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Biomedical subjects

James F Antaki

Publications and source records attributed to James F Antaki.

12 recordsLinked to original sources

Strain hardening of red blood cells by accumulated cyclic supraphysiological stress.

The effect of elevated shear stress upon cellular trauma has been studied for many years, but the effect of long-term cyclic stress trauma on hemorheology has never been explored systematically. This study investigated sublytic trauma of red blood cells (RBCs) caused by repeated exposure to shear stress. A suspension of bovine blood was throttled through a capillary tube (inner diameter 1 mm and length 70 mm) connected to a recirculating flow loop. Samples were withdrawn every 30 min to measure deformability and characteristic time. The deformability of the cell was measured microscopically by observing the shape of the cell during the shear flow. It was found that cyclic shear irreversibly stiffened the cell membrane while the effect was not so much as that of continuous shear. The cell deformability was dramatically reduced by 73% when the stress of 300 Pa was applied for 288 s, while it was 7% under 90 Pa. These results elucidate the need for improved models to predict cellular trauma within the unsteady flow environment of mechanical circulatory assist devices.

Animals↗

The PediaFlow pediatric ventricular assist device.

The very limited options available to treat ventricular failure in patients with congenital and acquired heart diseases have motivated the development of a pediatric ventricular assist device (VAD). Our effort involves a consortium consisting of the University of Pittsburgh, Carnegie Mellon University, Children's Hospital of Pittsburgh, World Heart Corporation, and LaunchPoint Technologies, LLC. The overall aim of our program is to develop a highly reliable, biocompatible VAD for chronic support (6 months) of the unique and high-risk population of children between 3 kg and 15 kg (patients from birth to 2 years of age). The innovative pediatric VAD we are developing (PediaFlow) is based on a miniature mixed-flow turbodynamic pump featuring magnetic levitation, with the design goal being to assure minimal blood trauma and risk of thrombosis. This article discusses the limitations of current pediatric cardiac assist treatment options and the work to date by our consortium toward the development of a pediatric VAD.

Biocompatible Materials↗

Microscopic investigation of erythrocyte deformation dynamics.

The understanding of erythrocyte deformation under conditions of high shear stress and short exposure time is central to the study of hemorheology and hemolysis within prosthetic blood contacting devices. A combined computational and experimental microscopic study was conducted to investigate the erythrocyte deformation and its relation to transient stress fields. A microfluidic channel system with small channels fabricated using polydimethylsiloxane on the order of 100 mum was designed to generate transient stress fields through which the erythrocytes were forced to flow. The shear stress fields were analyzed by three-dimensional computational fluid dynamics. Microscopic images of deforming erythrocytes were experimentally recorded to obtain the changes in cell morphology over a wide range of fluid dynamic stresses. The erythrocyte elongation index (EI) increased from 0 to 0.54 with increasing shear stress up to 123 Pa. In this shear stress range, erythrocytes behaved like fluid droplets, and deformed and flowed following the surrounding fluid. Cells exposed to shear stress beyond 123 Pa (up to 5170 Pa) did not exhibit additional elongation beyond EI=0.54. Two-stage deformation of erythrocytes in response to shear stress was observed: an initial linear elongation with increasing shear stress and a plateau beyond a critical shear stress.

Animals↗

Design optimization of blood shearing instrument by computational fluid dynamics.

Rational design of blood-wetted devices requires a careful consideration of shear-induced trauma and activation of blood elements. Critical levels of shear exposure may be established in vitro through the use of devices specifically designed to prescribe both the magnitude and duration of shear exposure. However, it is exceptionally difficult to create a homogeneous shear-exposure history by conventional means. This study was undertaken to develop a Blood Shearing Instrument (BSI) with an optimized flow path which localized shear exposure within a rotating outer ring and a stationary conical spindle. By adjustment of the rotational speed and the gap dimension, the BSI is designed to generate shear stress magnitudes up to 1500 Pa for exposure time between 0.0015 and 0.20 s with a pressure drop of 100 mm Hg. Computational fluid dynamics (CFD) revealed that a flow path designed by first-order analysis and intuition exhibited unfavorable pressure gradient, vortices, and undesirable regions of reverse flow. An optimized design was evolved utilizing a parameterized geometric model and automatic mesh generation to eliminate vortices and reversal flow and to avoid unfavorable pressure gradients. Analysis of the flow and shear fields for the extreme limits of the shear gap demonstrated an improvement in homogeneity due to shape optimization and the limitations of an annular shear device for achieving completely uniform shear exposure.

