Bacterial biofilms in infective endocarditis: an in vitro model to investigate emerging technologies of antimicrobial cardiovascular device coatings.

OBJECTIVE: In spite of the progress in antimicrobial and surgical therapy, infective endocarditis (IE) is still associated with a high morbidity and mortality. IE is characterized by bacterial biofilms of the endocardium, especially of the aortic and mitral valve leading to their destruction. About one quarter of patients with formal surgery indication cannot undergo surgery. This group of patients needs further options of therapy, but due to a lack of models for IE prospects of research are low. Therefore, the purpose of this project was to establish an in vitro model of infective endocarditis to allow growth of bacterial biofilms on porcine aortic valves, serving as baseline for further research. METHODS AND RESULTS: A pulsatile two-chamber circulation model was constructed that kept native porcine aortic valves under sterile, physiologic hemodynamic and temperature conditions. To create biofilms on porcine aortic valves the system was inoculated with Staphylococcus epidermidis PIA 8400. Aortic roots were incubated in the model for increasing periods of time (24 h and 40 h) and bacterial titration (1.5 × 104 CFU/mL and 1.5 × 105 CFU/mL) with 5 L cardiac output per minute. After incubation, tissue sections were analysed by fluorescence in situ hybridization (FISH) for direct visualization of the biofilms. Pilot tests for biofilm growth showed monospecies colonization consisting of cocci with time- and inocula-dependent increase after 24 h and 40 h (n = 4). In n = 3 experiments for 24 h, with the same inocula, FISH visualized biofilms with ribosome-containing, and thus metabolic active cocci, tissue infiltration and similar colonization pattern as observed by the FISH in human IE heart valves infected by S. epidermidis. CONCLUSION: These results demonstrate the establishment of a novel in vitro model for bacterial biofilm growth on porcine aortic roots mimicking IE. The model will allow to identify predilection sites of valves for bacterial adhesion and biofilm growth and it may serve as baseline for further research on IE therapy and prevention, e.g. the development of antimicrobial transcatheter approaches to IE.

Noninvasive assessment of blood pressure in rotary blood pump recipients using a novel ultrasonic Doppler method.

In rotary blood pump recipients with low blood pressure pulsatility, current oscillometric methods to measure blood pressure are not applicable. The aim of this study was to use ultrasonic Doppler flow measurements to determine blood pressure in this patient population noninvasively. In 28 rotary blood pump recipients, blood pressure was measured three times with the developed Doppler method and compared to the invasive arterial line (n = 15) or to the oscillometric Terumo Elemano BP monitor (n = 13). Blood velocities in the radial artery were recorded by the new Doppler sensor during cuff deflation. A sigmoid curve was fitted to a preprocessed velocity signal and the systolic and mean arterial pressures were determined. A total of 84 measurements were performed, and 17 recordings were visually excluded from further analysis due to obvious artifacts. Both the systolic and mean pressures derived by the Doppler method were in good accordance with the invasively measured pressure (3.7 ± 6.6 mmHg for the systolic and -2.1 ± 7.3 mmHg for the mean pressure). A good agreement between the oscillometric monitor and the Doppler method for the systolic (0.0 ± 6.0 mmHg) and mean (1.0 ± 5.9 mmHg) pressures was observed. In this study, a new Doppler blood pressure measurement system was developed and clinically validated. The novel sensor allows easier placement above the radial artery compared to commercial probes. An algorithm was developed which processes the Doppler signal robustly and is able to determine the systolic as well as the mean arterial blood pressure.

Couette shearing device for the investigation of shear-induced damage of the primary hemostasis by left ventricular assist devices.

