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.

Relief by naloxone of morphine-induced spasm of the sphincter of Oddi in a post-cholecystectomy patient.

Spasm of the sphincter of Oddi is a well-recognized effect of the narcotic class of drugs. Although it is usually clinically silent, such spasm occasionally causes debilitating pain that may be mistaken for more serious disorders. We present the case of a patient who had undergone cholecystectomy previously, but in whom morphine given in the Emergency Department precipitated pain consistent with biliary colic; the pain resolved promptly after administration of naloxone. This entity may considered in the differential diagnosis of acute onset of colicky abdominal pain in the patient given narcotics.

HeartMate left ventricular assist devices: a multigeneration of implanted blood pumps.

The HeartMate family of implanted left ventricular assist devices (LVADs) developed by Thermo Cardiosystems, Inc. (TCI) span a time frame that goes back to the beginning of clinical use of mechanical circulatory support and will stretch well into the foreseeable future. Associated blood pump technology employed in the HeartMates range from an original pusher plate concept to the most advanced rotary pump devices. Starting initially with a pneumatic actuated pusher plate pump, clinical use of the HeartMate I began in 1986. In 1990, electric motor-actuated versions of the HeartMate I began to be used clinically. Presently, the HeartMate I has been implanted in some 2,300 patients worldwide, and this LVAD is a standard by which all others are currently measured. Following the HeartMate I is TCI's next-generation, the HeartMate II, a rotary-pump-based LVAD that uses an axial flow blood pump having blood immersed mechanical bearings. Clinical trials of the HeartMate II were initiated in 2000. The HeartMate III, representing TCI's next-generation LVAD, is structured around a centrifugal blood pump that uses a magnetically levitated rotating assembly. Compared to the HeartMate II, the HeartMate III has the potential for higher overall efficiency. The pump's operating life is not dependent on bearing wear. Given the significantly advanced LVAD technology represented by HeartMates II and III, coupled with the experience of HeartMate I, TCI is well-poised to keep its LVAD products as industry standards in the future.

HeartMate II left ventricular assist system: from concept to first clinical use.

The HeartMate II left ventricular assist device (LVAD) (ThermoCardiosystems, Inc, Woburn, MA) has evolved from 1991 when a partnership was struck between the McGowan Center of the University of Pittsburgh and Nimbus Company. Early iterations were conceptually based on axial-flow mini-pumps (Hemopump) and began with purge bearings. As the project developed, so did the understanding of new bearings, computational fluid design and flow visualization, and speed control algorithms. The acquisition of Nimbus by ThermoCardiosystems, Inc (TCI) sped developments of cannulas, controller, and power/monitor units. The system has been successfully tested in more than 40 calves since 1997 and the first human implant occurred in July 2000. Multicenter safety and feasibility trials are planned for Europe and soon thereafter a trial will be started in the United States to test 6-month survival in end-stage heart failure.

Fluid dynamic characterization of operating conditions for continuous flow blood pumps.

As continuous flow pumps become more prominent as long-term ventricular assist devices, the wide range of conditions under which they must be operated has become evident. Designed to operate at a single, best-efficiency, operating point, continuous flow pumps are required to perform at off-design conditions quite frequently. The present study investigated the internal fluid dynamics within two representative rotary fluid pumps to characterize the quality of the flow field over a full range of operating conditions. A Nimbus/UoP axial flow blood pump and a small centrifugal pump were used as the study models. Full field visualization of flow features in the two pumps was conducted using a laser based fluorescent particle imaging technique. Experiments were performed under steady flow conditions. Flow patterns at inlet and outlet sections were visualized over a series of operating points. Flow features specific to each pump design were observed to exist under all operating conditions. At off-design conditions, an annular region of reverse flow was commonly observed within the inlet of the axial pump, while a small annulus of backflow in the inlet duct and a strong disturbed flow at the outlet tongue were observed for the centrifugal pump. These observations were correlated to a critical nondimensional flow coefficient. The creation of a "map" of flow behavior provides an additional, important criterion for determining favorable operating speed for rotary blood pumps. Many unfavorable flow features may be avoided by maintaining the flow coefficient above a characteristic critical coefficient for a particular pump, whereas the intrinsic deleterious flow features can only be minimized by design improvement. Broadening the operating range by raising the band between the critical flow coefficient and the designed flow coefficient, is also a worthy goal for design improvement.

