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.

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.

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.

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.

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.

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.

Electrospun small-diameter polyurethane vascular grafts: ingrowth and differentiation of vascular-specific host cells.

No small-diameter synthetic graft has yet shown comparable performance to autologous vessels. Synthetic conduits fail due to their inherent surface thrombogenicity and the development of intimal hyperplasia. In addressing these shortcomings, electrospinning offers an interesting alternative to other nanostructured, cardiovascular substitutes because of the close match of electrospun materials to the biomechanical and structural properties of native vessels. In this study, we investigated the in vivo behavior of electrospun, small-diameter conduits in a rat model. Vascular grafts composed of polyurethane were fabricated by electrospinning. Prostheses were implanted into the abdominal aorta in 40 rats for either 7 days, 4 weeks, 3 months, or 6 months. Retrieved specimens were evaluated by histology, immunohistochemical staining, confocal laser scanning microscopy, and scanning electron microscopy. At all time points, we found no evidence of foreign body reaction or graft degradation. The overall patency rate of the intravascular implants was 95%. Within 7 days, grafts revealed ingrowth of host cells. CD34+ cells increased significantly from 7 days up to 6 months of implantation (P < 0.05). Myofibroblasts and myocytes showed increasing cell numbers up to 3 months (P < 0.05). Ki67 staining indicated unaltered cell proliferation during the whole follow-up period. Besides biomechanical benefits, electrospun polyurethane grafts exhibit excellent biocompatibility in vivo. Cell immigration and differentiation seems to be promoted by the nanostructured artificial matrix.

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.

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.

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.

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.

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.

A passive magnetically and hydrodynamically suspended rotary blood pump.

A combined hydrodynamic-magnetic bearing allows the design of rotary blood pumps that are not encumbered with mechanical bearings and magnets requiring sensors or electrical power. However, such pumps have so far needed very small and accurately manufactured gaps between rotor and housing to assure effective hydromagnetic bearing behavior. In order to use this concept in disposable pump heads, a design that allows larger rotor-housing gaps, and thus larger manufacturing tolerances, is needed. A pump with passive magnetic bearings and a gap between rotor and housing in the range of 0.5 mm was designed. Numerical simulations were performed to optimize the rotor geometry at low levels of shear stress. An experimental test stand was used to find a range of speeds and gap settings that resulted in low levels of vibration and useful pressure-flow relationships. Three different rotor geometries were tested using a viscosity-adjusted test fluid. Blood damage tests were conducted within the desirable range of speeds and gap settings. In this study stable pump performance was demonstrated at total gap widths between 0.3 and 0.7 mm at flows of 0-10 L/min, with afterloads up to 230 mm Hg. Best performance was achieved with rotors sliding on a fluid pillow between the rotor and the outer housing at a gap distance of 50 to 250 microm. The inner gap distance, between the rotor and the inner housing, could be as great as 500 microm. Hemolysis tests on the prototype within the chosen operating range showed lower values (NIH = 0.0029 +/- 0.0012 g/100 L) than the Biomedicus BP-80 pump (NIH = 0.0033 +/- 0.0011 g/100 L). In conclusion, it is possible to build rotary blood pumps with passive hydromagnetic bearings that have large gaps between their rotors and housings. Rotor behavior is sensitive to the position of the permanent magnetic drive unit. To minimize vibration and blood damage, the fluid gaps and the rotational speed have to be adjusted according to the desired operating point of the pump. Further study is needed to optimize the magnetic drive unit and to ascertain its ability to withstand inertial loads imposed by sudden movements and external shock.

Systemic pressure does not directly affect pressure gradient and valve area estimates in aortic stenosis in vitro.

AIMS: Hypertension is a frequent finding in patients with aortic stenosis (AS). However, controversial data about the influence of systemic blood pressure on the quantification of AS have been published. METHODS AND RESULTS: Various models of AS (plates and biological valves) were studied in an in vitro circuit. Valve areas were calculated with the Doppler continuity equation and the Gorlin formula. Systolic systemic pressures were increased from 80 to 200 mmHg while flow rates were maintained constant. In addition, a computational fluid dynamics (CFD) model was constructed to test the effect of systemic pressures on pressure gradient and valve area estimates. When systemic pressure was raised, pressure gradients as well as valve areas did not change (mean difference 3.4 +/- 1.8 mmHg, range 0.4-6.8 mmHg; mean difference 0.01 +/- 0.03 cm(2), range -0.02 to 0.05 cm(2)). By multivariable analysis, neither valve area nor pressure gradient were independently affected by systemic pressure. In addition, CFD analysis revealed no effect of systemic pressure on pressure gradient and valve area. CONCLUSION: Our results suggest that blood pressure itself does not directly affect pressure gradients and valve area estimates in AS. Thus, when observed in vivo, these changes are most likely due to afterload-related variations of ejection fraction and, therefore, flow rate.

Biomechanical properties of decellularized porcine pulmonary valve conduits.

Tissue-engineered heart valves constructed from a xenogeneic or allogeneic decellularized matrix might overcome the disadvantages of current heart valve substitutes. One major necessity besides effective decellularization is to preserve the biomechanical properties of the valve. Native and decellularized porcine pulmonary heart valve conduits (PPVCs) (with [n = 10] or without [n = 10] cryopreservation) were compared to cryopreserved human pulmonary valve conduits (n = 7). Samples of the conduit were measured for wall thickness and underwent tensile tests. Elongation measurement was performed with a video extensometer. Decellularized PPVC showed a higher failure force both in longitudinal (+73%; P < 0.01) and transverse (+66%; P < 0.001) direction compared to human homografts. Failure force of the tissue after cryopreservation was still higher in the porcine group (longitudinal: +106%, P < 0.01; transverse: +58%, P < 0.001). In comparison to human homografts, both decellularized and decellularized cryopreserved porcine conduits showed a higher extensibility in longitudinal (decellularized: +61%, P < 0.001; decellularized + cryopreserved: +51%, P < 0.01) and transverse (decellularized: +126%, P < 0.001; decellularized + cryopreserved: +118%, P < 0.001) direction. Again, cryopreservation did not influence the biomechanical properties of the decellularized porcine matrix.

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.

Emergency reinforcement of cracked paracorporeal blood pumps.

In a patient with biventricular paracorporeal cardiac support, severe cracks in the outer pump housing occurred for unknown reasons (possibly because of the application of solvent). Pump replacement was considered but estimated to be a very high risk for this particular patient. Therefore, it was decided to glue the ventricles. Gluing was done after pilot tests in a two stage procedure: first, with a special glue that hardens under exposure to ultraviolet light and then with a two component low exothermic epoxy resin. The procedure resulted in very satisfying stability for the remainder of the bridging period, and the patient could be transplanted successfully 59 days after the event. It is concluded that a carefully selected gluing procedure (caveats: with previously tested glue, a validated procedure, and as a last resort only) may bring less risk in such rare cases of pump cracks than a pump exchange.