Tomohiro Nishinaka

Less Blood Damage in the Impeller Centrifugal Pump: A Comparative Study with the Roller Pump in Open Heart Surgery

A centrifugal pump with an impeller (Nikkiso Centrifugal Pump, Model HPM15; Nikkiso Co. Ltd.) was applied to cardiopulmonary bypass (CPB) in 14 patients who underwent elective coronary artery bypass grafting. Serum hemoglobin level, platelet count, and serum p-thromboglobulin (pTG) level were measured during CPB. The results were compared with those obtained in a comparative roller pump (RP) group (n = 10). There was no difference in the time on CPB between the NP (109 min) and RP (121 min) groups. The serum pTG level (ng/ ml) was lower in the NP group than in the RP group (obtained 90 min after the initiation of CPB). The plasma-free hemoglobin level also was lower in the NP group than in the RP group (obtained 90 min after the initiation of CPB, 120 min after the initiation of CPB, immediately after the termination of CPB, 3 h after termination of CPB; p < 0.01). There was no significant difference in platelet depletion. The HPM15 pump showed excellent hemodynamic performance with less blood trauma compared with the roller pump in its clinical application to open heart surgery.

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.

Prolonged nonpulsatile left heart bypass diminishes vascular contractility

We investigated possible functional changes in the vascular system accompanying the morphological change in prolonged nonpulsatile left heart bypass (LHB). Three adult goats underwent pulsatile LHB. Two weeks postoperatively, the pulsatile ventricular assist device was replaced with a centrifugal pump and nonpulsatile LHB was subsequently conducted for 4 weeks. The mean aortic pulse pressure was 39 and 16 mmHg during the pulsatile and nonpulsatile LHB, respectively. Systemic vascular resistance (SVR) and plasma norepinephrine levels were measured at the end of pulsatile LHB (PUL), and at the end of 1st, 2nd, 3rd, and 4th week of nonpulsatile LHB (NP1w, NP2w, NP3w, NP4w, respectively). At each point, 50 μg/kg nitroglycerin and 1μg/kg norepinephrine were injected and the minimal and maximal values of SVR after injection were calculated as parameters reflecting the vascular tonus and contractility. The SVR and plasma nor epinephrine level did not significantly change during the entire course (SVR: 1106, 895, 982, 920, and 938 dyne·sec·cm−5; norepinephrine level: 0.3, 0.2, 0.1, 0.2, and 0.1 ng/ml; at PUL, NP1w, NP2w, NP3w, and NP4w, respectively). The minimal value of SVR after nitroglycerin injection remained unchanged, indicating that vascular tonus was stable during the entire course (618, 687, 623, 560, 653 dyne·sec·cm−5, respectively). In contrast, the maximal value of SVR after norepinephrine injection at NP3w and NP4w (1695 and 1759 yne·sec·cm−5) became significantly reduced compared to that at PUL (2346 dyne·sec·cm−5). These results indicated that prolonged nonpulsatile left heart bypass did not affect the vascular tonus, but significantly diminished the vascular contractility.

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°.

Chronic nonpulsatile blood flow is compatible with normal end-organ function: implications for LVAD development.

Evolving blood pump technology has produced user-friendly continuous-flow left ventricular assist devices, but uncertainty exists about the safety of chronic nonpulsatile circulation. Recent experimental and clinical evidence suggest that pulse pressure is not required from a blood pump. End-organ function is well maintained with nonpulsatile systems, although pulse pressure may accelerate recovery from cardiogenic shock. Form follows function, so the effects of reduced pulse pressure on the arterial wall are not surprising. The ability to alter aortic wall morphology by reducing pulse pressure may have important implications for the future treatment of arterial pathology. Both centrifugal and axial-flow pumps can be miniaturized and are reliable and silent. Doubts about the feasibility of long-term circulation with reduced pulse pressure are disappearing.

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 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.

Influence of pulsatile and nonpulsatile left heart bypass on the hormonal circadian rhythm.

