Effects of feeding state on anticoagulation in adult goats treated with warfarin.

For the continued development of improved mechanical circulatory systems, longer term evaluation of new devices in animal model experiments may be critical. The effects of anticoagulants in adult goats have not been well studied. We assessed the effects of oral warfarin in three adult goats during fasting or after feeding. The goats [weighing 57.8 ± 8.1 kg (53.0-67.2 kg)] were administered warfarin orally beginning at a dose of 5 mg/day and then increasing to 10, 20, 40, and 60 mg every 2 weeks. One goat (receiving 10 mg/day warfarin) was killed on day 27 because of the inability to stand. After administration of 60 mg warfarin, the remaining goat received no warfarin for 4 days to return to coagulated state. The goats were then fasted and treated with 40 mg warfarin. During warfarin administration, both goats required a dose of 60 mg/day to achieve International Normalized Ratios (INRs) of approximately 2.5; however, when, the animals were in the fasted condition, precipitous extension of INR was observed in 5 days. After resuming feeding, the INR was reduced to the proper range. We showed the tendency that warfarin therapy in goats required higher doses than the doses administered to human patients and that the effects of therapy were related to the feeding state. The results of this study provide important information for development of anticoagulation protocols to assess mechanical circulatory support devices for long-term use in preclinical examination.

Influence of a novel electrocardiogram-synchronized rotational-speed-change system of an implantable continuous-flow left ventricular assist device (EVAHEART) on hemolytic performance.

We developed a novel controller for a continuous-flow left ventricular assist device (EVAHEART) that can change the pump's rotational speed (RS) in synchronization with a patient's myocardial electrocardiogram (ECG) with the aim of facilitating cardiac recovery. We previously presented various applications of this system in animal models, but there remained a concern that the repeated acceleration and deceleration of the impeller may induce additional hemolysis. In this study, we evaluated the blood trauma and motor power consumption induced by our system in a mock circulation. We evaluated our system with a 60-bpm pulse frequency and a variance between the high and low RSs of 500 rpm (EVA-P; n = 4). The continuous modes of EVAHEART (EVA-C; n = 4) and ROTAFLOW (n = 4) were used as controls. The pumps were examined at a mean flow rate of 5.0 ± 0.2 L/min against a mean pressure head of 100 ± 3 mmHg for a 4-h period. As a result, the normalized indexes of the hemolysis levels of EVA-P and EVA-C were 0.0023 ± 0.0019 and 0.0023 ± 0.0025, respectively, and their difference was not significant. The estimated mean motor power consumptions of EVA-C and EVA-P were 6.24 ± 0.33 and 7.19 ± 0.93 W, respectively. When a novel ECG-synchronized RS-change system was applied to EVAHEART, the periodic RS change with a 500-rpm RS variance did not affect the hemolysis at a 60-bpm pulse frequency.

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 x 8.5 x 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 x 13 mmHg, 3.9 x 0.9 l/min, and 12 x 1 W, and those for the second calf were maintained at 88 x 13 mmHg, 5.0 x 0.5 l/min, and 16 x 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.

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 degrees, 45 degrees, 90 degrees, 135 degrees, 180 degrees, and 270 degrees, where the OD opening toward the diaphragm was defined as 0 degrees ) 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 degrees. In contrast, the regional flow velocity in this area was highest at an OD of 135 degrees. 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 degrees.

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.