Artificial endocrine pancreas.
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Animals↗
Biomedical subjects
Y Nosé
Publications and source records attributed to Y Nosé.
Implantable total artificial heart developed by Abiomed gets FDA approval for clinical trials.
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Clinical Trials as Topic↗
Development of a new hollow fiber silicone membrane oxygenator: in vitro study.
An experimental silicone hollow fiber membrane oxygenator for long-term extracorporeal membrane oxygenation (ECMO) was developed in our laboratory using an ultrathin silicone hollow fiber. However, the marginal gas transfer performances and a high-pressure drop in some cases were demonstrated in the initial models. In order to improve performance the following features were incorporated in the most recent oxygenator model: increasing the fiber length and total surface area, decreasing the packing density, and modifying the flow distributor. The aim of this study was to evaluate the gas transfer performances and biocompatibility of this newly improved model with in vitro experiments. According to the established method in our laboratory, in vitro studies were performed using fresh bovine blood. Gas transfer performance tests were performed at a blood flow rate of 0.5 to 6 L/min and a V/Q ratio (V = gas flow rate, Q = blood flow rate) of 2 and 3. Hemolysis tests were performed at a blood flow rate of 1 and 5 L/min. Blood pressure drop was also measured. At a blood flow rate of 1 L/min and V/Q = 3, the O2 and CO2 gas transfer rates were 72.45 +/- 1.24 and 39.87 +/- 2.92 ml/min, respectively. At a blood flow rate of 2 L/min and V/Q = 3, the O2 and CO2 gas transfer rates were 128.83 +/- 1.09 and 47.49 +/- 5.11 ml/min. Clearly, these data were superior to those obtained with previous models. As for the pressure drop and hemolytic performance, remarkable improvements were also demonstrated. These data indicate that this newly improved oxygenator is superior to the previous model and may be clinically acceptable for long-term ECMO application.
Animals↗
Gas transfer performance of a hollow fiber silicone membrane oxygenator: ex vivo study.
Based on the results of in vitro studies of many experimental models, a silicone hollow fiber membrane oxygenator for pediatric cardiopulmonary bypass (CPB) and extracorporeal membrane oxygenation (ECMO) was developed using an ultrathin silicone hollow fiber with a 300 microm outer diameter and a wall thickness of 50 microm. In this study, we evaluated the gas transfer performance of this oxygenator simulating pediatric CPB and ECMO conditions. Two ex vivo studies in a pediatric CPB condition for 6 h and 5 ex vivo studies in an ECMO condition for 1 week were performed with venoarterial bypass using healthy calves. At a blood flow rate of 2 L/min and V/Q = 4 (V = gas flow rate, Q = blood flow rate) (pediatric CPB condition), the O2 and CO2 gas transfer rates were maintained at 97.44 +/- 8.88 (mean +/- SD) and 43.59 +/- 15.75 ml/min/m2, respectively. At a blood flow rate of 1 L/min and V/Q = 4 (ECMO condition), the O2 and CO2 gas transfer rates were maintained at 56.15 +/- 8.49 and 42.47 +/- 9.22 ml/min/m2, respectively. These data suggest that this preclinical silicone membrane hollow fiber oxygenator may be acceptable for both pediatric CPB and long-term ECMO use.
Animals↗
Hemodynamic exercise response in calves with an implantable biventricular centrifugal blood pump.