INTRODUCTION:: Continuous-flow left ventricular assist devices have evolved from short-time therapy into permanent or so-called destination therapy. One complication in long-term usage is bleeding, which is presumably attributed to shear-induced interference of left ventricular assist devices with the coagulation system. METHODS:: The influence of dynamic shear stresses on primary hemostasis by single or multiple passes through left ventricular assist devices was investigated. A novel Couette-type shearing device, especially fitted to simulate left ventricular assist devices with highly dynamic and repetitive stresses, was developed. To evaluate the clotting ability of the blood and thus the bleeding tendency, the closure time of the platelet function analyzer (PFA-100®, Dade Behring, Marburg, Germany) was used. The relationship of the PFA-100 closure time was fitted to measurement points with shear stress and exposure time as parameters. RESULTS:: 76 samples of human blood collected from four different healthy donors in sodium-citrate anticoagulant solution were tested, including 20 control samples. A damage model according to the power law approach could be developed. A linear correlation of shear stress and exposure time to the PFA-100 closure time could be determined. In addition, a model was developed to calculate the increase in the PFA closure time on the basis of shear stress over time curves. DISCUSSION:: With the shearing device, half-sine-wave-shaped shear stress patterns relevant to rotary blood pumps can be achieved with very good repeatability. The proposed damage model could be used to compare and optimize left ventricular assist devices under development. The tests showed a significant decrease in coagulability after only a few repetitions.

Turbulence measurements in an axial rotary blood pump with laser Doppler velocimetry.

BACKGROUND: The implantation of rotary blood pumps as ventricular assist devices (VADs) has become a viable therapy for quite a number of patients with end-stage heart failure. However, these rotary blood pumps cause adverse events that are related to blood trauma. It is currently believed that turbulence in the pump flow plays a significant role. But turbulence has not been measured to date because there is no optical access to the flow space in rotary blood pumps because of their opaque casings. METHODS: This difficulty is overcome with a scaled-up model of the HeartMate II (HM II) rotary blood pump with a transparent acrylic housing. A 2-component laser Doppler velocimetry (LDV) system was used for the measurement of time resolved velocity profiles and velocity spectra upstream and downstream of the rotor blades. Observing similarity laws, the speed and pump head were adjusted to correspond closely to the design point of the original pump - 10,600 rpm speed and 80 mmHg pressure head. A model fluid consisting of a water-glycerol mixture was used. RESULTS: The measured velocity spectra were scalable by the Kolmogorov length and the Kolmogorov length was estimated to be between 14 and 24 µm at original scale, thus being about 1.5 to 3 times the size of a red blood cell. CONCLUSIONS: It can be concluded that turbulence is indeed present in the investigated blood pump and that it can be described by Kolmogorov's theory of turbulence. The size of the smallest vortices compares well to the turbulence length scales as found in prosthetic heart valves, for example.

Experimental and Numerical Investigation of an Axial Rotary Blood Pump.

Left ventricular assist devices (LVADs) have become a standard therapy for patients with severe heart failure. As low blood trauma in LVADs is important for a good clinical outcome, the assessment of the fluid loads inside the pump is critical. More specifically, the flow features on the surfaces where the interaction between blood and artificial material happens is of great importance. Therefore, experimental data for the near-wall flows in an axial rotary blood pump were collected and directly compared to computational fluid dynamic results. For this, the flow fields based on unsteady Reynolds-averaged Navier-Stokes simulations-computational fluid dynamics (URANS-CFD) of an axial rotary blood pump were calculated and compared with experimental flow data at one typical state of operation in an enlarged model of the pump. The focus was set on the assessment of wall shear stresses (WSS) at the housing wall and rotor gap region by means of the wall-particle image velocimetry technique, and the visualization of near-wall flow structures on the inner pump surfaces by a paint erosion method. Additionally, maximum WSS and tip leakage volume flows were measured for 13 different states of operation. Good agreement between CFD and experimental data was found, which includes the location, magnitude, and direction of the maximum and minimum WSS and the presence of recirculation zones on the pump stators. The maximum WSS increased linearly with pressure head. They occurred at the upstream third of the impeller blades and exceeded the critical values with respect to hemolysis. Regions of very high shear stresses and recirculation zones could be identified and were in good agreement with simulations. URANS-CFD, which is often used for pump performance and blood damage prediction, seems to be, therefore, a valid tool for the assessment of flow fields in axial rotary blood pumps. The magnitude of maximum WSS could be confirmed and were in the order of several hundred Pascal.

A two-stage rotary blood pump design with potentially lower blood trauma: a computational study.

