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Biomedical subjects

Akio Funakubo

Publications and source records attributed to Akio Funakubo.

10 recordsLinked to original sources

In vitro evaluation of a newly developed implantable artificial lung.

A prototype of an implantable artificial lung without a pump (Prototype II) has been tested. A commercially available membrane oxygenator, MENOX AL6000alpha (Dainippon Ink and Chemicals, Inc., Tokyo, Japan), was used as a basic model. The packing density of the hollow fiber was decreased in order to achieve low resistance through the blood pathway. The configuration of its housing was also re-designed using computational fluid dynamics (CFD). The first prototype, known as Prototype I, was already tested in a 15 kg pig, which showed excellent gas exchange with normal hemodynamics. A second prototype, Prototype II, has a larger membrane surface area than Prototype I. The device was evaluated for resistance through the blood path and gas transfer rate in an in vitro setting by the single pass method using fresh bovine blood. The resistance through the blood path of Prototype II was 2.7+- 0.7 mmHg/(L/min) at Q = 5L/min. The oxygen (O2) transfer rate was 178 +- 5.3 ml/min at Q = 5 L/min, V/Q = 3, and the carbon dioxide (CO2) transfer rate was 149 +- 28 ml/min at Q = 5 L/min, V/Q = 2 (Q: blood flow rate, V: sweep oxygen flow rate through the artificial lung). For the purpose of implantation, this prototype showed sufficiently low resistance in the pulmonary circulation with reasonable gas exchange.

Artificial Organs↗

A prototype of a liquid ventilator using a novel hollow-fiber oxygenator in a rabbit model.

OBJECTIVE: A functional total liquid ventilator should be simple in design to minimize operating errors and have a low priming volume to minimize the amount of perfluorocarbon needed. Closed system circuits using a membrane oxygenator have partially met these requirements but have high resistance to perfluorocarbon flow and high priming volume. To further this goal, a single piston prototype ventilator with a low priming volume and a new high-efficiency hollow-fiber oxygenator in a circuit with a check valve flow control system was developed. DESIGN: Prospective, controlled animal laboratory study. SETTING: Research facility at a university medical center. SUBJECTS: Seven anesthetized, paralyzed, normal New Zealand rabbits INTERVENTIONS: The prototype oxygenator, consisting of cross-wound silicone hollow fibers with a surface area of 1.5 m2 with a priming volume of 190 mL, was tested in a bench-top model followed by an in vivo rabbit model. Total liquid ventilation was performed for 3 hrs with 20 mL.kg(-1) initial fill volume, 17.5-20 mL.kg(-1) tidal volume, respiratory rate of 5 breaths/min, inspiratory/expiratory ratio 1:2, and countercurrent sweep gas of 100% oxygen. MEASUREMENTS AND MAIN RESULTS: Bench top experiments demonstrated 66-81% elimination of CO2 and 0.64-0.76 mL.min(-1) loss of perfluorocarbon across the fibers. No significant changes in PaCO2 and PaO2 were observed. Dynamic airway pressures were in a safe range in which ventilator lung injury or airway closure was unlikely (3.6 +/- 0.5 and -7.8 +/- 0.3 cm H2O, respectively, for mean peak inspiratory pressure and mean end expiratory pressure). No leakage of perfluorocarbon was noted in the new silicone fiber gas exchange device. Estimated in vivo perfluorocarbon loss from the device was 1.2 mL.min(-1). CONCLUSIONS: These data demonstrate the ability of this novel single-piston, nonporous hollow silicone fiber oxygenator to adequately support gas exchange, allowing successful performance of total liquid ventilation.

Animals↗

An investigation of blood damage induced by static pressure during shear-rate conditions.

Many investigators have studied the effect of a mechanical force (shear rate, pressure, or temperature) on hemolysis. However, there exists no investigation of a relationship between the interactions of mechanical forces and hemolysis. The purpose of this study is to investigate the interactions of mechanical forces on hemolysis. We performed in vitro tests by using bovine blood, applying shear rate (0, 500, 1,000, and 1,500 s-1), positive pressure (0, 200, 400, and 600 mm Hg), and temperature (21, 28, and 35 degrees C) simultaneously. In all temperatures at the shear rate of 1,500 s-1, there are statistically significant differences in the hemolysis rate between 0 and 600 mm Hg (p < 0.05). However, to investigate the effect of temperature on hemolysis, shear stress was calculated at each blood temperature. There were no statistically significant differences among them. The results suggested that erythrocyte trauma caused by pressure related to the level of shear rate. It was found that the causes of hemolysis included the shear rate as well as shear rate and pressure.

Erythrocytes↗

Flow rate and pressure head estimation in a centrifugal blood pump.