An implantable biventricular assist device (BVAD) has been developed at Baylor College of Medicine using 2 centrifugal blood pumps. The aim of this study was to investigate the exercise-reflex response during nonpulsatile biventricular assistance and to evaluate to which degree the autoregulation of the system would accommodate the changed hemodynamic situation during physical exercise. The Baylor Gyro PI 710 BVAD has been implanted into 2 calves (strain half-Dexter) in a biventricular bypass fashion with native heart remaining. Allowing a 10 day convalescence, 2 animals were subjected to incremental exercise tests. The speed of the treadmill was increased at zero slope from 0.7 mph to 1.5 mph with increments of 0.2 mph every 3 min. During the exercise the pump flows were maintained at a fixed rate (6.93 +/- 0.01 L/min for the left ventricular assist device and 5.36 +/- 1.44 L/min for the right ventricular assist device). Hemodynamic parameters and pump performance were recorded continuously. The cardiac output (CO) and heart rate (HR) increased significantly during the exercise. CO increased from 11.1 +/- 0.3 to 13.1 +/- 0.4 L/min, and HR increased from 99 +/- 7.1 to 114 +/- 2.8 bpm, respectively. Mean aortic pressure, central venous pressure, and left arterial pressure did not change significantly. Also, no change was observed for the left and right pump flows. This totally implantable BVAD showed excellent long-term performance without any mechanical problems. It is feasible to operate without impairment under physical activity. However, the natural heart dominated the hemodynamic response during exercise under BVAD support. The left and the right pump flows did not increase spontaneously with exercise. We therefore conclude that a servo CO control system is necessary to regulate pump flows even during moderate exercise.
Animals↗
Development of the Baylor Gyro permanently implantable centrifugal blood pump as a biventricular assist device.
The Baylor Gyro permanently implantable centrifugal blood pump (Gyro PI pump) has been under development since 1995 at Baylor College of Medicine. Excellent results were achieved as a left ventricular assist device (LVAD) with survival up to 284 days. Based on these results, we are now focusing on the development of a biventricular assist device (BVAD) system, which requires 2 pumps to be implanted simultaneously in the preperitoneal space. Our hypothesis was that the Gyro PI pump would be an appropriate device for an implantable BVAD system. The Gyro PI 700 pump is fabricated from titanium alloy and has a 25 ml priming volume, pump weight of 204 g, height of 45 mm, and pump diameter of 65 mm. This pump can provide 5 L/min against 100 mm Hg at 2,000 rpm. In this study, 6 half-Dexter healthy calves have been used as the experimental model. The right pump was applied between the infundibular of the right ventricle and the main pulmonary artery. The left pump was applied between the apex of the left ventricle and the thoracic descending aorta. As for anticoagulation, heparin was administered at the first postoperative week and then converted to warfarin sodium from the second week after surgery. Both pump flow rates were controlled maintaining a pulmonary arterial flow of less than 160 ml/kg/min for the sake of avoidance of pulmonary congestion. Blood sampling was done to assess visceral organ function, and the data regarding pump performance were collected. After encountering the endpoint, which the study could not keep for any reasons, necropsy and histopathological examinations were performed. The first 2 cases were terminated within 1 week. Deterioration of the pump flow due to suction phenomenon was recognized in both cases. To avoid the suction phenomenon, a flexible conduit attached on the inlet conduit was designed and implanted. After using the flexible inflow conduit, the required power and the rotational speed were reduced. Furthermore, the suction phenomenon was not observed except for 1 case. There was no deterioration regarding visceral organ function, and pulmonary function was maintained within normal range except for 1 case. Even though the experimental animal survived up to 45 days with the flexible inflow conduit, an increase in power consumption due to thrombus formation behind the impeller became a problem. Lower rotational speed, which was probably produced by the effectiveness of the flexible inflow conduit, was speculated to be one of the reasons. And the minimum range of rotational speed was 1,950 rpm in these 6 BVAD cases and the previous 3 cases of LVAD. In conclusion, 6 cases of BVAD implantation were performed as in vivo animal studies and were observed up to 45 days. The flexible inflow conduit was applied in 4 of 6 cases, and it was effective in avoiding a suction phenomenon. The proper rotational speed of the Gyro PI 700 pump was detected from the viewpoint of antithrombogenicity, which is more than 1,950 rpm.
Animals↗
Historical perspectives of hybrid hepatic assist devices: tissue sourcing, immunoisolation, and clinical trial.
