Yukihiko Nosé

Can we develop a nonpulsatile permanent rotary blood pump? Yes, we can.

For many years, it was thought that nonpulsatile perfusion produced physiological and circulatory abnormalities. Since 1977, Yukihiko Nosé and his colleagues have challenged this misconception. Toward that end, they did show that if a 20% higher blood flow uses more than that required for a pulsatile blood pump, then there would be no circulatory or physiological abnormalities. These experimental findings confirm that there is no difference in clinical outcome using either a pulsatile or nonpulsatile blood pump. Furthermore, the nonpulsatile rotary blood pump demonstrates efficient and reliable performance in various clinical situations. The nonpulsatile blood pump is a simple and reliable design that is manufactured easily and that has several desirable features. There is no need to incorporate heart valves, which are the most thrombogenic and blood trauma-inducing component. A continuous flow pump does not require a large orifice inflow conduit and proves to be easier to implant in patients with minimal damage to the myocardium. There is no need to incorporate a compliance volume-shifting device, which is essential for a pulsatile blood pump. The nonpulsatile device is a continuous blood pumping system; therefore, the control system is simpler and more reliable than that of a pulsatile pump. Because of the rotary blood pumps structure, only one moving part is necessary for the blood-pumping motion. By using durable components for this moving part, a durable system becomes possible. Because the electrical motor operates continuously, the on-and-off motion required for a pulsatile pump is not necessary; therefore, it is a more efficient and durable system. Thus, this group is working on the development of a nonpulsatile blood pump as a permanently implantable assist device. To achieve this goal, it is necessary to incorporate seven features into the system: small size, atraumatic features, antithrombogenic features, antiinfection features, a simple and durable design, and low energy requirement with easy controllability.

Protein adsorption onto ceramic surfaces

Ceramics seldom have been used as blood-contacting materials. However, alumina ceramic (Al2O3) and polyethylene are incorporated into the pivot bearings of the Gyro centrifugal blood pump. This material combination was chosen based on the high durability of the materials. Due to the stagnant flow that often occurs in a continuous flow condition inside a centrifugal pump, pivot bearing system is extremely critical. To evaluate the thombogenicity of pivot bearings in the Gyro pump, this study sought to investigate protein adsorption, particularly albumin, IgG, fibrinogen, and fibronectin onto ceramic surfaces. Al2O3 and silicon carbide ceramic (SiC) were compared with polyethylene (PE) and polyvinylchloride (PVC). Bicinchoninic acid (BCA) protein assay revealed that the amount of adsorbed proteins onto Al2O3 and SiC was significantly less than that on PVC. The sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) indicated that numerous proteins adsorbed onto PVC compared to PE, Al2O3, and SiC. Identification of adsorbed proteins by Western immunoblotting revealed that the adsorption of albumin was similar on all four materials tested. Western immunoblotting also indicated lesser amounts of IgG, fibrinogen, and fibronectin on Al2O3 and SiC than on PE and PVC. In conclusion, ceramics (Al2O3 and SiC) are expected to be thromboresistant from the viewpoint of protein adsorption.

Development of the oxygenator: past, present, and future.

From the 1950s to the 1980s, the most widely used oxygenator in the clinical field was the disposable bubble oxygenator. However, membrane oxygenators have become the preferred clinical choice over the years. In the United States, membrane oxygenators used in cardiopulmonary bypass operations account for the majority of clinical oxygenator use. Membrane oxygenators have an equal capability for oxygenating venous blood compared with other type of oxygenators such as the bubble type and film type; however, the membrane oxygenator requires a smaller volume for priming to achieve a sufficient gas transfer rate and results in less blood trauma such as hemolysis because it uses a similar mechanism to the natural lung. In the 1980s, the first capillary-type oxygenator adopted the system of intracapillary blood perfusion. However, this induced high pressure resistance in the module and caused hemolysis. Thus, at present, capillary oxygenators commonly adopt the system of extracapillary blood perfusion. Microporous hollow-fiber membranes are primarily used for short-term cardiopulmonary bypass application, whereas nonmicroporous hollow-fiber membranes are primarily used for long-term extracorporeal membrane oxgenation application.

THREE-DIMENSIONAL ULTRASOUND IMAGING MODEL OF MITRAL VALVE REGURGITATION: DESIGN AND EVALUATION

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.

Development of a Pivot Bearing Supported Sealless Centrifugal Pump for Ventricular Assist

Since 1991, in our laboratory, a pivot bearing-supported, sealless, centrifugal pump has been developed as an implantable ventricular assist device (VAD). For this application, the configuration of the total pump system should be relatively small. The C1E3 pump developed for this purpose was anatomically compatible with the small-sized patient population. To evaluate an-tithrombogenicity, ex vivo 2-week screening studies were conducted instead of studies involving an intracorpore-ally implanted VADs using calves. Five paracorporeal LVAD studies were performed using calves for longer than 2 weeks. The activated clotting time (ACT) was maintained at approximately 250 s using heparin. All of the devices demonstrated trouble-free performances over 2 weeks. Among these 5 studies, 3 implantations were subjected to 1-month system validation studies. There were no device-induced thrombus formations inside the pump housing, and plasma-free hemoglobin levels in calves were within the normal range throughout the experiment (35, 34, and 31 days). There were no incidents of system malfunction. Subsequently, the mass production model was fabricated and yielded a normalized index of hemolysis of 0.0014, which was comparable to that of clinically available pumps. The wear life of the impeller bearings was estimated at longer than 8 years. In the next series of in vivo studies, an implantable model of the C1E3 pump will be fabricated for longer term implantation. The pump-actuator will be implanted inside the body; thus the design calls for substituting plastic for metallic parts.

