Sensorless control for a sophisticated artificial myocardial contraction by using shape memory alloy fibre.

The authors have been developing an artificial myocardium, which is capable of supporting natural contractile function from the outside of the ventricle. The system was originally designed by using sophisticated covalent shape memory alloy fibres, and the surface did not implicate blood compatibility. The purpose of our study on the development of artificial myocardium was to achieve the assistance of myocardial functional reproduction by the integrative small mechanical elements without sensors, so that the effective circulatory support could be accomplished. In this study, the authors fabricated the prototype artificial myocardial assist unit composed of the sophisticated shape memory alloy fibre (Biometal), the diameter of which was 100 microns, and examined the mechanical response by using pulse width modulation (PWM) control method in each unit. Prior to the evaluation of dynamic characteristics, the relationship between strain and electric resistance and also the initial response of each unit were obtained. The component for the PWM control was designed in order to regulate the myocardial contractile function, which consisted of an originally-designed RISC microcomputer with the input of displacement, and its output signal was controlled by pulse wave modulation method. As a result, the optimal PWM parameters were confirmed and the fibrous displacement was successfully regulated under the different heat transfer conditions simulating internal body temperature as well as bias tensile loading. Then it was indicated that this control theory might be applied for more sophisticated ventricular passive or active restraint by the artificial myocardium on physiological demand.

Morphological approach for the functional improvement of an artificial myocardial assist device using shape memory alloy fibres.

The authors have been developing a mechano-electric artificial myocardial assist system (artificial myocardium) which is capable of supporting natural contractile functions from the outside of the ventricle without blood contacting surface. In this study, a nano-tech covalent type shape memory alloy fibre (Biometal, Toki Corp, Japan) was employed and the parallel-link structured myocardial assist device was developed. And basic characteristics of the system were examined in a mechanical circulatory system as well as in animal experiments using goats. The contractile functions were evaluated with the mock circulatory system that simulated systemic circulation with a silicone left ventricular model and an aortic afterload. Hemodynamic performance was also examined in goats. Prior to the measurement, the artificial myocardial assist device was installed into the goat's thoracic cavity and attached onto the ventricular wall. As a result, the system could be installed successfully without severe complications related to the heating, and the aortic flow rate was increased by 15% and the systolic left ventricular pressure was elevated by 7% under the cardiac output condition of 3L/min in a goat. And those values were elevated by the improvement of the design which was capable of the natural morphological myocardial tissue streamlines. Therefore it was indicated that the effective assistance might be achieved by the contraction by the newly-designed artificial myocardial assist system using Biometal. Moreover it was suggested that the assistance gain might be obtained by the optimised configuration design along with the natural anatomical myocardial stream line.

Development of an implantable high-energy and compact battery system for artificial heart.

The purpose of this study was to demonstrate the feasibility of the use of an implantable, high-energy, and compact battery system for an undulation pump total artificial heart (UPTAH). The implantable battery system tested consists of six lithium-ion batteries in series, a charge unit, and a charge/discharge control unit. A lithium-ion battery is currently the best energy-storage device because it has more energy density, a better life cycle, and a smaller temperature rise than those of other secondary batteries. The performance of the implantable battery system was evaluated in an in vitro experiment using an electric load that simulated the UPTAH. Also, sufficiently reliable operation of a system for supplying energy to a UPTAH consisting of a transcutaneous energy transmission system (TETS) and an implantable battery system was confirmed in three experiments using goats. The results of the in vitro and in vivo experiments showed that the implantable battery system supplied sufficient current to the UPTAH for maintenance of physiological conditions in the goat with maximum rise in temperature to less than 43 degrees C.

Miniature vibrating flow blood pump using a cross-slider mechanism for external shunt catheter.

The prototype of the miniature vibrating flow pump (VFP) is developed for the external shunt catheter. The cross-slider mechanism is applied to vibrate the tube, which causes the pumping effect. This mechanism results in successful development of the miniature and lightweight VFP. By the use of the prototype VFP, the experiment of the basic pump performance is made in detail based on the authorized procedure in the research field of fluids engineering. The typical H-Q curve of VFP, which is the relationship between the pump head and the flow rate, can be obtained. This result suggests that the miniature VFP developed here can be expected to be used as the booster pump for the external shunt catheter in clinical applications.

Microvessels of bulbar conjunctiva in UPTAH goats.

