[show abstract][hide abstract] ABSTRACT: An implantable centrifugal blood pump has been developed with original features for a ventricle assist device (VAD). This pump is part of a multicenter and international study with objective to offer simple, affordable, and reliable devices to developing countries. Previous computational fluid dynamics investigations were performed followed by prototyping and in vitro tests. Also, previous blood tests for assessment of hemolysis showed mean normalized index of hemolysis (NIH) results of 0.0054 ± 2.46 × 10⁻³ mg/100 L (at 5 L/min and 100 mm Hg). To precede in vivo evaluation, measurements of magnetic coupling interference and enhancements of actuator control were necessary. Methodology was based on the study of two different work situations (1 and 2) studied with two different types of motors (A and B). Situation 1 is when the rotor of pump is closest to the motor and situation 2 its opposite. Torque and mechanical power were collected with a dynamometer (80 g/cm) and then plotted and compared for two situations and both motors. The results showed that motor A has better mechanical behavior and less influence of coupling. Results for situation 1 showed that it is more often under magnetic coupling influence than situation 2. The studies lead to the conclusion that motor A is the best option for in vivo studies as it has less influence of magnetic coupling in both situations.
ASAIO journal (American Society for Artificial Internal Organs: 1992) 08/2011; 57(5):462-5. · 1.39 Impact Factor
[show abstract][hide abstract] ABSTRACT: Our previous studies concluded Egyptian cotton was the most appropriate material for making a second generation granulocytapheresis (G-CAP) column as structural dimensions of the cotton fibers are able to attract granulocytes. Unfortunately, it is considered to be blood incompatible as its fibers are of non-synthetic origins. In this study we examined the alteration of the removal rates of blood cells with different surface modifications of Egyptian cotton to enhance its blood compatibility. The surface-modified cotton fibers were compared after three kinds of combination treatments. There were no differences in the removal rates of white blood cells (WBCs) and particularly neutrophils with the use of three kinds of biolized cottons. Next, an ex vivo animal study with a healthy dog was performed with the prototype of the G-CAP column. The dog's blood pressure (BP) decreased to approximately 80% of the initial values of BP at 20 min after the start of the extracorporeal circulation. The decrease in BP gradually reverted to normal. WBCs and particularly neutrophils decreased significantly at 15 min after the start of the extracorporeal circulation and remained low during the extracorporeal circulation. The ability of this column to remove WBCs was maintained during extracorporeal circulation. Especially, neutrophils at the inlet of the column were thoroughly removed for 1 h. Based upon these results, a second generation G-CAP column could be fabricated with Egyptian cotton and applied for clinical use on the condition that the biocompatibility of the Egyptian cotton needs to be improved by the appropriate biolization method.
Journal of Artificial Organs 06/2011; 14(4):342-7. · 1.41 Impact Factor
[show abstract][hide abstract] ABSTRACT: Controlled immunological shock, induced by bioincompatible material apheresis for cancer (BIC MAC) therapy, produces an immunoactive status in experimental subjects. However, in order to provide a safe, painless, effective, and reproducible BIC MAC therapy, it is mandatory to provide general anesthesia with endotracheal intubation not only during apheresis procedures of 1-h duration but also for an additional 5 h. Using this procedure, there was no mortality experienced during animal experiments. Also, there were no procedurally related physical or sensory abnormalities demonstrated. This general anesthesia of 6 h covered not only the initial 30 min of the hypotension and hypoxic stages but also the recovery stages to hemodynamically normalize the experimental animals. After 6 h, the accumulated leukocytes in the lung are released back to the systemic circulation. In general, granulocytes decreased almost 100% while lymphocytes decreased only 40-50%. During these 6 h, increases of cytokines (tumor necrosis factor-α, interleukin-6, etc.) sometimes up to 1000 times occurred. After the 6-h procedure, leukocytes returned nearly to preoperative levels but tended to be continuously increased. After the fourth day, leukocyte counts more than doubled. These cellular and humoral activations were normalized after 2 weeks. These studies were conducted on six normal mongrel dogs. Currently, similar studies are planned to be conducted on tumor-bearing experimental animals. This procedurally induced immunoactivation by apheresis may be able to produce effective apoptosis in malignant tumor cells.
