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.     

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.     

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.     

Results of animal experiments using an undulation pump total artificial heart: analysis of 10 day and 19 day survival

An undulation pump is a special rotary blood pump in which rotation of a brushless DC motor is transformed to an undulating motion by a disc in the pump housing attached by means of a special link mechanism. In the blood pump, a closed line between the disc and housing moves from the inlet to the outlet by this undulating disc motion, which sucks and pushes the blood from the inlet to the outlet. Because the same phenomena occurs at both sides of the disc, a continuous flow is obtained when the motor rotational speed is constant. The pump flow pattern can be easily changed from continuous flow to pulsatile flow by controlling the motor drive current pattern. A seal membrane made of segmented polyurethane protects the blood from invading the link mechanism as well as the motor. UPTAH is fabricated with two undulation pumps and two brushless DC motors. Its size is 75 mm in diameter and 80 mm long, and it has one of the great advantage of no compliance chamber required in the system. UPTAHs were implanted under cardiopulmonary bypass (CPB) into the chest cavities of 16 goats, each weighing between 41 and 72 kg. No anticoagulant and antiplatelet agent was used after the surgery. The left atrial pressure was automatically controlled to prevent its elevation and sucking of the atrial wall into the atrial cuff. The following results were obtained: (1) UPTAHs fit well into all the goats; (2) the longest survival was 19.8 days, the cause of death was bleeding from the aortic anastomosis; (3) No thrombus was observed in the blood pump despite no anticoagulant use. Hemolysis depended upon the length of CPB during surgery. When CPB time was within 2 hours, hemolysis level returned to baseline within a few days of the surgery. UPTAH is a promising implantable TAH, because of its small size and easy controllability.     

A case in which biventricular assist device support was required after aortic valve replacement with a bioprosthetic valve

We report the case of a 45-year-old man with severe aortic regurgitation. The patient underwent aortic valve replacement with a bioprosthetic valve, but was unable to be weaned from cardiopulmonary bypass (CPB). Intraoperative coronary angiography revealed stenosis of the right coronary orifice, so an intra-aortic balloon pump was inserted and coronary artery bypass grafting to the right coronary artery was conducted; however, weaning from CPB again failed. Left ventricular assist using a Gyro centrifugal pump was performed between the left atrium and left femoral artery, along with right ventricular assist using a Nikkiso centrifugal pump between the right atrium and pulmonary artery. Flow rates averaged from 2.0 to 2.8l/min for the left-side ventricular assist device (VAD) and 2.1–3.8l/min for the right-side VAD. The bypass rate reached approximately 70% at maximum. No thromboembolic events were documented during VAD support. The patient underwent explantation of VADs on postoperative day 4. No thrombus was identified on the bioprosthetic aortic valve by transesophageal echocardiography. The left-side pump displayed no thrombus, while the right-side pump had a small thrombus at the shaft. The patient was discharged from the hospital and was alive as of 2 year postoperatively. To the best of our knowledge, no clinical study has yet compared the antithrombotic properties of two centrifugal pumps in one patient where mechanical support was performed for the same duration and flow rate.     

Implantable total artificial heart: history and present status at the University of Tokyo

The University of Tokyo has been involved in research and development of the artificial heart since 1959. This paper is a brief review of 40 years of total artificial heart research in the University of Tokyo. Many types of artificial heart and various kinds of materials, blood pumps, valves, drive units, control methods, and pathophysiology have been investigated in our original fashion. The longest survival was 532 days for a goat with a total artificial heart (TAH) placed on the chest wall. These results made us take a step toward the development of an implantable TAH. Two kinds of implantable TAH are now being developed: FTPTAH (flow-transformed pulsatile total artificial heart) and UPTAH (undulation pump total artificial heart). Recently, a goat survived for 31 days with an UPTAH.     

Acute in vivo evaluation of an implantable continuous flow biventricular assist system

An implantable biventricular assist device offers a considerable opportunity to save the lives of patients with combined irreversible right and left ventricular failure. The purpose of this study was to evaluate the hemodynamic and physiologic performance of the combined implantation of the CorAide left ventricular assist device (LVAD) and the DexAide right ventricular assist device (RVAD). Acute hemodynamic responses were evaluated after simulating seven different physiological conditions in two calves. Evaluation was performed by fixing the speed of one individual pump and increasing the speed of the other. Under all conditions, increased LVAD or RVAD speed resulted in increased pump flow. The predominant pathophysiologic effect of independently varying DexAide and CorAide pump speeds was that the left atrial pressure was very sensitive to increasing RVAD speed above 2,400 rpm, whereas the right atrial pressure demonstrated much less sensitivity to increasing LVAD speed. An increase in aortic pressure and RVAD flow was observed while increasing LVAD speed, especially under low contractility, ventricular fibrillation, high pulmonary artery pressure, and low circulatory blood volume conditions. In conclusion, a proper RVAD-LVAD balance should be maintained by avoiding RVAD overdrive. Additional studies will further investigate the performance of these pumps in chronic animal models.     

