Track 11. Artificial Organs

6816 Fr, 08:15-08:30 (P50) Development of a highly integrated, extracorporeal membrane oxygenator (HEXMO) for safe and mobile treatment of patients with acute respiratory distress syndrome (ARDS) A. Strau6, H. Reul, U. Steinseifer, T. Schmitz-Rode. Chair for Applied Medical Engineering, Helmholtz-lnstitute, RWTH Aachen University, Aachen, Germany

Aim: Near-drowning, burnings, trauma and pneumonia can cause acute respi- ratory distress syndrome, a disease characterized by impaired gas exchange. Approximately 10,000,000 people worldwide suffer from ARDS annually, with a mortality rate of 40-60%. Extracorporeal membrane oxygenation (ECMO) might be able to reduce venti- lation induced lung injury but implies substantial risks of hemolysis, thrombosis and bleeding complications. Moreover, ECMO is very complex and cost- intensive. Our aim is the development of a compact, miniaturized oxygenation system with reduced blood contact surface and low priming volume for safe and sure ECMO application. Methods: The main feature of HEXMO is the integration of a miniaturized blood pump in the center of the system, which enables a very compact design without heat exchanger. In-vitro experiments with porcine blood have been carried out to determine blood damage as well as oxygen transfer and carbon dioxide elimination of the HEXMO system. Furthermore, hydraulic properties and heat exchange between the integrated pump, the blood, and the environment were evaluated. Results: The hemolysis of the HEXMO system lies within physiological ranges. Its gas transfer rate is efficient. The integrated pump ensures sufficient blood flow at relevant pressures. Heat loss to the environment is compensated by heat generation of the integrated blood pump. Conclusions: HEXMO presents a manageable and economical oxygenation system that can show the way to mobile ECMO application. The compact design enables safe, reliable, and convenient handling, especially in critical situations. Future activities will be related to in-vivo experiments and further design improvements.

5211 Fr, 08:30-08:45 (P50) Computational flow and mass transfer analysis of a pump-oxygenator B. Fill 1 , M. Gartner 1 , G. Johnson 1 , J. Ma 2, M. Horner 2. 1Ension, Inc., Pittsburgh, Pennsylvania, USA, 2Fluent, Inc., Lebanon, New Hampshire, USA

Computational fluid dynamics (CFD) techniques are an increasingly common tool in optimization of blood pump design. Ension is leveraging CFD for both fluid and mass transfer analysis of a pump-oxygenator utilizing a hollow fiber membrane (HFM)-based rotor. This novel application is unusually demanding due to the geometric complexity of the HFM rotor over a traditional vaned pump rotor. To render these analyses practical, we developed a porous media analog of the HFM rotor to reduce the computational demands associated with directly modeling individual hollow fibers. An initial direct model of our HFM-based rotor was created in Gambit (Fluent, Inc.) yielding a 12 million cell computational mesh. The flow through the domain was simulated using Fluent v6 (Fluent, Inc. Lebanon, NH). After completion of this direct model analysis, a periodic interstitial fluid domain of the HFM rotor was modeled and simulated at flow velocities observed in the direct model simulations. This allowed derivation of porous media characteristics of the HFM-based rotor. With these data, a new computational model of the HFM- based rotor was developed, replacing the individual fiber geometries with a porous media region. Both the direct fiber and porous media flow simulation models were verified with experimental data (bulk pressure, flow, and static pressure distribution) and showed good agreement. The porous media approach allowed for a reduction of the computational mesh from 12 million to 2 million cells, without significant loss in accuracy. This strategy is currently being extended toward mass transfer simulations (oxygenation and decarbonation) and to optimize full-scale pump-oxygenator configurations. This work was supported by a contract from the National Heart, Lung, and Blood Institute of the National Institutes of Health (NHLBI Contract No. HHSN268200449189C).

7281 Fr, 08:45-09:00 (P50) Progress toward a multi-objective model for artificial lung devices J. Zhang, T. Zhang, T.D.C. Nolan, B.P. Griffith, Z.J. Wu. Artificial Organs Laboratory, Department of Surgery, University of Maryland, Baltimore, Maryland, USA

Design objective of artificial lung devices is a multi-facet task, including effi- ciently transferring gas between blood and gas phases, reducing pressure loss, and minimizing flow-induced blood trauma and thrombosis. These functional and biocompatible objectives are closely related to local blood flow dynamics