[show abstract][hide abstract] ABSTRACT: As a therapeutic VAD to be combined with drugs, apheresis, and cellular implants, it is advisable to develop a wearable VAD for less than 6 months of application. Such an example was shown by describing the therapeutic BCM Gyro centrifugal VAD.
[show abstract][hide abstract] ABSTRACT: External microwave (EMW) hyperthermia system (2.45 GHz wave frequency) was evaluated by in vitro studies and in vivo pleural metastasis animal model. Three different non-small-cell lung cancer cells and normal fibroblast cells (control) were treated once a day for 3 days with the prototype EMW system applying mild (39 degrees C), moderate (43 degrees C), and severe (47 degrees C) hyperthermia. On Day-4, tested cells were retrieved and examined by apoptosis assay kit and Western blot analysis. Cancer cells treated with moderate hyperthermia showed significant apoptosis; yet no major damage was observed to normal fibroblast cells. Western blot analysis indicated cleavage on caspase-3, -9 and PARP. Also in the cell cycle analysis, increase of sub G0-G1 population was identified. After optimization of the heating intensity for in vivo environment, we created pleural metastatic animal model in 24 immune deficiency mice (male nu/nu mice) to evaluate inhibitory effect of systemic EMW hyperthermia for disseminated tumor growth. Out of 24 mice, 8 received mild and 8 received moderate hyperthermia, and remaining 8 were the no treatment control. Whole chest area of the experimental animals was irradiated 3 times a week for 2 weeks (total of 6 time irradiations). No significant adverse event was observed including abnormal weight loss, skin burn, ulceration, and death. Metastasized tumors around the pleura and chest cavity were 75% reduced in size and weight compared to non-treated control group. Harvested tumors were stained and TUNEL assay demonstrated significant apoptosis in a moderate hyperthermia group. The EMW hyperthermia system may be possible alternative tool as a systemic hyperthermia therapy in severely advanced lung cancer patients. Further study is necessary to determine device safeness, efficacy, and synergistic effect to other possible combination therapies.
[show abstract][hide abstract] ABSTRACT: The preliminary studies for developing a second generation granulocytapheresis (G-CAP) column were made. In the past, the G-CAP column has been used for the treatment of ulcerative colitis and rheumatoid arthritis. However, recent clinical studies have revealed that the therapeutic effects of the G-CAP column are not significant compared with those of the sham column. These results were considered to be due to insufficient reduction of granulocytes. Thus, development of a better granulocyte removal column was attempted. Realizing that white cells adhered on small-diameter synthetic fibers of 1-2 microm, small diameter cotton fibers were subjected to the studies of their granulocyte-removing capabilities. Three types of cotton, Pakistani, Australian and Egyptian cottons, were evaluated using normal human blood in vitro. Miniature columns were made of each fiber, and CBC and WBC differentiation was compared between pre- and post-filtered blood. The Egyptian cotton removed leukocytes, especially granulocytes, the most efficiently of the three types of cotton. The Egyptian cotton's granulocyte adhesion properties were not altered after different chemical treatments. A 4-ml column of packaged Egyptian cotton with a density of more than 0.125 g/ml could remove granulocytes effectively up to 80 ml of blood passages. Based upon these studies, second generation G-CAP could be carried out with Egyptian cotton fibers as a scaled-up clinical module.
Journal of Artificial Organs 04/2010; 13(2):92-6. · 1.41 Impact Factor
[show abstract][hide abstract] ABSTRACT: We have developed a new transcutaneous energy transmission (TET) system for a totally implantable biventricular assist device (BVAD) system in the New Energy and Industrial Development Organization (NEDO) artificial heart project. The TET system mainly consists of an energy transmitter, a hybrid energy coil unit, an energy receiver, an internal battery system, and an optical telemetry system. The hybrid energy coil unit consists of an air-core energy transmission coil and an energy-receiving coil having a ferrite core. Internal units of the TET system are encapsulated in a titanium alloy casing, which has a size of 111 mm in width, 73 mm in length, and 25 mm in height. In in vitro experiments, the TET system can transmit a maximum electric energy of 60 Watts, and it has a maximum transmission efficiency of 87.3%. A maximum surface temperature of 46.1 degrees C was measured at the ferrite core of the energy-receiving coil during an energy transmission of 20 Watts in air. The long-term performance test shows that the TET system has been able to operate stably for over 4 years with a decrease of energy-transmission efficiency from 85% to 80%. In conclusion, the TET system with the hybrid energy coil can overcome the drawback of previously reported TET systems, and it promises to be the highest performance TET system in the world.
