A nonpulsatile total artificial heart with 1/R control.

A total artificial heart (TAH) using continuous flow pumps is promising for size reduction of the device; however, the role of pulsatility in TAHs has been a subject of great debate. Additionally, it is unclear whether, in a nonpulsatile TAH, a physiological control method such as 1/R control can keep the experimental animal in good condition. To realize a nonpulsatile TAH with 1/R control, the artificial valves were removed from undulation pump total artificial hearts (UPTAHs), which can produce both pulsatile and nonpulsatile flows using a single device. The UPTAHs were implanted into 18 goats, and 4 goats survived for more than 1 month. Three weeks of long-term nonpulsatile TAH operation could be tested in the goat that survived for 72 days, and it was proved that 1/R control is possible not only with a pulsatile TAH but also with a nonpulsatile TAH. The general condition of the goat and its organ function did not change on the application of nonpulsatile mode. Cardiac output and arterial pressure changed with the condition of the goat in pulsatile and also in nonpulsatile modes, and the changes seemed almost identical. However, the sucking effect of the atria was very significant in nonpulsatile mode, resulting in hemolysis. Therefore, nonpulsatile TAHs under 1/R control are considered to be inadequate unless some pulsatility can be introduced to avoid fatal sucking effects and to ensure sufficient inflow. During nonpulsatile operation, regular fluctuations were sometimes found in the aortic pressure, and these were caused by the periodic sucking effect in the left atrium that was possibly influenced by respiratory changes.

Fundamental study to develop a fiber-optic gap sensor for a rotary undulation pump.

The rotary undulation pump is believed to be a good candidate for the next-generation artificial heart. Due to its complex movement, it is desirable to magnetically levitate the rotor and dynamically control the gap. In this article, the applicability of a fiber-optic gap sensor to the dynamic position control of the rotor in the rotary undulation pump was investigated. The fiber-optic gap sensor consisted of two plastic-core fibers and a reflection plate. Two 1-mm-diameter optical fibers were aligned parallel: one for source light propagation and the other for reflected light transmission. The basic properties of gap sensors using four different light sources were explored in five media (air, physiologic saline, and blood samples with three different hematocrit levels). The influence of the oxygen saturation level in the blood on sensing was investigated with two types of light sources. It is desirable to use a light source the wavelength of which shows similar absorption coefficients for both oxygenated blood and deoxygenated blood. The effect of the distance between the two fibers on the sensing and range was also investigated. The results indicated that the fiber-optic gap sensor is quite promising for the active control of rotor positioning in the rotary undulation pump.

Analysis of heat generation of lithium ion rechargeable batteries used in implantable battery systems for driving undulation pump ventricular assist device.

We have developed internal battery systems for driving an undulation pump ventricular assist device using two kinds of lithium ion rechargeable batteries. The lithium ion rechargeable batteries have high energy density, long life, and no memory effect; however, rise in temperature of the lithium ion rechargeable battery is a critical issue. Evaluation of temperature rise by means of numerical estimation is required to develop an internal battery system. Temperature of the lithium ion rechargeable batteries is determined by ohmic loss due to internal resistance, chemical loss due to chemical reaction, and heat release. Measurement results of internal resistance (R(cell)) at an ambient temperature of 37 degrees C were 0.1 Omega in the lithium ion (Li-ion) battery and 0.03 Omega in the lithium polymer (Li-po) battery. Entropy change (DeltaS) of each battery, which leads to chemical loss, was -1.6 to -61.1 J/(mol.K) in the Li-ion battery and -9.6 to -67.5 J/(mol.K) in the Li-po battery depending on state of charge (SOC). Temperature of each lithium ion rechargeable battery under a discharge current of 1 A was estimated by finite element method heat transfer analysis at an ambient temperature of 37 degrees C configuring with measured R(cell) and measured DeltaS in each SOC. Results of estimation of time-course change in the surface temperature of each battery coincided with results of measurement results, and the success of the estimation will greatly contribute to the development of an internal battery system using lithium ion rechargeable batteries.

Development of mechanical circulatory support devices at the University of Tokyo.

