs could be weaned in 34 cases (56%) and among these, 13 cases (21%) survived to discharge from the hospital. Causes of death in cases which could be weaned from the VAD included multiple organ failure/due to delayed institution of adequate circulatory support, renal failure and systemic infection. Small and minute thrombus formations were noted in 7 cases however, no pump originated thromboembolism were complicated. No troubles of the pump including leakage nor breakage, no mechanical failures of the driving consoles were experienced in any of the cases. Thus, it is concluded that the system was proved to be clinically effective and reliable.

Two air driven VAD and TAH driving and control units were developed for clinical use, one to be installed at the bedside and the other to be installed in an electric wheelchair. The reliability and safety of the bedside unit were shown by long-term TAH experiments using animal models and by clinical application in conjunction with VAD. A TAH goat was safety taken on a 12 hr trip to a destination 550 km away while attached to a bedside unit. The driving and control functions of the wheelchair unit were found to be practically identical to those of the bedside unit.

A TAH goat survived 344 days postoperatively. The cause of death was hypoxia due to lung embolism and anemia.

The purpose of this study was to clarify whether plasma ANP levels (p-ANP) are abnormal in TAH animals, and if ANP plays an important role in circulatory failure in TAH animals. In five TAH goats that survived for 51-171 days, changes in hemodynamic parameters, plasma levels of renin, angiotensin I and II, aldosterone (p-RAA), and p-ANP were measured, and correlations between p-ANP and other parameters were studied, and histologic study of ANP and assay of the ANP content in atrial tissue was undertaken. Generally, p-ANP of TAH goats fell temporarily after surgery but then recovered to preoperative levels. Histopathologic studies of atrial tissue and ANP granules proved almost normal, although the coronary blood supply was occluded for more than 170 days; the ANP content in the atrium did not show significant changes after 51 days of TAH pumping. In one case prominent correlations between p-ANP and p-RAA were observed, and in another case significant correlation between p-ANP and arterial pressure was observed. However, these correlations were not observed in every case. In TAH goats the plasma ANP level did not increase in spite of high atrial pressures. Plasma ANP levels in TAH animals are almost normal. In TAH animals no role in the pathogenesis of hemodynamic abnormalities is played by abnormality of plasma ANP levels. However, TAH animals may display an abnormality in sensitivity to the p-ANP.

Surface analysis has been carried out for Cardiothane 51 samples as commercially available balloon pumps and cast films prepared from the solution. Silicone contents on surfaces have been quantitatively determined by FT-IR-ATR spectroscopy coupled with a subtraction technique. The contents on the air-facing surface vary from 0.7 to 5.3% among six balloon pumps examined; three of them contain less silicone on the air-facing surface than on the substrate-facing surface, whereas just the opposite is true for one, and the other two have nearly and quite an equal content of it between the two surfaces. Silicone contents on surfaces of cast films vary also from a sample to another even when sample films were prepared from the same Cardiothane solution, indicating difficulty in quality control of Cardiothane surfaces. An appreciable fraction of silicone was found not to be covalently bonded to polyurethane in Cardiothane 51 for the cast film samples.

We developed control system of total artificial heart (TAH) during exercise simulating the circulatory response of natural heart. The following procedures were taken to develop this system. 1) Measurement of hemodynamics and physical activity rate (PAR) of natural heart goats during treadmill exercise. 2) Estimation of cardiac output from PAR using a non-linear model. 3) Development of a pneumatic artificial heart (AH) driver with high speed controllability and a control unit to deliver CO calculated from PAR beat by beat. 4) Evaluation of the physiological condition of the TAH goat during exercise controlled by this system. Using this control method, CO of TAH goats was similar to that of natural heart goats during treadmill exercise. Hypertension was observed during exercise. This hypertension was considered to be derived from two causes. One was high inflow and outflow resistance of cannulae between AH pump and living body. The other was the disorder of peripheral circulatory control mechanism in TAH animal. Such as increased sympathetic activity, insufficient secretion of atrial natriuretic polypeptide (ANP) and decreased sensitivity of peripheral circulatory system with ANP.