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.     

Development of compact ventricular assist device for chronic use

A compact and reliable mechanical ventricular assist device is expected for chronic use. A magnetically suspended centrifugal pump (MSCP) is a seal-less, bearingless pump that can be operated for a long time with-out fear of leak or thrombus formation around the shaft. This paper reports recent progress with the MSCP, including pulse-pressure generation: In three sheep with acute heart failure induced by injection of beta-blockers, left ventricular assist was instituted with an inflow cannula into the left atrium (LA) and left ventricle (LV), and the outflow cannula to the descending aorta. The timing of the pulsation was synchronized with the electrocardiogram. Cardiac performance was evaluated by a conductance catheter and a tipped manometer in the LV. As pump speed increased, the pump flow became almost continuous. After application of pulsation, the pulse pressure increased from 5 to 25 mmHg, irrespective of the inflow cannulation site and the timing of pulsation. With LA cannulation, LV pressure at copulsation was slightly higher than at counterpulsation. Chronic animal trial: The MSCP was implanted in three sheep. The inflow cannula was inserted into the LV. The native heart was kept intact. The inner surface was coated with heparin. Continuous hemodynamic monitoring as well as periodic blood sampling was performed. The duration of running of the pump was 60, 140, and 248 days. The causes of termination were infection and failure of magnetic suspension due to electrical short. No thrombus or embolic findings were observed in the whole body after sacrifice. Renal and hepatic functions were within normal range throughout the experiment. It is concluded that the MSCP can produce pulsation irrespective of the inflow cannulation site and timing of synchronization. It is a promising device for chronic ventricular support.     

Application of extremum seeking control to turbodynamic blood pumps

Ventricular assist devices now clinically used for treatment of end-stage heart failure require responsive and reliable control to accommodate the continually changing demands of the body. However, due to the varying physiologic conditions and the limited use of the sensors to detect hemodynamic load and suction, it is difficult to control pump speed appropriately. The author introduces an adaptive pump speed controller to provide maximum cardiac perfusion while avoiding ventricular suction. The controller is based on an extremum seeking control (ESC) algorithm and a slope seeking control (SSC) algorithm, which find and track unknown and moving peak points of a prescribed cost function. The controller was validated with in vivo data using time-averaged diastolic pump flow as the cost function for ESC/SSC. Initial results demonstrate the successful application of ESC/SSC as a physiologic pump speed controller.     

Mini hemoreliable axial flow LVAD with magnetic bearings: part 1: historical overview and concept advantages

Intec has been developing an ultra-miniature axial flow left ventricular assist device (LVAD) turbo pump that incorporates non-contacting magnetic bearings specifically designed to eliminate thrombus. The patent pending pump is similar in size to the Jarvik 2000, being 1.0 inch in diameter and having a volume of 25cc. This paper provides two decades of historical background regarding blood pumps and discusses new advances made possible by our contactless design. Design details are left for parts two and three. This LVAD is presently the smallest magnetically suspended turbo pump. It was made possible by use of new 1/2-inch diameter fringing ring magnetic bearings. These axial field bearings are 10 times smaller than equal capacity radial field conventional magnetic bearings currently in development in turbo pumps. Our LVAD is physiologically controllable, without the use of invasive sensors, by directly measuring pump differential pressure with the magnetic bearings. This mechanism will allow attainment of cyclic, closed-loop control of impeller revolutions per minute to achieve a high degree of pressure pulsatility. Pulsatile flow is important in obtaining long-term hemodynamic reliability without thrombus being generated in either the pump or body.     

