Collected nondimensional performance of rotary dynamic blood pumps.

"Nonpulsatile" or "continuous flow" blood pumps are a relatively new application of the rotary dynamic blood pumping principle. They fall outside the normal envelop of pumps, considering their small size, viscosity of the fluid pumped, need for particularly good internal flow patterns, and desire for high efficiency. This article establishes the state of the art in the field of blood pump performance. Trends in efficiency, shut off pressure coefficient, and nondimensional power behavior as a function of nondimensional flow are identified. Blood pumps show agreement with the published effects of low Reynolds numbers in conventional pumps.

Design of a continuous flow centrifugal pediatric ventricular assist device.

Thousands of pediatric patients suffering from cardiomyopathy or single ventricular physiologies secondary to debilitating heart defects may benefit from long-term mechanical circulatory support due to the limited number of donor hearts available. This article presents the initial design of a fully implantable centrifugal pediatric ventricular assist device (PVAD) for 2 to 12 year olds. Conventional pump design equations, including a nondimensional scaling approach, enabled performance estimations of smaller scale versions (25 mm and 35 mm impeller diameters) of our adult support VAD. Based on this estimated performance, a computational model of the PVAD with a 35 mm impeller diameter was generated. Employing computational fluid dynamics (CFD) software, the flow paths through the PVAD and overall performance were analyzed for steady state flow conditions. The numerical simulations involved flow rates of 2 to 5 LPM for rotational speeds of 2750 to 3250 RPM and incorporated a k-epsilon fluid turbulence model with a logarithmic wall function to characterize near-wall flow conditions. The CFD results indicated best efficiency points ranging from 25% to 28%, which correlate well with typical values of blood pumps. The results further demonstrated that the pump could deliver 2 to 5 LPM at 70 to 95 mmHg for desired physiologic conditions in resting 2 to 12 year olds. Scalar stress levels remained below 300 Pa, thereby signifying potentially low levels of hemolysis. Several flow regions in the pump exhibited signs of vortices, retrograde flow, and stagnation points, which require optimization and further study. This CFD model represents a reasonable starting point for future model enhancements, leading to prototype manufacturing and experimental validation.

The application of quantitative oil streaking to the HeartQuest left ventricular assist device.

Methods of flow visualization using oil streaking are established techniques for investigating surface shear and near wall flow patterns. Recent studies have used an array of oil dots on a surface which form streaks when exposed to shear forces. This method is generally qualitative, but it is possible to make quantitative measurements of the shear if the oil streaks have been calibrated. This paper presents the application of a quantitative oil streak method to the HeartQuest left ventricular assist device (LVAD). An array of dots was applied to the top housing of the pump, yielding quantitative values for the shear and qualitative patterns of the near wall flow in that region. The results were used to locate regions likely to promote thrombosis, such as stagnation points or recirculation regions. Regions of high shear, where hemolysis might occur, also can be identified with this method. In addition to being an important design technique, quantitative oil streaking assisted in the verification of computational fluid dynamics results within the HeartQuest LVAD.

Particle image velocimetry measurements of blood velocity in a continuous flow ventricular assist device.

The third prototype of a continuous flow ventricular assist device (CFVAD3) is being developed and tested for implantation in humans. The blood in the pump flows through a fully shrouded four-bladed impeller (supported by magnetic bearings) and through small clearance regions on either side of the impeller. Measurements of velocities using particle image velocimetry of a fluid with the same viscosity as blood have been made in one of these clearance regions. Particle image velocimetry is a technique that measures the instantaneous velocity field within an illuminated plane of the fluid field by scattering light from particles added to the fluid. These measurements have been used to improve understanding of the fluid dynamics within these critical regions, which are possible locations of both high shear and stagnation, both of which are to be avoided in a blood pump. Computational models of the pump exist and these models are currently being used to aid in the design of future prototypes. Among other things, these models are used to predict the potential for hemolysis and thrombosis. Measurements of steady flow at two operating speeds and flow rates are presented. The measurements are compared with the computed solutions to validate and refine, where necessary, the existing computational models.

Effects of radiation therapy on vascular responsiveness.

