Continuous-flow ventricular assist devices (VADs) have established themselves as a lifesaving therapy option in patients with severe cardiovascular disease. Unfortunately, complications with VADs resulting from the shear-induced formation of surface blood clots are common. In the current work, an antifouling coating based on the combination of mussel-inspired dendritic polyglycerol (MI-dPG) and linear polyglycerol (lPG) is tested for its cell-repelling properties, biocompatibility, and complement activating properties. Furthermore, the adhesion and activation of blood platelets are tested under static and flow conditions. The adhesion and proliferation of two cell types are studied by means of LIVE/DEAD cell staining, and it is clearly observed that the lPG-functionalized MI-dPG coating prevents cell adhesion. Additionally, no cell mortality is observed on all substrates, indicating the biocompatibility of the tested coatings. All coatings show lower (or equal) complement-activating properties than bare titanium, which is considered a highly biocompatible material. Most importantly, the lPG-functionalized system prevents the adhesion and activation of blood platelets under static and flow conditions. Finally, a prototype VAD is successfully coated with MI-dPG under flow conditions. In the current study, the efficient lPG-functionalization of the MI-dPG coating is proved to obtain cell- and platelet-repelling surfaces.

Objective: Most biofilm flow-chambers are designed for standardized homogeneous biofilms for research purposes. These do not mimic the complexity of prosthetic heart valves, which consist of both artificial and biological material. Infective endocarditis (IE) is still associated with a high morbidity and mortality. IE is characterized by bacterial biofilms of the endocardium leading to destruction of the valve. Current research demonstrates that about one quarter of the 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 exclude external contamination, sterility tests with sterile culture media were performed for 24h. During this time period, no growth of microorganisms was observed in the system and cultures after plating on standard media remained negative. The system was inoculated with Staphylococcus epidermidis PIA 8400 to create biofilms on porcine aortic valves. Porcine aortic roots were incubated in this system for increasing periods of time and bacterial titration to evaluate bacterial growth and biofilm development on the valves. After incubation, specimens were embedded and tissue sections were analyzed by Fluorescence in situ hybridization (FISH) for direct visualization of the biofilms and bacterial activity. Pilot tests for biofilm growth showed monospecies colonization consisting of cocci with time- and inocula-dependent increase. FISH visualized biofilms with ribosome-containing, and thus metabolic active cocci, tissue infiltration and similar colonization pattern as observed by FISH in human IE heart valves infected by S. epidermidis. Conclusion: These results demonstrate the establishment of a novel complex in vitro - model for bacterial biofilm growth on porcine aortic roots. The model will allow identifying predilection sites of heart 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.

Colonization of in-dwelling catheters by microbial biofilms is a major concern in patient health eventually leading to catheter-related blood stream infections. Biofilms are less susceptible to standard antibiotic therapies that are effective against planktonic bacteria. Standard procedure for the detection of microorganisms on the catheter tip is culture. However, viable but non-culturable cells (VBNCs) may be missed. The aim of this study was to evaluate the use of fluorescence in situ hybridization (FISH) as an indicator to visualize and quantify the effect of the antibiotics daptomycin and vancomycin on biofilms in situ. We established an in vitro catheter biofilm model of Staphylococcus epidermidis biofilms on polyurethane catheters. Biofilm activity was measured by FISH and correlated to colony forming units (CFU) data. Digital image analysis was used for quantification of total biofilm mass and the area of the FISH positive biofilm cells. FISH showed a pronounced effect of both antibiotics on the biofilms, with daptomycin having a significantly stronger effect in terms of both reduction of biofilm mass and number of FISH-positive cells. This supports the anti-biofilm capacity of daptomycin. Interestingly, neither antibiotic was able to eradicate all of the FISH-positive cells. In summary, FISH succeeded in visualization, quantification, and localization of antibiotic activity on biofilms. This technique adds a new tool to the arsenal of test systems for anti-biofilm compounds. FISH is a valuable complementary technique to CFU since it can be highly standardized and provides information on biofilm architecture and quantity and localization of survivor cells.

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.