A hybrid hepatic assist device using canine liver tissues was developed and clinically applied 38 years ago. However, for many years practical hybrid hepatic assist devices were not clinically introduced owing to the many difficulties encountered in employing cultured hepatocytes. These problems include: (1) maintenance of viable cultured cells, (2) maintenance of normal hepatocyte function with these cells, (3) elimination of toxic substances generated by non-viable cultured and/or stored cells, (4) elimination of immunological factors generated by cultured cells and by the patient, and (5) difficulties of the biocompatible immunological barrier for cells against the patient. Fortunately, recent progress in apheresis and biomaterial technologies enable us to isolate cultured cells immunologically and yet maintain effective metabolic functions for the patient. These technologies generate an immunological barrier of a hybrid hepatic assist device for the patients. Proper adsorption columns developed for apheresis procedures enable us to remove the toxic substances released by non-viable cells. Recent development of oxygen-carrying macromolecules enable us to provide sufficient oxygen supply to the cultured cells and to maintain their normal cellular function, not only during the cultured period of time, but also during their actual clinical application. Together with the advancement of cell culture technologies, including the proper cultured environments and cellular seeding environments, these technologies, primarily developed for therapeutic apheresis, should be able to provide more effective and safe hybrid artificial organs.
Animals↗
A clinical use of the Kyocera Gyro C1E3 centrifugal pump.
The Kyocera Gyro C1E3 centrifugal blood pump was clinically applied for a cardiopulmonary bypass (CPB) of coronary artery bypass grafting (CABG). The patient was 72-year-old male with postinfarction unstable angina. The surgery was carried out on November 20, 1998. The air inside the pump was easily and quickly removed, and its controllability was excellent. The pump flow during operation was maintained 2.2 L/m2. Total CPB time was 173 min. Perioperative parameters of hemolysis and cytotoxicity were not remarkably changed. Macroscopically and microscopically, there were no thrombi inside the pump after usage. This is the first reported case of clinical use of the Kyocera Gyro C1E3 pump.
Aged↗
In vitro evaluation study of the membrane autotransfusion system experimental prototype: MATS-I.
Membrane Autotransfusion System (MATS) utilizing plasmapheresis technology has been developed in our laboratory. A specially designed polyethylene hollow fiber membrane was utilized. This study was conducted to evaluate performance of the first experimental prototype, MATS-I. The results of this study showed that the MATS-I could concentrate diluted blood at 10% of the initial hematocrit concentration (HCTi) into over 40% after passing through the system at a transmembrane pressure of 70 mm Hg. Moreover, the MATS-I can continuously treat 10,000 ml of diluted blood at various HCTi levels without deteriorating its performances. Even though the MATS-I met all required performances as an autotransfusion system, several areas of improvement of the system were necessary to meet various clinical needs. The next prototype, MATS-II, can be designed based on experiences obtained from the MATS-I. The MATS is smaller, more atraumatic and continuous, and is a faster system when compared to the currently available centrifugal autotransfusion devices.
Animals↗
Development of the membrane autotransfusion system prototype-II: MATS-II.
This article is the second of a two-part series describing a membrane autotransfusion system, MATS, utilizing plasmapheresis technology. Based on experiences obtained from the first prototype (MATS-I), optimum blood filtration parameters with refined blood and flux pump synchronization were put into an original CPU-board and loaded on a miniaturized, self-operative, and preclinical prototype (MATS-II). This study was conducted to evaluate the MATS-II using diluted blood of various hematocrit concentrations. The results proved that this device could concentrate 4,000-10,000 ml of various hematocrit concentrations into higher than 40% while automatically controlling the flow speed from 250 to 400 ml/min. Also, no significant damage was generated to the red blood cells (RBC). Moreover, the MATS-II salvaged over 90% of platelets together with the RBC. These results suggest that the MATS-II achieves all clinical requirements of an autotransfusion device; it is a continuous hemoconcentration device with minimum damage to cellular components of the blood.
Animals↗
Analysis of the arterial blood pressure waveform using Fast Fourier Transform technique during left ventricular nonpulsatile assistance: in vitro study.
