Two-photon lithography for customized microstructured surfaces and their influence on wettability and bacterial load.

BACKGROUND: Device-related bacterial infections account for a large proportion of hospital-acquired infections. The ability of bacteria to form a biofilm as a protective shield usually makes treatment impossible without removal of the implant. Topographic surfaces have attracted considerable attention in studies seeking antibacterial properties without the need for additional antimicrobial substances. As there are still no valid rules for the design of antibacterial microstructured surfaces, a fast, reproducible production technique with good resolution is required to produce test surfaces and to examine their effectiveness with regard to their antibacterial properties. METHODS: In this work various surfaces, flat and with microcylinders in different dimensions (flat, 1, 3 and 9 µm) with a surface area of 7 × 7 mm were fabricated with a nanoprinter using two-photon lithography and evaluated for their antibiofilm effect. The microstructured surfaces were cultured for 24 h with different strains of Pseudomonas aeruginosa and Staphylococcus aureus to study bacterial attachment to the patterned surfaces. In addition, surface wettability was measured by a static contact angle measurement. RESULTS: Contact angles increased with cylinder size and thus hydrophobicity. Despite the difference in wettability, Staphylococcus aureus was not affected by the microstructures, while for Pseudomonas aeruginosa the bacterial load increased with the size of the cylinders, and compared to a flat surface, a reduction in bacteria was observed for one strain on the smallest cylinders. CONCLUSIONS: Two-photon lithography allowed rapid and flexible production of microcylinders of different sizes, which affected surface wettability and bacterial load, however, depending on bacterial type and strain.

Mechanical Characterization of Anchoring Devices for the Prevention of Driveline Infection in Left Ventricular Assist Device Patients.

Driveline infection (DLI) is associated with increased mortality and morbidity in left ventricular assist device (LVAD) patients. Because trauma to the driveline exit-site (DLES) is a risk factor for DLI, adhesive anchoring devices are used to immobilize the DL. In this study, commonly used products (identified through literature review and contact with nine international VAD implantation centers) were mechanically characterized to evaluate their effectiveness in preventing DLES trauma. Eight devices were tested in an in vitro abdominal model of the DLES, where a tensile force (10 N) was applied to a HeartMate 3 DL, whereas the resulting force ( FTotal ) on the DLES was recorded using a three-axis load cell. Four devices (CathGrip: FTotal = 2.1 ± 0.4 N, Secutape: FTotal = 2.6 ± 0.3 N, Hollister: FTotal = 2.7 ± 0.5 N, Tubimed: FTotal = 2.9 ± 0.2 N) were significantly ( p < 0.05) better at preventing tensile forces at the DLES compared to the other four devices (Main-Lock: FTotal = 3.7 [0.7] N, Secutape sensitive: FTotal = 3.9 ± 0.4 N, Foley Anchor: FTotal = 4.3 ± 0.5 N, Grip-Lok: FTotal = 5.4 ± 0.8 N). Immobilization of the DL with each anchoring device resulted in lower tensile force on the DLES than without an anchor ( FTotal = 8.2 ± 0.3 N). In conclusion, the appropriate selection of anchoring devices plays a critical role in reducing the risk of DLI, whereas the CathGrip, Secutape, Hollister, or Tubimed were superior in preventing trauma to the DLES in this study.

Electrospinning of small diameter vascular grafts with preferential fiber directions and comparison of their mechanical behavior with native rat aortas.

Conventional electrospun small diameter vascular grafts have a random fiber orientation. In order to achieve mechanical characteristics similar to a native blood vessel, a controllable fiber orientation is of interest. In this study the electrospinning jet was directly controlled by means of an auxiliary, changeable electrostatic field, so that the fibers could be deposited in adjustable orientations. Prostheses with circumferentially, axially, fenestrated and randomly aligned fibers were electrospun on Ø2mm mandrels out of a thermoplastic polyurethane (PUR) and a polylactid acid (PLLA). The impact of the materials and the various preferential fiber orientations on the resulting biomechanics was investigated and compared with that of the native rat aorta in quasistatic and dynamic hoop tensile tests. The test protocol included 3000 dynamic loading cycles in the physiological blood pressure range and ended with a quasistatic tensile test. Any orientation of the fibers in a particular direction resulted in a significant reduction in scaffold porosity for both materials. The standard randomly oriented PUR grafts showed the highest compliance of 29.7 ± 5.5 [%/100 mmHg] and were thus closest to the compliance of the rat aortas, which was 37.2 ± 6.5 [%/100 mmHg]. The maximum tensile force was increased at least 6 times compared to randomly spun grafts by orienting the fibers in the circumferential direction. During the 3000 loading cycles, creeping of the native rat aorta was below 1% whereas the electrospun grafts showed creeping up to 2.4 ± 1.2%. Although the preferred fiber orientations were only partially visible in the scanning electron micrographs, the mechanical effects were evident. The investigations suggest a multi-layer wall structure of the vascular prosthesis, since none of the preferred fiber directions and the materials used could imitate the typical j-shaped mechanical characteristics of the rat aorta.

