Hydrodynamic characteristics of the helical flow pump.

The helical flow pump (HFP) was invented to be an ideal pump for developing the TAH and the helical flow TAH (HFTAH) using two HFPs has been developed. However, since the HFP is quite a new pump, hydrodynamic characteristics inside the pump are not clarified. To analyze hydrodynamic characteristics of the HFP, flow visualization study using the particle image velocimetry and computational fluid dynamics analysis were performed. The experimental and computational models were developed to simulate the left HFP of the HFTAH and distributions of flow velocity vectors, shear stress and pressure inside the pump were examined. In distribution of flow velocity vectors, the vortexes in the vane were observed, which indicated that the HFP has a novel and quite unique working principle in which centrifugal force rotates the fluid in the helical volutes and the fluid is transferred from the inlet to the outlet helical volutes according to the helical structure. In distribution of shear stress, the highest shear stress that was considered to be occurred by the shunt flow across the impeller was found around the entrance of the inlet helical volute. However, it was not so high to cause hemolysis. This shunt flow is thought to be improved by redesigning the inlet and outlet helical volutes. In distribution of pressure, negative pressure was found near the entrance of the inlet helical volute. However, it was not high. Negative pressure is thought to be reduced with an improvement in the design of the impeller or the vane shape.

Computational fluid dynamics analysis of the pump parameters in the helical flow pump.

The helical flow pump (HFP) was invented to develop a total artificial heart at the University of Tokyo in 2005. The HFP consists of the multi-vane impeller involving rotor magnets, a motor stator and pump housing having double-helical volutes. To investigate the characteristics of the HFP, computational fluid dynamics analysis was performed. Validation of the computational model was performed with the data of the actual pump. A control computational model in which the vane area corresponded approximately to that of the actual pump was designed for the parametric study. The parametric study was performed varying the vane height, vane width and helical volute pitch. When the vane height was varied from 0.5 to 1.5 times that of the control computational model, the H-Q (pressure head vs. flow) and efficiency curves were translated in parallel with the vane height. When the vane height was two and three times that of the control computational model, the profile of these curves changed. From the results, the best proportion for the vane was considered to be a vane height between 1.5 and 2 times the vane width. The effect of vane width was not very strong compared to that of the vane height. A similar tendency in vane height was observed by varying the helical volute pitch. The best helical volute-pitch size is considered to be between 1.5 and 2 times the vane width. Although further study is necessary to determine the best values for these parameters, the characteristics of the pump parameters in the HFP could be approximately clarified.

Emergency Life Support System aiming preprimed oxygenator.

Development have been achieved of a new blood pump for next generation Percutaneous Cardio-Pulmonary Support (PCPS) system and a novel surface coating method for silicone membrane hollow fiber by physical adsorption using a copolymer composed of a 2-Methacryloyloxyethyl phosphorylcholine (MPC) unit and a hydrophobic unit. The new blood pump, named the Troidal Convolution Pump (TCP), is based on the principle of a cascade pump and perfused 5 L/min and 350 mmHg at 2450 rpm. The novel copolymer composed of 30% MPC unit and 3-(methacryloyloxy) propyltris (trimethylsiloxy) silane (MPTSSi) unit (PMMSi30) was the most suitable molecular design on a silicone surface. The PMMSi30 coated surface adsorbed 7.2 % as much protein a non-coated surface adsorbed.

The helical flow total artificial heart: implantation in goats.

To realize a total artificial heart (TAH) with high performance, high durability, good anatomical fitting, and good blood compatibility, the helical flow TAH (HFTAH) has been developed with two helical flow pumps having hydrodynamic levitation impeller. The HFTAH was implanted in goats to investigate its anatomical fitting, blood compatibility, mechanical stability, control stability, and so on. The size of the HFTAH was designed to be 80 mm in diameter and 84 mm wide. The maximum output was 19 L/min against 100 mmHg of pressure head. Eight adult female goats weighting from 45 to 56.3 kg (average 49.7 kg) were used. Under the extracorporeal circulation, natural heart was removed at the atrioventricular groove and the HFTAH was implanted. The HFTAH was driven with a pulsatile mode. The 1/R control was applied when the right atrial pressure recovered. The HFTAH could be implanted with good anatomical fitting in all goats. Two goats survived for more than a week. One goat is ongoing. Other goats did not survive for more than two days with various reasons. In the goats that survived for more than a week, the hydrodynamic bearing was worn and broken, which indicated that the bearing touched to the shaft. The cause was supposed to be the influence of the sucking effect. The potential of the HFTAH could be demonstrated with this study. The stability of the hydrodynamic bearing in a living body, especially the influence of the sucking effect, was considered to be very important and a further study should be necessary.

Pulsatile driving of the helical flow pump.