We investigated endocrine circadian rhythm (CR) during pulsatile and nonpulsatile left heart bypass (PLHB and NLHB). A ventricular assist device (VAD) was installed in five goats. After 2 weeks of PLHB, NLHB was subsequently conducted for 4 weeks. The levels of melatonin, cortisol, and renin activity were measured every 2 hours for 24 hours on the last day of the second PLHB week and the second and fourth NLHB weeks. Acquired data were compared with those of the normal control goats (Cont) to determine the presence or absence of CR, as well as the timing, acrophase, amplitude, and mesor of CR. Variations in melatonin, CR were consistently detected at all sampling points. In contrast, CR of cortisol during PLHB and NLHB was observed in a few cases, although considerable CR was noted in most of the Cont cases. The variations in renin activity indicated CR in most of the Cont cases and in all cases at all sampling points during PLHB and NLHB, whereas their acrophases were diversified. In conclusion, the CR of melatonin, reflecting the fundamental circadian clock, was maintained during both PLHB and NLHB, while it could be modified for stress sensitive cortisol and hemodynamic responsive renin during these bypass modalities.

Myocardial size and fibrosis changes during left ventricular assist device support.

Previous studies have demonstrated that left ventricular assist device (LVAD) implantation significantly decreases myocyte size and reduces fibrosis of the left ventricle (LV). The objectives of the present study were to evaluate LV functional recovery after LVAD implantation and to assess its predictive factors, including histological findings of LV. Six patients with idiopathic cardiomyopathy underwent LVAD support with an EVAHEART implantable centrifugal pump (Sun Medical Technology Research, Nagano, Japan) for an average support duration of 2.91 years. Histologic samples were obtained from their LV apexes at the time of implantation. At 1 month and at 24 months after implantation, brain natriuretic peptide (BNP) and echocardiographic parameters were evaluated. Brain natriuretic peptide values, LV end-diastolic dimension, LV end-systolic dimension, functional shortening, and right ventricular systolic pressure (RVSP) were improved after LVAD implantation. Patients with developing fibrosis had longer durations of heart-failure history and higher pulmonary artery pressures. Patients with hypertrophic myocytes had smaller FS preoperatively. There was a correlation between the amount of fibrosis and the rate of BNP value change after LVAD implantation. In patients with less fibrosis and smaller myocytes preoperatively, improvement in LV function was observed during LVAD support.

Current status of development and in vivo evaluation of the National Cardiovascular Center electrohydraulic total artificial heart system

We have been developing an electrohydraulic total artificial heart system. The system has a pumping unit, consisting of diaphragm-type blood pumps and an energy converter, and an electronics unit, consisting of an internal controller, an internal battery, and transcutaneous energy transfer and optical telemetry subunits. The energy converter, designed to be placed outside the pericardial space, reciprocates and delivers hydraulic silicone oil to the alternate blood pumps through a pair of flexible oil conduits. The left-right output balance is achieved with an interatrial shunt made in the composite atrial cuff. In vivo performance of the pumping unit has been evaluated by chronic implantation of 16 calves weighing 54–88 kg. Five calves survived for more than a week, and the longest-surviving animal lived for over 12 weeks until its accidental death. In this animal, a cardiac output of 6–81/min was maintained by the device with power consumption of 13.5±0.9W and 9%–11% efficiency. The left and right atrial pressures were 16±4 and 14±4 mm Hg, respectively, and the left-right output difference was adequately balanced with the interatrial shunt. The mixed venous oxygen saturation was 65±6% and the serum lactate level was 5±1 mg/dl, representing favorable oxygen metabolic conditions. The temperatures of the energy converter and the blood pump surfaces were 39.4±0.7° and 38.8±1.5°C, respectively, indicating that heat generation and dissipation were acceptable. The serum and tissue silicon levels were within normal (<1 μg/ml or <1 μg/g), indicating that permeation of silicone oil through the blood pump diaphragm was inconsequential and unlikely to be detrimental. We conclude that the system has the potential to be a totally implantable cardiac replacement.