11.4. Artificial Lungs and Oxygenators $255

in the devices. The overall objectives of this study are to develop functional relationships between the blood flow and these objectives and to integrate them into a computational fluid dynamics (CFD) based platform for simultaneous analyses toward design optimization of artificial lung devices. Hollow fiber membranes for gas exchange between blood and gas phases are modeled as porous medium. An added momentum sink for the porous medium model is incorporated into the incompressible Navier-Stokes governing equa- tion for blood flow in the porous medium. A general mass transport equation predicting gas transfer from hollow fiber membranes to blood (plasma and red blood cells) by both diffusion and convention is derived from the standard convection-diffusion equation. The flow-induced hemolysis model is based on an Eulerian-Lagrangian approach to consider both the shear stress and exposure time as the primary factors. Flow-induced platelet activation potential is considered as functions of shear stress and residence time in a similar fashion as hemolysis. The porous medium model of hollow fiber membranes, the blood flow gov- erning equations, and the above functional models are tested in a series of specifically designed benchmark devices using a combined experimental and computational approach with bovine blood and a blood analog fluid, including gas transfer, flow visualization, hemolysis, platelet activation and deposition potential, and CFD based numerical simulations. Initial results indicated that computational predicted results correlated generally well with experimentally measured data. Integrated simultaneous modeling of blood flow, gas transfer and biocompatibility is a critical step toward to design optimization of artificial lung devices.

4627 Fr, 09:00-09:15 (P50) Right heart responses to a thoracic artificial lung: a computational model C.E. Perlman 1 , L.F. Mockros 2. 1Department of Physiology and Cellular Biophysics, Columbia University, New York, NY, USA, 2Department of Biomedical Engineering, Northwestern University, Evanston, IL, USA

Thoracic artificial lung (TAL) attachment to the pulmonary circulation alters pulmonary pressures and flow rates. Pulmonary flow rates, in turn, determine gas exchange potential. A computational model comprising a TAL, a normal or diseased pulmonary circulation, the systemic circulation and the heart, is used to predict the hemodynamics of TAL attachment. Time-varying compliance of the cardiac chambers drives the system and generates resultant pressures and flows. The TAL is attached with an inlet graft from the proximal main pulmonary artery (PA) and outlet graft(s) to the distal main PA and/or left atrium. Banding of selective conduits enables TAL attachment in series with the natural lungs (NL), in parallel or in an intermediate hybrid configuration. In all configurations, the right ventricle drives blood flow through the TAL. We verify the model by comparison to data from a series of porcine experi- ments. To recommend effective treatment strategies, we simulate attachment of a redesigned, yet feasible, TAL in four configurations: full series with 100% cardiac output (CO) to TAL and 100% CO to NL; hybrid with 100% to TAL and 40% to NL; parallel with 67% to TAL and 33% to NL; and partial series with 50% to TAL and 100% to NL. If NL oxygenation is severely impaired, blood flow through the TAL will deter- mine oxygen delivery. Hybrid and full series provide the greatest TAL flow rates, 4.9 and 4.41/min, respectively, despite elevated natural/artificial pulmonary system resistance, elevated PA pressure and depressed CO. All configurations provide at least 2 I/min to the NL, ensuring a minimal but sufficient level of non- respiratory lung function. Full series forces total CO through the NL, which is advantageous for embolic clearance. Hybrid, however, allows 60% CO to bypass the NL, which is beneficial with severely elevated pulmonary vascular resistance. Hybrid TAL attachment should be hemodynamically feasible and capable of supporting basal gas exchange needs.

4616 Fr, 09:15-09:30 (P50) Compliant artificial lungs K.E. Cook. University of Michigan Departments of Surgery and Biomedical Engineering, Ann Arbor, Michigan, USA

The last decade has seen great advances in design and development of thoracic artificial lungs (TALs), leading to devices with reduced resistance, increased compliance, and, ultimately, decreased impedance. Despite these improvements, in series artificial lung attachment continues to result in sig- nificantly depressed cardiac output. Therefore, our laboratory continues to work on TALs with higher compliance and smaller fluid mechanical energy losses in device inlets and outlets. This work has lead to TALs with compliant housings that employ gradual expansions and contractions at the inlet and outlet, respectively. Initially, various solid-housing designs were examined within Fluent to determine their impedance to pulsatile blood flow. From these results, we selected a small subset to prototype with compliant, Biospan housings for in vitro testing. Results have been highly promising. Devices were constructed with a 75 degree, angled inlet and a 0.5mm wall thickness and