Effect of Timings of the Lavare Cycle on the Ventricular Washout in an In Vitro Flow Visualization Setup.

Left ventricular assist devices inherently alter the intraventricular flow field and create areas of blood stasis with potential thrombus formation. The Lavare cycle of the Medtronic HeartWare HVAD was designed to improve ventricular washout. This study aims to evaluate its effects on ventricular washout in a pulsatile in vitro setting with a focus on the timing of pump speed changes. Ventricular flow fields were obtained via particle image velocimetry in two modes: With constant left ventricular assist devices speed and with the Lavare cycle applied. The start of the Lavare cycle was shifted over an entire cardiac cycle, and ventricular washout was evaluated based on velocity fields, kinetic energy, and normalized pulsatility of flow fields. The ventricular flow fields showed dependence on the timing of the Lavare cycle and interaction between speed changes and the cardiac phase. Higher apical velocity was observed for speed decreases at the late E wave and for increases at mid systole by 29% (P = 0.002) and 61% (P < 0.001), respectively. Mean apical kinetic energy for these phases also increased by 21% (P = 0.0013) and 46% (P < 0.001). The Lavare cycle generally promotes higher apical washout and can specifically generate further improved washout if speed steps are applied at the correct timing on the cardiac cycle.

Driveline Features as Risk Factor for Infection in Left Ventricular Assist Devices: Meta-Analysis and Experimental Tests.

Background: Risk factors for driveline infection (DLI) in patients with left ventricular assist devices are multifactorial. The aim of this study was to analyze the correlation between mechanical driveline features and DLI occurrence. Methods: A meta-analysis was conducted that included studies reporting DLI rates at 6 months after implantation of any of three contemporary devices (HVAD with Pellethane or Carbothane driveline, HeartMate II, and HeartMate 3). Further, outer driveline diameter measurements and ex-vivo experimental three-point bending and torsion tests were performed to compare the stiffness of the four different driveline types. Results: 21 studies with 5,393 patients were included in the meta-analysis. The mean weighted DLI rates ranged from 7.2% (HeartMate II) to 11.9% (HeartMate 3). The HeartMate II driveline had a significantly lower maximal bending force (Loadmax) (4.52 ± 0.19 N) compared to the Carbothane HVAD (8.50 ± 0.08 N), the HeartMate 3 (11.08 ± 0.3 N), and the Pellethane HVAD driveline (15.55 ± 0.14 N) (p < 0.001). The maximal torque (Torquemax) of the HeartMate II [41.44 (12.61) mNm] and the Carbothane HVAD driveline [46.06 (3.78) mNm] were significantly lower than Torquemax of the Pellethane HVAD [46.06 (3.78) mNm] and the HeartMate 3 [95.63 (26.60) mNm] driveline (p < 0.001). The driveline of the HeartMate 3 had the largest outer diameter [6.60 (0.58) mm]. A relationship between the mean weighted DLI rate and mechanical driveline features (Torquemax) was found, as the the HeartMate II driveline had the lowest Torquemax and lowest DLI rate, whereas the HeartMate 3 driveline had the highest Torquemax and highest DLI rate. Conclusions: Device-specific mechanical driveline features are an additional modifiable risk factor for DLI and may influence clinical outcomes of LVAD patients.

Left ventricular assist device driveline infections in three contemporary devices.

