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Design of a perfusion system for fetal cardiopulmonary bypass
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Journal o f Biomechanics 2006, Vol. 39 (Suppl 1)
Oral Presentations
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 . 0 3 1 Q + 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.
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 equations 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.
5214 Fr, 09:30-09:45 (P50) Design of a perfusion system for fetal c a r d i o p u l m o n a r y bypass S. Wright 1, M. Gartner 1,2, J. Speakman 1, J. Tamblyn 1, E Pigula 2. 1Ension,
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 2 0 120. 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.
5248 Fr, 11:30-11:45 (P51) Shear dependant platelet accumulation 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
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 additional 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.
6980 Fr, 11:45-12:00 (P51) Role o f stent design in platelet thrombosis: A computational analysis A.S. Bedekar, K. Pant, S. Sundaram. Biomedical Technology Branch, CFD
Research Corporation, Huntsville, AL, USA
11.5. Thrombosis in Devices and Cardiovascular Pathologies 7127 Fr, 11:00-11:30 (P51) Platelet activity measurements and numerical simulations of flow induced thrombus formation in cardiovascular pathologies 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 hemodynamic stresses that may induce platelet activation and potentiate their interaction with the endothelium. In-vitro platelet measurements were conducted in a Hemodynamic Shearing Device (HSD) which is driven by a computercontrolled motor fed with dynamic waveforms that can mimic almost any stress loading combination. The loading waveforms are obtained from CFD simulations, 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
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 subsequent 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 dependent 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 deposition in stented artery models and their correlation to flow 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 subsequent 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
Journal o f Biomechanics 2006, Vol. 39 (Suppl 1)
Oral Presentations
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 . 0 3 1 Q + 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.
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 equations 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.
5214 Fr, 09:30-09:45 (P50) Design of a perfusion system for fetal c a r d i o p u l m o n a r y bypass S. Wright 1, M. Gartner 1,2, J. Speakman 1, J. Tamblyn 1, E Pigula 2. 1Ension,
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 2 0 120. 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.
5248 Fr, 11:30-11:45 (P51) Shear dependant platelet accumulation 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
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 additional 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.
6980 Fr, 11:45-12:00 (P51) Role o f stent design in platelet thrombosis: A computational analysis A.S. Bedekar, K. Pant, S. Sundaram. Biomedical Technology Branch, CFD
Research Corporation, Huntsville, AL, USA
11.5. Thrombosis in Devices and Cardiovascular Pathologies 7127 Fr, 11:00-11:30 (P51) Platelet activity measurements and numerical simulations of flow induced thrombus formation in cardiovascular pathologies 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 hemodynamic stresses that may induce platelet activation and potentiate their interaction with the endothelium. In-vitro platelet measurements were conducted in a Hemodynamic Shearing Device (HSD) which is driven by a computercontrolled motor fed with dynamic waveforms that can mimic almost any stress loading combination. The loading waveforms are obtained from CFD simulations, 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
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 subsequent 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 dependent 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 deposition in stented artery models and their correlation to flow 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 subsequent 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