Pathological studies using routine pathological technics, microangiography and electron microscopy were performed on the 28 goats with an artificial heart (including 2 goats which survived for 30 and 37 days). In this paper, the brain, natural heart, and lungs of the goats were discussed. No special findings were seen in the brain except for rare infarcted areas. The natural heart almost always showed infarction-like lesions in the sub-endocardium and myocardium at the cut surface. The longer the animal survive, these findings became the more serious. The light microscopic findings on the lungs were classified into 6 groups. The most important findings of them are massive, diffuse exsudation with hemorrhage and its changes to chronic status. The main pathophysiological status, causing the pulmonary lesions, seemed to be peripheral circulatory insufficiency with increased permeability of peripheral vessels, especially of venulae. Thrombi were detected more frequently in the kidneys and lungs than in any other organs. The vascular walls where the thrombi were attached to, where often seen to be damaged, so that almost all thrombi were thought to be formed in the local vessels in situ, but not in the artificial heart. The main clinical causes to the pulmonary insufficiency were thought to be surgical operation including anesthesia, functional incompleteness of the artificial heart, etc.

The natural heart could be preserved in the beating state, with appropriate afterload, for more than 24 hrs if supported by blood compatible artificial organs and biomedical engineering techniques. An artificial environment was developed using this philosophy. The system was constructed from four subsystems: circulatory, respiratory, metabolic, and environmental. In the circulatory subsystem, diastolic pressure was held at 70 to 100 mmHg by computer aided peripheral resistance, and a left ventricular assist device (LVAD) could be added when cardiac function was weakened. The respiratory subsystem was composed of an artificial lung and computer aided gas mixer for O2, CO2, and air, which kept blood PO2 and PCO2 within physiologic levels. In the metabolic subsystem, glucose and insulin were injected by infusion pump so as to maintain blood sugar within 100 to 200 mg/dl, whereas the environmental system preserved the isolated heart at 37 degrees C in a sterile water bath. Goats' hearts were connected to this system, and continued to beat for a maximum of 24 hours.

High output AH pumping causes a marked decrease in hematocrit, as well as peripheral circulatory insufficiency. By the application of a new control method, based on our hypothesis of regulating the output of the pump, maintenance of normal outputs, long term survival, after total heart replacement, has improved from 10 days to 37 days, with the average survival of 18 days. In addition, the experimentsl animals' general condition has been markeldy improved.

By fixing the function of one ventricle, a total right heart bypass model can clarify the function and regulatory mechanism of the natural heart, and the etiology of abnormal hemodynamics in TAH animals such as increased CVP blood pressure and hepatic congestion. The pulmonary artery of a right heart bypass in a goat was clamped proximally; the pulmonary circulation was thus supplied entirely by the artificial heart and the systemic circulation by the natural heart. This model enabled studies of long-term effects of an artificial right heart on systemic circulation at a right heart output of 80-100 ml/kg/min; the response of the natural left heart to changes in output of the right heart; and the response of the natural left heart and artificial right heart to treadmill exercise. It was found that only slight increase in CVP or no increase in blood pressure was observed during the experiment (112 days); a rapid increase in output of the RAH resulted in an increase in left atrial pressure, stroke volume and output of the left ventricle, and a decrease in its heart rate at rest; and significant increase in both artificial right heart and natural left heart output and heart rates were observed during treadmill exercise, despite the marked decrease in left atrial pressure. The above results suggest that the increase in CVP and blood pressure in total artificial heart animals are not due to factors involving the artificial right heart, and that although left ventricular function acts in accordance with Starling's law at rest, this is no longer true during treadmill exercise.

