Tomonori Tsukiya

A novel counterpulsation mode of rotary left ventricular assist devices can enhance myocardial perfusion

The effect of rotary left ventricular assist devices (LVADs) on myocardial perfusion has yet to be clearly elucidated, and several studies have shown decreased coronary flow under rotary LVAD support. We have developed a novel pump controller that can change its rotational speed (RS) in synchronization with the native cardiac cycle. The aim of our study was to evaluate the effect of counterpulse mode, which increases the RS in diastole, during coronary perfusion. Experiments were performed on ten adult goats. The EVAHEART LVAD was installed by the left ventricular uptake and the descending aortic return. Ascending aortic flow, pump flow, and coronary flow of the left main trunk were monitored. Coronary flow was compared under four conditions: circuit-clamp, continuous mode (constant pump speed), counterpulse mode (increased pump speed in diastole), and copulse mode (increased pump speed in systole). There were no significant baseline changes between these groups. In counterpulse mode, coronary flow increased significantly compared with that in continuous mode. The waveform analysis clearly revealed that counterpulse mode mainly resulted in increased diastolic coronary flow. In conclusion, counterpulse mode of rotary LVADs can enhance myocardial perfusion. This novel drive mode can provide great benefits to the patients with end-stage heart failure, especially those with ischemic etiology.

Electrocardiogram‐Synchronized Rotational Speed Change Mode in Rotary Pumps Could Improve Pulsatility

Continuous-flow left ventricular assist devices (LVADs) have greatly improved the prognosis of patients with end-stage heart failure, even if continuous flow is different from physiological flow in that it has less pulsatility. A novel pump controller of continuous-flow LVADs has been developed, which can change its rotational speed (RS) in synchronization with the native cardiac cycle, and we speculated that pulsatile mode, which increases RS just in the systolic phase, can create more pulsatility than the current system with constant RS does. The purpose of the present study is to evaluate the effect of this pulsatile mode of continuous-flow LVADs on pulsatility in in vivo settings. Experiments were performed on eight adult goats (61.7 ± 7.5 kg). A centrifugal pump, EVAHEART (Sun Medical Technology Research Corporation, Nagano, Japan), was installed by the apex drainage and the descending aortic perfusion. A pacing lead for the detection of ventricular electrocardiogram was sutured on the anterior wall of the right ventricle. In the present study, we compared pulse pressure or other parameters in the following three conditions, including Circuit-Clamp (i.e., no pump support), Continuous mode (constant RS), and Pulsatile mode (increase RS in systole). Assist rate was calculated by dividing pump flow (PF) by the sum of PF and ascending aortic flow (AoF). In continuous and pulsatile modes, these assist rates were adjusted around 80-90%. The following three parameters were used to evaluate pulsatility, including pulse pressure, dp/dt of aortic pressure (AoP), and energy equivalent pulse pressure (EEP = (∫PF*AoP dt)/(∫PF dt), mm Hg). The percent difference between EEP and mean AoP is used as an indicator of pulsatility, and normally it is around 10% of mean AoP in physiological pulse. Both pulse pressure and mean dp/dt max were decreased in continuous mode compared with clamp condition, while those were regained by pulsatile mode nearly to clamp condition (pulse pressure, clamp/continuous/pulsatile, 25.0 ± 7.6/11.7 ± 6.4/22.6 ± 9.8 mm Hg, mean dp/dt max, 481.9 ± 207.6/75.6 ± 36.2/351.1 ± 137.8 mm Hg/s, respectively). In clamp condition, %EEP was 10% higher than mean AoP (P = 0.0078), while in continuous mode, %EEP was nearly equivalent to mean AoP (N.S.). In pulsatile mode, %EEP was 9% higher than mean AoP (P = 0.038). Our newly developed pulsatile mode of continuous-flow LVADs can produce pulsatility comparable to physiological pulsatile flow. Further investigation on the effect of this novel drive mode on organ perfusion is currently ongoing.