The development of mechanical circulatory support devices at the University of Tokyo has focused on developing a small total artificial heart (TAH) since achieving 532 days of survival of an animal with a paracorporial pneumatically driven TAH. The undulation pump was invented to meet this purpose. The undulation pump total artificial heart (UPTAH) is an implantable TAH that uses an undulation pump. To date, the UPTAH has been implanted in 71 goats weighting from 39 to 72 kg. The control methods are very important in animal experiments, and sucking control was developed to prevent atrial sucking. Rapid left-right balance control was performed by monitoring left atrial pressure to prevent acute lung edema caused by the rapid increase in both arterial pressure and venous return associated with the animal becoming agitated. Additionally, 1/R control was applied to stabilize the right atrial pressure. By applying these control methods, seven goats survived more than 1 month. The maximum survival period was 63 days. We are expecting to carry out longer term animal experiments with a recent model of TAH. In addition to the TAH, an undulation pump ventricular assist device (UPVAD), which is an implantable ventricular assist device (VAD), has been in development since 2002, based on the technology of the UPTAH. The UPVAD was implanted in six goats; three goats survived for more than 1 month. While further research and development is required to complete the the UPVAD system, the UPVAD has good potential to be realized as an implantable pulsatile-flow VAD.

Numerical estimation of heat distribution from the implantable battery system of an undulation pump LVAD.

We have been developing an implantable battery system using three series-connected lithium ion batteries having an energy capacity of 1,800 mAh to drive an undulation pump left ventricular assist device. However, the lithium ion battery undergoes an exothermic reaction during the discharge phase, and the temperature rise of the lithium ion battery is a critical issue for implantation usage. Heat generation in the lithium ion battery depends on the intensity of the discharge current, and we obtained a relationship between the heat flow from the lithium ion battery q(c)(I) and the intensity of the discharge current I as q(c)(I) = 0.63 x I (W) in in vitro experiments. The temperature distribution of the implantable battery system was estimated by means of three-dimentional finite-element method (FEM) heat transfer analysis using the heat flow function q(c)(I), and we also measured the temperature rise of the implantable battery system in in vitro experiments to conduct verification of the estimation. The maximum temperatures of the lithium ion battery and the implantable battery case were measured as 52.2 degrees C and 41.1 degrees C, respectively. The estimated result of temperature distribution of the implantable battery system agreed well with the measured results using thermography. In conclusion, FEM heat transfer analysis is promising as a tool to estimate the temperature of the implantable lithium ion battery system under any pump current without the need for animal experiments, and it is a convenient tool for optimization of heat transfer characteristics of the implantable battery system.

Influence of flow design on microcirculation in conditions of undulation pump-left ventricle assist device testing.

To study the microvessels in bulbar conjunctiva, we conducted an experiment in goat with a pneumatically driven left heart bypass pump, which was replaced with an undulation pump-left ventricle assist device for 9 days. Three flow patterns were tested: complete pulsatile, continuous, and percentage of pulsatile. We studied the morphology of arterioles and venules of the bulbar conjunctiva using photograph records. The setting up of continuous flow caused global vasoconstriction (significant in venules-P < 0.05). During the pumping in the pulsatile and percentage of pulsatile modes, no significant changes of microvessel morphology were observed. The findings described could point to some disturbances in the microcirculatory bed in conditions of continuous flow.

Estimation of early-stage malfunction using implantable artificial heart sound in animal experiments.

We have developed an automatic diagnosis system of an artificial heart in order to ensure the safety of the patient implanted with the artificial heart. The automatic diagnosis system is composed of an electro-stethoscope system, adaptive noise canceller (ANC), and artificial neural network (ANN). The ANC effectively eliminates ambient noise from the sound signal of the artificial heart detected by the electro-stethoscope, and a filtered sound signal is separated into each frequency components by fast Fourier transformation. Each frequency component of an artificial heart's acoustic signal is fed into the ANN in order to make a diagnosis of pump condition. The automatic diagnosis system was evaluated in mock circulatory tests and a long-term animal experiment using a goat implanted with an undulation pump ventricular assist device (UPVAD). In mock circulatory tests, the ANN was able to detect pump failing conditions, which were occlusion of inflow and outflow cannula and deterioration of the ball bearing. In a long-term animal experiment, after training the ANN using UPVAD's sound signal in normal condition, the diagnosis system continuously monitored UPVAD's sound signal detected by the electro-stethoscope placed on the surface of the left thoracic cavity of the goat. The UPVAD was stopped by rupture of a diaphragm in the pump on the ninth day of operation. We were able to identify initial signs of malfunction of the pump on the eighth day, while the UPVAD was able to operate normally. In conclusion, the automatic diagnosis system for malfunction of the artificial heart has enough performance to detect early stages of malfunction of the artificial heart, and it contributes to ensure the patient's safety.