[show abstract][hide abstract] ABSTRACT: A new antithrombogenic stent using ion beam surface modification nanotechnology was evaluated. The ion stent is being developed to inhibit acute and chronic stent-related thrombosis. Thirty self-expanding mesh stents were fabricated from Ti-Ni metal wires with a dimension of 4 mm (diameter) x 25 mm (length) x 0.15 mm (thickness). Twenty stents were coated with type I collagen and irradiated with a He(+) ion beam at an energy of 150 keV with fluences of 1 x 10(14) ions/cm(2) (ion stent group). Ten stents had no treatment (non-ion stent group). The self-expanding stents were implanted into the right and left peripheral femoral arteries of 15 beagle dogs (vessel diameter approximately 3 mm) via a 6Fr catheter under fluoroscopic guidance. Heparin (100 units/kg) was administered intravenously before implantation. Following stent implantation, no antiplatelet or anticoagulant drugs were administered. The 1-month patency rate for the non-ion stent group was 10% (1/10), and for the ion stent group it was 80% (16/20) with no anticoagulant or antiplatelet drugs given after stent implantation (P = 0.0004 by Fisher's exact test). Ten stents remain patent after 2 years in vivo with no anticoagulant or antiplatelet drugs. These results indicate that He(+) ion-implanted collagen-coated Ti-Ni self-expanding stents have excellent antithrombogenicity and biocompatibility. This ion stent is promising for coronary and cerebral stent applications.
[show abstract][hide abstract] ABSTRACT: The proximal isovelocity surface area (PISA) method is useful in the quantitation of aortic regurgitation (AR). We hypothesized that actual measurement of PISA provided with real-time 3-dimensional (3D) color Doppler yields more accurate regurgitant volumes than those estimated by 2-dimensional (2D) color Doppler PISA.
We developed a pulsatile flow model for AR with an imaging chamber in which interchangeable regurgitant orifices with defined shapes and areas were incorporated. An ultrasonic flow meter was used to calculate the reference regurgitant volumes. A total of 29 different flow conditions for 5 orifices with different shapes were tested at a rate of 72 beats/min. 2D PISA was calculated as 2pi r(2), and 3D PISA was measured from 8 equidistant radial planes of the 3D PISA. Regurgitant volume was derived as PISA x aliasing velocity x time velocity integral of AR/peak AR velocity.
Regurgitant volumes by flow meter ranged between 12.6 and 30.6 mL/beat (mean 21.4 +/- 5.5 mL/beat). Regurgitant volumes estimated by 2D PISA correlated well with volumes measured by flow meter (r = 0.69); however, a significant underestimation was observed (y = 0.5x + 0.6). Correlation with flow meter volumes was stronger for 3D PISA-derived regurgitant volumes (r = 0.83); significantly less underestimation of regurgitant volumes was seen, with a regression line close to identity (y = 0.9x + 3.9).
Direct measurement of PISA is feasible, without geometric assumptions, using real-time 3D color Doppler. Calculation of aortic regurgitant volumes with 3D color Doppler using this methodology is more accurate than conventional 2D method with hemispheric PISA assumption.
Journal of the American Society of Echocardiography: official publication of the American Society of Echocardiography 02/2009; 22(3):306-13. · 2.98 Impact Factor
[show abstract][hide abstract] ABSTRACT: Gastric emptying of solids is abnormally slow after vagotomy. To determine whether it was possible to accelerate emptying by electrical stimulation either of the gastric wall directly or of a “foreign” nerve brought in to reinnervate the stomach, eight dogs underwent truncal vagotomy (TV); five of the dogs received intercostal nerve muscle pedicle (NMP) implants. Gastric atony was demonstrated postoperatively in all animals up to 4. months later by means of radiological contrast studies. After allowing time for neurotization to occur (mean 78 days), the cervical vagi were stimulated to confirm that TV was complete. Gastric peristalsis, intraluminal pressures, and emptying were assessed during stimulation of the NMPs and of the gastric wall, followed by sacrifice for histologic study. Neither reinnervation alone nor stimulation of the NMPs improved emptying. Although viable somatic nerve was found in the gastric wall, nerve sprouting was not. By contrast, stimulation of the gastric wall with trains of pulses (20 Hz, 2–10 ms, 2–5 mA) evoked peristalsis in all animals. We conclude that somatic nerve tissue cannot produce functional reinnervation of a visceral organ; however, direct muscular stimulation can accelerate gastric emptying after TV.