Current circulatory assist methods, such as intra-aortic balloon pumping (IABP), are not always adequate to save acute circulatory failure patients. Therefore, a stronger, percutaneously accessible method is required. We found that the combination of IABP and CP generated a profound circulatory assist effect, and we have consequently developed a new assist system in this study. A sac type blood pump with a volume of 20 ml and a single port without a valve, was developed for CP. In the mock circulatory test, a 20 ml stroke volume was obtained using a cannula with a 5 mm diameter under the following driving conditions: air pressure = 200/-100 mmHg; S/D = 50%; pulse rate = 100 bpm. In vivo experiments were performed using four mongrel dogs with body weights of 12-20 kg. A cannula for CP was inserted via the brachial artery or subclavian artery into the aortic root. The pump flow (PF), coronary artery flow (CF), renal arterial flow (RF), and aortic pressure (AP) were measured, and the combined effects of IABP and CP were compared with their individual effects. In the most effective case, a marked increase in diastolic AP (60%), cardiac output (40%), and CF (100%) was obtained by the combination of IABP and CP, which produced a remarkable effect compared with the single use of IABP and CP. There was no negative effect on RF by this assist method. As this new circulatory support system has many circulatory assist effects, and is percutaneously accessible, it will be available for clinical use.

We began applying of our VAD system clinically in 1982 and have subsequently obtained good results. The first case treated with the VAD returned to normal life. In a total of 70 cases of clinical applications this system there has been instance of apparatus dysfunction. Confirming the reliability and safety promised by the results of biological experiments. Here, we report the results of clinical application of the system in a total of 61 cases between August, 1985 and March, 1989. The following conclusions were reached: 1) Satisfactory weaning and survival rates were obtained i.e. 18 cases out of 61 cases (30%) survived over one month and 13 cases (21%) are currently surviving, even in elderly patients of 60 years of age or older. 2) The weaning rate and survival rates were good after approximately 1 week of support. Detailed evaluation of the recovery of the heart and functions of other major organs has led to the conclusion that the results can be improved further when the weaning period is carefully determined. 3) With regard to surgical factors, good findings were obtained when the artificial heart-lung bypass time was less than 6 hours. The VAD can be used in the early stages without vainly attempting weaning from the artificial heart-lung bypass. 4) There were no mechanical problems with the hardware of the blood pump drive assembly, etc., or noteworthy side effects.

No control method has yet been established for the total artificial heart (TAH) during exercise. As the simple intrinsic control method does not significantly increase cardiac output (CO), this study attempted to develop a new TAH control method that increases the CO during exercise in a manner similar to a natural heart (NH) by predicting changes in CO as a time function (TF) at various treadmill speeds. The control method for TAH was as follows: 1) an arbitrary grade of treadmill exercise was loaded onto the TAH goat; 2) a TF at this grade of treadmill exercise was determined from the physical activity rate (PAR) measurement, defined as the time average of the increase in vertical acceleration of the body; 3) operating parameters of both pumps were controlled in accordance with the TF using the computer algorithm. With the predictive control method changes in CO in the TAH were almost the same as in the NH, whereas no increase in CO occurred with the fixed control method (FC), in which operating parameters remained unchanged during exercise. Changes in blood lactate and catecholamines tended to be less than with the FC.

Bjork-Shiley and Hall valves used in most artificial heart blood pumps have often induced problems, which include 1) An expensive valve must be used even when the AH is used for only a few days, 2) Ring thrombus was often formed at the interface between the valve ring and blood pump, seamless fabrication was not possible, and 3) Mechanical failure often occurred. To improve these circumstances, a new jellyfish valve was designed and manufactured. The valve has a simple structure: The center of a thin circular polyurethane membrane is fixed on a polyurethane base plate, which has many holes or slits to reduce flow resistance and help hold the membrane during the diastolic phase. In a mock circulation study, the valve displayed performance similar to the Bjork-Shiley valve. A small amount of regurgitant flow was observed at valve closure, in comparison with the Bjork-Shiley valve. It was recognized in the flow visualization study that the central region of the membrane was washed out well by the flapping of the membrane. This jellyfish valve is promising for use in a AH blood pump.