Driveline infections (DLI) are common adverse events in left ventricular assist devices (LVADs), leading to severe complications and readmissions. The study aims to characterize risk factors for DLI readmission 2 years postimplant. This single-center study included 183 LVAD patients (43 HeartMate II [HMII], 29 HeartMate 3 [HM3], 111 HVAD) following hospital discharge between 2013 and 2017. Demographics, clinical parameters, and outcomes were retrospectively analyzed and 12.6% of patients were readmitted for DLI, 14.8% experienced DLI but were treated in the outpatient setting, and 72.7% had no DLI. Mean C-reactive protein (CRP), leukocytes and fibrinogen were higher in patients with DLI readmission (P < .02) than in outpatient DLI and patients without DLI, as early as 60 days before readmission. Freedom from DLI readmission was comparable for HMII and HVAD (98% vs. 87%; HR, 4.52; 95% CI, 0.58-35.02; P = .15) but significantly lower for HM3 (72%; HR, 10.82; 95% CI, 1.26-92.68; P = .03). DLI (HR, 1.001; 95% CI, 0.999-1.002; P = .16) or device type had no effect on mortality. DLI readmission remains a serious problem following LVAD implantation, where CRP, leukocytes, and fibrinogen might serve as risk factors already 60 days before. HM3 patients had a higher risk for DLI readmissions compared to HVAD or HMII, possibly because of device-specific driveline differences.

Advanced three-dimensionally engineered simulation model for aortic valve and proximal aorta procedures.

OBJECTIVES: A 3-dimensionally (3D) engineered model for simulation of aortic valve and proximal aortic procedures is a reliable tool both for training young surgeons and for simulating complex cases. To achieve a realistic simulation, the artificial model should reproduce the angles and orientations of the cardiac structures based on the patient's anatomical condition, reproduce tissue mechanical characteristics and be easy to obtain and easy to use. The goal of the study was the production and validation of realistic training models, based on the patient's actual anatomical characteristics, to provide training for aortic valve procedures. METHODS: An anatomical model was manufactured using 3D printing and silicone casting. The digital anatomical model was obtained by segmenting computed tomography imaging. The segmented geometrical images were processed and a casting mould was designed. The mould was manufactured on a 3D printer. Silicone was cast into the mould; after curing, the finished model was ready. The realistic reproduction was evaluated by mechanical hardness tests and a survey by cardiac surgeons. RESULTS: Six 3D silicone models were produced that represented the patient's anatomy including aortic valve leaflets, aortic root with coronary ostia, ascending aorta and proximal arch. Aortic valve replacement was performed, and 100% of the participants evaluated the model in a survey as perfectly reproducing anatomy and surgical handling. CONCLUSIONS: We produced a realistic, cost-effective simulator for training purposes and for simulation of complex surgical cases. The model reproduced the real angulation and orientation of the aortic structures inside the mediastinum, permitting a real-life simulation of the desired procedure. This model offers opportunities to simulate various surgical procedures.

Impact of the testing protocol on the mechanical characterization of small diameter electrospun vascular grafts.

AIM: For the proper function of small diameter vascular grafts their mechanical properties are essential. A variety of testing methods and protocols exists to measure tensile strength, compliance and viscoelastic material behavior. In this study the impact of the measurement protocol in hoop tensile tests on the measured compliance and tensile strength was investigated. METHODS: Vascular grafts made out of two different materials, a thermoplastic polyurethane (PUR) and polylactid acid (PLLA), with three different wall thicknesses were produced by electrospinning. Samples were tested with a measurement protocol that allowed the comparison of dynamic sample loading to a common quasistatic tensile test. Influence of measurement temperature, preconditioning cycles and the influence of a high number of loading cycles was also investigated. Compliance and tensile strength were evaluated and compared between the different samples and the different load cases. RESULTS: In all samples a significant difference in the measured compliance was seen between an unloaded sample and a sample that was already in a preloaded state. For example in the PUR group with 100 µm wall thickness at 37 °C, the first compliance was 32.6 ± 9.6%/100 mmHg, which reduced to 15.4 ± 2.9%/100 mmHg at preloaded state. The PLLA group showed 7.5 ± 4.3%/100 mmHg vs. 0.94 ± 0.11%/100 mmHg respectively. The measurements showed the importance of dynamic testing, as the samples viscoelastic behavior had a considerable influence on the measured compliance. The quasistatic ultimate tensile test alone was not able to predict the sample's in vivo compliance. The measurement temperature had a significant influence on tensile strength and compliance. Both, the number of preconditioning cycles and the high number of loading cycles had a minor influence on the sample's compliance. CONCLUSION: With a quasistatic tensile tests alone, overestimated compliance values are measured in viscoelastic electrospun vascular samples, therefore dynamic loading cycles are required. Measurements at 37 °C are mandatory, as temperature has a significant influence on the mechanical properties.