Development of integrated electronics unit for drive and control of undulation pump-left ventricular assist device.

In this study, we have developed an implantable electronics unit (IEU) for driving an undulation pump-left ventricular assist device (UP-LVAD). The IEU consists of a pump driver, three series-connected lithium ion batteries (1800 mAh), a charger, and a transcutaneous information transmission system. These electronic subunits were encapsulated in a case (110 x approximately 80 x approximately 30 mm) made of epoxy resin. The IEU was evaluated in two animal experiments using goats implanted with the UP-LVAD. The lithium ion batteries in the IEU provided 30-min energy supply daily to the UP-LVAD. The transcutaneous information transmission system transmitted data bidirectionally between the IEU and the personal computer at the data transmission ratio of 56 kbps without any transmission error. We could obtain survival days of 27 and 28 days supporting cardiac function with the UP-LVAD system. The temperature inside the IEU case was maintained under 45 degrees C, and there was evidence of a burn on the surrounding tissue in autopsies in each experiment. Based on the results, the IEU is promising to be suitable for drive and control of an implantable UP-LVAD.

Development of a novel intrafascicular nerve electrode.

Artificial organs could be controlled using autonomic neural signals, because they exhibit rapid responses to physical needs similar to those of natural organs. A nerve electrode must satisfy many requirements to measure autonomous neural signals such as a long lifetime, high signal-to-noise ratio, multichannel recording, simple installation into a nerve fascicle, and good manufacturing productivity. The purpose of our study is to propose and evaluate a novel nerve electrode that satisfies these conditions, which to date has not been developed. A novel intrafascicular nerve electrode was designed, fabricated, and evaluated on autonomic nerves. Conventional extrafascicular and intrafascicular nerve electrodes were fabricated and tested for comparison to our novel intrafascicular nerve electrode. The novel intrafascicular nerve electrode had a 3-week lifetime, whereas the conventional extrafascicular nerve electrode had a 2-week lifetime. The signal-to-noise ratio was improved from 1.6 to 2.0 compared with the conventional extrafascicular nerve electrode. The novel intrafascicular nerve electrode was easier to install into a nerve fascicle and had better manufacturing productivity than the conventional intrafascicular nerve electrode. We succeeded in demonstrating the feasibility of our novel intrafascicular nerve electrode.

Microcirculation of the bulbar conjunctiva in the goat implanted with a total artificial heart: effects of pulsatile and nonpulsatile flow.

A new system to observe the microcirculation on the bulbar conjunctiva was developed using a digital high definition microscope to investigate the influence of the flow patterns on the microcirculation in a goat with a total artificial heart (TAH). The undulation pump TAH was implanted into the goat. When the whole body condition became stable, the flow pattern was modulated between the pulsatile and the nonpulsatile mode, and the changes in the microcirculation were observed. When the flow pattern was changed from pulsatile to nonpulsatile mode, the erythrocyte velocity in capillaries dropped from 526+/-83 to 132+/-41 microm/s and remained at a low level. The number of perfused capillaries decreased as well. Then the nonpulsatile flow mode was maintained for 20 minutes. After the flow pattern was returned to the pulsatile mode again, the erythrocyte velocity recovered to the initial level (433+/-71 microm/s). In many cases, the flow of the nonperfused capillaries in the nonpulsatile mode recovered to the initial level after the flow pattern was changed to the pulsatile mode again. The perfused capillary density in the nonpulsatile mode (19.7+/-4.1 number of capillaries/mm) was significantly lower than that in the pulsatile mode (34.7+/-6.3 number of capillaries/mm). It is thought that the basal and flow stimulated endothelium derived nitric oxide release in the microvessels decreased because of the disappearance of pulsatility and that the nitric oxide induced the constriction of arterioles after the flow pattern was changed to the nonpulsatile mode. At the same time, the baroceptors might sense the decrease in the arterial peak pressure or dp/dt, and the sympathetic nerve increases activities and induce the constriction of arterioles. Then, the erythrocyte velocity in capillaries would decrease. Because of the flow pattern further in the chronic phase, it is important to follow the change in the microcirculation.

