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Biomedical subjects

S Takatani

Publications and source records attributed to S Takatani.

At least 19 recordsLinked to original sources

Effect of hemolysis on oxygen and hematocrit measurements by near infrared reflectance spectroscopy.

A short review of the principles of near infrared reflectance spectroscopy (NIRS) in whole blood is followed by a discussion on the influence of hemolysis. The increase of free plasmahemoglobin (PHb) has a strong influence on the continuous measurement of hematocrit and oxygen saturation (O(2)S) by NIRS. In view of the relative stability of hematocrit values in vivo this effect may be used to detect a change of the hemolysis rate induced by blood pumps in case of malfunction. The aim of this study is, therefore, the assessment of the hemolysis rate within an in vitro mock loop comprising a rotary blood pump by means of NIRS at constant hematocrit levels compared to the photometric reference method. Reflected light is measured by an integrated optical sensor working at three wavelengths (660 nm, 730 nm, and 830 nm). The experimental results demonstrate that the increase of free hemoglobin in plasma due to mechanical pumping leads to a decrease of detected reflected light at all three wavelengths. Influencing parameters such as adhering proteins on the sensor surface and the blood flow rate are briefly discussed. Finally, the possibility of using NIRS sensors for detecting malfunctions of blood pumps in vitro and in vivo is discussed, together with the option of using these sensors for supervision of long-term implantable pumps.

Biosensing Techniques↗

Control strategy for rotary blood pumps.

The control strategy for ventricular support with a centrifugal blood pump was examined in this study. The control parameter was the pump rpm that determines pump flow. Optimum control of pump rpm that reflects the body's demand is important for long-term, effective, and safe circulatory support. Moreover, continuous, reliable monitoring of ventricular function will help successfully wean the patients from the ventricular assist device (VAD). The control strategy in this study includes determination of the target pump rpm that can provide the flow required by the body, fine-rpm-tuning to minimize deleterious effects such as suction in the ventricle, and assessment of ventricular function for successful weaning from VADs. To determine the target pump rpm, we proposed to use the relation between the native heart rate and cardiac output, and the relation between the pump rpm and centrifugal pump output. For fine-tuning of the pump rpm, the motor current waveform was used. We computed the power spectral density of the motor current waveform and calculated the ratio of the fundamental to the higher order components. When this ratio was larger than approximately 0.2, we assumed there would be a suction effect in the ventricle. As for assessment of ventricular function, we used the amplitude of the motor current waveform. The control system implemented using a DSP functioned properly in the mock circulatory loop as well as in acute animal experiments. The motor current also showed a good correlation with the ventricular pressure in acute animal experiments.

Animals↗

Design and evaluation of a single-pivot supported centrifugal blood pump.

In order to develop a centrifugal blood pump that meets the requirements of a long-term, implantable circulatory support device, in this study a single-pivot bearing supported centrifugal blood pump was designed to evaluate its basic performance. The single-pivot structure consisted of a ceramic ball male pivot mounted on the bottom surface of the impeller and a polyethylene female pivot incorporated in the bottom pump casing. The follower magnet mounted inside the impeller was magnetically coupled to the driver magnet mounted on the shaft of the direct current brushless motor. As the motor rotated, the impeller rotated supported entirely by a single-pivot bearing system. The static pump performance obtained in the mock circulatory loop revealed an acceptable performance as a left ventricular assist device in terms of flow and head pressure. The pump flow of 5 L/min against the head pressure of 100 mm Hg was obtained at rotational speeds of 2,000 to 2,200 rpm. The maximum pump flow was 9 L/min with 2,200 rpm. The maximum electrical-to-hydraulic power conversion efficiency was around 14% at pump flows of 4 to 5 L/min. The stability of the impeller was demonstrated at the pump rpm higher than 1,400 with a single-pivot bearing without an additional support at its top. The single-pivot supported centrifugal pump can provide adequate flow and pressure as a ventricular assist device, but its mechanical stability and hemolytic as well as thrombotic performances must be tested prior to clinical use.

Equipment Design↗

Estimation of left ventricular recovery level based on the motor current waveform analysis on circulatory support with centrifugal blood pump.