Dynamic measurement of centering forces on transvalvular cannulas.

In heart failure therapy, minimally invasive devices (transcatheter valves, catheter-based cannulas or pumps) are increasingly used. The interaction with the valve is of special importance as valve damage, backflow, and thrombus formation are known complications. Therefore, the aim of this in vitro study was to characterize the forces acting on different sized transvalvular cannulas at various transvalvular pressures for four different valves. In a pulsatile setup radial and tangential forces on transvalvular cannulas were measured for bioprosthetic, artificial pericardial tissue, fresh, and fixated porcine valves. The cannula position was varied from a central position to the wall in 10° rotational steps for the whole circular range and the use of different cannula diameters (4, 6, and 8 mm) and transvalvular pressures (40-100 mmHg). Centering forces of four different aortic valve types were identified and the three leaflets were visible in the force distribution. At the mid of the cusps and at the largest deflection the forces were highest (up to 0.8 N) and lowest in the commissures (up to 0.2 N). Whereas a minor influence of the cannula diameter was found, the transvalvular pressure linearly increased the forces but did not alter the force patterns. Centering forces that act on transvalvular cannulas were identified in an in vitro setup for several valves and valve types. Lowest centering forces were found in the commissures and highest forces were found directly at the cusps. At low pressures, low centering forces and an increased cannula movement can be expected.

A novel miniature in-line load-cell to measure in-situ tensile forces in the tibialis anterior tendon of rats.

Direct measurements of muscular forces usually require a substantial rearrangement of the biomechanical system. To circumvent this problem, various indirect techniques have been used in the past. We introduce a novel direct method, using a lightweight (~0.5 g) miniature (3 x 3 x 7 mm) in-line load-cell to measure tension in the tibialis anterior tendon of rats. A linear motor was used to produce force-profiles to assess linearity, step-response, hysteresis and frequency behavior under controlled conditions. Sensor responses to a series of rectangular force-pulses correlated linearly (R2 = 0.999) within the range of 0-20 N. The maximal relative error at full scale (20 N) was 0.07% of the average measured signal. The standard deviation of the mean response to repeated 20 N force pulses was ± 0.04% of the mean response. The step-response of the load-cell showed the behavior of a PD2T2-element in control-engineering terminology. The maximal hysteretic error was 5.4% of the full-scale signal. Sinusoidal signals were attenuated maximally (-4 dB) at 200 Hz, within a measured range of 0.01-200 Hz. When measuring muscular forces this should be of minor concern as the fusion-frequency of muscles is generally much lower. The newly developed load-cell measured tensile forces of up to 20 N, without inelastic deformation of the sensor. It qualifies for various applications in which it is of interest directly to measure forces within a particular tendon causing only minimal disturbance to the biomechanical system.

Feasibility of profound hypothermia as part of extracorporeal life support in a pig model.

OBJECTIVE: To investigate the feasibility of a refined aortic flush catheter and pump system to induce emergency preservation and resuscitation before extracorporeal cardiopulmonary resuscitation in a normovolemic cardiac arrest swine model simulating near real size/weight conditions of adults. METHODS: In this feasibility study, 8 female Large White breed pigs weighing 70 to 80 kg underwent ventricular fibrillation cardiac arrest for 15 minutes, followed by 4°C aortic flush (150 mL/kg for the brain; 50 mL/kg for the spine) via a new hardware ensued by resuscitation with extracorporeal cardiopulmonary resuscitation. RESULTS: Brain temperature was lowered from 39.9°C (interquartile range [IQR] 39.6-40.3) to 24.0°C (IQR 20.8-28.9) in 12 minutes (IQR 11-16) with a median cooling rate of 1.3°C (IQR 0.7-1.6) per minute. A median of 776 mL (IQR 673-840) per minute with a median pump pressure of 1487 mm Hg (IQR 1324-1545) were pumped to the brain. CONCLUSIONS: With the new hardware, we were able to cool the brain within a few minutes in a large pig cardiac arrest model. The exact position; the design, diameter, and length of the flush catheter; and the brain perfusion pressure seem to be critical to effectively reduce brain temperature. Redistribution of peripheral blood could lead to sterile inflammation again and might be avoided.

Acquired von Willebrand factor deficiency caused by LVAD is ADAMTS-13 and platelet dependent.