This study was designed to establish a method for determining the optimal time of the application of the left ventricular assist device from the viewpoint of the metabolism of the vital organs. Quantitative systemic low flow states were made utilizing goats with total artificial hearts. During these experiments, arterial lactate and pyruvate values were sequentially measured. The behavior of anaerobic metabolism during low cardiac output states and in the recovery process following normalization of the cardiac output was quantitatively described and evaluated. The experimental results are summarized as follows: If a time when the decay of arterial lactate ceases at a level above the normal level by greater than 30 mg/dl is observed despite the use of intraaortic balloon pumping, that time is the exact optimal time for application of the left ventricular assist device. There is a great possibility that circulatory failure will be irreversible if left ventricular assist pumping is not initiated before the arterial lactate value increases to greater than or equal to 140 mg/dl. The method of evaluating the alteration of anaerobic metabolism described in this study is useful for determining the application time of the left ventricular assist device.

Twenty-eight goats with an artificial heart (AH) were studied pathologically. Being continued from the previous report, the liver, gastrointestinal tract, and kidneys were taken up in this paper and finally, general discussion was done to get our ideas in shape concerning the pathophysiological status of the goat. Central necrosis of the liver was always observed in the goats which survived for over 140 hours. This finding seemed to be caused mainly by circulatory insufficiency of the portal vein at the latter half of the survival time. Microscopic findings of degeneration, necrosis, and edema were commonly observed at the walls of gastrointestinal tracts, when goats showed poor apetite, mucous feces and constipation. But these problems have been improved by application of a new control method to regulate the output of AH system within a goat's physiological range since October 1974. The lesions seen in the kidneys are classified into 5 groups. The most important findings of them are lower nephron nephrosis and cortical necrosis, both of which indicate the occurrence of long standing vasoconstriction of proximal renal arteries. By means of microangiographic method and others, thrombi were detected frequently in the kidneys. The vascular walls, where thrombi were attached to, were often damaged. Therefore, these thrombi were thought to be formed in the local vessels in situ through renal circulatory insufficiency. The renal pathological lesions have been also improved and severe renal failure from which the previous goats could not escape, has been lessened since the application of a new AH control method. As a whole, the main pathophysiological status of the animals replaced by the AH are thought conclusively to be peripheral circulatory insufficiency. This would be caused by abnormal hemodynamics, so that, the essential clinical etiology is thought to be AH function itself.

A practical model (Model-1) of a jellyfish valve was developed, which was composed of a valve seat and a flexible membrane. The valve seat has 12 spokes to hold the membrane, and is made of solution-cast polyurethane coated with segmented polyurethane or Cardiothane. The flexible membrane is 200 microns thick, and made of segmented polyurethane or Cardiothane by a casting method. The valves were built into a sac type blood pump. In mock circulation tests, this jellyfish valve revealed performance superior to Bjork-Shiley (B-S) valves. No stagnation point was observed in the flow visualization study, and durability testing is ongoing beyond 7.5 months. The valves were used in animal artificial heart experiments for up to 112 days with good performance. No thrombi were formed on the valve membrane or around the spokes. Although a ring thrombus was observed behind the valve, it would be prevented by perfect adhesion of the valve seat to the blood pump. The plasma free hemoglobin level was less than 2 mg/dl during these experiments. These results suggest that a jellyfish valve (Model-1) is useful in ventricular assist devices, and in short-term bridge use of a total artificial heart.

The research and development on the total artificial heart (TAH) in the University of Tokyo can be divided chronologically into the three stages, i.e., the first stage (1959-1970); trial and error stage to find appropriate hardwares, the second stage (1970-1985); software stage to find how to control pneumatic TAH and to manage the animals, and the third stage (1985- ); final goal to develop implantable TAH for animal and human. This paper reviews the process of research and development in each stage.