In a mock circulatory loop simulating the left heart bypass using a centrifugal blood pump, analysis of the motor current waveform of the centrifugal pump was performed to derive a useful parameter to evaluate the status of ventricular function. The relationship between the peak, amplitude, and the peak of the fundamental frequency of the power spectral density of the periodic motor current waveform (MCpsdP) that reflected the pulsatile ventricular pressure, and the peak of the left ventricular pressure (LVP) was examined. Although both peak and amplitude of the motor current waveform showed an excellent correlation with the peak LVP, they failed to predict the opening of the aortic valve. The MCpsdP that corresponds to the frequency of the heart rate showed an excellent correlation with the peak LVP throughout the LVP levels, but the slope between them changed with the opening of the aortic valve. Thus, it is possible to follow the change in the LVP and detect even the opening of the aortic valve, and, hence, the recovery of the left ventricle. However, the slope of the linear regression equation varied, depending on the pump speed. This result implies that the MCpsdP can be possibly used to follow the change of ventricular function during circulatory assistance with a centrifugal blood pump as well as to control the pump speed in response to varying ventricular function.

Centrifugation↗

Simulation of the BP-80 blood pump.

In this study, computational fluid dynamics (CFD) analysis was applied to investigate the flow within a commercially available Biopump, BP-80 (Medtronic, Minneapolis, MN, U.S.A.). The Biopump was selected because, for this purpose, a great number of experimental hemolysis data is available. The process of geometry representation and grid generation was focused on, due to its high impact on the numerical results. This process incorporated the use of three commercially available software packages for three-dimensional computer-aided design (3D-CAD), grid generation, and solving, respectively. For the purpose of validation, the head/flow characteristics of the pump were experimentally obtained and compared to the computed data. The results showed a rough agreement between CFD data and experimental data. Further investigations should cover detailed shear stress analyses and computation of other hemolysis-related quantities.

Computer Simulation↗

A multi-element carotid tonometry sensor for non-invasive measurement of pulse wave velocity.

A new pulse wave velocity (PWV) measurement system has been developed using a novel multi-element tonometry carotid sensor combined with a heart sound sensor. In this system, PWV is derived from the time lag between the second heart sound (S2) obtained from the heart sound sensor and the dicrotic notch in the carotid pulse waveform, and the physical distance between the heart and the neck. We assessed the accuracy of the system in an animal model. The study was divided into two groups: in Group I the tonometric sensor was directly applied to the exposed artery, while in Group II the sensor was applied over the skin and subcutaneous tissues covering the artery. To examine the fidelity of the dicrotic notch, the ejection time with the tonometry sensor was compared with that obtained from the intra-arterial catheter measurement. The correlation coefficients between them were 0.99 in both groups. The bias error (defined as the mean of the differences between the tonometry and the catheter measurements) +/-2SD was 0.13+/-1.45 ms in Group I and 0.16+/-1.64 ms in Group II. These results confirmed that the arterial wall, subcutaneous tissue and skin did not affect the accuracy of the dicrotic notch fidelity. The reproducibility of the system was assessed in 18 human subjects. The 2SD of intraobserver and interobserver reproducibility of the S2-carotid PWV measurement were 0.54 and 0.38 m/s, respectively, demonstrating high reproducibility of the measurement. From a clinical point of view, the S2-carotid PWV was compared with the aortic PWV. The bias error +/-2SD between the two measurements was -0.14+/-3.24 m/s with the correlation coefficient being 0.73. Although the S2-carotid PWV may not replace the aortic PWV directly, we believe that the S2-carotid PWV with the new system may become a new clinical parameter for early detection of cardiovascular disorders such as cerebrovascular diseases.

Adult↗

Development of a compact, sealless, tripod supported, magnetically driven centrifugal blood pump.