INTRODUCTION: The high shear rates induced by left ventricular assist devices cause acquired von Willebrand disease (aVWD). We hypothesised that an ex vivo model could be established to study whether mechanical shear stress alone causes aVWD or whether this process depends also on the VWF cleavage protein ADAMTS-13 and on platelets. MATERIALS AND METHODS: Healthy volunteers and two patients with congenital ADAMTS-13 deficiency donated blood. In vitro closed extracorporeal circuits were established using medically approved left ventricular assist devices (LVAD). VWF multimers were quantified by gel electrophoresis; VWF antigen, ristocetin cofactor activity (VWF:RCo), ADAMTS-13 levels and platelet function were assessed. RESULTS: The high shear stress in the extracorporeal circulation rapidly decreased VWF:RCo and thereby the VWF:RCo/VWF:Ag ratio by 47% (p<0.01) to pathologically low values. Concomitantly, high molecular weight multimers (HMWM) decreased: up to 14-15 mers were visible on the gels at baseline, which were reduced by a maximum of 6-7 mers, corresponding to an average 68% lower densitometry signal of HMWM (p<0.001). This was accompanied by marked reduction of aggregation by various agonists (p<0.005). In contrast, the two patients with congenital thrombocytopenic purpura with virtually complete deficiency of ADAMTS-13 activity had only a minimal or no decrease in multimers (p<0.005 vs. healthy controls). Similarly, no or minimal depletion of large multimers occurred, when normal plasma circulated without platelets. CONCLUSION: An in vitro model for LVAD associated aVWD demonstrated that ADAMTS-13 and platelets contribute to the depletion of HMWM of VWF.

Dietary Silicon Deficiency Does Not Exacerbate Diet-Induced Fatty Lesions in Female ApoE Knockout Mice.

BACKGROUND: Dietary silicon has been positively linked with vascular health and protection against atherosclerotic plaque formation, but the mechanism of action is unclear. OBJECTIVES: We investigated the effect of dietary silicon on 1) serum and aorta silicon concentrations, 2) the development of aortic lesions and serum lipid concentrations, and 3) the structural and biomechanic properties of the aorta. METHODS: Two studies, of the same design, were conducted to address the above objectives. Female mice, lacking the apolipoprotein E (apoE) gene, and therefore susceptible to atherosclerosis, were separated into 3 groups of 10-15 mice, each exposed to a high-fat diet (21% wt milk fat and 1.5% wt cholesterol) but with differing concentrations of dietary silicon, namely: silicon-deprived (-Si; <3-µg silicon/g feed), silicon-replete in feed (+Si-feed; 100-µg silicon/g feed), and silicon-replete in drinking water (+Si-water; 115-µg silicon/mL) for 15-19 wk. Silicon supplementation was in the form of sodium metasilicate (feed) or monomethylsilanetriol (drinking water). RESULTS: The serum silicon concentration in the -Si group was significantly lower than in the +Si-feed (by up to 78%; P < 0.003) and the +Si-water (by up to 84%; P < 0.006) groups. The aorta silicon concentration was also lower in the -Si group than in the +Si-feed group (by 65%; P = 0.025), but not compared with the +Si-water group. There were no differences in serum and aorta silicon concentrations between the silicon-replete groups. Body weights, tissue wet weights at necropsy, and structural, biomechanic, and morphologic properties of the aorta were not affected by dietary silicon; nor were the development of fatty lesions and serum lipid concentrations. CONCLUSIONS: These findings suggest that dietary silicon has no effect on atherosclerosis development and vascular health in the apoE mouse model of diet-induced atherosclerosis, contrary to the reported findings in the cholesterol-fed rabbit model.

Atraumatic Pulsatile Leukocyte Circulation for Long-Term In Vitro Dynamic Culture and Adhesion Assays.

