Undulation Pump Total Artificial Heart Research Articles

Appropriate control time constant in relation to characteristics of the baroreflex vascular system in 1/R control of the total artificial heart.

1/R control is a physiological control method of the total artificial heart (TAH) with which long-term survival was obtained with animal experiments. However, 1/R control occasionally diverged in the undulation pump TAH (UPTAH) animal experiment. To improve the control stability of the 1/R control, appropriate control time constant in relation to characteristics of the baroreflex vascular system was investigated with frequency analysis and numerical simulation. In the frequency analysis, data of five goats in which the UPTAH was implanted were analyzed with first Fourier transform technique to examine the vasomotion frequency. The numerical simulation was carried out repeatedly changing baroreflex parameters and control time constant using the elements-expanded Windkessel model. Results of the frequency analysis showed that the 1/R control tended to diverge when very low frequency band that was an indication of the vasomotion frequency was relative high. In numerical simulation, divergence of the 1/R control could be reproduced and the boundary curves between the divergence and convergence of the 1/R control varied depending on the control time constant. These results suggested that the 1/R control tended to be unstable when the TAH recipient had high reflex speed in the baroreflex vascular system. Therefore, the control time constant should be adjusted appropriately with the individual vasomotion frequency.

Results of Animal Experiments With the Fourth Model of the Undulation Pump Total Artificial Heart

Animal experiments using a total artificial heart in a goat are not easy to perform. The fourth model of the undulation pump total artificial heart (UPTAH4), which was designed to perform a long-term physiological experiment including pulsatile and nonpulsatile TAH operations with a conductance- and arterial pressure-based control method named 1/R control, was implanted in 31 goats weighing 38.5 to 60.4 kg (average of 46.8 kg). The 1/R control is a physiological flow control method of TAH developed with a conductance (1/R: reciprocal of a resistance) parallel circuit model. The survival periods were from 0.1 to 153 days (average of 14.5 days). The causes of termination were postoperative bleeding in eight goats, respiratory failure in five goats, device failure in 14 goats, dissected aneurysm in two goats, and thrombus in one goat. The thrombus case was the longest surviving goat. The respiratory failure tended to occur when the extracorporeal circulation time was prolonged. Autotransfusion was effective for the prolongation of survival time. The left-right balance control and the suction control were performed successfully in all goats. The 1/R control was performed for a long time in five goats that survived for more than 1 month. With three goats that survived for 48, 52, and 53 days mainly with the pulsatile mode, the 1/R control was stable. With a goat that survived for 73 days, the nonpulsatile mode with the 1/R control could be tested for 3 weeks. With the longest surviving goat that was maintained mainly with the pulsatile mode, the 1/R control was unstable, possibly due to the mismatching of the response time of the control system between the computer and the body. However, liver and kidney functions were almost normal, and the total protein level recovered. Further study to stabilize the 1/R control in the UPTAH is necessary.

Acute and chronic consequences of non-pulsatile blood flow pattern in long-term total artificial heart experiment

Vessel pulsation is presumably a key physiological function for the optimal supply of peripheral tissues and vital organs by oxygen and nutrients. The absence of pulsatility might impair the peripheral perfusion stability and trigger microvascular dysfunction of vital organs. The main purpose of this study was to investigate the influence of non-pulsatile flow on the microcirculation in experimental goat with implanted undulation pump total artificial heart (UPTAH). A microscopic system (Keyence, Japan) for the direct observation of the microcirculation of bulbar conjunctiva was used. Following the acute flow pattern change (from pulsatile to non-pulsatile one), the number of perfused capillaries decreased significantly (from 34.7 ± 6.3 to 19.7 ± 4.1 number of capillaries/mm; P < 0.05). The velocity of erythrocytes dropped (from 526 ± 83 to 132 ± 41 μm/s; P < 0.05). The velocity of erythrocytes and capillary density were only partly recovered, when the pulsatile flow mode was restored. Histopathological analysis after 33 days of pumping in non-pulsatile mode revealed the presence of chronic venostasis, tissue edema, hemorrhages, hypoxia and ischemic necroses in the tissue samples from liver, kidneys and lung. These findings could be regarded as a direct effect of the chronic non-pulsatile pumping mode and inadequate blood supply. We conclude that the presence of pulsatile flow should be considered as a vital condition for a successful long-term survival after total artificial heart implantation.

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.