The use of radiation therapy to inhibit vascular proliferative diseases has produced encouraging results in several clinical trials. However, little is known about the possible side effects of radiation on vascular responsiveness. Our goal was to study the in vitro vascular responses of the rabbit aorta to various agonists immediately after several regimens of radiation therapy administered at doses prescribed in clinical protocols and at two different dose rates. High-dose-rate radiation was administered either by brachytherapy, using a gamma source, iridium 192, or an external electron beam producing beta radiation. Low-dose-rate radiation was administered by brachytherapy using a liquid-filled balloon with the beta emitter 32P. Vascular reactivity after the various regimens of irradiation was determined using the organ bath pharmacology assay. Various agonists were applied to the rabbit aorta to produce full cumulative concentration-response curves. Radiation, administered using an external electron beam, did not alter endothelium-dependent relaxation of the aorta induced by acetylcholine. However, the use of a catheter-based system to deliver radiation disrupted the endothelial cell lining of the vessel, causing a lack of relaxation by acetylcholine. Therefore, to compare all modalities of radiation therapy on vascular responsiveness, the agonists used in this study are known to act directly on the smooth muscle. Radiation therapy had no effect on the contractile responses induced by the following agonists: phenylephrine and potassium chloride. Vascular dilatation induced by nitroglycerin, a nitric oxide donor, was unaffected by radiation therapy. The contractile response induced by des-Arg9-bradykinin, a kinin B1 receptor agonist, was significantly increased twofold to threefold by all types of irradiation under study. This enhanced response is attributable to an increase of mRNA levels coding for this receptor. In all cases, radiation therapy did not alter the effective concentration producing 50% of maximal responsiveness (EC50) and did not reduce the vascular responsiveness induced by agonists. Taken together, we conclude that radiation therapy does not hinder endothelium-independent vascular responsiveness and increases the kinin B1 receptor-mediated vasoconstriction.

Synaptic interactions regulate gephyrin expression in avian cholinergic neurons in vivo.

Our recent studies of chick parasympathetic ciliary ganglion (CG) neurons demonstrate a unique postsynaptic receptor microheterogeneity - under one presynaptic terminal, excitatory nicotinic acetylcholine receptor (nAChR) clusters and separate inhibitory glycine receptor (GlyR) clusters coexist in distinct membrane microregions. Gephyrin, a peripheral membrane protein that is required for GlyR clustering at synapses in the rodent central nervous system, is also expressed in chick CG neurons where it codistributes with GlyRs, but not nAChRs. We now extend these findings by characterizing the regulation of gephyrin expression in chick CG neurons in vivo. We show that developmental increases in gephyrin transcript levels occur during pre- and postganglionic synapse formation. The increases are induced by both innervation and target tissue interactions, with the target tissues having the greater regulatory influence. The time course of the developmental rise in gephyrin mRNA levels most closely resembles that reported for functional GlyR expression, but not that of functional nAChRs nor GABA(A) receptors. We also demonstrate that gephyrin is concentrated in the postsynaptic density of a subset of synapses on both the ciliary and choroid neurons in the CG and is stably expressed from embryonic to adult stages. Altogether, our results suggest that gephyrin is a synapse organizing molecule that functions to localize GlyRs, but not nAChRs, to discrete postsynaptic membrane microregions in chick CG neurons in vivo.

Numerical studies of blood shear and washing in a continuous flow ventricular assist device.

The third prototype of a continuous flow ventricular assist device (CF3) is being developed and tested for implantation in humans. The blood in the pump flows through a fully shrouded four bladed impeller (supported by magnetic bearings) and through small clearance regions on either side of the impeller. Computational fluid dynamics (CFD) solutions for this flow have been obtained by using TascFlow, a software package available from AEA Technology, UK. These flow solutions have been used to estimate the shear stresses on the blood in the pump and, hence, to minimize hemolysis. In addition, the solutions are informative for achieving a design that will provide good washing of the blood to minimize the possibility of stagnation points that can lead to thrombosis. This study presents numerical studies of these phenomena in the CF3. The calculated shear rate results are compared with values published in the open literature. The comparisons indicate that hemolysis will not be a problem with CF3, which is in agreement with preliminary experimental measurements. Flow studies are being conducted to determine the optimal size of the clearance regions.

Numerical analysis of blood flow in the clearance regions of a continuous flow artificial heart pump.

The CFVAD3 is the third prototype of a continuous flow ventricular assist device being developed for implantation in humans. The pump consists of a fully shrouded 4-blade impeller supported by magnetic bearings. On either side of this suspended rotating impeller is a small clearance region through which the blood flows. The spacing and geometry of these clearance regions are very important to the successful operation of this blood pump. Computational fluid dynamics (CFD) solutions for this flow were obtained using TascFlow, a software package available from AEA Technology, U.K. Flow in these clearance regions was studied parametrically by varying the size of the clearance, the blood flow rate into the pump, and the rotational speed of the pump. The numerical solutions yield the direction and magnitude of the flow and the dynamic pressure. Experimentally measured pump flow rates are compared to the numerical study. The results of the study provide guidance for improving pump efficiency. It is determined that current clearances can be significantly reduced to improve pump efficiency without negative impacts.

Computational flow study of the continuous flow ventricular assist device, prototype number 3 blood pump.