Low flow rate pumping of cell suspensions finds current applications in bioreactors for short-term dynamic cell culture and adhesion assays. The aim of this study was to develop an atraumatic pump and hemodynamically adapted test circuit to allow operating periods of at least several hours. A computer-controlled mini-pump (MP) was constructed based on non-occlusive local compression of an elastic tube with commercial bi-leaflet valves directing the pulsatile flow into a compliant circuit. Cell damage and activation in the system were tested with whole blood in comparison with a set with a conventional peristaltic pump (PP). Activation of circulating THP-1 monocytes was tested by measuring the expression of CD54 (ICAM-1). Additionally, monocyte-endothelial interactions were monitored using a parallel-plate flow chamber with an artificial stenosis. The system required a priming volume of only 20 mL, delivering a peak pulsatile flow of up to 35 mL/min. After 8 h, blood hemolysis was significantly lower for MP with 11 ± 3 mg/dL compared with PP with 100 ± 16 mg/dL. CD142 (tissue factor) expression on blood monocytes was 50% lower for MP. With MP, THP-1 cells could be pumped for extended periods (17 h), with no enhanced expression of CD54 permitting the long-term co-culture of THP-1 with endothelial cells and the analysis of flow pattern effects on cell adhesion. A low-damage assay setup was developed, which allows the pulsatile flow of THP-1 cells and investigation of their interaction with other cells or surfaces for extended periods of time.

The influence of bicuspid aortic valves on the dynamic pressure distribution in the ascending aorta: a porcine ex vivo model.

OBJECTIVES: The aim of the study was to simulate the effect of different bicuspid aortic valve configurations on the dynamic pressure distribution in the ascending aorta. METHODS: Aortic specimens were harvested from adult domestic pigs. In Group 1, bicuspidalization was created by a running suture between the left and the right coronary leaflets (n = 6) and in Group 2 by a running suture between the left and the non-coronary leaflets (n = 6). Eleven tricuspid specimens served as controls. Two intraluminal pressure catheters were positioned at the concavity and the convexity of the ascending aorta. The specimens were connected to a mock circulation (heart rate: 60 bpm, target pressure: 95 mmHg). A comparison of the different conditions was also done in a numerical simulation. RESULTS: At a distal mean aortic pressure of 94 ± 10 mmHg, a mean flow rate of 5.2 ± 0.3 l/min was achieved. The difference of maximal dynamic pressure values (which occurred in systole) between locations at the convexity and the concavity was 7.8 ± 2.9 mmHg for the bicuspid and 1.0 ± 0.9 mmHg for the tricuspid specimens (P < 0.001). The numerical simulation revealed an even higher pressure difference between convexity and concavity for bicuspid formation. CONCLUSIONS: In this hydrodynamic mock circulation model, we were able to demonstrate that bicuspid aortic valves are associated with significant pressure differences in different locations within the ascending aorta compared with tricuspid aortic valves. These altered pressure distributions and flow patterns may further add to the understanding of aneurismal development in patients with bicuspid aortic valves and might serve to anticipate adverse aortic events due to a better knowledge of the underlying mechanisms.

Extended in vivo evaluation of a miniaturized axial flow pump with a novel inflow cannula for a minimal invasive implantation procedure.

BACKGROUND: Minimally invasive techniques are desirable to minimize surgical trauma during left ventricular assist device (LVAD) implantation. This is particularly challenging for full-flow support. In this study, a minimally invasive implantation technique was developed for a microaxial rotary pump. The system was evaluated in a chronic sheep model. METHODS: A HeartWare MVAD (HeartWare, Miami Lakes, FL) pump (length, 50 mm; diameter, 21 mm; maximum flow, 7-8 liters/min) was combined with a novel inflow cannula, including a new flow-optimized tip. The device was implanted into sheep (range, 60-80 kg, mean, 71.6 ± 6.8 kg) through a right-sided minithoracotomy. The inflow cannula was inserted through the superior pulmonary vein, passing through the left atrium into the left ventricle. Scheduled implant period was 30 days for 8 sheep and 100 days for 3 sheep. Mean support flow was set to half of the nominal cardiac output. RESULTS: Six of 8 sheep finished the scheduled 30-day investigation period (one failed due to early non-pump-related post-operative bleeding and one due to prototype controller failure). The 3 sheep scheduled for 100 days reached the study end point. Peak pump flows of up to 6.9 liters/min were achieved. At necropsy, no signs of mitral valve lesions or thrombus formation around the cannula, the tip, or the insertion site were observed, except for valve leaflet erosion in 1 animal, where the cannula had been entangled in the sub-valvular chords due to lack of ultrasound monitoring. CONCLUSIONS: The minimally invasive implantation technique using the HeartWare MVAD pump, together with a new cannula, provided excellent results in a chronic animal model.

Repair of left ventricular assist device driveline damage directly at the transcutaneous exit site.

