Progress in the development of a transcutaneously powered axial flow blood pump ventricular assist system

Development of the Jarvik 2000 intraventricular assist system for long-term support is ongoing. The system integrates the Jarvik 2000 axial flow blood pump with a microprocessor based automatic motor controller to provide response to physiologic demands. Nine devices have been evaluated in vivo (six completed, three ongoing) with durations in excess of 26 weeks. Instrumented experiments include implanted transit-time ultrasonic flow probes and dual micromanometer LV/AoP catheters. Treadmill exercise and heart pacing studies are performed to evaluate control system response to increased heart rates. Pharmacologically induced cardiac dysfunction studies are performed in awake and anesthetized calves to demonstrate control response to simulated heart failure conditions. No deleterious effects or events were encountered during any physiologic studies. No hematologic, renal, hepatic, or pulmonary complications have been encountered in any study. Plasma free hemoglobin levels of 7.0 +/- 5.1 mg/dl demonstrate no device related hemolysis throughout the duration of all studies. Pathologic analysis at explant showed no evidence of thromboembolic events. All pump surfaces were free of thrombus except for a minimal ring of fibrin, (approximately 1 mm) on the inflow bearing. Future developments for permanent implantation will include implanted physiologic control systems, implanted batteries, and transcutaneous energy and data transmission systems.     

Noninvasive pump flow estimation of a centrifugal blood pump

A flow rate estimating method was investigated for a centrifugal blood pump developed in our institute. The estimated flow rate was determined by the power consumption, the rotating speed of the motor, and the hematocrit value. The power consumption and the rotating speed of the motor were measured with a wattmeter. The examinations were performed in a closed mock loop filled with goat blood with hematocrit values of 21.5%, 28%, 34%, and 42%. Measured values of blood viscosity were 2.47, 3.09, 3.71, and 5.07 mPa.s at a share rate of 37.5/s, respectively. A linear correlation between the power consumption and the pump flow rate was observed in all hematocrit values. But variations in hematocrit caused a difference in the flow rate up to 1.1 L/min at the same power consumption and rotating speed. Effects of blood viscosity on the flow estimation were corrected by the hematocrit value. The value of the coefficient of determination, R2, between the estimated flow rate and the measured flow rate was 0.988. These results may indicate that the flow estimating method calculated by the power consumption of the motor, the rotating speed, and the hematocrit value is useful in the clinical situation.     

Right ventricular blood flow during left ventricular support in an experimental porcine model

BACKGROUND: Right ventricular blood flow may be adversely affected during left ventricular assist device (LVAD) use leading to right ventricular (RV) ischemia and RV dysfunction. This study characterized normal RV blood flow responses to LVAD operation. METHODS: Seven Yorkshire pigs weighing 74.4 +/- 3.4 kg underwent right coronary artery blood flow measurements with an ultrasonic flow probe and injection of radiolabeled microspheres. A Thoratec LVAD was used in either synchronous or asynchronous modes and RV loading was increased using a pulmonary artery snare. RESULTS: The RV blood flow was compared between three regions that differed in proximity to the right coronary artery: proximal segment, mid-RV, and distal. The right ventricular distal flow was 0.93 +/- 0.07 mL x min-1 x g-1 compared with 0.74 +/- 0.06 mL x min-1 x g-1 at right ventricular proximal flow during control measurements (p = 0.0001). This difference was maintained during LVAD operation in either synchronous or asynchronous modes and also during pulmonary artery constriction. CONCLUSIONS: Global RV flow is not adversely affected by LVAD use. A flow gradient occurs along the right coronary artery with the distal vascular bed having relatively less reserve, which may be more susceptible to ischemia in patients with preexisting coronary disease or RV distention during LVAD use.     

In vitro and in vivo assessment of an intravenous axial flow pump for right heart assist

Right ventricular (RV) function is a limiting factor in maintaining systemic circulation with circulatory assist. There is, however, no easy way to institute RV assist, such as the intraarterial axial flow pump (Hemopump) used for left heart assist. In this study, the feasibility and hemodynamic effect of intravenous use of an axial flow pump was examined. A pump system was developed with an outflow cannula and an impeller that were newly designed for intravenous insertion with a Hemopump driving system. The pump system characteristics using goat blood at a hematocrit of 26% indicated that maximum flow at a pressure differential against 40 mmHg is 3.2 l/min at a pump speed of 28,000 rpm. The pump was tested in adult goats by intravenous insertion through a 14 mm, low porosity graft anastomosed to the infrarenal inferior vena cava. The pump was advanced until the tip of the cannula was positioned at the main pulmonary artery, using balloon catheter guidance under fluoroscopy. RV assistance was evaluated by pressure tracing, and aortic flow (AF) measured by electromagnetic flowmeter under 1) induced pulmonary stenosis (PS), and 2) electrically induced ventricular fibrillation (VF) in combination with left heart assist. Under PS, right atrial pressure decreased from 11 to 2 mmHg and AF increased from 1.0 to 4.1 l/min after initiation of the pump. Under VF, AF and aortic pressure were 2.6 l/min and 78 mmHg, respectively, with left ventricular assist. After initiation of the pump, they increased to 4.0 l/min and 98 mmHg, respectively. In chronic experiments using three adults goats for up to 48 hr, levels of plasma hemoglobin and platelet counts were maintained within an acceptable range. There was no prominent damage to the hearts. These data suggest that an axial flow pump introduced by an intravenous approach without thoracotomy is feasible and provides sufficient right heart assist.     