Considering a miniaturization of percutaneous cardiopulmonary support (PCPS) system, we have developed a pump system that can estimate flow rate and pressure head in the circuit. A commercially available centrifugal blood pump (C1E3, Kyocera Co., Ltd., Kyoto, Japan) with an exclusive motor driver was used in the experiment. In this system, the motor revolutions per minute and torque were used to derive an estimation equation. Taking into consideration fluid viscosity, the accuracy of the estimation was increased. Bovine blood was used to evaluate the system in vitro. The average maximum difference between the estimated flow rate and the measured flow rate was 0.56 L/min (for 98% accuracy). The average difference between the estimated pressure head and the measured pressure head was 30.7 mm Hg (for 94.2% accuracy). Because of the stability of the estimations, we believe this system has the possibility of use for real-time monitoring and miniaturization of PCPS system.

Animals↗

Newly developed ventricular assist device with linear oscillatory actuator.

The goal of this study was to develop a new direct electromagnetic left ventricular assist device (DEM-LVAD) with a linear oscillatory actuator (LOA). The DEM-LVAD is a pulsatile pump with a pusher plate. The pusher plate is driven directly by the mover of the LOA. The LOA provides reciprocating motion without using any movement converter such as a roller screw or a hydraulic system. It consists of a stator with a single winding excitation coil and a mover with two permanent magnets. The simple structure of the LOA is based on fewer parts to bring about high reliability and smaller size. The mover moves back and forth when forward and backward electric current is supplied to the excitation coil. The pump housings have been designed using three-dimensional computer aided design software and fabricated with the aid of computer aided manufacturing technology. Monostrut valves (Bjork-Shiley #21) were used for the prototype. The DEM-LVAD dimension is 96 mm in diameter and 50 mm thick with a mass of 0.62 kg and a volume of 280 ml. An in vitro test (afterload 100 mm Hg; preload 10 mm Hg; input power 10 W) demonstrated more than 6 L/minute maximum output and 15% maximum efficiency at 130 beats per minute (bpm). Dynamic stroke volume ranged between 40 and 60 ml. The feasibility of the DEM-LVAD was confirmed.

Biophysical Phenomena↗

Arterial sound based noninvasive malrotation detection of rotary LVAD.

A number of advanced cardiovascular assist devices have been developed recently with the capability to prolong the life expectancy of patients with cardiac disease. To allow long-term use, it is necessary to assemble these devices using as few accessories as possible; however, a sensor for mechanical disorder detection is typically included to ensure mechanical reliability. Although a rotary left ventricular assist device (LVAD) has a simple mechanism, a malrotation caused by thrombogenesis can occur at any time. This situation could cause fatal damage to the cardiovascular circulation of the patient. In this study, we propose a simple, noninvasive method based on Korotkoff sounds, which would be able to detect the pressure-flow state during circulation supported by a rotary LVAD. Korotkoff sounds provide a means to noninvasively measure blood pressure in auscultation. We have found that the sounds are directly influenced by the pressure-flow state. We measured the arterial sound generated by an occluded brachial artery, as well as the Korotkoff sound generated during rotary LVAD circulation. To verify the effectiveness of the system, a circulatory simulator, rather than a human subject, was used. The arterial sound of several abnormal pressure-flow conditions was investigated. The simulator consists of a pulsatile blood pump, a compliance chamber, flow valves, a venous reservoir, and a rotary LVAD. Abnormal pressure-flow states are generated by simply changing the rotational speed of the rotary LVAD. We established the relationship between an abnormal pressure-flow state and the characteristics of the arterial sound, thus demonstrating that a malrotation of the rotary LVAD can be detected by the change of the arterial sound.

Aorta↗

Design and development of an artificial implantable lung using multiobjective genetic algorithm: evaluation of gas exchange performance.

In this study, we constructed an automatic optimization system applying the multiobjective genetic algorithm (MOGA) and developed an artificial implantable lung possessing antithrombogenicity and high gas exchange performance based upon fluid dynamics. This system consists of a three dimenstional CAD system, computational fluid dynamics software, and the multiobjective optimization tool modeFRONTIER (ESTECO CO., Trieste, Italy). The objectives were to minimize the volume of the region having a flow rate of less than 0.5 mm/s by assuming that thrombus formation occurs at this limit (ObjTF) and to minimize the standard deviation of the flow rate in the hollow fiber to obtain high gas exchange performance (ObjGEP). In optimization 1, the arc heights (six variables) and the distance between cross-sections (two variables) were used as design variables in the inflow and outflow portions. In optimization 2, the edges (two variables) of the inflow and outflow portions were optimized in the resulting designs from optimization 1. The optimum designs were manufactured using the rapid prototyping system and were examined by evaluating gas exchange performance (ObjGEP) in vitro. Gas exchange performance increased as the improvement ratio of ObjGEP became higher. For the optimum design (improvement ratio of 74.8% for ObjGEP), O2 transfer increased by an average of 18.4%, and CO2 transfer increased by an average of 40.5% when compared with the original design. The results suggest that this system was not only effective for reducing the time, cost, and labor of developing artificial organs but was also useful as a design and development support system for high performance artificial organs for transplantation.

