Kou Imachi

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 μm/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 μm/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.

Electrical Stimulation of Skeletal Muscles

The aim of this study was to investigate whether electrical stimulation of skeletal muscles could represent a rehabilitation alternative for patients with chronic heart failure (CHF). Thirty patients with CHF and NYHA class II-III were randomly assigned to a rehabilitation program using either electrical stimulation of skeletal muscles or bicycle training. Patients in the first group (n = 15) had 8 weeks of home-based low-frequency electrical stimulation (LFES) applied simultaneously to the quadriceps and calf muscles of both legs (1 h/day for 7 days/week); patients in the second group (n = 15) underwent 8 weeks of 40 minute aerobic exercise (3 times a week). After the 8-week period significant increases in several functional parameters were observed in both groups: maximal VO2 uptake (LFES group: from 17.5 +/- 4.4 mL/kg/min to 18.3 +/- 4.2 mL/kg/min, P < 0.05; bicycle group: from 18.1 +/- 3.9 mL/kg/min to 19.3 +/- 4.1 mL/kg/min, P < 0.01), maximal workload (LFES group: from 84.3 +/- 15.2 W to 95.9 +/- 9.8 W, P < 0.05; bicycle group: from 91.2 +/- 13.4 W to 112.9 +/- 10.8 W, P < 0.01), distance walked in 6 minutes (LFES group: from 398 +/- 105 m to 435 +/- 112 m, P < 0.05; bicycle group: from 425 +/- 118 m to 483 +/- 120 m, P < 0.03), and exercise duration (LFES group: from 488 +/- 45 seconds to 568 +/- 120 seconds, P < 0.05; bicycle group: from 510 +/- 90 seconds to 611 +/- 112 seconds, P < 0.03). These results demonstrate that an improvement of exercise capacities can be achieved either by classical exercise training or by home-based electrical stimulation. LFES should be considered as a valuable alternative to classical exercise training in patients with CHF.

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.

Domestic and foreign trends in the prevalence of heart failure and the necessity of next-generation artificial hearts: a survey by the Working Group on Establishment of Assessment Guidelines for Next-Generation Artificial Heart Systems.

A series of guidelines for development and assessment of next-generation medical devices has been drafted under an interagency collaborative project by the Ministry of Health, Labor and Welfare and the Ministry of Economy, Trade and Industry. The working group for assessment guidelines of next-generation artificial hearts reviewed the trend in the prevalence of heart failure and examined the potential usefulness of such devices in Japan and in other countries as a fundamental part of the process of establishing appropriate guidelines. At present, more than 23 million people suffer from heart failure in developed countries, including Japan. Although Japan currently has the lowest mortality from heart failure among those countries, the number of patients is gradually increasing as our lifestyle becomes more Westernized; the associated medical expenses are rapidly growing. The number of heart transplantations, however, is limited due to the overwhelming shortage of donor hearts, not only in Japan but worldwide. Meanwhile, clinical studies and surveys have revealed that the major causes of death in patients undergoing long-term use of ventricular assist devices (VADs) were infection, thrombosis, and mechanical failure, all of which are typical of VADs. It is therefore of urgent and universal necessity to develop next-generation artificial hearts that have excellent durability to provide at least 2 years of event-free operation with a superior quality of life and that can be used for destination therapy to save patients with irreversible heart failure. It is also very important to ensure that an environment that facilitates the development, testing, and approval evaluation processes of next-generation artificial hearts be established as soon as possible.

Can total artificial heart animals control their TAH by themselves? One year survival of a TAH goat using a new automatic control method (1/R control).

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.

Development of transcutaneous energy transmission system for totally implantable artificial heart

A transcutaneous energy transmission system (TETS) was composed of a couple of coils, which formed a transformer across the skin, a driving circuit, and a rectifying circuit. By using coreless coils and a high driving frequency (100–160 kHz), more than 25 W of electric power could be transmitted with 78.5% of maximum efficiency (dc to dc). In animal experiments, the primary coil temperature during operation was under 39°C on thermograms. After 10 months of implantation of a secondary coil coated with epoxy resin, it was wrapped by a thin capsule of connecting tissue. No obvious tissue reaction was recognized.

Over 500 Days’ Survival of a Goat with a Total Artificial Heart with 1/R Control

The 1/R control was developed to provide control over the output of a total artificial heart (TAH) by the central nervous system by using the peripheral vascular conductance (1/R) the vasodilatation in for the control signal. The physiologic stability of the 1/R control algorithm was tested by using goats with TAH. To apply the 1/R control equation to TAH in goats, real-time and continuous measurements of cardiac output, aortic pressure, and right atrial pressure were performed throughout the survival period. Left atrial pressure was also measured, to prevent lung edema. Under the 1/R control, 532 days’ survival was obtained in a goat with a TAH. Findings over the course of the experiment showed no hemodynamic or metabolic abnormality. Autopsy findings showed macroscopically no congestion in the liver. The experiment demonstrated the physiologic stability of the 1/R control algorithm for an extended period. Improvement of methods for measurement, such as the development of feasible techniques for the noninvasive measurement of the required hemodynamic parameters, will make it possible to use 1/R control in practice, especially for a totally implantable TAH system.

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.

The second and third model of the flow transformed pulsatile total artificial heart.

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 Jellyfish Valve: A Polymer Membrane Valve for the Artificial Heart

The development of a polymer membrane valve for artificial heart blood pumps is very much required, since the mechanical valves, such as the Bjork-Shiley (BS) and Hall valves, used in the present artificial heart (AH) blood pumps have the following problems: 1. A ring thrombus is often formed at the interface between the valve ring and pump housing, because these cannot be fixed seamlessly. 2. Valve failure sometimes occurs at the disc and stent due to a water-hammer effect. 3. Regurgitant and leakage flow generated in the mechanical valve induces hemolysis and the AH patient becomes mildly anemic. 4. The valves are too expensive to popularize the AH as a therapeutic method.