Nobumasa Katagiri

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.

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.

Development of a compact wearable pneumatic drive unit for a ventricular assist device

The purpose of this study was to develop a compact wearable pneumatic drive unit for a ventricular assist device (VAD). This newly developed drive unit, 20 × 8.5 × 20 cm in size and weighing approximately 1.8 kg, consists of a brushless DC motor, noncircular gears, a crankshaft, a cylinder-piston, and air pressure regulation valves. The driving air pressure is generated by the reciprocating motion of the piston and is controlled by the air pressure regulation valves. The systolic ratio is determined by the noncircular gears, and so is fixed for a given configuration. As a result of an overflow-type mock circulation test, a drive unit with a 44% systolic ratio connected to a Toyobo VAD blood pump with a 70-ml stroke volume achieved a pump output of more than 7 l/min at 100 bpm against a 120 mmHg afterload. Long-term animal tests were also performed using drive units with systolic ratios of 45% and 53% in two Holstein calves weighing 62 kg and 74 kg; the tests were terminated on days 30 and 39, respectively, without any malfunction. The mean aortic pressure, bypass flow, and power consumption for the first calf were maintained at 90 × 13 mmHg, 3.9 × 0.9 l/min, and 12 × 1 W, and those for the second calf were maintained at 88 × 13 mmHg, 5.0 × 0.5 l/min, and 16 × 2 W, respectively. These results indicate that the newly developed drive unit may be used as a wearable pneumatic drive unit for the Toyobo VAD blood pump.

Observation of alveolar fibrosis in a goat following venoarterial bypass for up to 5 months using extracorporeal membrane oxygenation

Prolonged cardiopulmonary bypass such as venoarterial bypass with extracorporeal membrane oxygenation (VA-ECMO) is becoming a potent therapeutic option in treating patients with severe respiratory and circulatory failure. However the chronic effects of this bypass modality have not yet been fully clarified. Recently, we developed an extremely durable thrombo-resistant ECMO system, and were successful with more than 5 months of continuous heparinless VA-ECMO in an animal experiment. This article presents the pathological findings on the lungs of the animal.A goat underwent VA-ECMO for a scheduled period of 151 days. This animal demonstrated a good general condition during the course of the experiment. On autopsy, however, the lungs of the animal showed severe alveolar fibrosis with topical atelectasis. von Willebrand factor levels on the endothelial cells in the alveolar capillaries were increased compared with those of normal goats. The ultrastructure of these cells showed ischemia-induced endothelial swelling. The pathological findings indicated that the vascular endothelial phenotypes had changed from respiratory type to nutrient type. The results of this study indicated that prolonged VA-ECMO may cause pulmonary alveolar fibrosis as a result of ischemia of the lungs accompanying reduced pulmonary blood flow.

Optimal drainage cannula position in dual cannulation for veno-venous extracorporeal membrane oxygenation.

Introduction: Recently, the use of veno-venous extracorporeal membrane oxygenation for adult patients with severe acute respiratory failure has increased. We previously investigated the optimal return cannula position; however, the optimal drainage cannula position has not yet been fully clarified. The aim of this study was to investigate the optimal drainage cannula position. Methods: Veno-venous extracorporeal membrane oxygenation was performed in four adult goats (mean body weight 59.6 ± 0.6 kg). The position of the drainage cannula was varied among the right atrium, the upper inferior vena cava, and the lower inferior vena cava, whereas the position of the return cannula was fixed in the superior vena cava. The recirculation fraction and arterial oxygen saturation and pressure (SaO2, PaO2) were measured in all drainage cannula positions. Results: In the lower inferior vena cava drainage cannula position, the recirculation fraction was the lowest. In the lower inferior vena cava, upper inferior vena cava, and right atrium drainage cannula positions at 3 L/min, SaO2 and PaO2 after 20 min were 92.9% ± 4.9% and 75.1 ± 26.0 mm Hg, 99.5% ± 0.5% and 113.8 ± 20.9 mm Hg, and 93.8% ± 6.2% and 91.9 ± 17.7 mm Hg, respectively. Conclusion: With respect to blood oxygenation, the optimal position for the drainage cannula was the upper inferior vena cava. These findings suggested that blood from the superior vena cava, inferior vena cava, and hepatic vein was most efficiently drained in the upper inferior vena cava cannula position.

Evaluation of the Novel Centrifugal Pump, CAPIOX SL, in Chronic Large Animal Experiments: Thoughts and Progress

In the development of a new device for extracorporeal circulation, long-term durability and biocompatibility are required. The CAPIOX SL Pump (SL pump, Terumo Corporation, Tokyo, Japan), which is a centrifugal pump using a two-pivot bearing, was developed with the hope of suppressing pump thrombus formation around the bearings. This study aimed to evaluate the in vivo performance of the SL pump in the condition assumed severe clinical situation for long-term extracorporeal membrane oxygenation (ECMO) support. Extracorporeal circulation using the SL pump was installed in three goats, with drainage from the inferior vena cava and infusion into the right jugular artery. The animals were maintained with target pump flow of 2.0-3.0 L/min for 3 or 7 days. Anticoagulation was performed by continuous infusion of heparin with a target activated coagulation time (ACT) of 200 ± 50 s. Blood tests were performed regularly. After 3 or 7 days, autopsies were performed on all animals. The pumps were disassembled and observed for thrombus formation. The results were compared with those of our previous study of the current model of the centrifugal pump (SP pump). All animals were successfully managed within target pump flows and ACT values during the scheduled period, with no adverse events. No thrombus formation was found around the bearing of the SL pump. The blood tests showed normal major organ functions, and platelet consumption and hemolysis were significantly lower in this study compared to the previous study of the SP pump. The CAPIOX SL Pump showed excellent durability and biocompatibility in a large animal experiment.

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.