[show abstract][hide abstract] ABSTRACT: Two well-known centrifugal and axial pumping principles are used simultaneously in a new blood pump design. Inside the pump housing is a spiral impeller, a conically shaped structure with threads on the surface. The worm gears provide an axial motion of the blood column through the threads of the central cone. The rotational motion of the conical shape generates the centrifugal pumping effect and improves the efficiency of the pump without increasing hemolysis. The hydrodynamic performance of the pump was examined with a 40% glycerin-water solution at several rotation speeds. The gap between the housing and the top of the thread is a very important factor: when the gap increases, the hydrodynamic performance decreases. To determine the optimum gap, several in vitro hemolysis tests were performed with different gaps using bovine blood in a closed circuit loop under two conditions. The first simulated condition was a left ventricular assist device (LVAD) with a flow rate of 5 L/min against a pressure head of 100 mm Hg, and the second was a cardiopulmonary bypass (CPB) simulation with a flow rate of 5 L/min against 350 mm Hg of pressure. The best hemolysis results were seen at a gap of 1.5 mm with the normalized index of hemolysis (NIH) of 0.0063 ± 0.0020 g/100 L and 0.0251 ± 0.0124 g/100 L (mean ± SD; n = 4) for LVAD and CPB conditions, respectively.
[show abstract][hide abstract] ABSTRACT: ABSTRACTA TAH system utilizing two pusher-plate type pumps was developed and tested in two calves for 45 and 108 days with excellent results. A Hall effect sensor was utilized to operate each pump with a full stroke at variable rates (VR); each pump was then allowed to run independently at different rates depending on its own preload and afterload. With this system, the animals' atrial pressures were kept to near-normal levels (less than 10 mmHg). However, significant differences in the left and right pump flows were observed (left higher than right) and they ranged from 5 to 30% of the left flow with a mean of 15%. These flow differences may be due to the bronchial circulation and related shunts. Right pump flows averaged 70 to 95 ml/min-kg and circulating blood volume ranged from 67 to 95 ml/kg. When various control modes including fixed rate and master-slave type simultaneously or alternately ejecting VR modes were applied in the same animals and both pump flows were forced to be equal, unphysiological atrial pressures resulted. This result indicates that perhaps left and right flow differences are necessary physiological conditions to regulate the atrial pressures within normal ranges. Metabolic data also indicated that under simultaneously and alternately ejecting modes, A-V O2 content differences were increased due to decreased right pump flow as compared with those of the free-running VR mode. The left and right free-running VR mode of operation imposed minimal constraints on the animals' cardiovascular system and therefore yielded excellent hemodynamic and metabolic results.
[show abstract][hide abstract] ABSTRACT: A collaborative effort between Baylor College of Medicine and NASA/Johnson Space Center is underway to develop an axial flow ventricular assist device (VAD). We evaluated inducer/impeller component designs in a series of in vitro hemolysis tests. As a result of computational fluid dynamic analysis, a flow inducer was added to the front of the pump impeller. According to the surface pressure distribution, the flow inducer blades were connected to the impeller long blades. This modification eliminated high negative pressure areas at the leading edge of the impeller. Comparative studies were performed between inducer blade sections that flowed smoothly into the impeller blades (continuous blades) and those that formed discrete separate pumping sections (discontinuous blades). The inducer/impeller with continuous blades showed significantly (p < 0.003) lower hemolysis with a normalized index of hemolysis (NIH) of 0.018 ±< 0.007 g/100 L (n = 3), compared with the discontinuous model, which demonstrated an NIH of 0.050 ± 0.007 g/100 L (n = 3). The continuous blade model was evaluated in vivo for 2 days with no problems. One of the pumps evaluated ran for 5 days in vivo although thrombus formation was recognized on the flow straightener and the inducer/impeller. As a result of this study, the pump material was changed from polyether polyurethane to polycarbonate. The fabrication method was also changed to a computer numerically controlled (CNC) milling process with a final vapor polish. These changes resulted in an NIH of 0.0029 ± 0.0009 g/100 L (n = 4). which is a significant (p < .0001) value 6 times less than that of the previous model. This model was used for in vivo studies and achieved 9 days of operation with a sufficient flow between 3.6 and 4.7 L/min against 80 to 100 mm Hg mean arterial pressure. Plasma free hemoglobin levels remained at 2–3 mg/dl with a hematocrit of 20%.
