Katsuyuki Kuwana

Hemocompatibility Evaluation With Experimental and Computational Fluid Dynamic Analyses for a Monopivot Circulatory Assist Pump

The hemocompatibility of a newly developed monopivot circulatory assist pump was evaluated by the computational fluid dynamic (CFD) analyses with the particle tracking velocimetry measurement. Results were compared with those of the hemolysis test and in vitro antithrombogenic test to prevent hemolysis and thrombus formation inside the pump. The results of the CFD analysis and the particle tracking velocimetry had a good agreement with each other. The flow distributions by the CFD analysis indicated that the radial jet out of the impeller was adequately weak so that the wall shear stress was lower than 300 Pa on the volute casing wall. It corresponded with the hemolysis tests results, indicating that the hemolysis level was lower than that of the commercially available pump. However, the flow distributions also indicated that the pivot that was easy to stagnate was washed out, not only by the secondary flow through the back gap of the impeller, but also by the vortices generated by the secondary vanes. It corresponded with the in vitro antithrombogenic test results, indicating that thrombus formation could be removed only by redesigning the geometry of the secondary vanes.

Enhancement of Hemocompatibility of the MERA Monopivot Centrifugal Pump: Toward Medium-Term Use

The MERA monopivot centrifugal pump has been developed for use in open-heart surgery, circulatory support, and bridge-to-decision for up to 4 weeks. The pump has a closed-type, 50-mm diameter impeller with four straight paths. The impeller is supported by a monopivot bearing and is driven by a radial-flux magnet-coupling motor. Because flow visualization experiments have clarified sufficient pivot wash and stagnation at the sharp corner of the pivot support was suggested, sharp corners were removed in the design stage. The index of hemolysis of the pump operating at more than 200 mm Hg was found to be lower than that of a commercial pump. Four-week animal tests were then conducted two times; improvement of thrombus formation was seen in the female pivot through modification of female pivot geometry. Overall antithrombogenicity was also recorded. Finally, to assure mid-term use, an additional 4-week durability test revealed that the rate of the axial pivot wear was as small as 1.1 µm/day. The present in vitro and in vivo studies revealed that the MERA monopivot centrifugal pump has sufficient hemocompatibility and durability for up to 4 weeks.

Effect of Impeller Geometry on Lift‐Off Characteristics and Rotational Attitude in a Monopivot Centrifugal Blood Pump

The effect of the flow path geometry of the impeller on the lift-off and tilt of the rotational axis of the impeller against the hydrodynamic force was investigated in a centrifugal blood pump with an impeller supported by a single-contact pivot bearing. Four types of impeller were compared: the FR model with the flow path having both front and rear cutouts on the tip, the F model with the flow path having only a front cutout, the R model with only a rear cutout, and the N model with a straight flow path. First, the axial thrust and the movement about the pivot point, which was loaded on the surface of the impeller, were calculated using computational fluid dynamics (CFD) analysis. Next, the lift-off point and the tilt of the rotational axis of the impeller were measured experimentally. The CFD analysis showed that the axial thrust increased gently in the FR and R models as the flow rate increased, whereas it increased drastically in the F and N models. This difference in axial thrust was likely from the higher pressure caused by the smaller circumferential velocity in the gap between the top surface of the impeller and the casing in the FR and R models than in the F and N models, which was caused by the rear cutout. These results corresponded with the experimental results showing that the impellers lifted off in the F and N models as the flow rate increased, whereas it did not in the FR and R models. Conversely, the movement about the pivot point increased in the direction opposite the side with the pump outlet as the flow rate increased. However, the tilt of the rotational axis of the impeller, which oriented away from the pump outlet, was less than 0.8° in any model under any conditions, and was considered to negligibly affect the rotational attitude of the impeller. These results confirm that a rear cutout prevents lift-off of the impeller caused by a decrease in the axial thrust.

Flow uniformity in oxygenators with different outlet port design.

This study reports on evaluation of the optimum design of a blood outlet port structure for providing uniform flow by visualizing the blood flow in an extracapillary membrane oxygenator. We tested a cylindrical type extracapillary membrane oxygenator, HPO-20. The HPO-20 has a tangential blood outlet port and is thus referred to as “Tangential HPO-20.” We engineered “Vertical HPO-20” with a vertical blood outlet port by modifying the Tangential HPO-20. To visualize the blood-side flow, a total of 120 insulated copper-wire electrodes were placed in the “Tangential” and the Vertical HPO-20s. The test solution flow was visualized by the dimensionless fluid arrival time reaching each electrode. The test solution flow in the Tangential HPO-20 was not uniform, particularly at the outside blood channel. The flow was more uniform in the Vertical HPO-20. The blood flow in an extracapillary membrane oxygenator with a vertical blood outlet port is well distributed so that it produces more uniform blood flow than that with a tangential outlet port because of the small stagnation and reduced channeling.