Aiming to observe directly the microcirculation after total artificial heart (TAH) implantation, we performed a long-term follow-up in 2 goats using conjunctival angioscopy. A short segment of parallel arteriole and venule was photographed and analyzed on computer picture program (magnification 40x). Three main parameters were measured: arteriole diameter, venule diameter, and arteriovenous ratio (A/V ratio). The intrathoracically implanted TAH was the undulation pump total artificial heart (UPTAH) with cardiac output of 100 ml/kg/min. To stabilize the peripheral hemodynamics a 1/R biofeedback control system was used. Our results provided only elementary data about morphology of bulbar microvessels. The main finding was the tendency to general vasoconstriction, more intensive on the venous side (*P < 0.05 in one goat). We did not observe any pathological shapes (e.g., tortuosities, varicosities, or sludge); this result could be attributed to the high effectivity of 1/R control method. These preliminary results should be considered only as an attempt to apply the widely used clinical method of conjunctival angioscopy to the conditions of TAH.

Automatic monitoring system for artificial hearts using self organizing map.

This study presents an automatic monitoring system for artificial hearts. The self organizing map (SOM) was applied to monitoring and analysis of an aortic pressure (AoP) signal measured from an adult goat equipped with a total artificial heart. In the proposed system, two different SOMs were used to detect and classify abnormalities in the measured AoP signal. In the first stage, an ordinary SOM, taught with only normal AoP data, was used for detection of abnormalities on the basis of the quantization error in the real-time monitoring task. In the second stage, a supervised SOM was used for classification of abnormalities. The supervised SOM can be regarded as an ordinary SOM with an extra class vector for solving the classification problem. The class vector is assigned to every node in the second SOM as an output weight learned according to Kohonen's learning rule. The effectiveness of detection and classification of abnormalities using these two SOMs was confirmed.

Design improvement of the jellyfish valve for long-term use in artificial hearts.

In a previous communication, we reported a leaflet fracture in a Jellyfish valve that was incorporated into a blood pump, after a 312-day animal implant duration. Subsequent finite element analysis revealed that the fracture location was consistent with an area of maximum strain concentration. Therefore, the aim of this study was to improve the durability in the light of these findings. Based on the engineering analysis results, a new valve seat having a concentric ring of 0.5-mm width, located at a radius of 7.0 mm, was designed and fabricated. Accelerated fatigue tests, conducted under the conditions recommended by ISO 5840, demonstrated that the durability of this new prototype was extended by a factor of 10, as compared to the original valve. Moreover, further finite element analysis indicated that the maximum equivalent elastic strain of the proposed new valve was reduced by 52.3% as compared to the original valve. Accordingly, it has been confirmed that the modified Jellyfish valve is suitable for use in long-term artificial hearts.

One month survival with the undulation pump total artificial heart in a goat.

The undulation pump is a small continuous flow displacement-type blood pump. The undulation pump total artificial heart (UPTAH) is a unique implantable total artificial heart using undulation pumps. An adult female goat weighing 45.8 kg was used for implantation. The natural heart was replaced with the UPTAH under extracorporal circulation. The cardiac output (CO) was maintained to 100 ml/kg/min by controlling the right pump manually. To prevent lung edema, the left pump was controlled automatically to maintain the left atrial pressure below 20 mm Hg. The CO was maintained for 2 weeks. Thereafter, the CO gradually decreased. The goat suddenly died because of a brain stroke on the 31st postoperative day. At autopsy, the cavity of the left atrial cuff was almost occupied by the big pannus-like thrombus, which was thought to be the cause of death. Improvement of the atrial cuff is necessary to obtain longer survival and is being modified. No thrombus was found inside the pumps. However, temperature rise in a left motor was a problem. Improvement of the efficiency in a motor is necessary. Although many problems still remained, 1 month survival could be obtained with this unique implantable TAH using continuous flow displacement-type blood pumps.

Development of a miniature undulation pump for the distributed artificial heart.

Research of the distributed artificial heart is important not only to acquire the means of individual organ perfusion but also to clarify the characteristics of the organ and the mechanism of blood distribution. To investigate the distributed artificial heart, the miniature undulation pump was developed. The outer diameter and the thickness of the developed pump were 38 mm and 11 mm, respectively. The priming volume of the pump was 3.2 ml. The total size including the motor unit was 38 mm in diameter and 32 mm in length. The total weight was 67.5 g. The total volume was 27.5 ml. The pump was driven with pulse width modulation by using a 1 chip motor controller. More than 5 L/min of continuous output could be obtained. The results showed that the developed miniature undulation pump system had enough performance for individual organ perfusion.

Using one rotary blood pump to produce separate pulsatile circulations in the upper and lower halves of the body.

Separate systemic circulations with pulsatile flow were obtained using 1 rotary blood pump as a left ventricular assist device. The outlet of the pump was divided into 2 conduits, 1 connected to the upper half of the body and the other connected to the lower half. An electric actuator that clamped the 2 outlet conduits alternately provided pulsatile flows. An in vitro experiment showed that the pulsatility phases of the upper and lower halves of the body were complementary with pulsatile flow, and an in vivo experiment showed that controlled flow distributions of continuous flows could be obtained.