In this study, a tripod supported sealless centrifugal blood pump was designed and fabricated for implantable application using a specially designed DC brushless motor. The tripod structure consists of 3 ceramic balls mounted at the bottom surface of the impeller moving in a polyethylene groove incorporated at the bottom pump casing. The follower magnet inside the impeller is coupled to the driver magnet of the motor outside the bottom pump casing, thus allowing the impeller to slide-rotate in the polyethylene groove as the motor turns. The pump driver has a weight of 230 g and a diameter of 60 mm. The acrylic pump housing has a weight of 220 g with the priming volume of 25 ml. At the pump rpm of 1,000 to 2,200, the generated head pressure ranged from 30 to 150 mm Hg with the maximum system efficiency being 12%. When the prototype pump was used in the pulsatile mock loop to assist the ventricle from its apex to the aorta, a strong correlation was obtained between the motor current and bypass flow waveforms. The waveform deformation index (WDI), defined as the ratio of the fundamental to the higher order harmonics of the motor current power spectral density, was computed to possibly detect the suction occurring inside the ventricle due to the prototype centrifugal pump. When the WDI was kept under the value of 0.20 by adjusting the motor rpm, it was successful in suppressing the suction due to the centrifugal pump in the ventricle. The prototype sealless, centrifugal pump together with the control method based on the motor current waveform analysis may offer an intermediate support of the failing left or right ventricle bridging to heart transplantation.

Centrifugation↗

Cardiac prosthesis as an advanced surgical therapy for end-stage cardiac patients: current status and future perspectives.

This paper reviews the current status and future perspectives of the artificial heart research that was started in 1957 by Akutsu and Kolff. During the 1960's, although not much progress was made in increasing animal survival time with artificial hearts, clinical applications were already made for both a ventricular assist device in 1962 and total artificial heart (TAH) in 1969 followed by a second TAH application in 1981. Both TAH applications were done as bridges to heart transplantation. Meanwhile, the animal survival time improved during the 1970's because of the availability of better biomaterials, better understanding of the circulatory system, and improvement in surgical techniques. Continuous flow pumps were also investigated during the 1970's, which demonstrated feasibility for chronically supporting circulation in healthy animals. Four permanent cases of TAH application were done early 1980's for patients who could not be the candidates for heart transplantation. Although the patients were tethered to the external drive-console, one of them survived for nearly two years. Complications due to thromboembolism and infection were the major causes of death in these patients. The patients' quality of life was questionable and the permanent application of the TAH was then stopped to make improvements in the system in terms of implantability and biocompatibility. During the 1980's, efforts were then switcthed to development of totally implantable VAD and TAH systems, which led to the first discharge of a VAD patient from the hospital in 1992. In the early 1990's, implantable electric VADs, Novacor and ThermoCardio System (TCI), became available to support the circulation of end-stage cardiac patients until a donor heart could be found. The transplantation rate of the VAD patients ranged around 70% with the average waiting time of 80 to 100 days. The number of patients transplanted with VADs are more than 5000 and those with the pneumatic TAH exceed 200. Because of the larger size, requirement of heart valves, and complicated control mechanism of the pulsatile VADs, continuous flow pumps have been gaining popularity among clinicians. The clinical applications of the continuous flow devices have just begun, demonstrating remarkable performance in bridging to heart transplantation. In, the 21st century, we will see prevalent clinical applications of various circulatory support devices from pulsatile VAD, pulsatile TAH to continuous flow VAD. These devices will be combined with genetic treatment to re-generate the myocardium and recover the failing heart. Complete recovery of the myocardium may become possible through therapy combining circulatory assist devices and biotechnology.

Animals↗

Evaluation of an implantable motor-driven left ventricular assist device.

A console based implantable motor-driven left ventricular assist device (LVAD) was developed and tested. Ten sheep weighing 42-73 kg (mean, 54.4 kg) were used as the experimental animals. Four animals survived 5-12 h (mean, 9.5 h). The mean pump flow was 1.63 L/min, ranging from 0.8 to 2.5 L/min. The cause of termination was respiratory failure in 3 animals, bleeding in 2, ventricular fibrillation in 2, vent tube obstruction in 1, thrombus formation in 1, and mechanical failure of the driving console in 1. Following the in vivo studies, the computer regulated controller was tested in a mock circulatory system. The LVAD provided 5.34 L/min of maximum output against a mean afterload of 80 mm Hg with a filling pressure of 15 mm Hg when the pump rate was 80 bpm in the fixed rate mode. With an increase in the pump afterload from 80 to 140 mm Hg, the total system efficiency varied from 7.81 to 8.34% when the pump preload was 15 mm Hg. An ultracompact, completely implantable electromechanical VAD has been under development. This device should fit in a 60 kg adult. As the next step, we are preparing to implant this ultracompact implantable VAD with an electronic controller in an animal model with better results being expected.