Antithrombogenic Properties of a Monopivot Magnetic Suspension Centrifugal Pump for Circulatory Assist

The National Institute of Advanced Industrial Science and Technology (AIST) monopivot magnetic suspension centrifugal pump (MC105) was developed for open-heart surgery and several weeks of circulatory assist. The monopivot centrifugal pump has a closed impeller of 50 mm in diameter, supported by a single pivot bearing, and is driven through a magnetic coupling to widen the fluid gap. Design parameters such as pivot length and tongue radius were determined through flow visualization experiments, and the effectiveness was verified in preliminary animal experiments. The maximum overall pump efficiency reached 18%, and the normalized index of hemolysis tested with bovine blood was as low as 0.0013 g/100 L. Animal experiments with MC105 were conducted in sheep for 3, 15, 29, and 35 days in a configuration of left ventricle bypass. No thrombus was formed around the pivot bearing except when the pump speed was reduced by 20% of normal operational speed, which reduced the pump flow by 40% to avoid inlet suction. Subsequently, the antithrombogenic design was verified in animal experiments for 5 weeks at a minimum rotational speed of greater than 1500 rpm and a minimum pump flow greater than 1.0 L/min; no thrombus formation was observed under these conditions.

Stabilized sensing of heparin in whole blood using the ‘gate effect’ of heparin-imprinted polymer grafted onto an electrode

Abstract A real-time heparin monitor is required to optimize the dosage of heparin and its antidote, protamine sulfate, during extracorporeal circulation procedures. The gate effect of molecularly imprinted polymer (MIP) is a potential tool for the rapid and selective sensing of heparin. We here present a method to stabilize the measurement of heparin concentration in whole blood using an MIP-grafted electrode. An initiator of radical polymerization, the diethyldithiocarbamicbenzyl group, was introduced onto the surface of an indium-tin oxide (ITO) electrode. Heparin sodium, methacryloxethyltrimethoxysilane, and acrylamide were dissolved in water, and methylenebisacrylamide was dissolved in dimethylformamide. A mixture of the two solutions was introduced into the 50 μm gap between the surfaces of a quartz crystal plate and the treated ITO electrode. Ultraviolet light was irradiated onto the surface of the ITO to graft the copolymer of the monomers, then the ITO was washed with a 1 M sodium chloride aqueous solution to remove the heparin template and obtain the MIP-grafted electrode. Cyclic voltammetry was performed with the MIP-grafted electrode in physiological saline or bovine whole blood containing 0-8 units/ mL heparin and 5 mM ferrocyanide as a redox marker, and the relationship between the current intensity and the heparin concentration was analyzed. The current intensity decreased as the heparin concentration in either saline or whole blood increased, and the sensitivity of the electrode to heparin in blood was approximately 52% of its sensitivity to heparin in saline. The grafted-electrode was washed with a protease-containing detergent (Sterizyme® S, Maruishi Pharmaceutical) between measurements in blood. The heparin-sensitivity of the washed electrode in blood was 77% of that in saline. No sensitivity to chondroitin sulfate C was observed but sensitivity to low molecular weight heparin was demonstrated. We thus conclude that selective and stable sensing of heparin can be achieved using an electrode grafted with heparinimprinted polymer.

Properties of a monopivot centrifugal blood pump manufactured by 3D printing

An impeller the same geometry as the impeller of a commercial monopivot cardiopulmonary bypass pump was manufactured using 3D printing. The 3D-printed impeller was integrated into the pump casing of the commercially available pump to form a 3D-printed pump model. The surface roughness of the impeller, the hydraulic performance, the axial displacement of the rotating impeller, and the hemolytic properties of the 3D-printed model were measured and compared with those of the commercially available model. Although the surface roughness of the 3D-printed model was significantly larger than that of the commercially available model, the hydraulic performance of the two models almost coincided. The hemolysis level of the 3D-printed model roughly coincided with that of the commercially available model under low-pressure head conditions, but increased greatly under high-pressure head conditions, as a result of the narrow gap between the rotating impeller and the pump casing. The gap became narrow under high-pressure head conditions, because the axial thrust applied to the impeller increased with increasing impeller rotational speed. Moreover, the axial displacement of the rotating impeller was twice that of the commercially available model, confirming that the elastic deformation of the 3D-printed impeller was larger than that of the commercially available impeller. These results suggest that trial models manufactured by 3D printing can reproduce the hydraulic performance of the commercial product. However, both the surface roughness and the deformation of the trial models must be considered to precisely evaluate the hemolytic properties of the model.