The arterial blood pressure waveform is variable during left ventricular assistance. The aim of this study is to examine the correlation between the left ventricular assist device (LVAD) condition and the arterial blood pressure waveform in a fixed cardiac output condition using a mock circuit. This mock circulation loop was composed of an aortic compliance chamber, a left atrial compliance chamber, a pneumatic pulsatile pump as a native heart, and a rotary blood pump representing the LVAD with left atrial drainage. The Fast Fourier Transform technique was utilized to analyze the arterial blood pressure waveform and calculate the pulsatility index (PI) and the pulse power index (PPI). The PI and PPI decreased with the increase of the LVAD rotational speed, exponentially. There was a significant negative correlation between the PI, PPI, and the LVAD rotational speed, flow rate, and assist ratio. The best correlation was observed between the PPI and the assist ratio (r = 0.986). From this viewpoint, an ideal LVAD condition may be estimated from the pulsatility change of the arterial blood pressure waveform.
Blood Pressure↗
Estimation of pump flow rate and abnormal condition of implantable rotary blood pumps during long-term in vivo study.
The control system for an implantable rotary blood pump is not clearly defined. A detection system is considered to be necessary for pump flow monitoring and abnormal conditions such as back flow or a sucking phenomenon where the septum or left ventricle wall is sucked into the cannula, etc. The ultrasound flowmeter is durable and reliable but the control system should not be totally dependent on the flowmeter. If the flowmeter breaks, the rotary blood pumps have no control mechanism. Therefore, the authors suggest controlling the pumps by an intrinsic parameter. One left ventricular assist device (LVAD) calf model was studied where the flow rate and waveform of the pump flow proved to identify the sucking phenomenon. Thus, the pump flow rate was calculated from the required power, motor speed, and heart rate. The value of the coefficient of determination (R2) between the measured and estimated pump flow rate was 0.796. To estimate this abnormal phenomenon, 2 methods were evaluated. One method was the total pressure head in which the pump flow rate and motor speed were estimated. During normal conditions the total pressure head is 79.5 +/- 7.0 mm Hg whereas in the abnormal condition, it is 180.0 +/- 2.8 mm Hg. There was a statistical difference (p < 0.01). Another method is using a current waveform. There is an association between the current and pump flow waves. The current was differentiated and squared to calculate the power of the differentiated current. The normal range of this value was 0.025 +/- 0.029; the abnormal condition was 11.25 +/- 15.13. There was a statistical difference (p < 0.01). The predicted flow estimation method and a sucking detection method were available from intrinsic parameters of the pump and need no sensors. These 2 methods are simple, yet effective and reliable control methods for a rotary blood pump.
Animals↗
Right ventricular assist system feedback flow control parameter for a rotary blood pump.
At least 25-30% of patients with a permanent implantable left ventricular assist device (LVAD) experience right ventricular failure; therefore, an implantable biventricular assist system (BiVAS) with small centrifugal pumps is being developed. Many institutions are focusing and developing a control system for a left ventricular assist system (LVAS) with rotary blood pumps. These authors feel that the right ventricular assist system (RVAS) with rotary blood pumps should be developed simultaneously. A literature search indicated no recent reports on the effect of hemodynamics and exercise with this type of nonpulsatile implantable RVAS. In this study, a calf with an implantable right ventricular assist system (RVAS) was subjected to 30 min of exercise on a treadmill at 1.5 mph, resulting in excellent hemodynamics. The input voltage remained unchanged. Hemodynamic recordings were taken every 5 min throughout the testing period, and blood gas analysis was done every 10 min. Oxygen uptake (VO2), oxygen delivery (DO2), and oxygen extraction (O2ER) were calculated and analyzed. Two different pump flows were investigated: Group 1 low assist (<3.5 L/min) and Group 2 high assist (>3.5 L/min). In both groups, the RVAS flow rates were unchanged while the pulmonary artery (PA) flow increased during exercise; also, the heart rate and right atrial pressure (RAP) increased during exercise. There were no significant differences in the 2 groups. The PA flow correlates to the heart rate during exercise. In all of the tests, the VO2 and DO2 increased during exercise. Regarding VO2, no changes were observed during the different flow conditions; however, the DO2 of Group 2 was higher than that of Group 1. Because the implantable RVAS did not have pump flow changes during the test conditions, it was necessary to incorporate a flow control system for the implantable RVAS. During exercise with an implantable RVAS rotary blood pump, incorporating the heart rate and VO2 as feedback parameters is feasible for controlling the flow rate.