Results of animal experiments using an undulation pump total artificial heart: analysis of 10 day and 19 day survival.

An undulation pump is a special rotary blood pump in which rotation of a brushless DC motor is transformed to an undulating motion by a disc in the pump housing attached by means of a special link mechanism. In the blood pump, a closed line between the disc and housing moves from the inlet to the outlet by this undulating disc motion, which sucks and pushes the blood from the inlet to the outlet. Because the same phenomena occurs at both sides of the disc, a continuous flow is obtained when the motor rotational speed is constant. The pump flow pattern can be easily changed from continuous flow to pulsatile flow by controlling the motor drive current pattern. A seal membrane made of segmented polyurethane protects the blood from invading the link mechanism as well as the motor. UPTAH is fabricated with two undulation pumps and two brushless DC motors. Its size is 75 mm in diameter and 80 mm long, and it has one of the great advantage of no compliance chamber required in the system. UPTAHs were implanted under cardiopulmonary bypass (CPB) into the chest cavities of 16 goats, each weighing between 41 and 72 kg. No anticoagulant and antiplatelet agent was used after the surgery. The left atrial pressure was automatically controlled to prevent its elevation and sucking of the atrial wall into the atrial cuff. The following results were obtained: (1) UPTAHs fit well into all the goats; (2) the longest survival was 19.8 days, the cause of death was bleeding from the aortic anastomosis; (3) No thrombus was observed in the blood pump despite no anticoagulant use. Hemolysis depended upon the length of CPB during surgery. When CPB time was within 2 hours, hemolysis level returned to baseline within a few days of the surgery. UPTAH is a promising implantable TAH, because of its small size and easy controllability.

Analysis of hemodynamic response with 1/R control on biventricular bypass goat.

A conductance and arterial pressure based method (1/R control) to determine the cardiac output (CO) of a total artificial heart (TAH) was developed to provide a central nervous system with control over the output of TAH. In order to clarify the deference in hemodynamic response between natural heart and 1/R control, biventricular bypass was introduced in the goat. After 2 pneumatically driven sac-type blood pumps were connected to the natural heart, the pulmonary artery was totally clamped to acquire 100% right heart bypass, and the ascending aorta was stenosed to acquire about 60 to 90% left heart bypass; 1/R control was performed substituting the output of the right artificial heart for the CO. The results demonstrated that stable control could be achieved. A discrepancy was often seen between the pulse rate (PR) of the artificial heart and the heart rate (HR) in absolute value. However, the relative changes of PR were quite similar to that of HR for the most part, indicating that the responses of 1/R control were the duplication of natural cardiac responses in normal daily activity.

Implantation of the undulation pump total artificial heart in the goat.

The undulation pump total artificial heart (UPTAH) was developed by using small-size continuous-flow displacement-type blood pumps (undulation pump). To clarify and improve the problems accompanied by the implantation in the chest, 14 animal experiments were performed on goats weighing 41.3-79.2 kg. The UPTAH could be implanted in the chest of all goats and was driven with a modulation pulsatile mode. The first problem was the atrial suction effect. This problem could be prevented to some extent by developing the soft disk and by improving atrial cuffs. An automatic detection and releasing of the atrial suction effect was also tried. The next problem was acute lung edema accompanied by the postural change of the animal. Development of the automatic control of left atrial pressure could prevent this problem. Small blood leakage from a pinpoint hole in the seal membrane was the next problem. Improvement of the manufacturing procedure of the membrane prevented this. With these improvements, a 10 day survival could be obtained with this unique implantable total artificial heart.

Present status of the total artificial heart at the University of Tokyo.

At the University of Tokyo, various types of total artificial heart (TAH) systems have been studied since 1959. At the present time, 2 types of implantable TAH have been developed. One is an undulation pump TAH (UPTAH) and the other is a flow transformed pulsatile TAH (FTPTAH). Using the UPTAH, 14 cases of implantation were performed in goats and 10 days' survival obtained. The new type of FTPTAH is under a prototype study. To prevent ring thrombus, a polyurethane membrane valve, a jellyfish valve, has been developed. The longest in vivo experiences with this valve in the TAH blood pump have been 312 days in the left side blood pump and 414 days in the right side blood pump. Conductance and arterial pressure based control (1/R control) can realize the physiological control of the TAH. Using 1/R control, 532 days of survival could be obtained in a goat with a paracorporeal TAH. The technique required to apply this control method to a implantable TAH is under development. We have proposed a new 5 year research project of the implantable TAH entitled "Comprehensive Basic Research on the Development of a Japanese Original Implantable Total Artificial Heart" to The Ministry of Welfare.

[Dorsal root identification using spinal endoscopy and electro-physiology].