AIM: In current rotary blood pumps, complications related to blood trauma due to shear stresses are still frequently observed clinically. Reducing the rotor tip speed might decrease blood trauma. Therefore, the aim of this project was to design a two-stage rotary blood pump leading to lower shear stresses. METHODS: Using the principles of centrifugal pumps, two diagonal rotor stages were designed with an outer diameter of 22 mm. The first stage begins with a flow straightener and terminates with a diffusor, while a volute casing behind the second stage is utilized to guide fluid to the outlet. Both stages are combined into one rotating part which is pivoted by cup-socket ruby bearings. Details of the flow field were analyzed employing computational fluid dynamics (CFD). A functional model of the pump was fabricated and the pressure-flow dependency was experimentally assessed. RESULTS: Measured pressure-flow performance of the developed pump indicated its ability to generate adequate pressure heads and flows with characteristic curves similar to centrifugal pumps. According to the CFD results, a pressure of 70 mmHg was produced at a flow rate of 5 L/min and a rotational speed of 3200 rpm. Circumferential velocities could be reduced to 3.7 m/s as compared to 6.2 m/s in a clinically used axial rotary blood pump. Flow fields were smooth with well-distributed pressure fields and comparatively few recirculation or vortices. Substantially smaller volumes were exposed to high shear stresses >150 Pa. CONCLUSIONS: Hence, blood trauma might be reduced with this design. Based on these encouraging results, future in vitro investigations to investigate actual blood damage are intended.

Role of flow for the deposition of platelets.

Implants inside the cardiovascular system are subjected to blood flow. Platelet deposition usually takes place, eventually leading to thrombus formation. Tests must be performed in order to select a suitable biomaterial, but no generally accepted test method exists for biomaterials in contact with blood. At a first glance, the flow appears to play only a minor role in the complex interaction between platelets and biomaterials. However, experiments and models have indeed demonstrated the importance of flow. Flow is the mechanism by which platelets are transported to the site of deposition, enabling deposition and forming the shape of a growing thrombus. This interaction is investigated here by means of two experimental models. The first model generates the simplest shear flow, the plane Couette flow. It serves to quantify the role of the shear rate. The second model, the stagnation point flow model, features a more complex shear flow. This model is used to understand the influence of a changing flow field along the wall over which the platelets travel. The platelet deposition is observed using the two experimental models, and a numerical model is developed to reproduce and simulate the experimental results. In the numerical model, the movement of platelets is computed with a combination of convective and stochastic movements due to diffusion. The combined motion brings some platelets close to the wall. The deposition of the platelet at the wall is modeled by a stochastic model. Probability determines whether the individual platelet deposits or flows onwards. This probability is the product of three different probabilities, which are the properties of the platelet, the wall, and the flow. The results of the models are compared with the experimental results and are used to understand the experiments.

Numerical Analysis of Blood Damage Potential of the HeartMate II and HeartWare HVAD Rotary Blood Pumps.

Implantable left ventricular assist devices (LVADs) became the therapy of choice in treating end-stage heart failure. Although survival improved substantially and is similar in currently clinically implanted LVADs HeartMate II (HM II) and HeartWare HVAD, complications related to blood trauma are frequently observed. The aim of this study was to compare these two pumps regarding their potential blood trauma employing computational fluid dynamics. High-resolution structured grids were generated for the pumps. Newtonian flow was calculated, solving Reynolds-averaged Navier-Stokes equations with a sliding mesh approach and a k-ω shear stress transport turbulence model for the operating point of 4.5 L/min and 80 mm Hg. The pumps were compared in terms of volumes subjected to certain viscous shear stress thresholds, below which no trauma was assumed (von Willebrand factor cleavage: 9 Pa, platelet activation: 50 Pa, and hemolysis: 150 Pa), and associated residence times. Additionally, a hemolysis index was calculated based on a Eulerian transport approach. Twenty-two percent of larger volumes above 9 Pa were observed in the HVAD; above 50 Pa and 150 Pa the differences between the two pumps were marginal. Residence times were higher in the HVAD for all thresholds. The hemolysis index was almost equal for the HM II and HVAD. Besides the gap regions in both pumps, the inlet regions of the rotor and diffuser blades have a high hemolysis production in the HM II, whereas in the HVAD, the volute tongue is an additional site for hemolysis production. Thus, in this study, the comparison of the HM II and the HVAD using numerical methods indicated an overall similar tendency to blood trauma in both pumps. However, influences of turbulent shear stresses were not considered and effects of the pivot bearing in the HM II were not taken into account. Further in vitro investigations are required.

