Akimasa Kouno

In vitro and in vivo evaluation of a jellyfish valve for practical use.

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

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.

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.

Fabrication of a jellyfish valve for use in an artificial heart

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

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.

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.

A new hypothesis on the mechanism of calcification formed on a blood-contacted polymer surface

Calcification on a blood-contacting polymer surface in an artificial heart is one of the most serious problems. Recently, we maintained a goat with a total artificial heart (AH) for 532 days without systemic anticoagulation. Sactype blood pumps coated with segmented polyurethane and incorporating jellyfish valves, thin polymer membrane valves, were used in the experiment. The pump was exchanged for a new one on the 312th day on the left side and the 414th day on the right side. They were analyzed with a scanning electron microscope (SEM) and an X-ray microanalyzer. The valve membrane after 312 days of pumping revealed plastic deformation expanding toward upstream between the spokes by creep fatigue with blood pressure difference when the valve closed. Calcification on the membrane was concentrated in the limited portions that received a strong stretching force: the upstream side of the membrane between the spokes and downstream side of the membrane on the spokes. Slight or no calcification was observed on the opposite side of the membrane that received a compression force, and no calcification was found on nonmoving parts such as the center of the membrane and spokes. A new hypothesis on the mechanism of calcification at the portion that received repeated stretching force was raised. The repeated stretching force would extend the polymer membrane, causing some loosening between polymer molecules and generating microgaps. The blood protein and phospholipid would invade into these microgaps, which would then attract Ca ions followed by phosphate ions to make their complexation. The hypothesis could well explain the calcification phenomena on a blood-contacting polymer surface, and gave a good clue on how to protect from calcification.