Biventricular support with the Jarvik 2000 axial flow pump: a feasibility study

Patients with congestive heart failure who are supported with a left ventricular assist device (LVAD) may experience right ventricular dysfunction or failure that requires support with a right ventricular assist device (RVAD). To determine the feasibility of using a clinically available axial flow ventricular assist device as an RVAD, we implanted Jarvik 2000 pumps in the left ventricle and right atrium of two Corriente crossbred calves (approximately 100 kg each) by way of a left thoracotomy and then analyzed the hemodynamic effects in the mechanically fibrillated heart at various LVAD and RVAD speeds. Right atrial implantation of the device required no modification of either the device or the surgical technique used for left ventricular implantation. Satisfactory biventricular support was achieved during fibrillation as evidenced by an increase in mean aortic pressure from 34 mm Hg with the pumps off to 78 mm Hg with the pumps generating a flow rate of 4.8 L/min. These results indicate that the Jarvik 2000 pump, which can provide chronic circulatory support and can be powered by external batteries, is a feasible option for right ventricular support after LVAD implantation and is capable of completely supporting the circulation in patients with global heart failure.     

Left ventricular heart failure model for testing cardiac assist devices

During the development of a new circulatory support system, we have used different animal models with and without heart failure for hemodynamic testing. As the normally functioning heart does not always allow for proper evaluation of a circulatory support system, a good and adjustable animal heart failure model is needed. The aim of the study was to develop a left ventricular failure model in calves for acute hemodynamic studies. The principle is based on the negative inotropic effect of drugs with bypass of the right ventricle. Seven calves were used in the study. Metoprolol and verapamil were both given intravenously as a bolus, and verapamil was continued as an infusion. The animals were equipped with a VVI pacemaker to treat the expected arteriovenous blockade. A centrifugal pump provided an adjustable flow with a two-stage inflow cannula draining both the upper and lower caval veins and with the outflow cannula in the pulmonary artery. The pump counteracted the effects of right ventricular failure and enabled us to increase the left atrial pressure to more than 20 mm Hg. Pressure in the left atrium rose from 5+/-3 to 25+/-4 mm Hg (p < 0.001), the left ventricular diastolic pressure increased from 2+/-3 to 17+/-7 mm Hg (p = 0.003), and the mean pulmonary pressure increased from 17+/-5 to 33+/-5 mm Hg (p < 0.001). Cardiac output was not significantly changed from 4.0+/-0.8 L/min in the healthy animals to 3.5+/-0.5 L/min (p = 0.25) in failure. The model allowed us to create an adjustable and isolated left ventricular failure well suited for short-term hemodynamic testing of a left ventricular support device.     

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.     

Biventricular support using a centrifugal pump in a 6 year old with fulminant myocarditis

We experienced a case of ventricular assist with both a pulsatile-flow and a continuous-flow pump in a pediatric patient, and herein report the clinical course and characteristics of the pumps. A 6-year-old female was diagnosed with fulminant myocarditis and transferred to our hospital for mechanical support. After 12 days of extracorporeal membrane oxygenation, we implanted a left ventricular assist device (LVAD) and a right ventricular assist device (RVAD) using centrifugal Gyro pumps with a membrane oxygenator in a paracorporeal fashion. The membrane oxygenator was removed on postoperative day (POD) 4, and the patient was weaned from the respirator on POD 6. The LVAD was exchanged on POD 13 and 17, and the RVAD was exchanged on POD 14 because of thrombus formation inside the pumps. The RVAD was removed on POD 25. On POD 32, the patient experienced cerebral infarction and the centrifugal Gyro pump was switched to an extracorporeal pulsatile pump. No thromboembolic event occurred after pump conversion, although continuous administration of vasodilators was required to avoid hypertension. She underwent successfully heart transplantation in the USA after 8 months of ventricular support. A centrifugal pump is considered useful for pediatric patients, as pump flow and blood pressure can be relatively easily controlled in the postoperative acute phase compared with the pulsatile pump. However, special care should be taken to monitor for thrombus formation when support length becomes longer than 13 days, and a switch to a pulsatile pump should be considered once the hemodynamic status stabilizes.     

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?CQ (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.     

Hemodynamic effects of a new percutaneous circulatory support device in a left ventricular failure model