Algorithms↗

Inlet and outlet devices for rotary blood pumps.

The purposes of inlet and outlet devices for rotary blood pumps, including inducers and diffusers for axial pumps, inlet and exit volutes for centrifugal pumps, and inlet and outlet cannulas, are to guide the blood into the impeller, where the blood is accelerated, and to convert the high kinetic energy into pressure after the impeller discharge, respectively. The designs of the inlet and outlet devices have an important bearing on the pump performance. Their designs are highly dependent on computational fluid dynamics (CFD) analysis, guided by intuition and experience. For inlet devices, the design objectives are to eliminate separated flow, to minimize recirculation, and to equalize the radial components of velocity. For outlet devices, the design goals are to reduce speed, to minimize energy loss, and to avoid flow separation and whirl. CFD analyses indicate the velocity field and pressure distribution. Geometrical optimization of these components has been implemented in order to improve the flow pattern.

Assisted Circulation↗

Computational fluid dynamics prediction of blood damage in a centrifugal pump.

This study explores a quantitative evaluation of blood damage that occurs in a continuous flow left ventricular assist device due to fluid stress. Computational fluid dynamics (CFD) analysis is used to track the shear stress history of 388 particle streaklines. The accumulation of shear and exposure time is integrated along the streaklines to evaluate the levels of blood trauma. This analysis, which includes viscous and turbulent stresses, provides a statistical estimate of possible damage to cells flowing through the pump. In vitro normalized index of hemolysis values for clinically available ventricular assist devices were compared to our damage indices. This allowed for an order of magnitude comparison between our estimations and experimentally measured hemolysis levels, which resulted in a reasonable correlation. This work ultimately demonstrates that CFD is a convenient and effective approach to analyze the Lagranian behavior of blood in a heart assist device.

Centrifugation↗

Effects of turbulent stresses upon mechanical hemolysis: experimental and computational analysis.

Experimental and computational studies were performed to elucidate the role of turbulent stresses in mechanical blood damage (hemolysis). A suspension of bovine red blood cells (RBC) was driven through a closed circulating loop by a centrifugal pump. A small capillary tube (inner diameter 1 mm and length 70 mm) was incorporated into the circulating loop via tapered connectors. The suspension of RBCs was diluted with saline to achieve an asymptotic apparent viscosity of 2.0 +/- 0.1 cP at 23 degrees C to produce turbulent flow at nominal flow rate and pressure. To study laminar flow at the identical wall shear stresses in the same capillary tube, the apparent viscosity of the RBC suspension was increased to 6.3 +/- 0.1 cP (at 23 degrees C) by addition of Dextran-40. Using various combinations of driving pressure and Dextran mediated adjustments in dynamic viscosity Reynolds numbers ranging from 300-5,000 were generated, and rates of hemolysis were measured. Pilot studies were performed to verify that the suspension media did not affect mechanical fragility of the RBCs. The results of these bench studies demonstrated that, at the same wall shear stress in a capillary tube, the level of hemolysis was significantly greater (p < 0.05) for turbulent flow as compared with laminar flow. This confirmed that turbulent stresses contribute strongly to blood mechanical trauma. Numerical predictions of hemolysis obtained by computational fluid dynamic modeling were in good agreement with these experimental data.

Animals↗

In vitro evaluation of multiobjective hemodynamic control of a heart-assist pump.

Ventricular assist devices now clinically used for treatment of end-stage heart failure require responsive and reliable hemodynamic control to accommodate the continually changing demands of the body. This is an essential ingredient to maintaining a high quality of life. To satisfy this need, a control algorithm involving a trade-off between optimal perfusion and avoidance of ventricular collapse has been developed. An optimal control strategy has been implemented in vitro that combines two competing indices: representing venous return and prevalence of suction. The former is derived from the first derivative of diastolic flow with speed, and the latter derived from the harmonic spectra of the flow signal. The responsiveness of the controller to change in preload and afterload were evaluated in a mock circulatory simulator using a HeartQuest centrifugal blood pump (CF4b, MedQuest Products, Salt Lake City, UT). To avoid the need for flow sensors, a state estimator was used, based on the back-EMF of the actuator. The multiobjective algorithm has demonstrated more robust performance as compared with controllers relying on individual indices.

Algorithms↗

Elimination of adverse leakage flow in a miniature pediatric centrifugal blood pump by computational fluid dynamics-based design optimization.