UNDULATION PUMP TOTAL ARTIFICIAL HEART EMPLOYING PULSATILE FLOW WITHOUT ANY VALVE

The undulation pump total artificial heart (UPTAH) employs usually pulsatile flow by changing the motor speed periodically, and has usually one artificial valve at the aortic outflow canula to prevent regurgitation during the diastolic phase. However, if we can select an adequate diastolic motor speed, UPTAH can work without any valve. The UPTAH without any valve was tested using 4th model (UPTAH4) in the goat. The heart was replaced with UPTAH under the extracorporal circulation. The diastolic drive parameter of left pump was determined to obtain near zero or a small quantity in output to prevent regurgitation at the diastolic phase. The systolic drive parameter and the systolic duration of left pump were automatically controlled to balance right and left atrial pressures and to prevent left atrial sucking. Right pump was driven having some pulsatility on continuous flow. The flow rate was automatically controlled with right pump in accordance with 1/R flow control algorithm. Set point of right atrial pressure was fixed between 5–10 mmHg. Right pump was also controlled automatically to prevent right atrial sucking. An identical rate was given to both pumps. Up to the present, 9 experiments were performed. The maximum survival period was 48 days. Almost no regurgitation was observed with fixed diastolic drive parameter. The 1/R flow control could work in stable condition.

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.

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.

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.

EVALUATION OF PULSATILE AND NON-PULSATILE FLOW IN CAPILLARIES OF THE BULBAR CONJUNCTIVA IN THE GOAT IMPLANTED A TOTAL ARTIFICIAL HEART

PURPOSE: To investigate the influence of flow patterns on the microcirculation (MC) in the goat implanted a total artificial heart (TAH). METHODS: The digital high definition microscope was used to observe the MC of the bulbar conjunctiva. An undulation pump total artificial heart (UPTAH) was implanted into the goat, which could produce arbitrary flow patterns. When the whole body condition became stable after the surgery, the flow pattern was changed from pulsatile to non-pulsatile and the change in the MC was observed. RESULTS: When the flow pattern was changed from pulsatile to non-pulsatile, the arteriolae were constricted and the velocity of erythrocytes in the capillaries dropped remarkably (from 526±83 μm/sec to 132±41 μm/sec), and remained low level. And the number of perfused capillaries decreased. After the flow pattern was returned to pulsatile again, the velocity of erythrocytes recovered to the initial level. In many cases, the flow of non-perfused capillaries recovered to the initial level. CONCLUSION: When the flow pattern was changed from pulsatile to non-pulsatile, the decrease in velocity of erythrocytes in the capillaries and the deterioration in capillary density are observed. There is a possibility that non-pulsatile perfusion causes microvascular dysfunction. That could become more severe with prolonged non-pulsatile VAD use or permanent non-pulsatile TAH implantation in the future. This severity needs to be addressed in chronic studies.

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.

Third model of the undulation pump total artificial heart.

The undulation pump is a small, continuous flow displacement type blood pump, and the undulation pump total artificial heart (UPTAH) is a unique, implantable total artificial heart based on this pump. To improve the durability of the UPTAH for investigating long-term pathophysiology with UPTAH, a third model (UPTAH3) has been developed. UPTAH3 was designed to separate the left and right undulation shafts and to be more durable. The undulation pumps were also redesigned. UPTAH3 was implemented with a diameter of 76 mm, width of 78 or 79 mm, total volume of 292 ml, and weight of 620 g. The priming volumes of the left and right pumps are 26 and 21 ml, respectively. The atrial cuffs and outflow cannulae were also redesigned for UPTAH3. The maximum output against an arterial pressure load of 100 mm Hg is about 11 L/min. The maximum pump efficiency is about 15% in the left pump and 18% in the right pump, giving a maximum total efficiency for both of about 11%. To date, UPTAH3 has been tested in 17 goats, and the longest survival period was 46 days. This third model will be useful for investigating pathophysiology with UPTAH.

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.

612 波動型人工心臓

Undulation pump artificial heart is a rotary blood pump in which a special mechanism converts the rotation of a motor to the undulation motion of a disc in the pump. Undulation pump total artificial heart(UPTAH) is the most compact total artificial heart in the world. In this paper, performance, control method, animal experimental results and engineering problems of UPTAH will be discussed.