Up to 151 days of continuous animal perfusion with trivial heparin infusion by the application of a long-term durable antithrombogenic coating to a combination of a seal-less centrifugal pump and a diffusion membrane oxygenator

We developed a new coating material (Toyobo-National Cardiovascular Center coating) for medical devices that delivers high antithrombogenicity and long-term durability. We applied this coating to an extracorporeal membrane oxygenation (ECMO) system, including the circuit tube, cannulae, a seal-less centrifugal pump, and a diffusion membrane oxygenator, to realize prolonged cardiopulmonary support with trivial anticoagulant infusion. The oxygenator consisted of a hollow-fiber membrane made of polymethylpentene, which allows the transfer of gas by diffusion through the membrane. The centrifugal pump was free of seals and had a pivot bearing. We performed a venoarterial bypass in a goat using this ECMO system, and the system was driven for 151 days with trivial anticoagulant infusion. Plasma leakage from the oxygenator did not occur and sufficient gas-exchange performance was well maintained. In the oxygenator, thrombus formation was present around the top and the distributor of the inlet portion and was very slight in the outlet portion. In the centrifugal blood pump, there was some wear in the female pivot region and quite small amounts of thrombus formation on the edge of the shroud; the pivot wear seemed to be the cause of the hemolysis observed after 20 weeks of perfusion and which resulted in the termination of the perfusion. However, no significant amounts of thrombus were observed in other parts of the system. This ECMO system showed potential for long-term cardiopulmonary support with minimal use of systemic anticoagulants.

Characterization and optimization of the flow pattern inside a diaphragm blood pump based on flow visualization techniques.

We applied two different flow visualization techniques to obtain detailed information on the inside flow of the diaphragm blood pump of our electrohydraulic total artificial heart system to determine the optimum washout effect that would result in better antithrombogenicity. Major orifice directions of the inflow and outflow Bjork-Shiley valves of the left blood pump were independently changed to create 17 varied patterns. The character and velocity of the main flow at the diaphragm-housing junction were acquired using a laser light sheet method with polyethylene tracers. Wall shear flow, a major factor governing washout in the blood pump, was estimated by a newly developed paint erosion method. In this method, quantitative evaluation for an index of washout effect was made by calculating the residual ratio of the paint on the blood pump inner surface at 30 sec of pumping. When a single circular flow was consistently observed by the laser light sheet method, the paint residual ratio become low, indicating washout was relatively good. At the lowest paint residual ratio, the center of the circular flow observed by the laser light sheet method was located at the geometric center of the blood chamber. In conclusion, the flow pattern inside the blood pump could be characterized by combined use of these two flow visualization techniques, and the significant role of circular flow in better washout was clarified.

Effects of mechanical valve orifice direction on the flow pattern in a ventricular assist device

We have been developing a pneumatic ventricular assist device (PVAD) system consisting of a diaphragm-type blood pump. The objective of the present study was to evaluate the flow pattern inside the PVAD, which may greatly affect thrombus formation, with respect to the inflow valve-mount orientation. To analyze the change of flow behavior caused by the orifice direction (OD) of the valve, the flow pattern in this pump was visualized. Particle image velocimetry was used as a measurement technique to visualize the flow dynamics. A monoleaflet mechanical valve was mounted in the inlet and outlet ports of the PVAD, which was connected to a mock circulatory loop tester. The OD of the inlet valve was set at six different angles (OD = 0°, 45°, 90°, 135°, 180°, and 270°, where the OD opening toward the diaphragm was defined as 0°) and the pump rate was fixed at 80 bpm to create a 5.0 l/min flow rate. The main circular flow in the blood pump was affected by the OD of the inlet valve. The observed regional flow velocity was relatively low in the area between the inlet and outlet port roots, and was lowest at an OD of 90°. In contrast, the regional flow velocity in this area was highest at an OD of 135°. The OD is an important factor in optimizing the flow condition in our PVAD in terms of preventing flow stagnation, and the best flow behavior was realized at an OD of 135°.

The National Cardiovascular Center electrohydraulic total artificial heart and ventricular assist device systems: current status of development.

Electrohydraulic total artificial heart (EHTAH) and electrohydraulic ventricular assist device (EHVAD) systems have been developed in our institute. The EHTAH system comprises a pumping unit consisting of blood pumps and an actuator, as well as an electronic unit consisting of an internal controller, internal and external batteries, and transcutaneous energy transfer (TET) and optical telemetry (TOT) subunits. The actuator, placed outside the pericardial space, reciprocates and delivers hydraulic silicone oil to the alternate blood pumps through a pair of flexible oil conduits. The pumping unit with an external controller was implanted in 10 calves as small as 55 kg. Two animals survived for more than 12 weeks in a good general condition. The assumed cardiac output ranged between 6 and 10 L/min, the power consumption was 12–18 W, and the energy efficiency was estimated to be 9–11%. Initial implantation of subtotal system including electronic units was further conducted in another calf weighing 73 kg. It survived for 3 days with a completely tether free system. The EHVAD system is developed by using the left blood pump and the actuator of the EHTAH, which were packaged in a compact metal casing with a compliance chamber. In vitro testing demonstrated maximum output more than 9 L/min and more than 13% maximum efficiency. The initial animal testing lasted for 25 days. These results indicate that our EHTAH and EHVAD have the potential to be totally implantable systems.