Development of an Optical Detector of Thrombus Formation on the Pivot Bearing of a Rotary Blood Pump.

Continuous optical monitoring of thrombus formation in extracorporeal mechanical circulatory support (EMCS) devices will contribute to safe, long-term EMCS. A clinically applicable optical detector must be able to distinguish among the optical characteristics of oxygen saturation (SaO2 ), hematocrit (Hct), and thrombus formation. In vitro studies of spectral changes at wavelengths from 400 to 900 nm associated with SaO2 , Hct, and thrombus formed around the top pivot bearing of a Gyro C1E3 pump were conducted. Fresh porcine blood anticoagulated with sodium citrate was circulated in a mock circuit using the pump. The SaO2 , Hct, and anticoagulation activity were altered using an oxygenator, autologous plasma, and calcium chlorite injection, respectively. Light from a xenon lamp was guided by an incident fiber perpendicularly fixed on the top bearing. This light was scattered by blood pooled between the male and female pivots. The detection fiber was perpendicularly fixed against the incident fiber, and the side-scattered light was detected and guided to a spectrophotometer. As a result, light at two different wavelengths, 420 and 810 nm, was identified as suitable for thrombus detection because it was negligibly influenced by SaO2 and was able to detect the optical characteristics of fibrin. The light at these two wavelengths responded more quickly to thrombus formation than the inlet or outlet pressure, and flow rate change. The optical changes showed the changes in Hct around the top pivot bearing, which is caused by the reduction in density of fibrin-trapped red blood cells (RBCs) due to the RBCs being swept away by the surrounding blood flow. The proposed method was also able to detect fibrin production by extracting subtle differences in the optical characteristics between the Hct and thrombus formation.

Development of real-time and quantitative monitoring of thrombus formation in an extracorporeal centrifugal blood pump

We developed an optical detector of thrombus formed on the pivot bearing of an extracorporeal centrifugal blood pump (MERA HCF-MP23; Senko Medical Instrument Mfg. Co., Ltd., Tokyo, Japan) which is frequently used for long-term extracorporeal circulation support to bridge to an implantable artificial heart, which in turn is used for bridge to heart transplantation in Japan. In this study, we investigated the quantitative performance of the thrombus formation in acute animal experiments. A total of three experiments of extracorporeal left ventricular assist using Japanese specific pathogen-free pigs were conducted. The optical fibers were set in the pump driver unit. The incident light at nearinfrared wavelength aiming at the pivot bearing and the resulting scattered light were guided to respective fibers. The detected signal was analyzed to obtain thrombus formation level (TFL) calculated by a specially developed software. When the increase in TFL was confirmed, the pump was exchanged and the extracorporeal circulation was restarted. The number of pump exchanges were four times at each experiment so a total of twelve pumps were evaluated. 3-dimentional data surrounding the pivot bearing and the adhered thrombus was captured by a 3-dimantional surface measurement system to calculate the thrombus surface area (TSA) formed on the pivot bearing. As a result, the correlation coefficient between TFL and TSA was 0.878. The accuracy of TSA estimated by the optical detector was 3.6±2.3 mm2. This was small enough to not have the pump exchanged in clinical judgement. The developed detector would be useful for optimal anti-coagulation management.

Development of a real-time and quantitative thrombus sensor for an extracorporeal centrifugal blood pump by near-infrared light

We developed an optical thrombus sensor for a monopivot extracorporeal centrifugal blood pump. In this study, we investigated its quantitative performance for thrombus detection in acute animal experiments of left ventricular assist using the pump on pathogen-free pigs. Optical fibers were set in the driver unit of the pump. The incident light at the near-infrared wavelength of 810 nm was aimed at the pivot bearing, and the resulting scattered light was guided to the optical fibers. The detected signal was analyzed to obtain the thrombus formation level. As a result, real-time and quantitative monitoring of the thrombus surface area on the pivot bearing was achieved with an accuracy of 3.6 ± 2.3 mm2. In addition, the sensing method using the near-infrared light was not influenced by changes in the oxygen saturation and the hematocrit. It is expected that the developed sensor will be useful for optimal anticoagulation management for long-term extracorporeal circulation therapies.