Animals↗

Ex vivo evaluation of a roller screw linear muscle actuator for an implantable ventricular assist device using trained and untrained latissimus dorsi muscles.

In this study, the power output and contraction length of trained and untrained canine latissimus dorsi (LD) muscles were measured using a roller screw linear muscle actuator (RSLMA). The RSLMA consisted of a roller screw-nut assembly and translation unit to convert the linear pull force of the muscle into an axial displacement of the roller screw. When a cable wound around a spool attached at each end of the roller screw nut was pulled in either direction, the nut was rotated which in turn advanced the roller screw in the axial direction. Under anesthesia, a Telectronics myostimulator (Model 7220) was implanted in the subcutaneous area of the canine left thoracic region with its bipolar intramuscular leads implanted around the thoracodorsal nerve and the distal muscle. A total of 6 dogs went through the myostimulator implantation, followed with 8 weeks of continuous stimulation. After completion of the training, the contraction lengths of the trained and untrained LD muscles were measured, and they were 4.25 and 5.5 cm, respectively, while the instantaneous power outputs were 4.24 and 8 W, respectively. Although untrained muscles could provide much higher instantaneous power immediately following the start of the stimulation, it diminished rapidly. On the other hand, the trained muscle showed prolonged fatigue resistance. The thoracolumbar and humeral approaches in attaching the actuator cable did not show a difference with respect to muscle power output. The trained LD muscle can provide sufficient power in the range of 3-4 W to drive a left heart assist device, but its long-term evaluation awaits development of an appropriate muscle-device interface for chronic in vivo application.

Animals↗

Ultracompact, completely implantable permanent use electromechanical ventricular assist device and total artificial heart.

An ultracompact, completely implantable permanent use electromechanical ventricular assist device (VAD) and total artificial heart (TAH) intended for 50-60 kg size patients have been developed. The TAH and VAD share a miniature electromechanical actuator that comprises a DC brushless motor and a planetary roller screw. The rotational force of the motor is converted into the rectilinear force of the roller screw to actuate the blood pump. The TAH is a one piece design with left and right pusher plate type blood pumps sandwiching an electromechanical actuator. The VAD is one half of the TAH with the same actuator but a different pump housing and a backplate. The blood contacting surfaces, including those of the flexing diaphragm and pump housing, of both the VAD and TAH were made of biocompatible polyurethane. The diameter, thickness, volume, and weight of the VAD are 90 mm, 56 mm, 285 cc, and 380 g, respectively, while those of the TAH are 90 mm, 73 mm, 400 cc, and 440 g, respectively. The design stroke volume of both the VAD and TAH is 60 cc with the stroke length being 12 mm. The stroke length and motor speed are controlled solely based on the commutation signals of the motor. An in vitro study revealed that a maximum pump flow of 7.5 L/min can be obtained with a pump rate of 140 bpm against a mean afterload of 100 mm Hg. The power requirement ranged from 4 to 6 W to deliver a 4-5 L/min flow against a 100 mm Hg afterload with the electrical-to-hydraulic efficiency being 19-20%. Our VAD and TAH are the smallest of the currently available devices and suitable for bridge to transplant application as well as for permanent circulatory support of 50-60 kg size patients.

Evaluation Studies as Topic↗

Measurement of blood hematocrit inside the magnetically suspended centrifugal pump using an optical technique: application to assessment of pump flow.