A computational fluid dynamics study of blood flow in the continuous flow ventricular assist device, Prototype No. 3 (CFVAD3), which consists of a 4 blade shrouded impeller fully supported in magnetic bearings, was performed. This study focused on the regions within the pump where return flow occurs to the pump inlet, and where potentially damaging shear stresses and flow stagnation might occur: the impeller blade passages and the narrow gap clearance regions between the impeller-rotor and pump housing. Two separate geometry models define the spacing between the pump housing and the impeller's hub and shroud, and a third geometry model defines the pump's impeller and curved blades. The flow fields in these regions were calculated for various operating conditions of the pump. Pump performance curves were calculated, which compare well with experimentally obtained data. For all pump operating conditions, the flow rates within the gap regions were predicted to be toward the inlet of the pump, thus recirculating a portion of the impeller flow. Two smaller gap clearance regions were numerically examined to reduce the recirculation and to improve pump efficiency. The computational and geometry models will be used in future studies of a smaller pump to determine increased pump efficiency and the risk of hemolysis due to shear stress, and to insure the washing of blood through the clearance regions to prevent thrombosis.

Receptors with opposing functions are in postsynaptic microdomains under one presynaptic terminal.

Fast excitatory synaptic transmission through vertebrate autonomic ganglia is mediated by postsynaptic nicotinic acetylcholine receptors (nAChRs). We demonstrate a unique postsynaptic receptor microheterogeneity on chick parasympathetic ciliary ganglion neurons-under one presynaptic terminal, nAChRs and glycine receptors formed separate but proximal clusters. Terminals were loaded with [3H]glycine via the glycine transporter-1 (GlyT-1), which localized to the cholinergic presynaptic terminal membrane; depolarization evoked [3H]glycine release that was calcium independent and blocked by the GlyT-1 inhibitor sarcosine. Ganglionic synaptic transmission mediated by nAChRs was attenuated by glycine. Coexistence of separate clusters of receptors with opposing functions under one terminal contradicts Dale's principle and provides a new mechanism for modulating synaptic activity in vivo.

A magnetic bearing system for a continuous ventricular assist device.

This article describes a prototype continuous flow ventricular assist device (CFVAD3) supported in magnetic bearings. The VAD is a small centrifugal four bladed pump. The pump's geometry is explained. The CFVAD3 is the first compact VAD completely supported in magnetic bearings. The magnetic bearings are composed of an inlet side actuator divided into eight pole sets, and an outlet side actuator, also divided into eight pole sets. The pump operating performance was tested and found to be within the design flow rate of up to 9 L/min, and head up to 170 mm Hg for human circulatory support. Magnetic bearing operation out of center positions under various operating orientations were measured and found to be < 1/6 of the bearing clearance, well within specifications. The expected magnetic bearing power loss has been calculated at approximately 6.5 watts.

Blood flow in a continuous flow ventricular assist device.

A numerical analysis was performed to predict the shear stresses, flow rates, and the velocity profiles in a continuous flow ventricular assist device, the CFVAD3. The problem was modeled as a rotating disk over a stationary disk. A variety of clearances was tested for the CFVAD3 coupled with a range of rotational speeds and pressure gradients. Velocity fields were generated using solutions obtained with FLOW3D software (AEA Technology, Pittsburgh, PA, U.S.A.) Analysis of these solutions shows that the pressure differential effect has a stronger influence on the flow than the rotational effect of the impeller Ekman layer. The predicted shear stresses reflect these changes in the volume flow rates and the speeds shown in the velocity profiles. Based on the predictions of the software, the optimum clearance and rotational speed were chosen. The conclusion is that a speed in the range of 2,200-2,400 rpm should be chosen depending on the efficiency of the pump.

Characterization of a magnetic bearing system and fluid properties for a continuous flow ventricular assist device.

This article presents the performance test results of the CFVAD3 continuous flow blood pump in an artificial human circulation system. The CFVAD3 utilizes magnetic bearings that support a thin pancake impeller, the shape of which allows for a very compact pump whose total axial length is less than 5 cm with a radial length of about 10 cm. This gives a total volume of about 275 cc. The impeller itself has 4 vanes with a designed operating point of 6 L/min at 100 mm Hg of differential pressure and 2,000 rpm. The advantages of magnetic bearings, such as large clearance spaces and no mechanical wear, are elaborated upon. Furthermore, bearing model parameters such as load capacity and current gains are described. These parameters in conjunction with the operating conditions during testing are then used to estimate the fluid forces, stiffness, and damping properties while pumping. Knowledge of these parameters is desirable because of their effects on pump behavior. In addition, a better plant model will allow more robust control algorithms to be devised that can boost pump performance and reliability.

Test controller design, implementation, and performance for a magnetic suspension continuous flow ventricular assist device.