We investigated a miniature magnetically levitated centrifugal blood pump intended to deliver 0.3-1.5 l/min of support to neonates and infants. The back clearance gap between the housing and large volume of the rotor, where the suspension and motor bearings are located, forms a continuous leakage flow path. Within the gap, flow demonstrates a very complex three-dimensional structure: the fluid adjacent to the rotating disk tends to accelerate by centrifugal force to flow radially outwards toward the outlet of the impeller against an unfavorable pressure gradient, which in turn forces blood to return along the stationary housing surfaces. Consequently, one or multiple vortices may be generated in the gap to block blood flow and cause the formation of a retrograde and antegrade leakage flow phenomenon at the gap outlet using an optimization process including extensive computational fluid dynamics (CFD) analysis of impeller refinements, we found that secondary blades located along the back or extended to the side surfaces of the rotor have the capacity to reduce and eliminate the retrograde flow in the back clearance gap. Flow visualization confirmed the CFD-predicted flow patterns. This work demonstrates the utility of CFD-based design optimization to optimize the fluid path of a miniature centrifugal pump.

Centrifugation↗

Hemodynamic modes of ventricular assist with a rotary blood pump: continuous, pulsatile, and failure.

Pulsatile operation of rotary blood pumps (RBPs) has received interest due to potential concern with nonphysiological hemodynamics. This study aimed to gain insight to the effects of various RBP modes on the heart-device interaction. A Deltastream diagonal pump (Medos Medizintechnik GmbH) was inserted in a cardiovascular simulator with apical-to-ascending aorta cannulation. The pump was run in continuous mode with incrementally increasing rotating speed (0-5000 rpm). This was repeated for three heart rates (50-100-150 bpm) and three levels of left ventricular (LV) contractility. Subsequently, the Deltastream was run in pulsatile mode to elucidate the effect of (de)synchronization between heart and pump. LV volume and pressure, arterial pressure, flows, and energetic parameters were used to evaluate the interaction. Pump failure (0 rpm) resulted in aortic pressure drops (17-46 mm Hg) from baseline. In continuous mode, pump flow compensated by diminished aortic flow, thus yielding constant total flow. High continuous rotating speed resulted in acute hypertension (mean aortic pressure up to 178 mm Hg). In pulsatile mode, unmatched heart and pulsatile pump rates yielded unphysiologic pressure and flow patterns and LV unloading was found to be highly dependent on synchronization phase. Optimal unloading was achieved when the minimum rotating speed occurred at end-systole. We conclude that, in continuous mode, a perfusion benefit can only be achieved if the continuous pump flow exceeds the preimplant (baseline) cardiac output. Pulsatile mode of support results in complex pressure and volume variations and requires accurate triggering to achieve optimal unloading.

Data Interpretation, Statistical↗

Modeling ventricular function during cardiac assist: does time-varying elastance work?

The time-varying elastance theory of Suga et al. is widely used to simulate left ventricular function in mathematical models and in contemporary in vitro models. We investigated the validity of this theory in the presence of a left ventricular assist device. Left ventricular pressure and volume data are presented that demonstrate the heart-device interaction for a positive-displacement pump (Novacor) and a rotary blood pump (Medos). The Novacor was implanted in a calf and used in fixed-rate mode (85 BPM), whereas the Medos was used at several flow levels (0-3 l/min) in seven healthy sheep. The Novacor data display high beat-to-beat variations in the amplitude of the elastance curve, and the normalized curves deviate strongly from the typical bovine curve. The Medos data show how the maximum elastance depends on the pump flow level. We conclude that the original time-varying elastance theory insufficiently models the complex hemodynamic behavior of a left ventricle that is mechanically assisted, and that there is need for an updated ventricular model to simulate the heart-device interaction.

Animals↗

Hemodynamic guidelines for design and control of a turbodynamic pediatric ventricular assist device.

The design of mechanical circulatory support devices typically requires a priori knowledge of the hemodynamic requirements of their intended use. These requirements are difficult to determine because of limited clinical experience. This is especially true for the pediatric population, for whom there is a dearth of longitudinal data. This report aims to provide both engineers and physicians with benchmarks for determining the optimal flow requirements and settings for pediatric ventricular assist devices that are currently being developed. Criteria were developed on the basis of estimates derived from various sources. The potential patient population was estimated by using the prevalence of children on the heart transplant waiting list and those placed on extracorporeal membrane oxygenation. Cardiac outputs were determined for individual weights and body surface areas, using published values for healthy and sick pediatric patients. The recommended pump range was optimized to include the most patients, while considering the design constraints. This study identifies a significant population of patients who would benefit from a device providing 0.52 to 1.92 l/min.

Body Weight↗