Development of the Nimbus/University of Pittsburgh innovative ventricular assist system.

BACKGROUND: Nimbus Inc, and the University of Pittsburgh's McGowan Center for Artificial Organ Development have been collaborators on rotary blood pump technology initiatives since 1992. Currently, a major focus is an innovative ventricular assist system (IVAS) that features an implantable, electrically powered axial flow blood pump. In addition to the blood pump, a major development item is the electronic controller and the control algorithm for modulating pump speed in response to varying physical demand. METHODS: Methods used in developing the IVAS include computational fluid dynamic modeling of the pump's interior flow field, flow visualization of the flow field using laser-based imaging, computer simulation of blood pump-physiological interactions, vibroaccoustic monitoring, and an extensive in vivo test program. RESULTS: Results to date, which are presented below, include successful in vivo tests of blood pumps with blood-immersed bearings, and feasibility demonstration of vibroacoustic monitoring in this application. CONCLUSIONS: This unique blend of industrial experience and technologies with the University-based Research and Development Center has greatly enhanced the progress made on this IVAS project.

A computational and experimental comparison of two outlet stators for the Nimbus LVAD. Left ventricular assist device.

Two designs of an outlet stator for the Nimbus axial flow left ventricular assist device (LVAD) are analyzed at nominal operating conditions. The original stator assembly (Design 1) has significant flow separation and reversal. A second stator assembly (Design 2) replaces the original tubular outer housing with a converging-diverging throat section with the intention of locally improving the fluid dynamics. Both stator designs are analyzed using computational fluid dynamics (CFD) analysis and experimental particle imaging flow visualization (PIFV). The computational and experimental methods indicate: 1) persistent regions of flow separation in Design 1 and improved fluid dynamics in Design 2; 2) blade-toblade velocity fields that are well organized at the blade tip yet chaotic at the blade hub for both designs; and 3) a moderate decrease in pressure recovery for Design 2 as compared with Design 1. The CFD analysis provides the necessary insight to identify a subtle, localized flow acceleration responsible for the decreased hydraulic efficiency of Design 2. In addition, the curiously low thrombogenicity of Design 1 is explained by the existence of a three-dimensional unsteady vortical flow structure that enhances boundary advection.

Chronic animal health assessment during axial ventricular assistance: importance of hemorheologic parameters.

Chronic testing of the Nimbus/UOP Axial Flow Pump was performed on 22 calves for periods of implantation ranging from 27 to 226 days (average, 74 days). The following parameters were measured: plasma free hemoglobin, blood and plasma viscosity, erythrocyte deformability and mechanical fragility, oxygen delivery index (ODI), blood cell counts, hematocrit, hemoglobin, blood urea nitrogen, creatinine, bilirubin, total protein, fibrinogen, and plasma osmolality. Most of the above parameters were stable during the full course of support. Compared with baseline, statistically significant differences during the entire period of implantation were only found in: hematocrit (p<0.001), hemoglobin (p<0.005), red blood cell (RBC) count (p<0.001), and whole blood viscosity (p<0.01). Plasma viscosity and ODI were mostly stable during the period of implantation. In some animals, an acute increase in fibrinogen concentration, plasma and blood viscosity, and a decrease in ODI were found to be early signs of the onset of infection. A small (10%) decrease in deformability of RBCs was found during the first 2 weeks after implantation. This alteration in RBC deformability was highly correlated (r = 0.793) with changes in total plasma protein concentration that fell more than 15% (p<0.001) during the same period. Mechanical fragility of RBCs was found to be slightly increased after implantation. Plasma free hemoglobin remained close to baseline level (p>0.2). After the first 2 weeks of the postoperative period, pump performing parameters for all animals were consistent and stable. In general, the Nimbus/UOP Axial Flow Pump demonstrated basic reliability and biocompatibility and did not produce significant alterations in the mechanical properties of blood or animal health status. The pump provided adequate hemodynamics and was well tolerated by the experimental animal for periods as long as 7.5 months. Monitoring rheologic parameters of blood is very helpful for evaluation of health during heart-assist device application.

Progress on development of the Nimbus-University of Pittsburgh axial flow left ventricular assist system.