Pulsatile ocular blood flow variations with axial length and refractive error

Benign symmetric lipomatosis (BSL), also known as Madelung's disease, is a rare condition and characterized by diffuse but painless growth of unencapsulated lipomas. A close correlation to alcohol and nicotine abuse, metabolic disturbances and malignant tumours have been observed. Surgical treatment is frequently followed by recurrence, nevertheless, it can yield satisfactory functional and cosmetic results. A case of BSL with uncommonly distributed tumors is reported.     

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.     

轴向柱塞泵故障的模糊诊断

利用模糊综合评判的方法对轴向柱塞泵进行故障诊断,能在液压泵多种可能的故障中找出可能性较大故障,可得到准确的结论.     

Left heart bypass using the oscillated blood flow with totally implantable vibrating flow pump

Palliative care was initiated in Italy towards the end of the 1970s, mainly through the efforts of Professor Ventafridda and his colleagues. This article describes some of the most important steps made in this country to gain widespread acceptance for the principles and practice of palliative care. After about 15 years the Italian situation is still confusing. While some Regions have made progress, others are far from reaching even minimal goals. The efforts of many charities and of the Italian Society for Palliative Care and the Italian School for Palliative Medicine, have been huge, but still not sufficient to promote widespread involvement of the National Health Authorities. In the absence of clear Regional and central laws, the recent changes in the Italian health system combined with increasing financial difficulties threaten the advances already made.     

Basic performance of a miniature intraventricular axial pump

Lubeluzole is a neuroprotective compound in the final stages of clinical evaluation. We evaluated the effects of intravenous followed by intraperitoneal doses of lubeluzole on histological outcome after reversible tandem middle cerebral/common carotid artery occlusion in Long-Evans rats, with particular emphasis on the time window of efficacy. Lubeluzole, started 15 min after the onset of ischemia, had no adverse physiological or behavioral effects and reduce maximal infarct volume produced by 120 min or more of arterial occlusion by approximately 50%, from 143.2 +/- 11.8 mm3 (p < 0.05). Lubeluzole did not prolong the duration of middle cerebral artery occlusion which could be tolerated before histological damage occurred. Lubeluzole was still effective if started 30 min after the onset of ischemia (34% reduction of maximal infarct volume; p < 0.05), but not after delays of 60 or 120 min. we conclude that lubeluzole has promise as a neuroprotective drug, particularly for more severe strokes, but must be started very rapidly after the onset of ischemia to be effective.     

Durability testing of components for the Jarvik 2000 completely implantable axial flow left ventricular assist device

A cable-lead tester and real time bearing tester have been developed with provisions to test future implantable electronics, transcutaneous energy transfer system (TETS), and related interconnect cabling designs. The cable/lead tester, used in 1997 to test a previously considered implantable bellows-connector-cabling system, can test up to 10 samples at a time. X-Y-Z-theta motions are applied to the proximal end of the test specimen with its distal end fixed. The real time bearing tester is of a mock loop configuration with the bearings under test housed in a fully functional, Good Manufacturing Practices assembled axial pump. A simulated left ventricular pulsatile preload is applied to the inflow of the axial pump, while its outflow is subjected to an 80 mmHg aortic afterload by pumping into a fixed height tube with no outflow restriction. The heated blood bath saline used in this system is UV sterilized and mechanically filtered by use of a commercial salt water conditioning system attached external to the main preload fluid reservoir. The cable-lead tester and real time bearing tester design include provisions to house a complete Jarvik 2000 left ventricular assist device (Transicoil Medical, Norristown, PA) for in vitro system testing.     