Animals↗
Development of the NEDO implantable ventricular assist device with Gyro centrifugal pump.
The Gyro centrifugal pump, PI (permanently implantable) series, is being developed as a totally implantable artificial heart. Our final goal is to establish a "functional TAH," a totally implantable biventricular assist system (BiVAS) with centrifugal pumps. A plastic prototype pump, Gyro PI 601, was evaluated through in vitro and in vivo studies as a single ventricular assist device (VAD). Based upon these results, the pump head material was converted to a titanium alloy, and the actuator was modified. These titanium Gyro pumps, PI 700 series, also were subjected to in vitro and in vivo studies. The Gyro PI 601 and PI 700 series have the same inner dimensions and characteristics, such as the eccentric inlet port, double pivot bearing system, secondary vane, and magnet coupling system; however, the material of the PI 700 is different from the PI 601. The Gyro PI series is driven by the Vienna DC brushless motor actuator. The inlet cannula of the right ventricular assist system (RVAS) specially made for this system consists of 2 parts: a hat-shaped silicone tip biolized with gelatin and an angled wire reinforced tube made of polyvinylchloride. The pump-actuator package was implanted into 8 calves in the preperitoneal space, bypassing from the left ventricle apex to the descending aorta for the left ventricular assist system (LVAS) and bypassing the right ventricle to the main pulmonary artery for the RVAS. According to the PI 601 feasibility protocol, 2 LVAS cases were terminated after 2 weeks, and 1 LVAS case and 1 RVAS were terminated after 1 month. The PI 700 series was implanted into 4 cases: 3 LVAS cases survived for a long term, 2 of them over 200 days (72-283 days), and 1 RVAS case survived for 1 month and was terminated according to the protocol for a short-term antithrombogenic screening and system feasibility study. Regarding power consumption, the plastic pump cases demonstrated from 6.2 to 12.1 W as LVAS and 7.3 W as RVAS, the titanium pump cases showed from 10.4 to 14.2 W as LVAS and 15.8 W as RVAS. All cases exhibited low hemolysis. The renal function and the liver function were maintained normally in all cases throughout these experimental periods. In the 2 RVAS cases, pulmonary function was normally maintained. No calves demonstrated thromboembolic signs or symptoms throughout the experiments except Case 1 with the plastic pump. However, in the plastic pump cases, bilateral renal infarction was suspected in 2 cases during necropsy whereas no abnormal findings were revealed in the titanium pump cases. There were also no blood clots inside the PI 700 series. As for the 601, the explanted pumps demonstrated slight thrombus formations at the top and bottom pivots except in 1 case. The Gyro PI series, especially the PI 700 series, demonstrated superior performance, biocompatibility, antithrombogenicity and low hemolysis. Also, the durability of the actuator was demonstrated. Based on these results, this titanium centrifugal pump is suitable as an implantable LVAS and RVAS. It is likely that the Gyro PI series is a feasible component of the BiVAS functional TAH.
Animals↗
Gyro pump wear and deformation analysis in vivo study: creep deformation.
