Tadashi Nakazawa

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.

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.

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.

Biocompatibility of alumina ceramic and polyethylene as materials for pivot bearings of a centrifugal blood pump

The double pivot bearings in the Gyro C1E3 centrifugal blood pump incorporate a high-purity alumina (Al2O3) ceramic and an ultra-high-molecular-weight polyethylene (UHMWPE). This centrifugal pump has been developed as a completely sealless pump for long-term usage. The combination of Al2O3 and UHMWPE are the materials of choice for the acetabular bearing in artificial joints, which have proven to be clinically reliable for over 10 years. Previous studies have examined the biocompatibility of Al2O3 and UHMWPE as bulky implant materials. The present study investigated this material as a blood-contacting material using a standard assessment in vitro and in vivo analysis. The examined items were systemic toxicity, sensitization (guinea pig maximization test), cytotoxicity (elution test), mutagenicity (Ames test), direct contact hemolysis, and thrombogenicity. The studies were performed according to the United States Pharmacopoeia and published previous studies. The samples of both Al2O3 and UHMWPE demonstrated no differences from the negative controls in all tests. These findings indicate that both Al2O3 and UHMWPE are biocompatible materials for double-pivot bearings in the centrifugal blood pump.

Preclinical evaluation of the Kyocera Gyro centrifugal blood pump for cardiopulmonary bypass

The Kyocera Gyro pump has been developed as a completely seal-less centrifugal pump to overcome the problems of the conventional centrifugal pumps. The Gyro pump is a double pivot bearing-supported centrifugal pump with several specific design features, including its eccentric inlet port. We investigated the feasibility of the Gyro pump for cardiopulmonary bypass (CPB) in a bovine model, comparing it with the BioMedicus pump (BP-80). Ten healthy calves (5: Gyro pump, 5: BP-80) underwent 6 h of mildly hypothermic CPB at approximately 33°C. Both pumps provided more than 50 ml/kg/min without any incidents. The haemodynamics of both groups remained stable within the normal range. All haematology and biochemistry data demonstrated no significant differences between the two groups. However, values of plasma-free haemoglobin and lactate dehydrogenase were less throughout the experiments of the Gyro pump than those of the BP-80. To obtain flow equivalent to that of the BP-80, the Gyro pump needed less rotational speeds than the BP-80 (2749.7 ± 233.3 versus 3170.6 ±300.8 rpm, p < 0.05). Less rotational speed in addition to the difference in operating principle may contribute to less blood damage during the CPB of the Gyro pump. After pumping for CPB, no leakage or thrombus formation was observed in either pump. The present study indicated that the Kyocera Gyro pump can be applied as a centrifugal pump for CPB with the same performance as the BP-80 and with relatively less haemolysis than the BP-80.

Recent advances in the gyro centrifugal ventricular assist device

The gyro pump was developed as an intermediate-term assist pump (C1E3) as well as a long-term centrifugal ventricular assist device (VAD). The antithrombogenic design concept of this pump was confirmed throughout three 1 month ex vivo studies. The normalized index of hemolysis (NIH) of this gyro C1E3 model was lower than that of the BP-80. In the next step, a miniaturized centrifugal blood pump (The Gyro permanently implantable model PI-601) has been developed for use as a permanently implantable device after design optimization. A special motor design of the magnet circuit 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, 65 mm in diameter, 145 ml of displacement volume, and 305 g in weight. This pump can provide 5 L/min against 120 mm Hg total pressure head at 2,000 rpm. The NIH value of this pump was comparable to that of the BP-80. The gyro PI-601 model is suitable for a VAD. The expected life from the endurance study is approximately 8 years. The evolution from C1E3 to the PI-601 converts this pump to a totally implantable centrifugal pump. Recent technologic advances in continuous flow devices are likely to realize a miniaturized and economical totally implantable VAD.

Effect of Surface Roughness on Hemolysis in a Centrifugal Blood Pump

Surface roughness of a blood pump is an important factor for blood cell damage. This study investigated the effect of surface roughness pertaining to hemolysis in a centrifugal pump. In vitro hemolysis tests were performed under cardiopulmonary bypass (CPB; 5 L/min, 350 mmHg) and left ventricular assist device (LVAD; 5 L/min, 100 mmHg) conditions using the pivot bearing supported Gyro centrifugal pump (C1E3). Seven types of pumps with impellers and housings with different surface roughness were prepared as follows: vapor polish (VP) housing and VP impeller; VP housing and sandpaper (SP) impeller; VP housing and fine sandblasting (FSB) impeller; VP housing and coarse sandblasting (CSB) impeller; SP housing and VP impeller; FSB housing and VP impeller; and CSB housing and VP impeller. The results revealed that 1) the effect of surface roughness on hemolysis was significantly larger with CPB than LVAD; 2) surface roughness, regardless of the impeller or housing, had little effect on hemolysis with LVAD; and 3) during CPB, the surface roughness of the pump housing had a larger effect on hemolysis than did that of the impeller. In conclusion, from a hemolytic point of view, it is likely that an extremely smooth pump housing is required for an impeller centrifugal pump for CPB. However, it is likely that a smooth surface is not as essential for this impeller centrifugal pump as for an LVAD.