Bionic approach for the prevention of exit-site infections of percutaneous devices.

Exit-site infections remain one of the main complications for percutaneous devices, such as catheters for peritoneal dialysis or drivelines for ventricular assist devices. Many efforts have been made to create a biological seal, yet without long-term success. This study investigates a new kind of percutaneous device which is coated with an extricable polymeric membrane. The bionic approach applies the naturally outwards directed growth of skin structures to technology: by pulling the protective membrane it slowly grows out of the body and a developing sulcus is exposed to dry air and an infection is avoided. In a feasibility study this kind of device was shown to reduce the rate of infection. To further investigate these devices, they were implanted in the skin of goats and observed for a period of more than 500 days. The membranes were pulled with a force of up to 2 N and the resulting movement was recorded. When being pulled, the membranes moved 0.4-0.9 mm per week, showing that the application of a continuously acting, defined force on the protective membrane causes the desired slow movement.

In vitro study of hemodynamic treatment improvement: Hunterian ligation of a fenestrated basilar artery aneurysm after coiling.

Hunterian ligation affecting hemodynamics in vessels was proposed to avoid rebleeding in a case of a fenestrated basilar artery aneurysm after incomplete coil occlusion. We studied the hemodynamics in vitro to predict the hemodynamic changes near the aneurysm remnant caused by Hunterian ligation. A transparent model was fabricated based on three-dimensional rotational angiography imaging. Arteries were segmented and reconstructed. Pulsatile flow in the artery segments near the partially occluded (coiled) aneurysm was investigated by means of particle image velocimetry. The hemodynamic situation was investigated before and after Hunterian ligation of either the left or the right vertebral artery (LVA/RVA). Since post-ligation flow rate in the basilar artery was unknown, reduced and retained flow rates were simulated for both ligation options. Flow in the RVA and in the corresponding fenestra vessel is characterized by a vortex at the vertebrobasilar junction, whereas the LVA exhibits undisturbed laminar flow. Both options (RVA or LVA ligation) cause a significant flow reduction near the aneurysm remnant with a retained flow rate. The impact of RVA ligation is, however, significantly higher. This in vitro case study shows that flow reduction near the aneurysm remnant can be achieved by Hunterian ligation and that this effect depends largely on the selection of the ligated vessel. Thus the ability of the proposed in vitro pipe-line to improve hemodynamic impact of the proposed therapy was successfully proved.

Numerical and experimental evaluation of platelet deposition to collagen coated surface at low shear rates.

Platelet deposition to collagen-coated surface under low shear conditions was investigated using an experimental model. The flow chamber was created by combining a stationary and a rotational glass plates spaced 50 µm apart. Blood filled into this space was subjected to a simple Couette flow. Both glass plates were covered with albumin to render them anti-thrombogenic. However, one spot 1×1 mm in size was covered with collagen. This spot was where the platelets deposited. The device was mounted on an inverted microscope and the platelet deposition was recorded. Platelets were dyed to render them fluorescent. The blood used was human blood from healthy volunteers. It was subjected to a range of low shear rates (below 7001/s) to find out how they act on platelet deposition. The results show a characteristic curve with elevated platelet deposition in the range of 1501/s. For the interpretation of these results a numerical model was developed. It applies the Monte Carlo method to model a random walk of platelets. This diffusive motion was superimposed on the convective motion by the Couette flow. A satisfactory match to the experimental data was achieved.

In vitro study of cerebrospinal fluid dynamics in a shaken basal cistern after experimental subarachnoid hemorrhage.