Direct Measurement of Proximal Isovelocity Surface Area by Real-Time Three-Dimensional Color Doppler for Quantitation of Aortic Regurgitant Volume: An In Vitro Validation

OBJECTIVE 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. METHODS 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. RESULTS 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). CONCLUSION 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.

Development of a totally implantable biventricular bypass centrifugal blood pump system

BACKGROUND During the past 2 years, the development of a totally implantable biventricular bypass rotary blood pump system has been made. METHODS An extracorporeal gyro centrifugal pump, the CIE3, was miniaturized and developed into the PI601, a totally implantable plastic pump. Two-day anatomic and hemodynamic feasibility studies demonstrated that these two pump systems were easily implantable inside a calfs abdominal wall, directly under the diaphragm. The priming volume of the pump was 20 mL, with sufficient cardiac outputs at approximately 2,000 rpm and requiring less than 10 W of power. Two-week antithrombogenic screening tests also revealed these pump systems to be quite antithrombogenic. In addition, 1-month system reliability studies demonstrated fail-safe reliable performances. RESULTS AND CONCLUSIONS Encouraged by these preliminary studies, the PI601 model was converted to the permanently implantable titanium gyro pump PI702 model. The long-term implantations were initiated approximately 3 months ago, and two such long-term LVAD studies are currently underway with no sign of difficulty (October 10, 1997). They were followed 283 days and 72 days, respectively. Both terminated due to functional inflow obstruction. There were no blood clots or emboli at autopsy.

Evaluation of the Wear of the Pivot Bearing in the Gyro C1E3 Pump

To estimate the lifetime of the pivot bearing system of the sealless centrifugal Gyro C1E3 pump, pivot bearing wear phenomena of the C1E3 were studied. The pivot bearing system consisted of a male and female pivot made of ceramics and ultrahigh molecular weight polyethylene (UHMWPE), respectively. First, many pumping tests were performed with the C1E3 under various pumping conditions, and the effects of impeller position and fluid on wear were analyzed. Through these preliminary tests, it was found that the wear progress of the pivot bearing consisted of initial wear and stationary wear. Most of this initial wear is caused by the plastic deformation of the polyethylene female pivot. It also was observed that bovine blood was almost comparable to water in its effect on the stationary wear rate at the same rotational speed. Based on these results, a long-term pumping test was performed with the C1E3, and initial and stationary wear rates were determined. At the same time, the maximal loosening distance (LDmax) (permissible total wear) of the C1E3 was determined experimentally from hemolytic and hydraulic performance perspectives. By using experimentally determined parameters the lifetime of the pivot bearing system of the C1E3 pump was estimated for various pumping conditions. The lifetime of the pivot bearing system of the C1E3 was typically 10 years for right ventricular assist, 8 years for left ventricular assist, and 5 years for cardiopulmonary bypass.

Experimental and clinical evaluation of a noninvasive reflectance pulse oximeter sensor

The objective of this study was to evaluate a new reflectance pulse oximeter sensor. The prototype sensor consists of 8 light-emitting diode (LED) chips (4 at 665 nm and 4 at 820 nm) and a photodiode chip mounted on a single substrate. The 4 LED chips for each wavelength are spaced at 90-degree intervals around the substrate and at an equal radial distance from the photodiode chip. An optical barrier between the photodiode and LED chips prevents a direct coupling effect between them. Near-infrared LEDs (940 nm) in the sensor warm the tissue. The microthermocouple mounted on the sensor surface measures the temperature of the skin-sensor interface and maintains it at a preset level by servoregulating the current in the 940-nm LEDs. An animal study and a clinical study were performed. In the animal study, 5 mongrel dogs (weight, 10–20 kg) were anesthetized, mechanically ventilated, and cannulated. In each animal, arterial oxygen saturation (SaO2) was measured continuously by a standard transmission oximeter probe placed on the dogs earlobe and a reflectance oximeter sensor placed on the dogs tongue. In the first phase of the experiment, signals from the reflectance sensor were recorded while the dog was immersed in ice water until its body temperature decreased to 30°C. In the second phase, the animals body temperature was normal, and the oxygen content of the ventilator was varied to alter the SaO2. In the clinical study, 18 critically ill patients were monitored perioperatively with the prototype reflectance sensor. The first phase of the study investigated the relationship between local skin temperature and the accuracy of oximeter readings with the reflectance sensor. Each measurement was taken at a high saturation level as a function of local skin temperature. The second phase of the study compared measurements of oxygen saturation by a reflectance oximeter (SpO2[r]) with those made by a co-oximeter (SaO2[IL]) and a standard transmission oximeter (SpO2[t]). Linear regression analysis was used to determine the degree of correlation between (1) the pulse amplitude and skin temperature; (2) SpO2(r) and SaO2(IL); and (3) SpO2(t) and SaO2(IL). Studentst test was used to determine the significance of each correlation. The mean and standard deviation of the differences were also computed. In the animal study, pulse amplitude levels increased concomitantly with skin temperature (at 665 nm,r=0.9424; at 820 nm,r=0.9834;p<0.001) and SpO2(r) correlated well with SaO2(IL) (r=0.982; SEE=2.54%;p<0.001). The results of the clinical study are consistent with these findings. The proto-type reflectance pulse oximeter sensor can yield accurate measurements of oxygen saturation when applied to the forehead or cheek. It is, therefore, an effective alternative to transmission oximeters for perioperative monitoring of critically ill patients.

Characteristics of a Blood Pump Combining the Centrifugal and Axial Pumping Principles: The Spiral Pump

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.