Algorithms↗

New method for the detection of thrombus formation in cardiovascular devices: optical sensor evaluation in a flow chamber model.

We proposed a new method of detecting the onset of thrombus formation based upon the backscattered light intensity changes caused by the alteration of blood flow behavior in the cardiopulmonary devices. In an optical senor based upon the First Order Scattering theory, the relationship between the backscattered light intensity and hematocrit exhibited a monotonically decaying curve for the hematocrit level greater than 45%. To distinguish the effect either by thrombus formation or erythrocyte aggregation on the back-scattered light intensity with a flow chamber connected to a rabbit arterial-venous bypass model, we generated an oscillatory flow using a roller pump and analyzed the results using a Fast Fourier Transform (FFT) method. Our hypothesis was that the nonclotting blood flow would yield an unchanged fundamental spectral power density of the oscillation frequency generated by a roller pump, whereas the thrombus formation would attenuate its power. We measured the back-scattered light intensity in the flow chamber of high shear region and low shear region (n = 5). The blood flow rate was 40 ml/min with the roller pump. The activated clotting time and the hematocrit level were adjusted to 170 +/- 10 s with heparin and 35 +/- 5% with a phosphate buffered sulfate solution, respectively. As a result, the backscattered light intensity from the low shear rate region gradually diminished with time (p < 0.05; 0-5 minutes vs. more than 10-15 minutes), whereas that from the high shear rate region remained fairly constant. The experimental finding supported the hypothesis that the decrease of the backscattered light intensity and diminished spectral power density were caused by the aggregation or clotting erythrocytes. In conclusion, we found that the measurement of the average backscattered light intensity level together with FFT analysis of the backscattered light from the flowing blood is a valuable approach in detecting the onset of thrombus formation.

Animals↗

Development of an implantable oxygenator with cross-flow pump.

Thrombogenicity, a problem with long-term artificial lungs, is caused by blood-biomaterial interactions and is made worse by nonuniform flow, which also causes decreased gas exchange. To overcome these obstacles, we changed the inlet and added a uniform flow pump to our previous oxygenator design. Conventional membrane oxygenators have a (1/2)-inch port for the inlet of blood. These port structures make it difficult for the blood to flow uniformly in the oxygenator. In addition, the complex blood flow patterns that occur in the oxygenator, including turbulence and stagnation, lead to thrombogenicity. A cross-flow pump (CFP) can result in uniform blood flow to the inlet side of an oxygenator. In this study, we evaluated the usefulness of an integrated oxygenator with a fiber bundle porosity of 0.6 and a membrane surface area of 1.3 m2. The inlet part of the oxygenator is improved and better fits the outlet of the CFP. Each of the three models of the improved oxygenator has a different inlet taper angle. The computational fluid dynamics analysis showed that, compared with the original design, uniform flow of the integrated oxygenator improved by 88.8% at the hollow fiber membrane. With the integrated oxygenator, O2 transfer increased by an average of 20.8%, and CO2 transfer increased by an average of 35.5%. The results of our experiments suggest that the CFP, which produces a wide, uniform flow to the oxygenator, is effective in attaining high gas exchange performance.

Blood Flow Velocity↗

Flow vectorial analysis in an artificial implantable lung.

An artificial implantable lung would be a useful device to support patients awaiting lung transplantation. A suitable device must offer low resistance and adequate gas exchange, be impermeable to plasma, and nonthrombogenic. Although plasma permeability is an intrinsic quality of the materials, the other requirements are largely a function of device geometry, particularly as it relates to fluid dynamics. Using a CAD system and the requirements of a membrane surface area of 1.5 m2 and an inlet outlet port distance of 12 cm, we designed 10 models that varied in their other dimensions. Computational fluid dynamic (CFD) software was applied to the models to determine which minimized regions of low flow velocity. A prototype built to these specifications was used in an in vivo ovine experiment to verify the CFD predictions. The prototype was placed in parallel to the native pulmonary circulation (pulmonary artery to left atrium) for 120 minutes while the activated coagulation times were kept between 110 and 120 seconds and device flow was maintained between 1.5 and 2.5 L/min. Examination of the prototype confirmed a correlation between predicted areas of low flow and thrombus formation. Although nearly identical low flow velocity conditions exist at both the inlet and outlet ports, thrombus formation occurs only near the outlet port. This finding agrees with detailed vectorial analysis, which predicts a more complex flow pattern near the outlet port. Although near the inlet port flow vectors are nearly parallel, near the outlet port flow vectors collide. This area of flow collision corresponds to the area of thrombus formation in vivo. The addition of microflow vectorial analysis to flow velocity predictions allows for improved accuracy in predicting regions at risk of thrombosis in an artificial implantable lung.

Animals↗