INFLUENCE OF THE FLOW PATTERNS ON THE MICROCIRCULATION OF THE BULBAR CONJUNCTIVA IN THE GOAT IMPLANTED A TOTAL ARTIFICIAL HEART

To investigate the influence of flow patterns on the microcirculations (MC) in the goat implanted a total artificial heart (TAH), a new system to observe the MC of the bulbar conjunctiva at the wake condition was developed. The digital high definition microscope that equipped on the 3-D stage fixed to a headgear of the goat was used to observe the MC. We implanted the undulation pump total artificial heart (UPTAH) to the goat, which can produce arbitrary flow patterns by computer control. When the whole body condition of TAH goat became stable after the surgery, we changed the flow pattern from pulsatile to non-pulsatile and observe the change in the MC. At first, we could observe that the arterioles were constricted, and the velocity of erythrocytes in the capillaries dropped remarkably. About 10 minutes later, the arterioles were dilated and the velocity of erythrocytes in the capillaries recovered to the initial level. These results indicate that at the acute phase of the flow pattern change from pulsatile to non-pulsatile, the baroceptor sensed the arterial pressure decrease and the sympathetic nerve activity increased, and the arterioles were constricted. After that the accumulation of products due to metabolism of the tissue led to the dilation of the arterioles.

Ripple reduction control of the undulation pump total artificial heart.

An undulation pump total artificial heart (UPTAH) in which the revolutions of the motor are converted to undulation motion of a disk has been developed. In an experiment, a goat using the UPTAH survived for 54 days. However, a large ripple was observed in the device's output pressure and flow waveform. In calculating the spectrum of the ripple, we found that the ripple mainly comprised 2 frequency sine waves: 1 having the same frequency as and 1 having double the frequency of the motor revolutions. To reduce the ripple, 2 sine waves, 1 having the same frequency as and 1 having double the frequency of the motor revolutions, were provided to the motor current to modulate the pulse width of the pulse width modulation controlling the motor revolutions. This ripple control method reduced the pressure ripple by 90% in a mock circulation and by 70% in animal experiments. These results revealed that the ripple generated in the UPTAH could be controlled through the use of motor control software.

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.

One Month Survival with the Undulation Pump Total Artificial Heart in a Goat

One Month Survival with the Undulation Pump Total Artificial Heart in a Goat

A step forward for the undulation pump total artificial heart

In the University of Tokyo, various types of total artificial heart (TAH) have been studied. Based on the experiences of TAH research, the development of the undulation pump total artifical heart (UPTAH) started in 1994. The undulation pump is a small-size, continuous-flow, displacement-type blood pump, and the UPTAH is a unique implantable total artificial heart that uses the undulation pump. To date, three models of UPTAH have been developed. The first model, UPTAH1, was developed to investigate the possibility of reducing the size of the device so it could be implanted in small adults, such as Japanese patients, in 1994. The second model, UPTAH2, which was the prototype of the animal experimental model, was developed in 1996 to investigate the possibility of survival with the UPTAH. The third model, UPTAH3, which is the present model, was developed in 1998 to enable long-term survival in animal experiments and to investigate the pathophysiology of the UPTAH. From July 1996 to October 1999, 22 implantations of UPTAH2 or UPTAH3 were performed in goats. In spite of the limitation of their small chest cavity, the UPTAH could be implanted into the chest of all goats. Using UPTAH3, survival of 31 days could be obtained. The research and development of UPTAH are ongoing.

ESSENTIAL BEHAVIOR OF 1/R CONTROL METHOD ON TOTAL ARTIFICIAL HEART (TAH)

In this study, the essential behavior of 1/R control method was deduced theoretically and proved on animal experiment. 1/R control method, which maintained TAH animal for over 500 days successfully, consists of two independent mechanisms, left and right heart control. On the left heart control, objective cardiac output (CO) is estimated with 1/R formula upon measured CO, aortic pressure (AoP) and right atrial pressure (RAP). The right heart control maintains constant difference between left and right atrial pressure (LAP and RAP, correspondingly). As 1/R formula is empirical non-linear equation, it is difficult to predict its behavior as it is. Therefore, the essential behavior of 1/R control was factorized theoretically as follows: Tracking control of AoP: AoP converges to mean AoP. This behavior maintains mean AoP cooperatively with baroreceptor reflex. Set-point tracking of RAP: RAP converges to RAP setting value. Controlled CO affects LAP and LAP propagates to RAP by right heart control. This behavior corresponds to Starling law. Adaptive control of AoP: Feedback gain of AoP control is regulated according to measured CO and mean AoP. Permission of fluctuation of AOP and CO: Around the optimal point, feedback gain of AoP control becomes rather small. This causes “control error” which allows migration of convergence point. These behaviors were confirmed by animal experiment with undulation pump total artificial heart.

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.