To measure blood hematocrit inside the magnetically suspended centrifugal pump, we have performed both forward and backward light scattering measurements using a specially designed optical cell. In the forward scattering measurement, an optical fiber was used to guide the near infrared light at 780 nm into a 250 microns gap region, and the light that forward scattered toward a detector fiber was measured using a phototransistor. The light intensity decreased exponentially with an increase in the hematocrit to around 20%. The forward scattering method suffered from sensitivity at the hematocrit levels around 25-45% due to the diffusion effect. By making the optical path length larger than several millimeters, the sensitivity of the forward scattering method in terms of hematocrit change can be improved. In the back scattering method, however, better sensitivity in terms of hematocrit change from 0-50% was obtained. By making the optical fiber separation distance less than 1 mm, the system will measure the first order back scattering from the shallow layer while, by making the fiber separation distance larger than several millimeters, the system will primarily measure the diffuse reflectance from the deeper layer. Both approaches will yield sensitive optical intensity change in terms of the physiological hematocrit range.

Algorithms↗

Detection of suction and regurgitation of the implantable centrifugal pump based on the motor current waveform analysis and its application to optimization of pump flow.

In this study, a detection algorithm for suction and regurgitation of the centrifugal pump during left heart bypass without relying on external flow or pressure sensors was developed and evaluated in acute studies using adult goats. The detection scheme relies on power spectral density (PSD) analysis of the motor current waveform through which the waveform deformation index (WDI) is obtained. This index is defined as the ratio of the fundamental component of the PSD to the higher PSD components, and its value increases with the deformation of the basic waveform. By assuming that the undistorted motor current waveform can be represented by a pure sine waveform, we theoretically synthesized various waveforms which have different second harmonic components. We were able to synthesize the waveform whose shape was close to the distorted motor current waveform under varying suction levels obtained in a mock loop study. From this study, we came to the conclusion that the WDI value of 0.2 can serve as a threshold level in deciding the suction and regurgitation speeds (rpm) during left heart bypass. In the study using adult goats, we were successful in minimizing both regurgitation and suction when the centrifugal pump speed was adjusted based on the WDI algorithm. The resultant bypass flow ranged from 1.5 to 2.0 L/min which was around 60% of the total flow. Further study is underway to evaluate the applicability of the WDI method in optimizing bypass pump flow.

Algorithms↗

Rapid adhesion and spread of non-adherent colon cancer Colo201 cells induced by the protein kinase inhibitors, K252a and KT5720 and suppression of the adhesion by the immunosuppressants FK506 and cyclosporin A.

We examined alterations in cell morphology and expression of adhesion molecules in response to a general protein kinase inhibitor K252a treatment of non-adherent colon adenocarcinoma Colo201 cells. K252a induced rapid cell adhesion and spreading with concomitant formation of actin stress fibers. A protein kinase A inhibitor KT5720 also induced cell adhesion, but the rate of spread was slower than that seen with K252a. These adhesions were mediated by integrin molecules since cell adhesion required Mg2+, Mn2+ or Ca2+, and was inhibited by monoclonal antibodies for integrins alpha2 and beta1. Indirect immunofluorescence microscopic observations revealed that integrin alpha2 and beta1 molecules in K252a-treated cells were concentrated at sites of focal adhesion, but expressions of integrin molecules were not modulated. Tyrosine phosphorylation of focal adhesion kinase (FAK) and paxillin increased during K252a- or KT5720-induced cell adhesion. Immunosuppressants FK506 and cyclosporin A suppressed the K252a-induced cell adhesion and abolished tyrosine phosphorylation of cellular proteins including FAK and paxillin. Furthermore, W7 and calmidazolium, inhibitors of calmodulin, also inhibited the cell adhesion. Based on findings that FK506 and cyclosporin A are inhibitors of the calcium calmodulin-dependent protein phosphatase, calcineurin, this phosphatase may regulate integrin-dependent cell adhesion and spread of Colo201 cells. This Colo201 cell model provides a pertinent system for studying molecules involved in signal transduction pathways and can shed light on mechanisms of metastasis and invasion of colon carcinoma cells.

Adenocarcinoma↗

Control of centrifugal blood pump based on the motor current.