With increasing support duration of cardiac assist devices, transcutaneous drivelines remain a weak point of the therapy. First, they can be an entry point for infections, and second, cable lesions and even electrical failures due to material fatigue and eventual carelessness can occur. We report a case of a damaged outer sheath of a ventricular assist device driveline cable directly at the exit site, where the standard repair procedure with self-fusing tape may lead to biocompatibility problems and irritation of the entrance through the skin. Therefore, a new procedure was developed using a special sleeve expander tool and a highly expandable latex tubing to stabilize the defect in a flexible and biocompatible manner. A patient experienced a fracture of the outer sheath of a HeartWare HVAD driveline directly at the skin entrance (approximately 15 mm long, 5 mm distal from the skin). The metal strands and the electrical functionality were yet not affected, therefore, a pump exchange was not indicated. After considering several conventional solutions for repair as not applicable, a new approach was developed: a sleeve expander tool was applied, which allowed radial stretching of the latex tubing. After preparations of the tool and the cable site, the pump was briefly disconnected, the tubing was moved over the connector and was released at the site of fracture. The problem could be solved by keeping the cable's flexibility and without additional risks to the skin. Within a still ongoing (5-month) follow-up, the skin entrance returned to perfect condition and no further intervention was necessary. In conclusion, this method allows a quick stabilization and repair of damaged driveline isolations even near the exit site, resulting in a biocompatible surface and consistent flexibility of the cable.

Investigation of hemodynamics in the assisted isolated porcine heart.

BACKGROUND: Currently, the interaction between rotary blood pumps (RBP) and the heart is investigated in silico, in vitro, and in animal models. Isolated and defined changes in hemodynamic parameters are unattainable in animal models, while the heart-pump interaction in its whole complexity cannot be modeled in vitro or in silico. AIM: The aim of this work was to develop an isolated heart setup to provide a realistic heart-pump interface with the possibility of easily adjusting hemodynamic parameters. METHODS: A mock circuit mimicking the systemic circulation was developed. Eight porcine hearts were harvested using a protocol similar to heart transplantation. Then, the hearts were resuscitated using Langendorff perfusion with rewarmed, oxygenated blood. An RBP was implanted and the setup was switched to the "working mode" with the left heart and the RBP working as under physiologic conditions. Both the unassisted and assisted hemodynamics were monitored. RESULTS: In the unassisted condition, cardiac output was up to 9.5 l/min and dP/dtmax ranged from 521 to 3621 mmHg/s at a preload of 15 mmHg and afterload of 70 mmHg. With the RBP turned on, hemodynamics similar to heart-failure patients were observed in each heart. Mean pump flow and flow pulsatility ranged from 0 to 11 l/min. We were able to reproduce conditions with an open and closed aortic valve as well as suction events. CONCLUSIONS: An isolated heart setup including an RBP was developed, which combines the advantages of in silico/vitro methods and animal experiments. This tool thus provides further insight into the interaction between the heart and an RBP.

Fixation and mounting of porcine aortic valves for use in mock circuits.

PURPOSE: Investigations of the circulatory system in vitro use mock circuits that require valves to mimic the cardiac situation. Whereas mechanical valves increase water hammer effects due to inherent stiffness and do not allow the use of pressure lines or catheters, bioprosthetic valves are expensive and of limited durability in test fluids. Therefore, we developed a cheap, fast, alternative method to mount valves obtained from the slaughterhouse in mock circuits. METHODS: Porcine aortic roots were obtained from the abattoir and used either in native condition or after fixation. Fixation was performed at a constant retrograde pressure to ensure closed valve position. Fixation time was 4 h in a 0.5%-glutaraldehyde phosphate buffer. The fixed valves were molded into a modular mock circulation connector using a fast curing silicone. Valve functionality was evaluated in a pulsatile setting (cardiac output = 4.7 l/min, heart rate = 80 beats/min) and compared before and after fixation. Leaflet motion was recorded with a high-speed camera and valve insufficiency was quantified by leakage flow under steady pressure application (80 mmHg). RESULTS: Under physiological conditions the aortic valves showed almost equal leaflet motion in native and fixed conditions. However, the leaflets of the native valves showed lower stiffness and more fluttering during systole than the fixed specimens. Under retrograde pressure, fresh and fixed valves showed small leakage flows of <30 ml/min. CONCLUSIONS: The new mounting and fixation procedure is a fast method to fabricate low cost biologic valves for the use in mock circuits.