BACKGROUND: Cerebral arterial vasospasm leads to delayed cerebral ischemia and constitutes the major delayed complication following aneurysmal subarachnoid hemorrhage. Cerebral vasospasm can be reduced by increased blood clearance from the subarachnoid space. Clinical pilot studies allow the hypothesis that the clearance of subarachnoid blood is facilitated by means of head shaking. A major obstacle for meaningful clinical studies is the lack of data on appropriate parameters of head shaking. Our in vitro study aims to provide these essential parameters. METHODOLOGY/PRINCIPAL FINDINGS: A model of the basal cerebral cistern was derived from human magnetic resonance imaging data. Subarachnoid hemorrhage was simulated by addition of dyed experimental blood to transparent experimental cerebrospinal fluid (CSF) filling the model of the basal cerebral cistern. Effects of various head positions and head motion settings (shaking angle amplitudes and shaking frequencies) on blood clearance were investigated using the quantitative dye washout method. Blood washout can be divided into two phases: Blood/CSF mixing and clearance. The major effect of shaking consists in better mixing of blood and CSF thereby increasing clearance rate. Without shaking, blood/CSF mixing and blood clearance in the basal cerebral cistern are hampered by differences in density and viscosity of blood and CSF. Blood clearance increases with decreased shaking frequency and with increased shaking angle amplitude. Head shaking facilitates clearance by varying the direction of gravitational force. CONCLUSIONS/SIGNIFICANCE: From this in vitro study can be inferred that patient or head shaking with large shaking angles at low frequency is a promising therapeutic strategy to increase blood clearance from the subarachnoid space.

Percutaneous devices: a review of applications, problems and possible solutions.

Percutaneous devices enable the transfer of mass, energy and forces through the skin. There is a wide clinical need for this, which is not likely to decrease or disappear. The emerging new artificial organs, such as wearable kidneys or lungs, will be in increased demand in the future. Any application lasting longer than days or weeks is endangered by infections entering the body via the exit site. The only carefree solution that has been found is for an exit site placed on the skull, where it can be securely immobilized. For the majority of the locations on the abdomen or chest, no solution for an infection-free device has been found. A solution may be possible with a better understanding of the physiology of keratinocytes as a barrier for microbes.

Tri-leaflet valve design with a purge flow for heart-assist devices: an in vitro optimization study.

The objective of this study is to assess the effect of a purge flow on valves of pulsatile heart-assist devices. Clinical applications of these devices are still limited because of frequent thromboembolic complications. These complications often originate at the valves and the unavoidable flow separation regions that are found behind the leaflets. The flow separations cause a long residence time of blood that is considered particularly detrimental. To solve this problem, a valve with a purge flow is proposed. A purge flow is a jet, which is separated from the main blood flow and directed behind the leaflets into the sinus to flush it. Even though the purge flow does not prevent a flow separation, it shortens the residence time of the blood in the sinus. Thus, the purge flow improves the periodic washout of the blood in the region of flow separation. The complex purge flow was investigated in a tri-leaflet valve. The geometrical parameters of the valve were varied systematically. A statistical technique--the Taguchi method--was used to reduce the number of investigated models to 12. The flows through the resulting valve models were numerically simulated and analyzed. The evaluated models with the best results were subsequently investigated experimentally using different methods: hemodynamic tests in a valve tester and flow visualization using the dye washout method. It was shown that the purge flow can effectively wash out the sinus. Therefore, the purge flow valve reduces the potential of a thrombus formation normally associated with the valve.

How can we achieve infection-resistant percutaneous energy transfer?

