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 degrees C and 28 degrees 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.

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 microm. 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.

Effect of wall hardness on hemolysis.

One of the major problems for artificial organs to develop and to improve is the reduction of hemolysis. The optimum designing of less hemolysis artificial organs is achieved through computational analysis and flow visualization techniques. However, it is impossible to know the quantitative relation between hemolysis and these analytic data. Thus, in vitro studies were performed to estimate these devices on hemolysis because there is no standard for designing these devices with less hemolysis. Therefore, it is essential to reveal the relation between blood flow behaviors and hemolysis. Previous studies reported that hemolysis was caused by a combination of physical factors. In particular, shear stress, pressure, and other fluid dynamical effects were shown to induce hemolysis. In another fluid dynamical experiment reported, the collision flow against the sanded wall was considered the most important factor that directly effected blood damage, which led to hemolysis. The blood flow impact of the collision against the wall effected serious damage to red blood cells. The objective of this study was to point out the relationship between physical force (pressure) in collision flow and hemolysis. In vitro tests using bovine blood and a circulation model that included a jet flow that collides against a wall were conducted. In these tests, we changed the material of the wall by replacing silicone rubber of various thicknesses. The thickness of the silicone rubber is inversely proportional to its hardness. The results show that the increasing rate of hemolysis was lower when the surface was coated by silicone rubber. In conclusion, we considered that it is possible to reduce hemolysis by adjusting the hardness of the material and contacted blood flow.

Engineering analysis of diamond-like carbon coated polymeric materials for biomedical applications.

Diamond-like carbon (DLC) films have received much attention recently owing to their properties, which are similar to diamond: hardness, thermal conductivity, corrosion resistance against chemicals, abrasion resistance, good biocompatibility, and uniform flat surface. Furthermore, DLC films can be deposited easily on many substrates for wide area coat at room temperature. DLC films were developed for applications as biomedical materials in blood contacting-devices (e.g., rotary blood pump) and showed good biocompatibility for these applications. In this study, we investigated the surface roughness by Atomic Force Microscopy (AFM) and Hi-vision camera, SEM for surface imaging. The DLC films were produced by radio frequency glow discharge plasma decomposed of hydrocarbon gas at room temperature and low pressure (53 Pa) on several kinds of polycarbonate substrates. For the evaluation of the relation between deposition rate and platelet adhesion that we investigated in a previous study, DLC films were deposited at the same methane pressure for several deposition times, and film thickness was investigated. In addition, the deposition rate of DLC films on polymeric substrates is similar to the deposition rate of those deposited on Si substrates. There were no significant differences in substrates' surface roughness that were coated by DLC films in different deposition rates (16-40 nm). The surface energy and the contact angle of the DLC films were investigated. The chemical bond of DLC films also was evaluated. The evaluation of surface properties by many methods and measurements and the relationship between the platelet adhesion and film thickness is discussed. Finally, the presented DLC films appear to be promising candidates for biomedical applications and merit investigation.

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.

Experimental study on hemolysis in centrifugal blood pumps: improvement of flow visualization method.

To evaluate rotary blood pumps, flow visualization is commonly applied to determine the flow patterns in a centrifugal blood pump, which have a relationship to its hemolytic performance. However, it is very troublesome to visualize the flow near the vanes due to the high rotational speed of the impeller. The rotational speed of the impeller in a centrifugal blood pump is usually several hundred revolutions per minute. In this study, we combined a high-speed video camera based imaging method and an optical system in which the image of the rotating impeller was kept stationary. In the optical system, a prism rotating at half the speed of the impeller reflected the image of the impeller. The resultant reflected image was observed by a high-speed video camera through a half mirror. With this optical setup, the image through the half mirror became stationary, and the path of a specific tracer particle could be traced for a longer duration. A longer duration of measurements and better quality of the obtained images were realized through this improvement. Movement of a specific tracer from the inlet portion to the outlet portion of the impeller could be examined using the developed method.

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.

Development of an intra blood circuit membrane oxygenator.

This paper deals with development of a prototype intra blood circuit membrane oxygenator. The shell of the oxygenator is made of a flexible polyvinyl chloride tube. The membrane surface area of the oxygenator is 0.3 m2. The total blood priming volume, including the oxygenator, was only 400-600 ml, which allows for extracorporeal circulation with no additional blood. Its potential was evaluated in in vitro experiments. The oxygen transfer rate was 140 ml/min, and the carbon dioxide transfer rate was 85 ml/min at a blood flow rate of 3 l/min. The device could make blood circuits simpler and more compact, with lower priming volumes. This indicates that it may prove useful for extracorporeal circulation.

Development of an all-in-one percutaneous cardiopulmonary support system.

This paper deals with development of an all-in-one percutaneous cardiopulmonary support (PCPS) system. In recent years, PCPS has been used for the treatment of acute myocardial infarction. A prototype of a compact all-in-one PCPS system was developed. The system contains a centrifugal pump and an extra-capillary flow-type membrane lung in one body. The system has a priming volume of 250 ml, which allows for PCPS with no additional blood. The in vitro tests and an ex vivo test were conducted. The system produces 1.6-5 L/min of flow in the experiments. The O2 transfer rate was 310 ml/min, and the CO2 transfer rate was 300 ml/min at a blood flow rate of 5 L/min. This device is compact, requires less priming volume than a standard system, and is easy-to-handle in the experiments. The system is considered applicable to percutaneous cardiopulmonary support.

Development of a compact extracorporeal membrane oxygenation (ECMO) system.

In recent years, extracorporeal membrane oxygenation (ECMO) has been used for treatment of neonates with respiratory failure. A prototype of a compact ECMO system for neonates was developed. A single-lumen catheter, inserted into the right atrium via a jugular vein, was used for withdrawal and infusion of blood through the catheter. An extracapillary flow hollow-fiber membrane lung made of microporous polypropylene has a total surface area of 0.6 m2. To prevent the increase of plasma free hemoglobin, the ratio of withdrawal/infusion is controlled by a microcomputer. The system is compact in size with a low priming volume (less than 90 ml), which allows for ECMO with no additional blood transfusions. Its potential application as a respiratory support system is evaluated in animal experiments. The total intermittent veno-veno bypass flow was 15-30 ml/min/kg. The O2 transfer rate was 20 ml/min and the CO2 transfer rate was 33 ml/min at a blood flow rate of 300 ml/min. The O2 and CO2 exchange with the ECMO system was efficient enough to eliminate the respiratory failure induced by mechanical ventilation. The increase in plasma free hemoglobin was only 4 mg/dl after 6 h of ECMO. The system was considered applicable to respiratory aid for neonates.