Characterization and optimization of the flow pattern inside a diaphragm blood pump based on flow visualization techniques

We applied two different flow visualization techniques to obtain detailed information on the inside flow of the diaphragm blood pump of our electrohydraulic total artificial heart system to determine the optimum washout effect that would result in better antithrombogenicity. Major orifice directions of the inflow and outflow Bjork-Shiley valves of the left blood pump were independently changed to create 17 varied patterns. The character and velocity of the main flow at the diaphragm-housing junction were acquired using a laser light sheet method with polyethylene tracers. Wall shear flow, a major factor governing washout in the blood pump, was estimated by a newly developed paint erosion method. In this method, quantitative evaluation for an index of washout effect was made by calculating the residual ratio of the paint on the blood pump inner surface at 30 sec of pumping. When a single circular flow was consistently observed by the laser light sheet method, the paint residual ratio become low, indicating washout was relatively good. At the lowest paint residual ratio, the center of the circular flow observed by the laser light sheet method was located at the geometric center of the blood chamber. In conclusion, the flow pattern inside the blood pump could be characterized by combined use of these two flow visualization techniques, and the significant role of circular flow in better washout was clarified.     

Development of a paracorporeal left ventricular assist pump system: an experimental study

Experiments were designed to compare the hemodynamic performance and metabolic effect of a paracorporeal left ventricular assist pump system (PLVAPS) with those of intra-aortic balloon pumping (IABP) in a series of 35 dogs with and without myocardial infarction (MI). The animals were subjected to a three-hour period of pumping seven days after implantation of catheters and loose left anterior descending coronary (LAD) snares. MI was produced by closed-chest snaring of the LAD 13 hours before the onset of pumping. Measurements in addition to blood chemistry included aortic, pulmonary, atrial and ventricular pressures, ECG, cardiac index, left ventricular stroke work index (LVSWI) and endocardial viability ratio (EVR). The hemodynamic effects of PLVAPS assistance in normal control dogs and dogs with induced MI closely paralleled those observed with IABP. Both assist devices significantly increased systemic perfusion, decreased LVSWI, and increased EVR by reducing the oxygen demand. Infarct sizes were not significantly reduced with the two modes of pumping. The parameters measured indicate that in our experimental infarct model there is no significant differences between PLVAPS and IABP.     

Induction of insulin resistance by glucosamine reduces blood flow but not interstitial levels of either glucose or insulin

Streptozocin-induced diabetes is associated with alterations in insulin signaling in rat skeletal muscle, including increased insulin receptor substrate-1 phosphorylation and phosphotidylinositol 3-kinase activity. In the current study, we determined the effects of streptozocin-induced diabetes and treatment of diabetes by islet cell transplantation on several proximal insulin-activated signaling proteins. Three groups of male Lewis rats (untreated streptozocin-diabetic animals, islet cell-transplanted diabetic rats, and nondiabetic control rats) were studied in the basal state or 30 min after i.p. insulin injection (20 U/rat). Mixed hindlimb skeletal muscle lysates were used to determine the expression and enzymatic activities of the extracellular regulated kinase 2 (ERK2), p90 ribosomal S6 kinase (RSK2), Akt, and p70 S6 kinase (p70S6k). In all three groups of rats, insulin significantly increased ERK2, RSK2, Akt, and p70S6k activities. There was no effect of diabetes on insulin-stimulated ERK2 activity or ERK2 protein levels. RSK2 expression and insulin-stimulated RSK2 activity were significantly elevated in diabetic rats compared with those in the control animals. Insulin-stimulated Akt activity was also significantly greater in the diabetic animals, but there was no change in protein expression. In contrast, there was a decrease in insulin-stimulated p70S6k activity with no change in protein expression in the diabetic rats. Islet transplantation partially (RSK2) or fully (Akt, p70S6k) normalized these diabetes-induced changes in insulin signaling proteins. We conclude that streptozocin diabetes results in the dysregulation of several critical insulin-activated proteins in rat skeletal muscle, but islet cell transplantation is an effective therapy to partially correct these alterations in insulin signaling.     

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.     

Blood flow analysis for the secondary impeller of an IVAS heart pump

The rotodynamic heart pump (IVAS), designed by the Cleveland Clinic Foundation, includes a secondary flow path along the journal bearing, through a secondary impeller, and over the rotor outer surface. The flow behaviors of the blood through the journal bearing and the secondary impeller are investigated by a computational fluid dynamics method that solves the 3-dimensional Navier-Stokes equations using a new solution algorithm. Results of the analyses include: 1) the blood flow patterns within the journal bearing, 2) the effect of the non-uniform bearing clearance on the flow patterns of the impeller cavity, 3) the flow patterns around a secondary impeller blade that include effects of tip clearance and the gap between the blade and the inner or outer side wall, 4) effects of the blade angles on the secondary impeller performance, and 5) the shear stress distribution.     