Passive flight in living things, such as in maple or dandelion seeds, is one of the most primitive methods of aerial dispersal. This mechanism is robust and efficient, as it utilizes the present wind conditions. Passive flight is used not only by plant seeds but also by some animals. Spiders use fine, flexible silk filaments to fly, a behavior known as ballooning. This capability is distinct from that of other winged insects, as some ballooning spiders can travel hundreds of kilometers, reaching as high as 4.5 km above sea level. Various hypotheses explain the physical mechanism of ballooning flight. Some studies have shown that turbulent flow in the atmospheric boundary layer enhances spiders’ flight endurance. This mechanism may be usefully applied in the exploration of hazardous weather conditions, such as severe storms, tornadoes, and clear-air turbulence, in the atmosphere, if we scale them up. In this paper, the authors briefly introduce the flight characteristics of the ballooning structure (i.e., the spider body and silk filaments), which were revealed in a simulation using a bead-spring model, and examine the possibility of scaling up ballooning flight from 25 mg to 1–2.5 kg for the exploration of hazardous weather conditions in the atmosphere.

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.

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.

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.

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.

When using artificial surfaces that come into contact with the bloodstream, it is important to consider the undesirable consequences of thrombus formation and embolization. Although great progress has been made by creating new surfaces and antithrombotic coatings or evaluating flow conditions, unexpected platelet adhesion and aggregation can lead to the sudden formation of an adverse thrombus. Our experiments in a stagnation point flow chamber with citrate-anticoagulated whole blood and ADP-stimulated platelets mimicked the situations of implanted artificial organs, e.g., mechanical circulatory support devices, or extravascular circulation. With video microscopy, real-time platelet characteristics were observed at shear rate levels between 50 and 500 s−1 on glass, von Willebrand factor, and polyurethane surfaces for at least 5 min after the first contact. Platelet adhesion and aggregation were observed with distinctness in aggregate size, surface coverage, aggregate size, probability of an embolic event, and platelet contraction. The probability of an embolic event increased at lower flow rates. Additionally, platelet contraction was affected by the flow rate. Raising the flow rate intensified the platelet contraction. With this setup, the microembolization caused by surface contact and flow and platelet contraction can be detected in a real-time direct observation. This capability addresses both technical and clinical issues, such as thrombus and embolus formation, and may improve the research on the hemocompatibility of biomaterials.

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.

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.

Zusammenfassung Im vorliegenden Beitrag entwerfen wir für ein neuartiges Blutdruckmesssystem eine kaskadierte Regelung aus zwei unterlagerten klassischen Rückführungen mit Vorfilter und einem iterativ lernenden Regler. Wir zeigen, dass die Bandbreite der klassischen Regelung durch das Messrauschen der Ultraschallsonde stark eingeschränkt ist und dass diese Einschränkung umgangen werden kann, wenn die repetitive Natur des Regelungsproblems ausgenutzt wird.

Drivelines for ventricular assist devices and catheters for peritoneal dialysis are percutaneous implants which are designed for a dwell time of at least one year. The testing of such percutaneous devices in animal experiments should represent this long period, since infection episodes can occur a long time after implantation. Usually, these animal experiments are the final step in the previous development of the implant and represent a high monetary value. However, a single malfunction is already sufficient to end the experiment. As part of a research project preclinical testing of percutaneous implants was performed in goats. Although the percutaneous devices do not cause pain, the animals will bite and pull at them and endanger the experiment. Therefore, protection of the implant is required. Standard wound dressing is not sufficient and appropriate protective garments for goats are not commercially available. Therefore, custom fit protective waistcoats were designed and manufactured. To this end the size of the goats was measured and a pattern for sewing was created. A polyester mesh fabric provides the necessary resistance and good breathability. The waistcoats were reinforced with polyethylene foam to prevent biting through the garment. Side-release buckles were chosen as fasteners. A total of six waistcoats were manufactured. They fit the goats tightly, while preserving the full range of motion. The goats tolerate them well. They are durable, secure and effectively protected the implants for a period of over one year.