Ultrastructural alterations in red blood cell membranes exposed to shear stress.

In the mechanism of damage to red blood cells (RBCs) caused by a centrifugal pump, the prolonged effects to the RBC membrane caused by exposure to shear stress remain unclear. We focused on the band 3 protein (B3), one of the major proteins in the membrane skeleton, and investigated the ultrastructural alterations of the RBC membrane with loaded shear stress. Using flow cytometry, the relative amount of B3 was examined in relation to RBC deformability. The results, with continuous exposure to low shear stress, showed cell downsizing, an increase in B3 density, and a decrease in the deformability of the RBC membrane. Exposure to high shear stress does not appear to exert any influence on the membrane skeleton of the RBC. Therefore, in addition to conventional processes including the instantaneous destruction of a cell due to intense shear stresses, the results of the present study indicate the presence of another process based on changes in membrane proteins leading to cell fragmentation. Under low shear stress, the RBC membrane skeleton shows delayed destruction, which is exhibited as a disorder of B3 distribution, and the related membrane dysfunction includes decreases in RBC deformability and stability.

Results of Chronic Animal Experiments With a New Version of a Magnetically Suspended Centrifugal Pump

We have developed a magnetically suspended centrifugal pump (MSCP) for long-term ventricular support. This study reports results of chronic animal experiments using a new version of the MSCP. Three sheep weighing 50-70 kg were used in this study. A left heart assist system was established with cannulas into the descending aorta and the left ventricular apex. In two sheep the MSCP was positioned outside the body and in one sheep implanted on the chest wall. The pumping flow was estimated by the motor current and motor speed. The temperature of the pump and the muscle near the pump was recorded for 10 days after operation. The duration of continuous pumping was 60, 140, and 230 days+ (ongoing), respectively. The cause of termination was infection associated with thrombus formation in the first, and failure of magnetic suspension in the second sheep. No thrombus or embolus was observed after sacrifice of the second sheep. The third sheep has been going well despite skin necrosis around the pump pocket. The estimation of pumping flow was reliable even at 140 days. Temperature of the pump surface was 42 degrees C immediately after the operation and gradually reduced to 41 degrees C. The MSCP is a reliable pump for long-term circulatory assist.

Development of a compact portable driver for a pneumatic ventricular assist device.

The Toyobo-National Cardiovascular Center pneumatic ventricular assist device (Toyobo-NCVC VAD) is widely used in Japan; however, the current pneumatic drivers have some drawbacks, including their large size, heavy weight, and high power consumption. These issues cause difficulty with mobility and contribute to an unsatisfactory quality of life for patients. Because it is urgently necessary to improve patients’ safety and quality of life, we have developed a compact, low-noise, portable VAD driver by utilizing an electrohydraulic actuator consisting of a brushless DC motor and a regenerative pump. This unit can be actuated for as long as 2 h with two rechargeable lightweight batteries as well as with external AC power. It is compact in size (33 × 25 × 43 cm) and light in weight (13 kg), and the unit is carried on a mobile wheeled cart. In vitro testing with a Toyobo-NCVC VAD demonstrated a sufficient pumping capacity of up to 8 l/min. We conclude that this newly-developed compact portable driver can provide a better quality of life and improved safety for patients using protracted pneumatic VAD support.

Observation of cavitation bubbles in monoleaflet mechanical heart valves.

Recently, cavitation on the surface of mechanical heart valves (MHVs) has been studied as a cause of fractures occurring in implanted MHVs. In the present study, we investigated the mechanism of MHV cavitation associated with the Björk–Shiley valve and the Medtronic Hall valve in an electrohydraulic total artificial heart (EHTAH). The valves were mounted in the mitral position in the EHTAH. The valve closing motion, pressure drop measurements, and cavitation capture were employed to investigate the mechanisms for cavitation in the MHV. There are no differences in valve closing velocity between the two valves, and its value ranged from 0.53 to 1.96 m/s. The magnitude of negative pressure increased with an increase in the heart rate, and the negative pressure in the Medtronic Hall valve was greater than that in the Björk–Shiley valve. Cavitation bubbles were concentrated at the edge of the valve stop; the major cause of these cavitation bubbles was determined to be the squeeze flow. The formation of cavitation bubbles depended on the valve closing velocity and the valve leaflet geometry. From the viewpoint of squeeze flow, the Björk–Shiley valve was less likely to cause blood cell damage than the Medtronic Hall valve in our EHTAH.