A temporal and spatial analysis of cavitation on mechanical heart valves by observing faint light emission.

Cavitation on mechanical heart valves (MHVs) could cause the mechanical failure of the occluder. A simple and reliable in vitro test method to evaluate cavitation potential must be developed. The bubble implosion damages the MHV material; thus, observing the behavior of the bubble implosion is essential. According to sonoluminescence, the collapsing cavity emits faint light. Therefore, in this study, the bubble collapse was analyzed both temporally and spatially by observing faint light emission. A photon counting system has been developed using a photomultiplier tube (H7360-01, Hamamatsu Photonics, Japan). The highest time resolution of this system is 5 microsec. A quartz optical fiber bundle of 2 mm diameter can be connected to this photomultiplier tube and traversed two-dimensionally over the MHV. The closure of the MHV triggers the photon counter, and the photons through 500 beats are recorded and integrated. A 20 mm Björk-Shiley valve was submerged in a water tank containing 10 L deionized water, and the pressure difference of 120 mm Hg was exerted on the valve at a rate of 60 bpm with a pulse duplicator. Approximately 700 microsec after the valve closure, light emission was detected along the edge of the occluder on the inflow side in the major orifice. Then, approximately 1,000 microsec after the closure, light along the occluder's edge in the minor orifice was recorded as well. Compared with the analysis, using a stroboscope and a high-speed camera, faint light was emitted from the collapsing cavities. In conclusion, sonoluminescnece was successfully observed around the MHV, and the photon counting technique and the traversing mechanism of the optical fiber bundle revealed the temporal and spatial distribution of the cavity collapse on the MHV.

Development of an electro-stethoscope system and design of an optimum filter based on tissue sound transmission for noninvasive early diagnosis of malfunction of an implanted mechanical total artificial heart.

Early diagnosis of the malfunction of a mechanical artificial heart implanted in a patient who has been discharged from hospital is very important. We have developed an electro-stethoscope system that enables the malfunction of an artificial heart to be detected from the analysis of sound signals from the artificial heart. The sound data can be transmitted to a hospital via a mobile telephone or the Internet, so that doctors can examine the condition of the artificial heart. The optimum frequency characteristics of a low-pass filter for the elimination of ambient sound through the electro-stethoscope casing were obtained by simulating sound transmission through tissue. We evaluated the usefulness of the electro-stethoscope system using a goat in which an undulation pump total artificial heart had been implanted. A frequency analysis of the sound signal provided information on the degree of degradation of each mechanical component of the artificial heart. The results of this study showed that the electro-stethoscope system is useful for the early detection of the malfunction of an artificial heart at home, and that the use of the system contributes to improvement in the quality of life of patients.

Open-loop analysis of transfer characteristics from blood pressure to heart rate using an effectively total artificial heart.

It is desirable for the dynamic behavior of the drive rate of the artificial heart to be as similar as possible to that of the recipient's heart rate (HR) before implantation. This requires a model which can simulate the behavior of HR on the basis of only the information measured with the limited number of approvable implanted sensors. This article provides a linear time series model for explaining the behavior of HR only with aortic pressure and right atrial pressure. This could be obtained from open-loop analysis using a total artificial heart, which was introduced for measuring HR in vivo and for eliminating its effect on blood pressure. The model was identified in a goat equipped with a special biventricular assist device called the effectively total artificial heart (ETAH). The ETAH was introduced to make an open loop and awake situation in the animal with almost intact autonomic nerves, which could enhance the accuracy and reliability of the identification of the model. The adequacy of the proposed model was ascertained in several data sets measured in two goats, which were different from the data set used for identification. Most of the mean estimation errors were less than 3 beats/min and auto-correlation analysis showed approvable statistical appropriateness. However, it was clarified through comparison with the 1/R control method that the proposed model has a few problems still to be solved before its future implementation as an automatic controller of the TAH.