The Gyro pump has a double pivot bearing system to support its impeller. In this study, the integrity of the bearing system was examined after ex vivo studies. The pumps were implanted into calves and evaluated for different periods as a paracorporeal left ventricular assist device (LVAD). One pump was subjected to a test of 30 days, 1 for 15 days, 4 for 14 days, 1 for 10 days, 1 for 7 days, 2 for 4 days, and 4 for 2 days. One additional pump was subjected to percutaneous cardiopulmonary support (PCPS) condition for 6 days (total pressure head 500 mm Hg with a pump flow rate of 3 L/min). The anticoagulation treatment consisted of a continuous administration of heparin to maintain an achieved clotting time (ACT) of 200-250 s during the LVAD study and 250-300 s during the PCPS study. After the experiment, the pumps were disassembled, and the wear and deformation of male and female bearings were analyzed. There were no dimensional changes on male bearings but there were on female bearings. Wear and deformation of the female bearings were calculated as follows: wear and deformation = (depth of female before pumping) - (depth after pumping). Thirteen assembled Gyro pumps were disassembled to measure the depth of the female bearings before pumping. There was no statistical relationship between the wear and deformation and the motor speed x driving period. From these results, the deformation was not due to wear but to the creep or elastic deformation. This study suggested that the double pivot bearing system of the Gyro pump is highly durable.
Animals↗
Antithrombogenicity evaluation of a centrifugal blood pump.
The Gyro C1E3 pump was developed not only for cardiopulmonary bypass but also as a short-term assist device. The main purpose of this study was to examine the correlation between the thrombus formation factor and the Gyro C1E3 pumps. Seven pumps were implanted into 3 calves and evaluated for different periods of duration as a paracorporeal left ventricular assist device (LVAD). One pump was subjected to percutaneous cardiopulmonary support condition (PCPS) (total pressure head 500 mm Hg with a pump flow rate of 3 L/min). The anticoagulation treatment consisted of a continuous administration of heparin to maintain an activated clotting time (ACT) of 200-250 during the LVAD study and 250-300 during the PCPS study. After the experiment, the pumps were disassembled and examined. In cases where there were any blood-derived deposits inside the pumps, the dry weight of these thrombi that adhered to the bearing area of the pump was measured. A multiple correlation was attempted to speculate possible thrombus formation. The estimated dry weight of thrombi was calculated from pump flow rate, pumping day, motor speed, and activated clotting time. This equation was estimated dry weight of thrombi = 1.140 x pump flow rate -0.001 motor speed + 1.652 pumping time -0.041 x ACT + 2.198 R2 = 0.944. This study suggested that there was a possibility to calculate the amount of adhered thrombus formation from pump flow rate, motor speed, pumping day, and ACT.
Animals↗
Particles released from the Gyro C1E3 during simulated extracorporeal circulation.
Evaluation of released particles from the blood pump during extracorporeal circulation is an important aspect because the particles may cause microembolism. The Gyro C1E3 is a centrifugal blood pump that has an impeller suspended by double pivot bearings inside the housing; therefore, it is important to evaluate the released particles. The C1E3 was driven for 14 days to simulate clinical left ventricular assist device (LVAD) and percutaneous cardiopulmonary support (PCPS). Also, a roller pump was driven for 2 days as a comparison. Released particles were weighed and examined by SEM. After 14 days of pumping, the particles from the C1E3 were 238.6 microg in an LVAD condition. The particles with the roller pump were 270.2 microg after only 2 days. Average particle sizes with the roller pump and C1E3 were 3.7 and 0.6 microm, respectively. These results suggest that the Gyro C1E3 substantially reduces the risk of microembolism from released particles.
Biocompatible Materials↗
Impeller design for a miniaturized centrifugal blood pump.
The impeller design for a miniature centrifugal blood pump is an important consideration since the small diameter impeller requires higher rotational speed, which may cause more blood trauma compared to the larger diameter impeller. Three different impeller vanes (straight vanes with a height of 4 mm and 8 mm, and 8 mm curved vanes) of which the diameter was 35 mm were subjected to hydraulic performance and hemolysis tests in the same pump housing. Both straight vane impellers attained left ventricular assist condition (5 L/min against 100 mm Hg) at 2,900 rpm while the curved vane required 3,280 rpm. There was no significant hemolysis difference between the tall and short vanes. The curved impeller vanes did not exhibit sufficient hydraulic performance when compared to the straight vanes. The straight vane impellers, even with different heights, were incorporated into the same pump housings, and the vane heights did not drastically change the hydraulic performance or hemolysis.
Equipment Design↗