Nimbus Inc. (Rancho Cordova, CA) and the University of Pittsburgh have completed the second year of development of a totally implanted axial flow blood pump under the National Institutes of Health Innovative Ventricular Assist System Program. The focus this year has been on completing pump hydraulic development and addressing the development of the other key system components. Having demonstrated satisfactory pump hydraulic and biocompatibility performance, pump development has focused on design features that improve pump manufacturability. A controller featuring full redundancy has been designed and is in the breadboard test phase. Initial printed circuit layout of this circuit has shown it to be appropriately sized at 5 x 6 cm to be compatible with implantation. A completely implantable system requires the use of a transcutaneous energy transformer system (TETS) and a diagnostic telemetry system. The TETS power circuitry has been redesigned incorporating an improved, more reliable operating topography. A telemetry circuit is undergoing characterization testing. Closed loop speed control algorithms are being tested in vitro and in vivo with good success. Eleven in vivo tests were conducted with durations from 1 to 195 days. Endurance pumps have passed the 6 month interval with minimal bearing wear. All aspects of the program continue to function under formal quality assurance.

Continued development of the Nimbus/University of Pittsburgh (UOP) axial flow left ventricular assist system.

Nimbus and the University of Pittsburgh (UOP) have continued the development of a totally implanted axial flow blood pump under the National Institutes of Health (NIH) Innovative Ventricular Assist System (IVAS) program. This 62 cc device has an overall length of 84 mm and an outer diameter of 34.5 mm. The inner diameter of the blood pump is 12 mm. It is being designed to be a totally implanted permanent device. A key achievement during the past year was the completion of the Model 2 pump design. Ten of these pumps have been fabricated and are being used to conduct in vitro and in vivo experiments to evaluate the performance of different materials and hydraulic components. Efforts for optimizing the closed loop speed control have continued using mathematical modeling, computer simulations, and in vitro and in vivo testing. New hydraulic blade designs have been tested using computational fluid dynamics (CFD) and flow visualization. A second generation motor was designed with improved efficiency. To support the new motor, a new motor controller fabricated as a surface mount PC board has been completed. The program is now operating under a formal QA system.

Survival for up to six months in calves supported with an implantable axial flow ventricular assist device.

This paper summarizes the authors' in vivo experience to date with an implantable axial flow blood pump designed for long-term ventricular support. This small, valveless pump with blood-lubricated bearings has been implanted in six calves (83 +/- 6 kg) as a left ventricular assist device (LVAS). The left ventricle and descending thoracic aorta were cannulated by left thoracotomy, and the pump was placed in a subcutaneous pocket below the costal margin. Animals remained hemodynamically stable throughout the course of support during partial left ventricular bypass. Five animals were killed after 15, 27, 52, 57, and 181 days. The longest survivor (181 days) demonstrated normal pump function at the time death. Pump speed was maintained at 10,100 +/- 100 rpm, with an average pump flow rate of 4.9 +/- 0.5 L/min under resting physiologic conditions. Average plasma free hemoglobin was 17.4 +/- 7.5 mg/dl. Renal, hepatic, and hematologic indices remained within physiologic range in all of these animals, except during the immediate postoperative period. Histopathologic analyses of major organs after death revealed small renal cortical infarcts in five of six animals; the remaining organs were normal. These animal studies support the feasibility of this small implanted axial flow pump for long-term ventricular assistance.

In vivo evaluation of an extracorporeal pediatric centrifugal blood pump.

This paper summarizes the authors' in vivo experience in evaluating a miniature centrifugal blood pump designed for pediatric/neonatal ventricular support. Left ventricular bypass was accomplished in two adult sheep and five juvenile lambs (5.5-80.0 kg) via either central (left ventricle to carotid artery) or peripheral (jugular vein to carotid artery) cannulation. Animals were weaned from mechanical ventilation and continuously monitored. Hemodynamic parameters remained within a normal range over the duration of the bypass. Two of five lambs were electively killed at 8, and 76 hours; the remaining three lambs died from respiratory complications at 33, 44, and 156 hours. There were no mechanical complications, and blood seal integrity was confirmed beyond 6 days. The pump speed was maintained at 3,000-4,500 rpm with pump flow rates between 0.4-1.5 L/min. Average plasma free hemoglobin was below 20 mg/dl in the five lamb experiments. Renal, hepatic, and hematologic indices also remained within physiologic ranges. Histopathologic analyses of major organs revealed renal cortical infarctions in two of five lambs. Examination of the pump surfaces after explant indicated small areas of thrombus in the housing adjacent to the outflow ports in two experiments. These encouraging results support further testing and refinement of this miniature centrifugal pump.