Preliminary study of a new type of energy transmission system for artificial hearts.

A transcutaneous energy transmission (TET) system is the most common way to power artificial hearts and ventricular assist devices. However, an external battery used with a TET system poses several problems, such as its heavy mass, small charge capacity, and long recharging time. The battery is indispensable when patients want to be ambulatory. This article proposes a new type of TET system that does not require an external battery because electrical energy is supplied remotely by using electromagnetic waves. For this system to operate, multiple transmitting antennas have to be mounted in a room or facility that has been shielded from electromagnetic waves, and a receiving antenna is attached to the patient. Electromagnetic waves transmit electrical power from the transmitting antennas to the receiving antenna. The received electrical power is sent to an implanted device through the TET system. The total power efficiency was plotted against the transmitter-receiver distance by measuring the power that was input to the transmitting antennas, and the final direct current (DC) power that was received by the receiving antenna. A 430-MHz frequency was applied in the experiments. The obtained efficiency was around 10% within a transmitter-receiver distance of 1 m when Yagi-Uda antennas were used for the transmitting antennas and two other types of antenna were used for the receiving antennas: a folded dipole with a reflector and a single loop with a reflector. The results suggested that the proposed system is worth considering. The proposed system would go a long way toward enhancing the patient's quality of life compared with the currently used conventional TET system.

Basic study to develop an electromagnetic drive method for the rotary undulation pump.

The rotary undulation pump, which is composed of a disk with a convex shape on both sides and a pump housing with one narrow side and one wide side, is a unique continuous flow pump with a new principle. The concept of the levitation drive method for this pump was proposed. The electromagnetic driver model and drive circuit were developed to examine the possibility and the difference among the delta wired, Y wired, and repulsion methods. In the repulsion method, the disk was driven by magnetic repulsion. The model could be driven with either method, and the repulsion method was demonstrated to also be possible. With either method, owing to the wide gap between the permanent magnets and coils, the output was not enough when the load was high. The efficiency was almost the same in the delta wired and Y wired methods. In the repulsion method, however, it was less than 50% of that in the other two methods. From the results, the delta wired and Y wired methods with an active control of the gap distance were considered to be better than the repulsion method, which required no active gap control.

Evaluation of pulsatile and nonpulsatile flow in microvessels of the bulbar conjunctiva in the goat with an undulation pump artificial heart.

This study has three purposes, as follows. The first is to develop a microscopic system to observe the microcirculation of animals implanted with an artificial heart. The second is to investigate the influence of flow pattern change from pulsatile to nonpulsatile on the microcirculation. The third is to study the effects of pulsatility in blood flow on endothelium-derived nitric oxide release in the microvasculature. When the flow pattern was changed from pulsatile to nonpulsatile, the velocity of erythrocytes in many capillaries dropped and remained at a low level, and the number of perfused capillaries decreased. After the flow pattern was returned to pulsatile, the velocity of erythrocytes recovered to the initial level. In many cases, the flow of nonperfused capillaries recovered to the initial level as well. Also, the pulsatile flow enhances the basal and flow-stimulated endothelium-derived nitric oxide release in microvessels.

Pathophysiologic study of goats with undulation pump total artificial heart: those that survived for more than 1 month.

The undulation pump total artificial heart is an implantable total artificial heart that is being developed at the University of Tokyo. Many advances in our system have been made by the adoption of hardware and software solutions that enabled the animals with the undulation pump total artificial hearts to survive more than 1 month. Pathophysiologic observations were performed for these goats that survived. In this article, the pathophysiologic findings are described in detail for three goats that survived for 46 (goat 9916), 54 (0030), and 63 (0107) days. The microscopic findings indicated that in goat 0107 the histologic changes in key organs occurred at the termination of the experiments. Therefore, the pathophysiologic changes in goats 9916 and 0030 were mainly investigated in this study to evaluate the chronic effect caused by our total artificial heart system. The signs of chronic ischemia and cell dystrophy were observed in both the liver and kidney. Until now, 13 goats had survived more than 1 week and 6 goats survived more than 1 month, including one that survived for 63 days, which is the longest in our experimental series. The pathophysiologic results of goats 9916 and 0030 showed that the undulation pump total artificial heart might still cause some damage to the liver and the kidney. To accomplish long-term survival with the undulation pump total artificial heart, further pathophysiologic studies are required, and the necessary modifications to the total artificial heart system will need to be made.