The helical flow pump (HFP) is newly developed blood pomp for total artificial heart (TAH). HFP can work with lower rotational speed than axial and centrifugal blood pump. It can be seen reasonable feature to generate pulsatile flow because high response performance can be realized. In this article, pulsatility of HFP was evaluated using mock circulation loop. Pulsatile flow was generated by modulating the rotational speed in various amplitude and heart rate. In the experiment, relationship between Pump flow, pump head, rotational speed amplitude, heart rate and power consumption is evaluated. As the result, complete pulsatile flow with mean flow rate of 5 L/min and mean pressure head of 100 mmHg can be obtained at ± 500 rpm with mean rotational speed of 1378 to 1398 rpm in hart rate from 60 to 120. Flow profiles which are non-pulsatile, quasi-pulsatile or complete flow can be adjusted arbitrarily. Therefore, HFP has excellent pulsatility and control flexibility of flow profile.

Effect of a bearing gap on hemolytic property in a hydrodynamically levitated centrifugal blood pump with a semi-open impeller.

We have developed a hydrodynamically levitated centrifugal blood pump with a semi-open impeller for long-term circulatory assist. The pump uses hydrodynamic bearings to enhance durability and reliability without additional displacement-sensors or control circuits. However, a narrow bearing gap of the pump has a potential for hemolysis. The purpose of this study is to develop the hydrodynamically levitated centrifugal blood pump with a semi-open impeller, and to evaluate the effect of a bearing gap on hemolytic property. The impeller levitates using a spiral-groove type thrust bearing, and a herringbone-groove type radial bearing. The pump design was improved by adopting a step type thrust bearing and optimizing the pull-up magnetic force. The pump performance was evaluated by a levitation performance test, a hemolysis test and an animal experiment. In these tests, the bearing gap increased from 1 to 63 µm. In addition, the normalized index of hemolysis (NIH) improved from 0.415 to 0.005 g/100 l, corresponding to the expansion of the bearing gap. In the animal experiment for 24 h, the plasma-free hemoglobin remained within normal ranges (<4.0 mg/dl). We confirmed that the hemolytic property of the pump was improved to the acceptable level by expanding the bearing gap greater than 60 µm.

The helical flow pump with a hydrodynamic levitation impeller.

The helical flow pump (HFP) is a novel rotary blood pump invented for developing a total artificial heart (TAH). The HFP with a hydrodynamic levitation impeller, which consists of a multi-vane impeller involving rotor magnets, stator coils at the core position, and double helical-volute pump housing, was developed. Between the stator and impeller, a hydrodynamic bearing is formed. Since the helical volutes are formed at both sides of the impeller, blood flows with a helical flow pattern inside the pump. The developed HFP showed maximum output of 19 l/min against 100 mmHg of pressure head and 11 % maximum efficiency. The profile of the H-Q (pressure head vs. flow) curve was similar to that of the undulation pump. Hydrodynamic levitation of the impeller was possible with higher than 1,000 rpm rotation speed. The normalized index of the hemolysis ratio of the HFP to centrifugal pump (BPX-80) was from 2.61 to 8.07 depending on the design of the bearing. The HFP was implanted in two goats with a left ventricular bypass method. After surgery, hemolysis occurred in both goats. The hemolysis ceased on postoperative days 14 and 9, respectively. In the first experiment, no thrombus was found in the pump after 203 days of pumping. In the second experiment, a white thrombus was found in the pump after 23 days of pumping. While further research and development are necessary, we are expecting to develop an excellent TAH with the HFP.

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.

Automatic calibration of the inlet pressure sensor for the implantable continuous-flow ventricular assist device.

Significant progress in the development of implantable ventricular assist devices using continuous-flow blood pumps has been made recently. However, a control method has not been established. The blood pressure in the inflow cannula (inlet pressure) is one of the candidates for performing an adequate control. This could also provide important information about ventricle sucking. However, no calibration method for an inlet pressure sensor exists. In this study, an automatic calibration algorithm of the inlet pressure sensor from the pressure waveform at the condition of ventricle sucking was proposed. The calibration algorithm was constructed based on the consideration that intrathoracic pressure could be substituted for atmospheric pressure because the lung is open to air. We assumed that the inlet pressure at the releasing point of the sucking would represent the intrathoracic pressure, because the atrial pressure would be low owing to the sucking condition. A special mock circulation system that can reproduce ventricle sucking was developed to validate the calibration algorithm. The calibration algorithm worked well with a maximum SD of 2.1 mmHg for 3-min measurement in the mock circulation system. While the deviation was slightly large for an elaborate calibration, it would still be useful as a primitive calibration. The influence of the respiratory change and other factors as well as the reliability of the calibration value should be investigated with an animal experiment as a next step.

Outline of the International Organization for Standardization Standard for Circulatory Support Devices (ISO 14708-5).