Anatomic fitting studies of a total artificial heart in heart transplant recipients. Critical dimensions and prediction of fit.

Anatomic fitting studies of the Cleveland Clinic-Nimbus total artificial heart were performed in 33 patients undergoing heart transplantation. The pump fit in the pericardial space in 20 men (80%) and 4 women (50%). There was no significant difference between the Fit and Non-Fit groups in external chest dimensions. Among 42 intrathoracic dimensions, the distance from the center of the mitral valve to the diaphragm (Fit: 5.6 +/- 2.2 cm, Non-Fit: 3.6 +/- 0.4 cm, p < 0.00001) and the distance from the caudal end of the pulmonary valve to the diaphragm (Fit: 9.4 +/- 1.6 cm, Non-Fit: 6.3 +/- 0.8 cm, p < 0.0001) were the most critical. To predict anatomic fit, an index (A x B x C) was obtained from chest X-ray measurements (A, the craniocaudal distance from the dorsal region of the 8th left rib to the left diaphragm; B, the maximum left chest width; and C, the maximum anteroposterior sternum-vertebrae dimension). The pump fit in 88.5% of the patients with an index above 1200 cm3, whereas it fit in only 14.3% of the patients with an index below 1200 cm3 (p < 0.001). This index was an easily obtainable, good predictor of anatomic fit.

Controller for an axial flow blood pump.

A rotary blood pump inherently provides only one noninvasive "observable" parameter (motor current) and allows for only one "controllable" parameter (pump speed.) To maintain the systemic circulation properly, the pump seed must be controlled to sustain appropriate outlet flows and perfusion pressure while preventing pulmonary damage caused by extremes in preload. Steady-state data were collected at repeated intervals during chronic trials of the Nimbus AxiPump (Nimbus, Inc., Rancho Cordova, California, U.S.A.) in sheep (n = 7) and calves (n = 12). For each data set, the pump speed was increased at increments of 500 rpm until left ventricular and left atrial emptying was observed by left atrial pressure diminishing to zero. The effect of decreasing preload was evaluated perioperatively by inferior vena cava occlusion at a constant pump speed. Fourier analysis established a relationship between changes in the pump preload and the power spectra of the pump current waveform. Based on these results, a control method was devised to avoid ventricular collapse and maintain the preload within a physiologic range. The objective of this controller is the minimization of the second and third harmonic of the periodic current waveform. This method is intended to provide a noninvasive regulation of the pump by eliminating the need for extraneous transducers.

Long-term animal survival with an implantable axial flow pump as a left ventricular assist device.

We are developing an axial flow blood pump with Nimbus Inc. (AxiPump). For in vivo evaluation the AxiPump has been used as a left ventricular assist device with a left ventricular and descending aorta cannulation and implantation in a small pocket on the left lateral abdominal wall just posterior to the costal margin. Electrical and flow probe leads exit the body transcutaneously. A purge line that delivers the purge fluid for lubrication of the seal between the rotor and stator bodies in the purge fluid bearing system is tunneled with the other leads. Following acute animal studies, 3 animals have been supported for over 1 month with this AxiPump system. All laboratory results were within normal limits except during a recovery period from surgical damage. Hemolysis was not a serious problem. In the first case, the purge system failed at 28 days, and in the second and third cases, the nonpurge bearing system worked well for 57 and 52 days, respectively. Bearings are still under development in this kind of pump. However, this success encourages us to improve the AxiPump as a long-term assist device.

Development and initial testing of a pediatric centrifugal blood pump.

BACKGROUND: We are developing a miniaturized centrifugal blood pump for use as a temporary cardiac assist device in neonatal and pediatric sized patients. This pump has a very low priming volume of 13 mL. A small motor stator has also been designed, which resulted in a device that can be placed very close to the patient, thereby minimizing overall circuit volume. METHODS: Testing to date has included in vitro hemodynamic performance, in vitro hemolysis generation, and in vivo evaluation in 5 lambs weighing 5.5 to 21 kg. Two lambs underwent peripheral cannulation from external jugular vein to carotid artery, whereas 3 others were cannulated from left atrium to carotid artery. RESULTS: In vitro data demonstrated pump capacity spanning 0.3 to 3.0 L/min and very low hemolysis generation at these conditions. In vivo, the pump functioned satisfactorily for periods up to 148 hours, and the bypass appeared to be well tolerated by the animals. Plasma free hemoglobin levels remained less than 25 mg/dL during all animal experiments. All devices were thrombus-free at explantation. CONCLUSIONS: We conclude that this device has merit as an alternative to current oversized systems used for neonatal and pediatric cardiac assistance. In addition, a chronic neonatal lamb model in which to evaluate pediatric circulatory assist devices has been developed successfully.