[show abstract][hide abstract] ABSTRACT: To test whether small bowel contraction can be induced by electrostimulation similar to in vitro results in anesthetized and awake animals, five dogs had stainless steel electrodes implanted on the serosal surface of the jejunum and ileum. Fifty milliamperes of 500-μs 910-Hz currents induced a 50–80-mm Hg pressure increase in the jejunum with a threshold of 25 mA. Transverse stimulation was studied long-term in two dogs. The mean pressure change for 500-μs 910-Hz 25-mA stimulation in 10 studies was 26 mm Hg (0–75). The thresholds ranged between 15 mA and currents not tolerated by the animal. For 200-μs 1.67-kHz 30-mA stimulation, the mean pressure change was 28 mm Hg (0–75 mm Hg, n = 16). On 10 occasions, the pressure increased further after termination of the stimulus (off response), with a mean of 48 mm Hg (10–85). Electrical currents elicit a mechanical response in the small intestine of the intact animal, which resembles the in vitro observations. Currents necessary to evoke contractions in the physiologic range are tolerated by the trained animal.
[show abstract][hide abstract] ABSTRACT: Previously, it was reported by our group that the superphysiological temperature of over 43°C affected leukocyte properties. It was speculated that heat treatment might alter the immunological properties of leukocytes. In order to take advantages of this phenomenon, attempts were made to develop a thermoconductive and thermoselective leukocyte filter. A stainless steel fiber was selected for the new material of a leukocyte filter due to its good heat conductance, stability during thermal change, and inertness to any chemicals. Preliminary studies were conducted to evaluate the effect of fiber diameter and temperature on the filtration of blood cells. As a result, more than 99% of white blood cells (WBCs) and platelets were removed utilizing a 4 μm diameter fiber filter. The environmental temperatures of the filtration process were varied to 4, 20, 36, and 50°C for 5 min. Almost 95% of WBCs and platelets were removed at 4, 20, and 36°C. However, the reduction of platelets was remarkably suppressed at 50°C (54%). Additionally, the removal of lymphocytes was significantly lower than that of neutrophils at 50°C (69% vs. 83%; p = 0.0002). These data demonstrate that effective heat treatment and removal of leukocytes are possible with an ultrafine stainless steel fiber filter.
[show abstract][hide abstract] ABSTRACT: Our newly developed axial flow pump consists of a flow tube, an internal rotating impeller, and a fixed flow stator (we call the stator) behind the impeller. This pump produces a flow of 3 to 8 L/min against 50 to 150 mm Hg pressure difference, respectively, in the range of 10,000 to 16,000 rpm. An axial flow pump that will be used as a ventricular assist device (VAD) has to have low hemolytic and good antithrombogenic characteristics. This paper will show how to decrease the hemolytic properties of this axial flow pump systematically using a test matrix. The test variables evaluated were impeller blade tip geometry, impeller flow tube clearance (radial clearance), impeller stator clearance (axial clearance), impeller blade number, stator blade number, and impeller length. All in vitro hemolysis tests were performed at 5.0 L/min against 100 mm Hg pressure difference using a total of 83 bags of fresh bovine blood. The results were as follows: the impeller blade tip geometry did not significantly effect hemolysis, a 0.005-inch and a 0.009-inch radial clearance were significantly (p < 0.01 or 0.001) less hemolytic than the other clearances, a 0.075-inch axial clearance was significantly (p < 0.05) more hemolytic than the other clearances, two-and six-bladed impellers were significantly (p < 0.01 and 0.02, respectively) less hemolytic than a four-bladed impeller, a five-bladed stator was significantly (p < 0.05 or 0.01) less hemolytic than the other stators, and the impeller length did not make a significant difference. Currently, the best index of hemolysis is 0.031 ± 0.018 g/100 L, and using parameters from these results, implantable devices are being fabricated.