In this study, centrifugal pump performance was examined in a mock circulatory loop to derive an automatic pump rotational speed (rpm) control method. The pivot bearing supported sealless centrifugal pump was placed in the left ventricular apex to aorta bypass mode. The pneumatic pulsatile ventricle was used to simulate the natural ventricle. To simulate the suction effect in the ventricle, a collapsible rubber tube was placed in the inflow port of the centrifugal pump in series with the apex of the simulated ventricle. Experimentally, the centrifugal pump speed (rpm) was gradually increased to simulate the suction effect. The pump flow through the centrifugal pump measured by an electromagnetic flowmeter, the aortic pressure, and the motor current were continuously digitized at 100 Hz and stored in a personal computer. The analysis of the cross-spectral density between the pump flow and motor current waveforms revealed that 2 waveforms were highly correlated at the frequency range between 0 and 4 Hz, with the coherence and phase angles being close to 1.0 and 0 degree, respectively. The fast Fourier transform analysis of the motor current indicated that the second harmonic component of the motor current power density increased with the occurrence of the suction effect in the circuit. The ratio of the fundamental to the second harmonic component decreased less than 1.3 as the suction effect developed in the circuit. It is possible to detect and prevent the suction effect of the centrifugal blood pump in the natural ventricle through analysis of the motor current waveform.

Algorithms↗

Ex vivo phase 1 evaluation of the DeBakey/NASA axial flow ventricular assist device.

A small ventricular assist device intended for long-term implantation has been developed by a cooperative effort between the Baylor College of Medicine and the NASA/Johnson Space Center. To date, in vitro tests have been performed to address hemolysis and pump performance issues. In this Phase 1 study, we assessed the durability and atraumatic features aiming for 2 day implantation. Eight pumps were implanted in 2 calves as paracorporeal left ventricular assist devices. The pump running times ranged from 18 to 203 h (78.1 +/- 23.7; mean +/- SEM). All the pump implantations were terminated because of thrombus formation. Plasma-free hemoglobin levels were below 13.7 mg/dl, except for 1 case complicated by inflow cannula obstruction. The pump speed was maintained between 10,100 and 11,400 rpm. Pump outputs were from 3.6 to 5.2 L/min. The electrical power required by the system ranged between 9 and 12 W. Clinically there was no detectable organ dysfunction noted, and postmortem evaluation demonstrated no pump related adverse effects in either calf except for small kidney infarctions. Thrombus deposition was observed mainly at the hub portions and the flow straightener.

Alanine Transaminase↗

The effect of the impeller-driver magnetic coupling distance on hemolysis in a compact centrifugal pump.

Blood trauma is one of the important performance parameters of centrifugal pumps. To investigate the blood trauma induced by these pumps, in vitro hemolysis tests have become an important procedure and are increasingly used for pump development and comparisons. The Baylor compact eccentric inlet port (CIE) centrifugal blood pump was developed as a long-term centrifugal ventricular assist device (VAD) as well as a cardiopulmonary bypass pump (CPB). The Baylor CIE pump incorporates a seal-less design with a blood stagnation-free structure. This pump can provide flows of 5 L/min against 350 mm Hg of total pressure head at 2,600 revolutions per minute. The pump impeller is magnetically coupled to the driver magnet in a seal-less manner. The latest hemolysis study revealed that hemolysis may be affected by the gap distance between the driver and the impeller magnet. The purpose of this study was to verify the effect of the magnetic coupling distance on the normalized index of hemolysis (NIH) with the CIE model and to obtain an optimal gap distance. The NIH value was clearly decreased by alteration of the magnetic coupling distance from 7.7 to 9.7 mm in CPB and left ventricular assist device (LVAD) conditions. The NIH, when using the pump as an LVAD condition, was reduced to a level of 0.0056 from 0.095 when the magnetic coupling distance was extended. The same results were also obtained when the pumps were used in a CPB condition. The magnetic coupling distance is an important factor for the CIE model in terms of hemolysis. Different coupling forces effect the bearings and impeller stability. These results suggest that an optimal driving condition with a proper magnetic coupling and an optimal force between the impeller and driver is necessary to develop an atraumatic centrifugal pump.

Blood Flow Velocity↗