Functions for detecting malposition of transcutaneous energy transmission coils.

A transcutaneous energy transmission system (TETS) for artificial hearts and ventricular assist devices uses electrical coupling of power between external and implanted coils. If the position of coils changes relative to each other, the TETS cannot feed the required power of the implanted device. During activity or sleep, the coils may move accidentally. TETS users and the people around them have to pay attention to this because the range of the position where the required power can be fed efficiently is not wide. Therefore, we added functions for the position changes of the coils to the TETS. Regular, cautious, and irregular positions were introduced, and the ranges of them were decided upon in our experiments. The cautious position was determined by the area where the change of the relative position of the coils was relatively small. When the coils were in the cautious position, the circuit was tuned by way of changing the resonant point. This modulation could give good power efficiency in the cautious position. When the coils were in the irregular position, an alarm switch was turned on. These functions ease the restriction of the coil position and give better quality of life (QOL) than do the conventional TETS.

A new approach to detection of the cavitation on mechanical heart valves.

The cavitation on the mechanical heart valves (MHVs) is thought to be a cause of the mechanical failure of the occluder; also, the free radicals that would be generated when the cavitation bubbles implode might affect the patients chemically. These cavitation effects are attributed to the bubble collapse. Therefore, it is important to detect the bubble implosion behavior to analyze the cavitation on MHVs. The cavitation bubbles induce the generation of free radicals at their implosion, and the excited hydroxyl radicals emit the faint light. Based on this fact, we have tried to observe the faint light emission from a MHV to specifically capture the implosion of the cavitation bubbles. A highly sensitive CCD (charge coupled device) camera (C2400-35 VIM camera, Hamamatsu Photonics, Hamamatsu, Japan) was adopted in this study. This camera can observe low light down to the single photon counting range, and it gives two-dimensional mapping of the light. A 20 mm Björk-Shiley valve was submerged in the water tank of 10 L deionized water with luminol as a light enhancer, and then the pressure difference of 150 mm Hg was exerted on the valve at a rate of 60 bpm with a pulse duplicator. The camera and the water tank were settled in the lightproof configuration. After 2 hours of exposure, faint light images have been obtained successfully. The light emits mostly from the edge of the occluder on the inflow side in the major orifice of the valve. Therefore the results suggest that the bubbles would implode around this region and that free radicals caused by cavitation might be produced on MHV, which has coincided with our preliminary result by an electron spin resonance spectrometry.

Advance in animal experiments with the undulation pump total artificial heart: 50 and 54 day survival periods with 1/R control.

The undulation pump total artificial heart (UPTAH) is a unique, implantable, total artificial heart (TAH) that uses undulation pumps. To achieve long-term survival in animals with physiologic hemodynamic conditions, a control method based on conductance and arterial pressure was applied to UPTAH. With this control method, called 1/R control, survival periods of 50 days (No. 0016, 49.6 kg) and 54 days (No. 0030, 42.5 kg) were obtained in adult female goats. In No. 0016, 1/R control was applied to the left pump, whereas in No. 0030, it was applied to the right pump. Another pump was used for left-right balance control. The control stability was better in No. 0030 than in No. 0016. The sucking effect of the left atrium was remarkable in No. 0016, possibly because of a time delay when left-right balance control was performed with the right pump. In No. 0016, the cause of death was probably a thrombus flown from a panus in the left atrium. It is possible that the left atrial suction effect influenced the thrombus and panus formation in the left atrium. In No. 0030, the cause of death was a small rupture of the membrane in the right pump. The rupture may have been caused by excessive negative pressure inside the pump. This pressure resulted from suction of the right atrium because of an unexpected control excursion, which was probably caused by a software bug. It will be necessary to redesign the undulation pump and improve the software to achieve longer survival periods for animals with physiologic hemodynamic conditions.