Kyoko Shioya

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.

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.

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.

Prostaglandin synthesis inhibitor prevents hypotension without impairing gut perfusion during normothermic cardiopulmonary bypass

Aortic pressure declines during cardiopulmonary bypass (CPB), particularly at normothermia. It has been reported that administering vasoconstrictors during normothermic CPB (NCPB) to restore perfusion pressure might induce hypoperfusion of splanchnic organs. We have reported that prostaglandin (PG), metabolized in the lung but increased during CPB, might have played a substantial role in hypotension, and that a PG synthesis inhibitor (PGSI) could improve hypotension during CPB. This study was designed to examine whether regional perfusion of splanchnic organs was reduced when PGSI restored systemic perfusion pressure during NCPB. NCPB was performed in eight adult goats for 60 minutes (body weight 57.0 ± 5.9 kg). PGSI was administered in group P (n = 4), while norepinephrine was administered in group C (n = 4), to keep aortic pressure in the range of 50 to 80 mm Hg. The total systemic flow was maintained at approximately 70 ml/kg/min. Tissue blood flow was measured by means of the colored microsphere method before and 30 and 60 minutes after the start of CPB. In group P, gut blood flows after the start of CPB were higher than those before CPB, significantly in the stomach and jejunum at 30 minutes (p < 0.05), whereas gut blood flows in group C were decreased or not changed. In conclusion, PGSI prevents hypotension without impairing gut perfusion during NCPB.

Proliferative changes in the media of the afferent arterioles under prolonged continuous-flow left heart bypass

Abstract We investigated morphological changes of the arterial system in the kidneys under prolonged, continuous-flow left heart bypass. After 2 weeks of pulsatile left heart bypass in 12 goats, continuous-flow left heart bypass was conducted for the next 4 weeks. After autopsy, the kidneys were subjected to pathological evaluation. The media of the afferent arterioles were frequently thickened by increased quantities of mature smooth muscle cells (SMC). The juxtaglomerular areas (JGA) were expanded due to increases in the number and size of SMCs and/or SMC-like cells. We speculate that prolonged continuous-flow left heart bypass causes SMCs and/or SMC-like cells to proliferate in the media and perivascular tissue of the afferent arterioles.

Development of an Electrohydraulic Total Artificial Heart System

An electrohydraulic total artificial heart (EHTAH) system has been developed. The EHTAH system consists of diaphragm-type blood pumps, an electrohydraulic actuator, an internal control unit, a transcutaneous energy transfer system (TETS), a transcutaneous optical telemetry system (TOTS), and an internal battery. The reciprocating rotation of the impeller generates oil pressure which drives the blood pumps at alternating intervals. The blood pumps and the actuator were successfully integrated into the pump unit without oil conduits. As a result of miniaturizing the blood pumps and the actuator, the displacement volume and weight of the EHTAH system decreased to 872 ml and 2492g, respectively. Furthermore, the maximum flow rate and efficiency increased up to 12 L/min and 15.4%. The pump units and the EHTAH systems were successfully implanted in 36 calves weighing from 55 to 87kg. In the longest case, the ca1f with the pump unit survived for 87 days and the calf with the EHTAH system survived for 70 days. The EHTAH system was powered by the TETS, and was powered everyday by the internal battery for 40 minutes. These results indicate that the EHTAH system has the potential to become a fully implantable cardiac replacement system.