Akio Funakubo

Improved blood compatibility of DLC coated polymeric material.

There is currently an increasing interest in the use of DLC (diamond like carbon) films in biomedical applications. These investigations making use of DLC in the biomedical area indicate its attractive properties. In this study, we succeeded in depositing DLC on polymer substrates and found the best conditions and method for this application. We evaluated the blood compatibility of polycarbonate substrates coated by DLC (PC-DLC) under different conditions by using epifluorescent video microscopy (EVM) combined with a parallel plate flow chamber. Segmented polyurethane (SPU), which has been used to fabricate medical devices including an artificial heart, and proven to have acceptable blood compatibility, was compared with polycarbonate substrates coated with DLC film. The EVM system measured platelet adhesion on the surface of the DLC, by using whole human blood containing Mepacrine labeled platelets perfuse at a wall shear rate of 100 s-1 at 1 min intervals for a period of 20 min. PC-DLC demonstrated that Tecoflex showed higher complement activation than PC-DLC. There were significant differences between the PC-DLC substrates. On the basis of these results, it is recommended for use as a coating material in implantable blood contacting devices such as artificial hearts, pacemakers, and other devices. This DLC seems to be a promising candidate for biomaterials applications and merits further investigation.

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.

An investigation of blood flow behavior and hemolysis in artificial organs

In our previous study, in vitro hemolysis tests showed that collision flow against wall roughness had an effect on hemolysis when the flow velocity was more than 3 m/s and surface roughness was more than Ra = 1.54 &mgr;m. However, the specific portion of the flow on the wall that induced hemolysis was not clarified.Therefore, the purpose of this study was to present the relationship between flow behavior and hemolysis by means of in vitro tests and computational fluid dynamics (CFD) analysis. We investigated the relationship between the location of surface roughness and hemolysis. In CFD, we investigated the flow behavior on the wall. The highest rate of hemolysis was observed in a region around the center of the surface roughness on the bottom plate. On CFD analyses, the flow behavior included the highest wall shear stress (304 Pa) and the highest flow acceleration (2.8 m/s2) around the center of the bottom plate. Therefore, it is concluded that the causes of hemolysis during collision flow depend upon wall shear stress and flow acceleration.

Influence of static pressure and shear rate on hemolysis of red blood cells.

The purpose of this study was to investigate the effect of multiple mechanical forces in hemolysis. Specific attention is focused on the effects of shear and pressure. An experimental apparatus consisting of a rotational viscometer, compression chamber, and heat exchanger was prepared to apply multiple mechanical forces to a blood sample. The rotational viscometer, in which bovine blood was subjected to shear rates of 0, 500, 1,000, and 1,500 s-1, was set in the compression chamber and pressurized with an air compressor at 0, 200, 400, and 600 mm Hg. The blood temperature was maintained at 21°C and 28°C. Free hemoglobin at 600 mm Hg was observed to be approximately four times higher than at 0 mm Hg for a shear rate of 1,500 s-1 (p < 0.05). The results suggest that the increase in hemolysis is strongly related to pressure when high shear rates are applied to the erythrocytes. The data acquired in this study will be helpful in the development of artificial organs, where it will facilitate the prediction of hemolysis in flow dynamics analysis, flow visualization, and computational fluid dynamics.

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 ½-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.

Fabrication of small-diameter polyurethane vascular grafts with microporous structure

Abstract Microporous polyurethane vascular grafts with a diameter of 3 mm were fabricated by a spray phase inversion technique (SPIT). The microporous structure and hydraulic permeability of the grafts were regulated by changing the fabrication conditions. The maximum hydraulic permeability of 26 ml/min/cm2, which was obtained in this series of grafts, satisfied the target value of about 10–40 ml/min/cm2, which our previous studies suggested would lead to satisfactory graft patency. Further investigation is, however, needed to optimize the microporous structure and hydraulic permeability of the grafts.

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.

Development of a Cooling Unit for the Emergency Treatment of Head Injury

In the emergency medicine, icing has been used as first aid treatment to the patient of head injury. By reducing cerebral temperature, prevent the generation of secondary brain damage such as discharge of neurotransmitter, and the reaction of free radical. The average boarding time is 15 minutes in an ambulance, however by icing treatment quantitative temperature control is very difficult as it always occur insufficient cooling or excessive cooling. Icing for 30 minutes or more has the danger of frostbite. As an other problem homeostasis, which happens when icing is stopped is suggested. Therefore, the issue is how and quickly cools an injured head without generating any secondary damage. In this study, we have developed a cooling unit using Peltier device. A Peltier is a thermo-electric semiconductor device that generates heat surface on one side and cool surface on the other, when passes electrical current. By adjusting passing current, heat controlling can be made easily. Other advantages are small size, light weight, vibration and noise free. A Peltier device is also harmless to the environment as it does not use any material like Freon. We have fabricated a helmet type unit that can cool a head from the surface. As a fundamental evaluation we have investigated electrical properties as well as cooling ability, and response time. The result of our investigation showed a uniform electrical properties without getting any interference of ambient temperature while use water as heat radiation coolant. An 80 watt device (39.6mm X 39.6mm X 3.94mm) is found sufficient to cool a helmet around 15 degree C. Only 30 second is necessary to reach the expected temperature when direct-current stabilization power supply of 11V-15V was used.

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.

DEVELOPMENT OF A MEMBRANE OXYGENATOR FOR ECMO USING A NOVEL FINE SILICONE HOLLOW FIBER

One of the limitations of conventional silicone hollow fiber oxygenators compared with microporous membrane oxygenators is poor gas permeability. However, the silicone hollow fiber is free from plasma leakage, which is the major life limiting factor of the microporous membrane oxygenator. It has been difficult to fabricate a fine, thin hollow fiber for reduction of resistance to gas permeability because of the poor mechanical strength of conventional silicone materials. The authors developed a novel silicone material with sufficient mechanical strength, and a fine silicone hollow fiber with a diameter of 30 microns and wall thickness of 50 microns, which is approximately half that of a conventional silicone hollow fiber. Using this newly developed silicone hollow fiber, the authors developed a compact extracapillary flow membrane oxygenator. The oxygenator consists of fine silicone hollow fibers inserted in a housing made of polycarbonate. The housing is a cylindrical case, 20 cm long and 55 mm in inside diameter. The hollow fibers are cross-wound. The surface area of the membrane is 2.0 m2, and priming volume is 230 ml. Gas transfer performance of the newly developed oxygenator was evaluated by in vitro experiments. Oxygen and carbon dioxide transfer rates were 195 ml/min and 165 ml/min, at a blood flow rate 3 L/min. The novel silicone membrane oxygenator developed in this study can be used for extended duration in such applications as extracorporeal membrane oxygenation.