Double Chamber Ventricular Assist Device With a Roller Screw Linear Actuator Driven by Left and Right Latissimus Dorsi Muscles

A double chamber ventricular assist device (VAD) with a roller screw linear muscle actuator (RSLMA) driven by the left and right latissimus dorsi muscles was developed. The inflow port of each chamber was connected to form the compound inflow port, and the outflow ports were connected to form the compound outflow port. The advantages of this system include 1) the contraction of each muscle contributes to ejection from each ventricle into the common outflow port, thus doubling the net outflow; 2) through proper adjustment of muscle length, the preload to each muscle can be optimized to yield the maximum muscle force; 3) muscle can be stimulated at a lower rate to reduce fatigue and to optimize muscle performance; and 4) the compliance chamber needed in the implantable VAD system is not required with this system. In vitro evaluation in the mock loop with the human arm actuating the RSLMA revealed that the double chamber VAD can provide pump flows of 2-4 L/min against an afterload of 100 mmHg at a stimulation rate of 35-50 beats per minute. The power requirement for each muscle ranged from 2.5 to 3 W at a muscle stroke length of 4 cm. These results verify that the double chamber VAD with the RSLMA driven by the left and right latissimus dorsi muscles can meet the design requirements of a muscle driven VAD to assist the left heart.

A PIVOT BEARING-SUPPORTED CENTRIFUGAL PUMP FOR A LONG-TERM ASSIST HEART

A pivot bearing-supported centrifugal blood pump has been developed. It is a compact, cost effective, and anti-thrombogenic pump with anatomical compatibility. A preliminary evaluation of five paracorporeal left ventricular assist studies were performed on pre-conditioned bovine (70-100 kg), without cardiopulmonary bypass and aortic cross-clamping. The inflow cannula was inserted into the left ventricle (LV) through the apex and the outflow cannula affixed with a Dacron vascular graft was anastomosed to the descending aorta. All pumps demonstrated trouble free performance over a two-week screening period. Among these five studies, three implantations were subjected for one month system validation studies. All the devices were trouble free for longer than 1 month. (35, 34, and 31 days). After achieving one month studies, all experiments were terminated. There was no evidence of device induced thrombus formation inside the pump. The plasma free hemoglobin levels were within normal ranges throughout all experiments. As a consequence of these studies, a mass production model C1E3 of this pump was fabricated as a short-term assist pump. This pump has a Normalized Index of Hemolysis of 0.0007 mg/100L and the estimated wear life of the impeller bearings is longer than 8 years. The C1E3 will meet the clinical requirements as a cardiopulmonary bypass pump. For the next step, a miniaturized pivot bearing centrifugal blood pump PI-601 has been developed for use as a permanently implantable device after design optimization. The evolution from C1E3 to the PI-601 converts this pivot bearing centrifugal pump as a totally implantable centrifugal pump. A pivot bearing centrifugal pump will become an ideal assist pump for the patients with failing heart.

Development of an Implantable Centrifugal Ventricular Assist Device (CVAD)

The centrifugal ventricular assist device (CVAD) was developed for long-term circulatory support, and is capable of either intracorporeal implantation or paracorporeal placement. The pump was designed based on our antithrombogenic concepts: (1) sealless pump casing, (2) elimination of stationary parts, and (3) blood flow acceleration under the impeller. To meet conditions (1) and (2), a pivot bearing system was adopted to support the impeller. The inlet port was placed slightly off-center and inclined 60° towards the same direction as the outlet port. This port configuration not only yielded a space where an inlet cup bearing could be directly embedded but also allowed for a significant reduction of the pump height, hence, resulting in easier placement inside the body cavity. Two small secondary vanes were installed in the bottom of the impeller to satisfy condition (3). Five paracorporeal left ventricular (LV) AD studies, using calves, were performed to evaluate the antithrombogenic design of the pump. The first two cases were subjected to 2-week tests. With the activated clotting time (ACT) kept at 250 s with heparin, the initial two cases had trouble-free performances over the 2 weeks. Following these successful results, another three cases were subjected to 1-month validation studies, in which there was no device-induced thrombus formation inside the pump housing. These results confirm that the CVAD, the C1E3, meets the requirements for a 1-month paracorporeal LVAD.