[show abstract][hide abstract] ABSTRACT: The Baylor C–Gyro Pump Eccentric Inlet Port Models (C1E) have been developed aiming for a longterm centrifugal ventricular assist device (VAD) as well as a cardiopulmonary bypass pump. The eccentric inlet port models are characterized by their unique inlet port and secondary impeller vanes. An inlet female pivot bearing, which was fixed to a supporting bar in the prototype model, is directly embedded into the ceiling of the pump casing. An inlet port is then placed off–center to avoid the bearing area, and it is angled between 0 to 90° from the upright position. In addition, small secondary vanes were incorporated into the impeller bottom to accelerate the washout flow behind the impeller. These features attained design objectives proposed for higher antithrombogenicity: a seal–less pump chamber, no stationary parts in the blood path, and acceleration of the secondary flow behind the impeller. The first in vivo experiment using C1E pumps showed excellent antithrombogenicity for up to 18 days when the experiment ceased due to severe infection in the calf.
[show abstract][hide abstract] ABSTRACT: To be able to salvage heart failure patients, the need for an economical permanent ventricular assist device is increasing. To meet this increasing demand, a miniaturized centrifugal blood pump has been developed as a permanently implantable device. The Gyro permanently implantable model (PI-601) incorporates a sealless design with a blood stagnation free structure. The pump impeller is magnetically coupled to the driver magnet in a sealless manner. This pump is atraumatic and antithrombogenic and incorporates a double pivot bearing system. A miniaturized actuator was utilized in this system in collaboration with the University of Vienna. The priming volume of this pump is 20 ml. The overall size of the pump actuator package is 53 mm in height and 65 mm in diameter, 145 ml of displacement volume, and 305 g in weight. Testing to date has included in vitro hydraulic performance and hemolysis. This pump can provide 5 L/min against a 110 mm Hg total pressure head at 2,000 rpm and 8 Limin against 150 mm Hg at 2,500 rpm. The normalized index of hemo-lysis (NIH) value of this pump was 0.0028 g/100 L at 5 Limin against 100 mm Hg. A preliminary anatomical study revealed the possibility of the implantability of 2 such systems in biventricular bypass at a preperitoneal location. This system is feasible for use as a permanently implantable biventricular assist device.
[show abstract][hide abstract] ABSTRACT: We describe the development of a cardiac flow model and imaging chamber to permit Doppler assessment of complex and dynamic flow events. The model development included the creation of a circulatory loop with variable compliance and resistance; the creation of a secondary regurgitant circuit; and incorporation of an ultrasound imaging chamber to allow two-dimensional (2D) and three-dimensional (3D) Doppler characterization of both simple and complex models of valvular regurgitation. In all, we assessed eight different pulsatile regurgitant volumes through each of four rigid orifices differing in size and shape: 0.15 cm(2) circle, 0.4 cm(2) circle, 0.35 cm(2) slot and 0.4 cm(2) arc. The achieved mean (and range) hemodynamic measures were: peak trans-orifice pressure gradient 117 mm Hg (40 to 245 mm Hg), trans-orifice peak Doppler velocity 560 cm/s (307 to 793 cm/s), Doppler time-velocity integral 237 cm (111 to 362 cm), regurgitant volume 43 mL (11 to 84 mL) and orifice area 0.32 cm(2) (0.15 to 0.4 cm(2)). The model was designed to optimize Doppler signal quality while reflecting anatomic structural relationships and flow events. The 2D color Doppler, 3D color Doppler and continuous wave Doppler quality was excellent whether the data were acquired from the imaging window parallel or perpendicular to the long-axis of flow. This model can be easily adapted to mimic other intracardiac flow pathology or assess future Doppler applications.
Ultrasound in Medicine & Biology 05/2008; 34(4):647-54. · 2.46 Impact Factor