Clinical records show ever increasing functional times of rotary blood pumps implanted in patients. With longer functional time, the problem of driveline infection is becoming more urgent. No material or scaffold has been found, which allows a permanent and stable ingrowth of skin cells that would prevent (pathogenic) germs entering the body. Usually, the epithelial cells die at the exit site and new cells form a sulcus around the driveline, which grows deeper and finally becomes infected. The purpose of this project is to present a solution to this problem by elaborating a new mechanism, the active skin-penetrating device. The device is composed of a tube with a 5-mm diameter, a protective sleeve that surrounds the catheter exit site, and an active traction device. The protective sleeve is made of thin polyurethane covered with polyethylenterephtalat (PET, i.e. Dacron) fibers to permit the attachment of keratinocytes, similar to the standard driveline. The active traction device exerts a constant pull on the protective sleeve. The ingrown keratinocytes slowly give way and the protective sleeve gradually moves out of the body at a rate of a few millimeters per week. Meanwhile, the keratinocytes transform into horny cells and are then shed as in natural skin. Therefore, the formation of a sulcus is avoided, and the protective sleeve remains infection-free. In a first proof of the concept, four of the new devices and 10 control devices were implanted in goats. The devices remained infection-free for a period of 420 days, whereas four of the 10 control devices became infected. On the basis of these experiments, the active skin-penetrating device has been further developed and is being tested again in goats in a refined version. The results so far indicate that with the active-skin penetrating device an infection-resistant percutaneous energy transfer can be achieved for a prolonged period of time.

Non-dimensional modeling in flow simulation studies of coronary arteries including side-branches: a novel diagnostic tool in coronary artery disease.

AIMS: Blood flow, vascular shape and size and local remodeling of the vascular wall are linked through wall shear stress (WSS) signaling. Inter-individual comparison of shape and WSS is hampered by large differences in size of flow and shape. We performed non-dimensional modeling to discriminate different types of coronary artery remodeling based on WSS patterns and vessel morphology. METHODS AND RESULTS: Blood flow was simulated in three-dimensional reconstructed right coronary artery trees from seven controls, five patients with coronary artery disease (CAD) and five patients with aneurysmatic CAD (AnCAD) classified by expert visual diagnosis. A discriminant model using low WSS area, a remodeling index, and cross-correlation of WSS in main trunks and complete trees (K) as non-dimensional parameters classified CAD and AnCAD correctly and identified three patients with high risk profile and functional disease in controls. The new model was compared with discriminant analysis of identical cases simulated without side-branches. The inclusion of K (information from side-branches) and replacement of the mean diameter by a non-dimensional remodeling index improved the model. We found significant (p<0.005) gender differences in the remodeling index. CONCLUSION: The combination of non-dimensional modeling and WSS profiling should be further investigated as a novel diagnostic tool in CAD beyond local stenosis.

Flow simulation studies in coronary arteries--impact of side-branches.

AIMS: Wall shear stress (WSS) may induce local remodeling of the vascular wall and the WSS pattern in turn depends on vascular geometry. We aimed to elucidate the impact of side-branches on local WSS. METHODS AND RESULTS: Steady numerical flow simulation studies were performed in three-dimensional reconstructed right coronary artery (RCA) trees. RCA from seven controls, five patients with coronary artery disease (CAD) and five patients with aneurysmatic CAD (AnCAD) classified by expert visual diagnosis were studied. Then three transient flow simulations were performed with cases representative for each group in order to evaluate the impact of pulsatile flow simulation. As vascular size and flow rates vary considerably between patients, non-dimensional approaches were applied for group comparison. A point-to-point comparison of the WSS in the same tree with and without side-branches revealed local differences in WSS of up to 12.0 Pa. This was caused by a reduction of volume flow of up to 78.7% in the trunk. Differences are not only limited to bifurcation sites but also affect local narrowings and strongly curved segments. The point-to-point comparison of steady and transient simulations found an average increase of WSS of below 7% in transient simulations. No significant differences were found between histograms of pulsatile and steady simulations, showing a high cross-correlation of >0.97. CONCLUSION: Side-branches must not be neglected in numerical flow simulation (steady and transient) studies. Steady simulations are valid for an assessment of time-averaged WSS distributions.

Theoretical modeling of the interaction between alveoli during inflation and deflation in normal and diseased lungs.