A quantitative visualization study of flow in a scaled-up model of a centrifugal blood pump

There is increasing evidence that adenosine (ADO) and dopamine (DA) interact directly in the basal ganglia via actions at ADO A2a and DA D2 receptors, respectively. The purpose of this study was to determine 1) the extent to which these receptors modulate endogenous GABA release in discrete regions of the rat basal ganglia and 2) whether GABA release is modulated by a direct and opposing interaction between ADO A2a and DA D2 receptors. Tissue slices of striatum (STR) containing globus pallidus (GP; STR/GP) and micropunches of STR, GP, and substantia nigra pars reticulata (SNr) were studied. Radioligand binding demonstrated that ADO A1, ADO A2a, and DA D2 receptors were present in each of the tissue preparations with the exception of SNr, in which ADO A2a receptors were not detected. Stimulation of ADO A2a receptors with CGS 21680 (1-10 nM) increased electrically stimulated GABA release in STR/GP slices and GP micropunches. Consistent with the lack of A2a receptors in SNr, CGS 21680 had no effect on GABA release from this region. In contrast, stimulation of DA D2 receptors with N-0437 (1-100 nM) inhibited evoked GABA release from STR/GP slices and both GP and SNr micropunches. The D2-mediated inhibition of GABA release in GP was abolished in the presence of CGS 21680 (10 nM). These experiments demonstrate that stimulation of ADO A2a and DA D2 receptors has opposing effects on endogenous GABA release in STR and GP. These opposing actions may explain the antagonistic interactions between ADO and DA that have been observed in behavioral studies and support the hypothesis that the striatopallidal efferent system is an important anatomical substrate for the A2a/D2 receptor interaction.     

Development of a new apparatus to observe microcirculation chronically in continuous flow blood pump research

To observe microcirculation chronically is an important key to the successful evaluation of the continuous flow blood pump. In this study, we succeeded in developing a new apparatus by which microcirculation could be observed chronically without a microscope in a conscious animal. The apparatus utilizes a charge coupled device (CCD). A thin living tissue, such as mesentery, is put directly on a highly integrated CCD and is lit up through the tissue with a light-emitting diode (LED). The vascular nets in the tissue are projected onto the CCD like a contact photograph, which is then sent to a television screen and which can be used to analyze their motion and function. A 0.5-inch CCD having 250,000 pixels was used in this study. The cover glass of the CCD was removed, and a fiber optic plate was fixed onto the surface of the CCD for the tissue to be able to contact with the apparatus surface without clearance. The CCD as well as the LED were molded with epoxy resin for electrical insulation. The apparatus was 35 mm wide and 12 mm high with a micro stand for an LED, which can be easily implanted into an animal. The apparatus was implanted into a rabbit for 12 h. The configuration of arterioles and venules, tens of micrometers in diameter, and their motions in subcutaneous tissue could be observed.     

Induction of axial mesoderm by zDVR-1, the zebrafish orthologue of Xenopus Vg1

The zebrafish DVR-1 (zDVR-1) gene, like Xenopus Vg1, is present maternally as an unprocessed precursor protein which is distributed ubiquitously along the future dorsoventral axis. Also, like Vg1, overexpression of zDVR-1 in zebrafish directs synthesis of more precursor, but no processed protein. However, the native zDVR-1 precursor is processed to mature protein when expressed in Xenopus. Like processed Vg1, mature zDVR-1 is a potent inducer of axial mesoderm. The parallels in expression pattern, apparent regulation of protein processing, and mesoderm-inducing activity support the hypothesis that localized protein processing controls production of a dorsal mesoderm inducer in these two species. Furthermore, using mutant mRNAs, we show that cleavage site sequences of the precursor protein are important in regulating protein processing.     

In vivo evaluation of the miniaturized Gyro centrifugal pump as an implantable ventricular assist device

A method has been developed for the rapid molecular mass determination and structural elucidation of mixtures of oligosaccharides derived from plant cell walls. The oligosaccharides were fractionated using gel permeation chromatography and 'analytical' high-performance anion-exchange chromatography (HPAEC), neutralized, dried and the mixtures of eluent salt and oligosaccharides were per-O-acetylated directly. The derivatized oligosaccharides were isolated by dissolution in dichloromethane and the salts were removed by aqueous partitioning. The per-O-acetylated oligosaccharides were analysed using electrospray (ES) and matrix-assisted laser desorption/ionization time of flight mass spectrometry (MS). Exploiting the fact that acid-catalysed per-O-acetylation of oligosaccharides can be achieved even under the extremely salty conditions that are found in post-column neutralized HPAEC fractions, and combining this derivatization step with off-line ESMS, allow rapid screening for molecular mass and thus yield information on the composition of the various oligosaccharides in these complex mixtures. Subsequent per-O-methylation of the per-O-acetylated, salt-free fractions and collision-induced dissociation tandem mass spectrometric analysis was used for additional sequence and branching determination of the oligosaccharides.     

Evaluation of a nonhemolytic left ventricular assist pump

In this paper, we have noted the ways in which regression to the mean can affect the measurement of treatment effects in clinical and epidemiologic studies. It is apparent that regression can have a sizeable effect and may lead to erroneous conclusions concerning treatment effects. Thus, the procedures outlined here should be useful in taking regression into account at the planning stage as well as at the time of analysis.