We aimed to develop a method of accurately identifying the dorsal root for the corresponding peripheral afferent nerve under endoscopic observation. We developed an endoscope with an external diameter of 1.8 mm. After small laminectomy on the lower thoracic vertebrae, we inserted this endoscope carefully into the epidural and then subarachnoid spaces. We observed structures in these spaces with the endoscope. We tried to determine the spatial relationship between these electrodes and dorsal root. After identifying each space, we inserted two electrodes into the visualized space to record evoked potentials; a bipolar electrode (protocol 1) and a catheter-type eight polar electrode (protocol 2). Each pole could be distinguished by marks. To stimulate peripheral nerves, we inserted needle-type electrodes into Th 10, 11 and 12 intercostal nerves. We attempted to record potentials from dorsal surface of the cord generated by intercostal nerve stimulus. Protocol 1: We moved the position of the bipolar recording electrodes between Th 9 and L 1 by 1 cm increment, and obtained evoked potentials correspondingly. Protocol 2: We chose the neighboring pairs of poles sequentially from the tip of the catheter for bipolar recording. At the end of each experiment, we dissected the animal and checked the intercostal nerve originating from the root. With the endoscope, we could clearly observe structures in the epidural and subarachnoid spaces. We could record evoked potentials from the dorsal spinal cord with the electrodes located either in epidural or in subarachnoid spaces. Shapes of evoked potentials changed characteristically according to the relative position between the root and the electrode. The largest potentials were obtained when the electrode was nearest to the dorsal root, of which the peripheral nerve was being stimulated. By combining endoscopy with the electrophysiological technique, we could accurately identify the dorsal roots for the corresponding peripheral afferent nerves. This method may be used for the selective dorsal root blockade under the visual field.

Physiological control of a total artificial heart: conductance- and arterial pressure-based control.

To obtain a physiological response by a total artificial heart (TAH), while eliminating the hemodynamic abnormalities commonly observed with its use, we proposed the use of a conductance- and arterial pressure-based method (1/R control) to determine TAH cardiac output. In this study, we endeavored to make use of a variable more closely tied to central nervous system (CNS) efferents, systemic conductance, to provide the CNS with more direct control over the output of the TAH. The control equation that calculates the target cardiac output of the TAH was constructed on the basis of measurement of blood pressures and TAH flow. The 1/R control method was tested in TAH-recipient goats with an automatic method by using a microcomputer. In 1/R control animals, the typical TAH pathologies, such as mild arterial hypertension and substantial systemic venous hypertension, did not occur. Cardiac output varied according to daily activity level and exercise in a manner similar to that observed in natural heart goats. These results indicate that we have determined a control method for the TAH that avoids hemodynamic abnormalities exhibited by other TAH control systems and that exhibits physiological responses to exercise and daily activities under the conditions tested. The stability of the control and the complete lack of inappropriate excursions in cardiac output is suggestive of CNS involvement in stabilizing the system.

Development of the undulation pump total artificial heart.

The undulation pump is a small size continuous flow displacement type blood pump that has been developed for an artificial heart. Using undulation pumps, 2 types of implantable total artificial hearts (TAHs), the undulation pump TAH (UPTAH) type 1 (UPTAH 1) and UPTAH type 2 (UPTAH 2) were developed. Both UPTAHs were designed to be small enough to implant into the chest of a goat, the experimental animal. UPTAH 1 could be reduced in size to 75 mm in diameter and 78 mm in length. The weight was 520 g. UPTAH 2 could be reduced in size to 75 mm in diameter and 80 mm in length. The weight was 650 g. UPTAH 2 could be tested in an animal experiment using an adult female goat weighing 52.3 kg. The UPTAH 2 could be implanted successfully into the goat's chest with a good fit. The goat stood after the surgery and extubation and survived for 3 h and 40 min; thus, the potential of the UPTAH for a practical implantable TAH was demonstrated.

Use of a catecholamine sensor in the control of an artificial heart system.

An electrochemical sensor system to allow real-time measurement and feedback of catecholamine concentrations was developed for use in the control of artificial hearts. Electrochemical analyses were carried out using a carbon fiber working electrode, an Ag-AgCl reference electrode, and a potentiostat. The operating parameters of the pneumatically-driven artificial heart system were altered in accordance with the algorithm for changes in the catecholamine concentration. The minimum detectable concentrations of both adrenaline and noradrenaline in a mock circulatory system using a phosphate-buffered solution were approximately 1-2 ng/ml (10(-8) mol/L). An artificial heart control system utilizing this set-up performed satisfactorily without delay, although sensor sensitivity decreased when placed in goat plasma instead of a phosphate-buffered solution, due to the adsorption of various substances such as plasma proteins onto the electrodes. This study demonstrated the future feasibility of a feedback control system for artificial hearts using catecholamine concentrations.