A new continuous flow ventricular assist device using full magnetic suspension has been designed, constructed, and tested. The magnetic suspension centers the centrifugal pump impeller within the clearance passages in the pump, thus avoiding any form of contact. The noncontact operation is designed to give very high expected mechanical reliability, large clearances, low hemolysis, and a relatively small size compared to current pulsatile devices. A unique configuration of magnetic actuators on the inlet side and exit sides of the impeller provides full 5 axis control and suspension of the impeller. The bearing system is divided into segments which allow for 3 displacement axes and 2 angular control axes. The controller chosen for the first suspension tests consists of a decentralized set of 5 proportional integral derivative (PID) controllers. This document describes both the controller and an overview of some results pertaining to the magnetic bearing performance. The pump has been successfully operated in both water and blood under design conditions suitable for use as a ventricular assist device.

Motor feedback physiological control for a continuous flow ventricular assist device.

The response of a continuous flow magnetic bearing supported ventricular assist device, the CFVAD3 (CF3) to human physiologic pressure and flow needs is varied by adjustment of the motor speed. This paper discusses a model of the automatic feedback controller designed to develop the required pump performance. The major human circulatory, mechanical, and electrical systems were evaluated using experimental data from the CF3 and linearized models developed. An open-loop model of the human circulatory system was constructed with a human heart and a VAD included. A feedback loop was then closed to maintain a desired reference differential pressure across the system. A proportional-integral (PI) controller was developed to adjust the motor speed and maintain the system reference differential pressure when changes occur in the natural heart. The effects of natural heart pulsatility on the control system show that the reference blood differential pressure is maintained without requiring CF3 motor pulsatility.

Numerical solution for blood flow in a centrifugal ventricular assist device.

A very small centrifugal pump, fully supported by magnetic bearings, is being developed for use as a ventricular assist device to be implanted in humans. In this paper, we apply computational fluid dynamics to model the blood flow to aid in the design of the ventricular assist device. The flow of blood through the pump has been modeled using computational fluid dynamics (CFD) software that is commercially available from AEA Technology, UK. The flow regions modeled in version 3 of the Continuous Flow Ventricular Assist Device (CF3) are the fully shrouded four bladed impeller and the two clearance regions around the impeller that are bounded by the pump hub and shroud. This paper describes the geometry and computational grids developed for the flow regions, and the equations of motion for the blood flow are developed. The overall numerically-evaluated flow rates and head rise have similar trends to the flow parameters experimentally measured, indicating that future pump designs can be effectively modeled numerically before being constructed and tested. Numerical solutions are presented and compared with experimentally-obtained overall pump performance results. These solutions are used to predict shear stress levels to be experienced by the blood flowing through the pump, and it is predicted that hemolysis will be insignificant. The solutions also indicate no regions of flow stagnation that can be a source of thrombosis in pumps. The calculations provide a viable design method to achieve improved efficiency in future versions of this pump.

Implantable centrifugal pump with hybrid magnetic bearings.

Test methods and results of in vitro assessment of a centrifugal pump with a magnetically suspended impeller are provided. In vitro blood tests have been completed with a resulting normalized milligram index of hemolysis (NmIH) of 12.4 +/- 4.1, indicating that hemolysis is not a problem. Hydraulic characterization of the system with water has shown that a nominal pumping condition of 6 L/min at 100 mmHg was met at 2,200 rpm. Maximum clinically usable cardiac output is predicted be 10 L/min. The magnetic bearing supported impeller did not contact the housing and was shown to be stable under a variety of pumping conditions. The driving motor efficiency is 75% at the nominal condition. Finally, a description of the clinical version of the pump under development is provided.

Performance of a continuous flow ventricular assist device: magnetic bearing design, construction, and testing.

A new centrifugal continuous flow ventricular assist device, the CFVAD III, which is fully magnetic bearing suspended, has been developed. It has only one moving part (the impeller), has no contact (magnetic suspension), is compact, and has minimal heating. A centrifugal impeller of 2 inch outer diameter is driven by a permanent magnet brushless DC motor. This paper discusses the design, construction, testing, and performance of the magnetic bearings in the unit. The magnetic suspension consists of an inlet side magnetic bearing and an outlet side magnetic bearing, each divided into 8 pole segments to control axial and radial displacements as well as angular displacements. The magnetic actuators are composed of several different materials to minimize size and weight while having sufficient load capacity to support the forces on the impeller. Flux levels in the range of 0.1 T are employed in the magnetic bearings. Self sensing electronic circuits (without physical sensors) are employed to determine the impellar position and provide the feedback control signal needed for the magnetic bearing control loops. The sensors provide position sensitivity of approximately 0.025 mm. A decentralized 5 axis controller has been developed using modal control techniques. Proportional integral derivative controls are used for each axis to levitate the magnetically supported impeller.