The rapid progress of artificial heart and circulatory support devices enables us to apply them to severe heart failure patients. Many types of circulatory support devices have been developed in the United States, Europe, and Japan. This situation urged the establishment of an International Organization for Standardization (ISO) Standard for the circulatory support devices. A new work, "Cardiac Ventricular Assist Devices," was proposed to the ISO/TC150/SC6 (TC150: Technical Committee of Implants for Surgery, SC6: Sub-committee of Active Implants) in 2000, and the work was finalized for publication at a 2009 meeting of the ISO/TC150 in Kyoto. In this article, the authors would like to introduce the ISO system and the outline of the ISO Standard for Circulatory Support Devices.

Japanese guidance for ventricular assist devices/total artificial hearts.

To facilitate research and development (R&D) and to expedite the review processes of medical devices, the Ministry of Health, Labor and Welfare (MHLW) and the Ministry of Economy, Trade and Industry (METI) founded a joint committee to establish guidance for newly emerging technology. From 2005 to 2007, two working groups held discussions on ventricular assist devices and total artificial hearts, including out-of-hospital programs, based on previous guidance documents and standards. Based on this discussion, the METI published the R&D Guidelines for innovative artificial hearts in 2007, and in 2008 the MHLW published a Notification by Director regarding the evaluation criteria for emerging technology.

Use of in vivo insert molding to form a jellyfish valve leaflet.

We developed an in vivo insert molding technique to form tissue-derived biomaterials into the desired shape, and with sufficient strength and durability, for use in artificial organs. Molds of acrylic resin with inserted velour cloth were implanted under the skin of goats to form a circular leaflet for a jellyfish valve. The valve leaflets were successfully produced in the molds after 17-60 days. Dense connective tissue covered the velour cloth, and loose connective tissue was formed within it. Tissue was radially formed from the hole in the mold. The tissue was simultaneously formed and shrunk. It is necessary to increase the connected portion between the tissue inside and outside the mold so that the tissue can completely cover the inserted materials without shrinkage.

Baroreflex sensitivity of an arterial wall during rotary blood pump assistance.

It is well known that the baroreflex system is one of the most important indicators of the pathophysiology in hypertensive patients. We can check the sensitivity of the baroreflex by observing heart rate (HR) responses; however, there is no simple diagnostic method to measure the arterial behavior in the baroreflex system. Presently, we report the development of a method and associated hardware that enables the diagnosis of baroreflex sensitivity by measuring the responses of both the heart and the artery. In this system, the measurements are obtained by monitoring an electrocardiogram and a pulse wave recorded from the radial artery or fingertip. The arterial responses were measured in terms of the pulse wave velocity (PWV) calculated from the pulse wave transmission time (PTT) from the heart to the artery. In this system, the HR change corresponding to the blood pressure change in time series sequence was observed. Slope of the changes in blood pressure and HR indicated the sensitivity of the baroreflex system of the heart. This system could also measure the sensitivity of the baroreflex system of an artery. Changes in the PWV in response to the blood pressure changes were observed. Significant correlation was observed in the time sequence between blood pressure change and PWV change after calculating the delay time by cross-correlation. The slope of these parameter changes was easily obtained and it demonstrated the sensitivity of the baroreflex system of an artery. We evaluated this method in animal experiments using rotary blood pump (RBP) with undulation pump ventricular assist device, and PTT elongation was observed in response to increased blood pressure with RBP assistance. Furthermore, when tested clinically, decreased sensitivity of the baroreflex system in hypertensive patients was observed. This system may be useful when we consider the ideal treatment and follow-up of patients with hypertension.

Analysis of baroreflex sensitivity during undulation pump ventricular assist device support.

The aim of this study was to examine the baroreflex sensitivity (BRS), which involves the autonomic nervous system, in a goat with a chronically implanted undulation pump ventricular assist device (UPVAD). The UPVAD involved transforming the rotation of a brushless DC motor into an undulating motion by a disc attached via a special linking mechanism, and a jellyfish valve in the outflow cannula to prevent diastolic backflow. The pump was implanted into the thoracic cavity of a goat by a left thoracotomy, and the inflow and outflow cannulae were sutured to the apex of the left ventricle and to the descending aorta, respectively. The driving cable was wired percutaneously to an external controller. Electrocardiogram and hemodynamic waveforms were recorded at a sampling frequency of 1 kHz. BRS was determined when awake by the slope of the linear regression of R-R interval against mean arterial pressure changes, which were induced by the administration of methoxamine hydrochloride, both with continuous driving of the UPVAD as well as without assistance. BRS values during the UPVAD support and without assistance were 1.60 +/- 0.30 msec/mm Hg and 0.98 +/- 0.22 msec/mm Hg (n = 5, P < 0.05), respectively. BRS was significantly improved during left ventricular assistance. Therefore, UPVAD support might decrease sympathetic nerve activity and increase parasympathetic nerve activity to improve both microcirculation and organ function.

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.

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.

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+/-41mum/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.

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.

Electrical stimulation of skeletal muscles. An alternative to aerobic exercise training in patients with chronic heart failure?

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.