$256 Journal o f Biomechanics 2006, Vol. 39 (Suppl 1) Oral Presentat ions

tested in vitro using a ventricular flow waveform of 3 cP glycerol at 80 beats/min. These devices demonstrated zeroth and first harmonic impedance moduli of Zo =0.040Q + 0.75 and Zl = -0 .031Q + 0.66, in which Q is the average flow rate in L/min and the impedance moduli are measured in mmHg/(L/min). We have also begun fluid-structure interaction (FSI) modeling using ADINA. An FSI model of a device with a 45 degree, angled inlet with a 0.76mm wall thickness was created, and a 3cP, Newtonian fluid was pumped through it using a ventricular flow waveform with Q =4 L/min at a rate of 100 beats/min. The results were similar to the experimental results, with a Zo and Zl of 1.1 and 0.66 mmHg/(L/min), respectively. Comparison of these results to recent in vivo studies suggest that TALs can be designed such that a) their impedances are equal to or smaller than those of the natural lungs, and b) in series attachment can be utilized with less than a 10% reduction in cardiac output.

5214 Fr, 09:30-09:45 (P50) Design of a per fus ion system for fetal card iopu lmonary bypass

S. Wright 1 , M. Gartner 1,2, J. Speakman 1 , J. Tamblyn 1 , E Pigula 2. 1Ension, Inc., Pittsburgh, PA, USA, 2Boston Children's Hospital, Harvard University, Boston, MA, USA

Prompt postnatal repair of life-threatening congenital heart lesions is now commonplace and thought to reduce long-term cardiovascular morbidity and mortality. However, recent research suggests such repairs may induce addi- tional morbidities as the patient ages. Earlier interventions, such as before the child is born, may circumvent these morbidities and provide additional benefit. For example, treatment of relatively simple lesions in the fetus may prevent anatomic maldevelopment of associated cardiac structures reducing long-term morbidity and mortality. However, a significant obstacle to fetal intervention is a reliable means of fetal cardiopulmonary support. Previous work has identified placental dysfunction as the primary obstacle to providing mechanical circulatory support to the fetus. In an attempt to attenuate placental dysfunction, a fetal cardiac bypass circuit was designed to minimize priming volume, deliver clinically-relevant pulsatile flow, and provide adequate gas exchange when the placenta is excluded from the fetal circulation. The circuit includes a custom-designed miniature centrifugal pump (priming volume of 20 ml) and oxygenator (priming volume of 12 ml) utilizing a flexible shaft drive system allowing the drive motor to be remotely located outside the surgical field. The system has been evaluated in a series in vitro experiments to assess basic functionality and biocompatibility. After confirmation of this functionality, we performed three successful acute (30-minute) in vivo experiments in the pregnant ewe model at Boston Children's Hospital. Preliminary data, such as VO2, VCO2, blood flow rates, pressures and pulsatility suggest our fetal cardiopulmonary bypass system may be useful enabling technology to facilitate these fetal interventions.

11.5. Thrombosis in Devices and Cardiovascular Pathologies

7127 Fr, 11:00-11:30 (P51) Platelet act iv i ty measurements and numerical s imulat ions of f low induced thrombus format ion in card iovascular patholog ies and devices

D. Bluestein 1 , S. Einav 1 , M. Titmus 1 , K. Dumont 1 , '~ Alemu 1 , B. Ghebrehiwet 2, J. Jesty 2, S. Okser 3, '~ Deng 3. 1Biomedical Engineering, Stony Brook University, Stony Brook, NY, USA, 2Hematology, Stony Brook University Hospital, Stony Brook, NY, USA, 3. Applied Math, Stony Brook University, Stony Brook, NY, USA

Thrombus formation in arterial pathologies is associated with elevated hemo- dynamic stresses that may induce platelet activation and potentiate their inter- action with the endothelium. In-vitro platelet measurements were conducted in a Hemodynamic Shearing Device (HSD) which is driven by a computer- controlled motor fed with dynamic waveforms that can mimic almost any stress loading combination. The loading waveforms are obtained from CFD simu- lations, by computing the stress histories along platelet trajectories. Platelet activity can be measured in the HSD in the presence of endothelial cells cultured on collagen-coated base plate, using the Platelet Activitation State (PAS) assay which measures the platelets' ability to support the activation of acetylated prothrombin by factor Xa (the prothrombinase complex). Acetylation results in generation of thrombin species that does not reactivate platelets, enabling the segregation of flow induced shear activation. Mechanisms of thrombus formation were also investigated using numerical simulations in prosthetic heart valves. A new platelet damage accumulation model incorporating damage history (senescence) was developed to estimate platelet activation resulting from the combined effect of flow induced stresses and exposure time in the device. An innovative discrete multiple particles dynamics multiscale approach was developed, using a multi-phase model of platelet response to flow stresses in devices and cardiovascular pathologies. The multiscale modeling concentrates

on flow regions in devices and pathologies that have a high propensity to activate platelets and form aggregates. Forces and potentials around particles representing platelets were carefully characterized using Lennard-Jones equa- tions and a summation of viscosity forces, to calculate the motion of particles representing the different phases in the domain (solid, fluid, etc.). This method, which widely departs from the traditional continuum approach, was first verified by simulating blood flow in simple geometries, and successfully generated correct viscous blood flow velocity distributions for the discrete particles in these geometries.