We have tested a new percutaneous circulatory support device in seven anesthetized calves with induced left ventricular failure. The device is based on a flexible catheter with a foldable propeller and cage at the distal end. The rotation of the propeller (1,000-15,000 rpm) is transmitted from a drive unit at the proximal end to the propeller by way of a rotating wire inside the catheter. This also contains an umbrella-like mechanism to open the pump head from the folded (diameter 4.6 mm) to the active position. The rotation of the propeller creates a pressure drop in front of the propeller and a pressure rise behind. Heart failure was induced with metoprolol and verapamil in combination with a VVI pacemaker to create a left atrial pressure greater than 20 mm Hg. A centrifugal pump was used to bypass the right ventricle and to ensure a sufficient filling of the left ventricle. After baseline recordings, the pump was run at 14,000 rpm, and the hemodynamic response was compared with the baseline. A 24 +/- 10 mm Hg pressure gradient was generated across the pump, resulting in a drop in the right carotid artery mean pressure from 80 +/- 11 to 71 +/- 13 mm Hg (p = 0.008) and a drop in the left ventricular systolic pressure from 109 +/- 17 to 100 +/- 19 mm Hg (p = 0.004). The pressure in the left atrium decreased from 25 +/- 3 to 20 +/- 5 mm Hg (p = 0.008). The mean femoral pressure increased from 78 +/- 10 to 95 +/- 20 mm Hg (p = 0.005). A moderate reduction in the right carotid flow was observed (15%, p = 0.029), whereas no significant changes were found in the coronary flow, the flow in the right femoral artery, or in the left kidney. The device showed a significant unloading of the left ventricle and an increased perfusion pressure for the lower part of the body. The moderate changes in flow were probably caused by still active autoregulation, and this needs to be tested with more pronounced circulatory failure.     

Improved Left Ventricular Performance by the Transmission of Pulse Waves through the Pulmonary Vascular Bed

Piene , H. Improved left ventricular performance by the transmission of pulse waves through the pulmonary vascular bed. Acta physiol. scand. 1976. 98. 450–456. The influence on left ventricular performance of pulsewaves transmitted through the pulmonary vascular bed was studied in a cat lung preparation with the right heart bypassed by a pulsatile blood pump. The pump worked at a frequency slightly different from the intrinsic heart rate; transmitted pulse waves were thereby forced to arrive the left atrium at different phases of the left heart cycle. Slow fluctuations of left atrial pressure, left ventricular systolic pressure and left ventricular dP/dt were observed. Left ventricular systolic pressure and left ventricular dP/dt were maximum when the transmitted pulsewaves arrived left atrium just prior to the atrial contraction. The observed variation in left ventricular systolic pressure was found to be directly dependent on the magnitude of pulsatile hydraulic power transmitted to the left atrium.     

In vitro controllability of the MagScrew total artificial heart system

The purpose of this study was to evaluate the in vitro responses to preload and afterload of our total artificial heart (TAH), the MagScrew TAH. The TAH consists of two blood pumps and a control logic, developed at the Cleveland Clinic, OH, and the MagScrew actuator and its electronic control system, developed by Foster-Miller Technologies, Inc., Albany, NY. Tests were performed on a mock circulatory loop, using water as a test fluid. Preload sensitivity of the Mag-Screw TAH demonstrated a Frank-Starling response to preload in automatic mode. A peak flow of 10 L/min was obtained, with a left atrial pressure of 13 mm Hg. The relationship between right atrial pressure and left atrial pressure was well balanced when tested with a left bronchial shunt flow of 5% and a range of pulmonary artery and aortic pressures. With respect to afterload response, the left pump showed a relatively low sensitivity, which allowed the pump to maintain perfusion over a wide range of aortic pressures. The right pump, on the other hand, was much more sensitive to pulmonary artery pressure, which provided a measure of protection against pulmonary congestion. The very effective physiologic response of the MagScrew TAH is believed to result from employment of a left master, alternating ejection control logic, high inherent sensitivity of the blood pumps to atrial pressure, a lower effective stroke volume for the right pump, and a scaling of right side motor ejection voltage to 80% of that used for the left side ejection.     

Cardiac myxoma

Summary Neoplasms are rare cardiac findings of which myxomas comprise about 75%. We report of 15 patients, predominantly female (60%) with a mean age of 58.8 years. Male patients (40%) were 20 years younger on average.80% of these tumors developed in the left atrium fixed to the atrial septum. In 2 patients the right ventricle and in 1 patient the right atrium was involved. No left ventricular or bilateral tumors were found. Clinical findings showed a great variety of symptoms. Often misdiagnosis was established until echocardiography was performed. Major symptoms were dyspnea (80%), elevated erythrocyte sedimentation rate (73%), arrhythmias (53%), lung edema (47%), embolization (40%) and anemia (40%).Pathological examination and tumor genesis are still in discussion. Several theories are reported in literature: a true thrombus, thrombus organization with malignant potential, true neoplasms as well as a familiar myxoma complex may explain clinical and histological features. Our findings did not confirm only one theory but emphasize different possibilities.Abbreviations LA Left atrium - RA Right atrium - RV Right ventricle