Continuous non-invasive blood pressure measurement for long-term application remains an unsolved technical challenge. Determining blood pressure by measuring pulse transit times is a promising technique; however, it needs repeated recalibration. The correlation between blood pressure and pulse transit time changes with the elastic properties of the arteries. Experimental data are required to develop a longer calibration interval with a model-based time series analysis. A polymeric vascular model of three artery sections connected by an arterial bifurcation was set up with physiological flow and pressure curves along with physiological pulse transit times. The elastic properties of the three modelled arteries can be changed separately within a physiological range during the experiments. The vascular model provides the pressure signal and pulse wave signal upstream and downstream of the bifurcation; the flow is determined in the inlet. Physiologic pulse transit time changes in the model are mainly realized through changes in the elasticity and not variations in fluid pressure.

With the ever-increasing clinical application of intra vascular implants like valves, stents, grafts and ventricular assist devices the problem of thrombo-embolism has received new attention. Such a thrombo-embolic adverse event starts with the adhesion of platelets. This is investigated with the stagnation flow chamber. Objective of this paper is to research the stagnation point flow with new methods in order to elucidate questions like: How does a thrombus form, what is the role of shear rate? In the new experiments reported here fresh human blood was used. It was drawn by venipuncture from a healthy donor into 1 mM citrate solution. Flow rates were 20 and 40 ml/h and the blood entered the circular flow chamber through a tube 650 mu m in diameter. Height of the flow space was 480 mu m. The platelets were dyed with Mepacrine. Before the blood entered the flow chamber a platelet-activating agent was added. This agent was mixed with the blood with the help of a micro mixer. The flow chamber was placed in an inverted microscope and platelets deposited on the bottom plate of the flow chamber. This was recorded with fluorescent video microscopy. With the help of image processing the surface coverage (coveraged area / total area) was determined and was plotted as a function of time and shear rate at the bottom plate. The shear rate was derived from computations of the blood flow using computational fluid dynamics (CFD). The platelet deposition of nearly 50 experiments was recorded, and of these a selection of 9 experiments were analyzed and described in this paper.

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.

Background: Side-branches have a crucial impact on calculation of wall shear stress (WSS) by numerical integration of the Navier-Stokes differential equations for incompressible fluids (CFD). This is due to splitting of flow (Q) at bifurcations. The relation of Q(branch1) to Q(branch2). is related to branch diameter (D) by a power law with exponents (E) experimentally determined between 2.6 and 2.3 somewhat below three as expected by Murray's law. The impact of these variations of modelling the splitting of flow at bifurcations on the sensitivity of WSS by CFD is analyzed.Methods: Vascular trees from 2 left coronary arteries stratified with respect to WSS - obstructive CAD with 16 outlets (WSShigh) and aneurysmatic CAD with 15 outlets (WSSlow) - were reconstructed from biplane angiograms. Flow simulations were performed by CFD based on patient specific data. Outlet conditions were assumed as Q similar to D boolean AND(2.6) and Q similar to D boolean AND(2.3) respectively. Percent area with WSS<0.4Pa, mean WSS and correlation were assessed.Results: Mean WSS was 4.2 +/- 3.3 Pa and 4.2 +/- 3.5 Pa in WSShigh and 1.87 +/- 1.69 Pa and 1.83 +/- 1.77 Pa in WSSlow. The difference is small, but increases with decreasing vessel diameter. Percent area with WSS<0.4 Pa was 1.15 % and 0.8 % in WSShigh and 7.56 % and 7.55 % in WSSlow. Squared correlation ranged between 0.9849 and 0.9867 and the regression slope was 1.059 with E=2.6 as y and E=2.3 as x.Conclusion: Calculation of wall shear stress in coronary arteries by numerical simulation is not sensitive to small changes in outlet boundary conditions.

Thrombus formation on artificial surfaces in blood pumps occurs as an adverse event and causes failure of devices. The formation results from an interaction of blood, flow and surface properties. A stagnation point flow considers these components in a reliable way. For that, fresh human blood is poured through a hollow needle (ID 0.65 mm) into the centre of a 480 mu m gap. The surface at the opposite side is coated with a test material (native glass, Pellethane, Carbothane, von-Willebrandfactor). Time-resolved thrombus formations on this side are obtained using video microscopy fluorescence. With this method, thrombus formation and side effects, e.g. aggregation detachment, can be analyzed and studied by variation of blood, flow and surface properties.