5248 Fr, 11:30-11:45 (P51) Shear dependant platelet accumulat ion in hemodynamic stenoses C.J. Flannery, A. Para, D.N. Ku. G.W. Woodruff School of Mechanical Engineering, Georgia Institute of Technology, Atlanta, Georgia, USA

Acute complications of atherosclerosis may lead to thrombotic occlusion of a critical artery. Our hypothesis is that the rate of platelet accumulation is a direct function of the hemodynamic shear rate. An anatomic model of a coronary artery stenosis is created in glass tubes of nominal i.d. 1.5 mm by drawing a stenosis in each tube, ranging from 0 to 82% by diameter. Whole blood is perfused through the test sections at upstream Reynolds numbers 20 - 120. The stenotic sections are coated with collagen and video photographed while simultaneously measuring flow rates and perfusion pressures. Thrombus volume and formation rate are compared quantitatively against time and shear rate. Thrombus formation was easily visualized in the glass test sections. During the first five minutes (Phase I), platelets initially adhered to the entire collagen coated surface. In the next ten minutes (Phase II), there was volumetric accumulation of thrombus. The thrombus first appeared as protrusions located at the throat of the stenosis and in the downstream recirculation zone. After 15 minutes, the thrombus filled most of the test section and either went to occlusion or remained stable until 240mL of blood had been perfused. The shear rate was estimated from the flow rate and hydraulic diameter. Accumulation rate increased with increasing shear rate or hydraulic stenosis. The maximum accumulation rate of 3.5 million platelets/cm2/s was found with the maximal shear rate of 42,000 s -1. A linear regression analysis of deposition rate versus shear rate revealed a correlation coefficient of 0.88 between the rate of platelet deposition and shear rate up to 42,000 s -1 , proving our hypothesis. Acute coronary syndromes and various therapies to prevent occlusion can be carefully studied using this quantitative in vitro model.

6980 Fr, 11:45-12:00 (P51) Role o f stent design in platelet thrombosis : A computat ional analys is A.S. Bedekar, K. Pant, S. Sundaram. Biomedical Technology Branch, CFD Research Corporation, Huntsville, AL, USA

Coronary stents are the leading class of vascular implants, with over two million stents being placed each year worldwide. Stent prototypes differing only in geometric features have been known to different significantly in their thrombotic response, specifically platelet activation / adhesion and the subse- quent triggering of the coagulation cascade. Prior computational studies have primarily focused on investigating hemodynamic flow patterns altered by stent implantation. We have developed an extended computational model, which, in addition to hemodynamics, also includes platelet response and interaction with the coagulation pathways. The model uses a Lagrangian approach to describe platelet transport and aggregation, coupled with a continuum model for transport of coagulation factors. Biochemical reactions involving plasma phase proteins as well as those bound to phospholipid membranes of platelets are represented by kinetic models. Primary stent design features investigated include axial strut pitch/spacing and strut amplitude/height. The thrombotic response is primarily quantified using the rate of platelet accumulation, coupled with thrombin generation, both of which are shown to be strongly depen- dent upon strut spacing. In addition, localized, spatio-temporal distribution of platelets and coagulation proteins is studied in correlation with altered flow features (recirculation zones, wall shear stress). This model can be used to screen coronary stent designs for acute thrombogenic risk and identify critical features and failure modes.

7189 Fr, 12:00-12:15 (P51) Platelet depos i t ion in stented ar tery models and their correlat ion to f low dynamics

J.E. Moore Jr. 1 , R.T. Schoephoerster 2, N. Duraiswamy 2. 1Department of Biomedical Engineering, Texas A&M University, USA, 2Department of Biomedical Engineering, Florida International University, USA

The initial thrombotic reaction in stented arteries certainly effects the sub- sequent reestablishment of the endothelium. A better understanding of the dynamics of platelet adhesion to stents under realistic flow conditions can serve to improve stents of all types in coronary and peripheral applications. For