Mechanisms of red blood cell trauma in assisted circulation. Rheologic similarities of red blood cell transformations due to natural aging and mechanical stress.

Clinical experience with circulatory support devices has typically shown alteration of patient blood rheology exhibited through increasing blood viscosity and decreasing erythrocyte deformability. Our hemorheologic studies have additionally shown a remarkable increase in red blood cell (RBC) aggregation in the blood of artificial heart patients as compared to healthy donors. These hemorheologic changes may be caused by mechanical trauma to RBCs. The authors hypothesize that the mechanical trauma process, from a rheologic point of view, could be analogous to an "accelerated" RBC aging process. The hypothesis was examined through in vivo and in vitro experiments on RBCs, age-separated on the basis of density, specifically to identify the rheologic similarities between aged and mechanically traumatized RBCs. Older RBCs demonstrated an increased mechanical fragility, a decreased deformability, and a increased ability to aggregate as compared to younger RBCs. RBCs exposed to mechanical stress demonstrated similar alterations in the same rheologic parameters. Our experiments have also shown that mechanical stress decreases the negative surface charge of RBCs as is known to occur in aged RBCs. Similarities found between the processes of RBC mechanical trauma and senescence enhance our understanding of mechanisms of subhemolytic trauma incurred in assisted circulation. This may improve the design and evaluation of future heart assist devices through minimizing shear induced blood trauma.

A sheep model for the study of hemorheology with assisted circulation. Effect of an axial flow blood pump.

Hemorheologic investigations were performed on nine sheep during the in vivo evaluation of a new axial flow ventricular assist device, the Nimbus AxiPump (Nimbus, Inc., Rancho Cordova, CA). Blood hematocrit, plasma and whole blood viscosity, red blood cell (RBC) deformability and aggregation, plasma fibrinogen, and free hemoglobin (hemolysis) levels were measured. Changes in the main rheologic parameters of sheep blood relative to the pre-implant values were minor and transient. The exception was RBC aggregation, which appeared on the third day of implantation. (Sheep blood does not normally demonstrate RBC aggregation.) Sheep RBCs started to form classic rouleaux typically on the third post-operative day simultaneously with increasing fibrinogen level. To investigate the relative effects of mechanical stress and elevated fibrinogen levels on RBC aggregability, in vitro studies were conducted with blood from control sheep. These studies indicated that neither mechanical trauma nor elevated fibrinogen alone caused RBC aggregation as seen in vivo. However, combined mechanical stress and elevated fibrinogen did cause this unusual effect for sheep blood.

Dynamic systemic vascular resistance in a sheep supported with a Nimbus AxiPump.

Changes in systemic vascular resistance (SVR) in response to diminished pulse perfusion were analyzed over a dynamic range of flow conditions. An axial flow LVAD (Nimbus AxiPump, Rancho Cordova, CA) was implanted in a sheep for 28 days, during which time SVR was determined over several conditions of posture and excitability. Total arterial resistance (TR) was calculated dynamically as an index of SVR by analysis of pump flow in diastole, and systemic pressure estimated from the characteristic pressure-flow-speed relation of the AxiPump. TR was evaluated over a range of flow rates, including maximum flow--for which the pressures and flows were essentially nonpulsatile. Throughout the course of support, and independent of pulsatility, TR dropped when the sheep stood and was significantly lower than that in the sitting position (P < 0.01). Response to excitement followed the same trend: TR was significantly higher during agitation than during normal temper (P < 0.01). In spite of changes in pulse pressure and flow rate, SVR changes occurred according to expected physiologic responses for pulsatile perfusion. Because pump flow and pressure are sensitive to afterload, the results of these studies suggest that pump speed control must compensate for changes in SVR to maintain acceptable perfusion.