Alveolar recruitment is a central strategy in the ventilation of patients with acute lung injury and other lung diseases associated with alveolar collapse and atelectasis. However, biomechanical insights into the opening and collapse of individual alveoli are still limited. A better understanding of alveolar recruitment and the interaction between alveoli in intact and injured lungs is of crucial relevance for the evaluation of the potential efficacy of ventilation strategies. We simulated human alveolar biomechanics in normal and injured lungs. We used a basic simulation model for the biomechanical behavior of virtual single alveoli to compute parameterized pressure-volume curves. Based on these curves, we analyzed the interaction and stability in a system composed of two alveoli. We introduced different values for surface tension and tissue properties to simulate different forms of lung injury. The data obtained predict that alveoli with identical properties can coexist with both different volumes and with equal volumes depending on the pressure. Alveoli in injured lungs with increased surface tension will collapse at normal breathing pressures. However, recruitment maneuvers and positive endexpiratory pressure can stabilize those alveoli, but coexisting unaffected alveoli might be overdistended. In injured alveoli with reduced compliance collapse is less likely, alveoli are expected to remain open, but with a smaller volume. Expanding them to normal size would overdistend coexisting unaffected alveoli. The present simulation model yields novel insights into the interaction between alveoli and may thus increase our understanding of the prospects of recruitment maneuvers in different forms of lung injury.

Coronary artery WSS profiling using a geometry reconstruction based on biplane angiography.

Computational fluid dynamics (CFD) methods based on three-dimensional (3D) vessel reconstructions have recently been shown to provide prognostically relevant hemodynamic data. However, the geometry reconstruction and the assessment of clinically relevant hemodynamic parameters may depend on the used imaging modality. In this study, the silicon model of the left coronary artery (LCA) was acquired with a biplane angiography. The geometry reconstruction was done using commercial CAAS 5.2 QCA 3D software and compared with an original geometry. The original model is an optically digitized post-mortem vessel cast. The biplane angiography reconstruction achieved a Hausdorff surface distance of 0.236 mm to the original geometry that is comparable with results obtained in our earlier study for computed tomography (CT) and magnetic resonance imaging (MRI) reconstructions. Steady flow simulations were performed with a commercial CFD program FLUENT. A comparison of the calculated wall shear stress (WSS) shows good correlation for histograms (r=0.97) and good agreement among the four modalities with a mean WSS of 0.65 Pa in the original model, of 0.68 Pa in the CT-based model, of 0.67 Pa in the MRI based model, and of 0.69 Pa in the biplane angiography-based model. We can conclude that the biplane angiography-based reconstructions can be used for the WSS profiling of the coronary arteries.

Local glycoprotein IIb/IIIa receptor inhibitor delivery from the pump surface attenuates platelet adhesion in continuous flow ventricular assist devices.

Shear-induced platelet activation (SIPA) has been identified to induce platelet adhesion and thrombus formation in continuous flow left ventricular assist devices (LVAD). Platelet glycoprotein (GP) IIb/IIIa receptor inhibitors are effective to prevent SIPA. However, systemic GP IIb/IIIa receptor inhibitor application is associated with severe bleeding complications. The aim of the study was to evaluate (i) the feasibility of absorption and elution of the GP IIb/IIIa receptor blocker TAK-029 from the Ti6Al4V surface of the pump; and (ii) the effect of local GP IIb/IIIa receptor blocker delivery regarding platelet adhesion on the surface of a continuous flow VAD model. Saturating concentrations of TAK-029 were adsorbed on the surface of a centrifugal pump. Whole human blood was perfused in circulatory mock loops using untreated (control), albumin-coated, or TAK-029-coated pumps. Peripheral resistance of the circulatory systems were adjusted accordingly to generate 5 L flow per min with impeller rotational speeds of 3500 (high-shear group) and 1500 rpm (low-shear group), respectively. Platelet adhesions on the respective impellers were quantified by ELISA and scanning electron microscopy (SEM). TAK-029 elution and half-life time were determined by ELISA. Compared with control, albumin-coated pumps showed 64 and 20% less platelet adhesions in the high- and low-shear group, respectively. TAK-029 coated pumps reduced platelet adhesion by additional 33 and 65%, respectively, compared with the albumin group. Elution of TAK 029 was initially very rapid and continued slowly. The results show that it is possible to adsorb and elute a small molecular weight GP IIb/IIIa receptor blocker from the pump surface. This drug elution reduced platelet adhesion on the pump significantly. Further studies are necessary to find a suitable drug bonding that will prolong the antiplatelet effect and preclude any bleeding complication caused by this procedure.