Abstract Short peripheral catheter thrombophlebitis (SPCT), a sterile inflammation of the vein wall, is the most common complication associated with short peripheral catheters (SPCs) and affects up ...to 80% of hospitalized patients receiving IV therapy. Extensive research efforts have been devoted for improvement and optimization of the catheter material, but means for examination of any novel design are limited, inaccurate and require costly comprehensive pre-clinical and clinical trials. Therefore, there is a conclusive need for a reliable quantitative method for evaluation of SPCT, in particular for research purposes examining the thrombophlebitis-related symptoms of any novel catheter design. In this study, we developed for the first time a quantitative MRI based tool for evaluation of SPCT. The extent and severity of SPCT caused by two different commercially available SPCs with known predisposition for thrombophlebitis, were studied in a rabbit model. MRI analysis was consistent with the standardized pathology evaluation and showed remarkable difference in the percent of edema between the experimental groups. These differences were in line with previous studies and provide evidence that this type of analysis may be useful for future assessment of SPCT in vivo . As a non-invasive method, it may constitute a cost effective solution for examination of new catheters and other medical devices, thereby reducing the need for animal sacrifice.
Short peripheral catheters are ubiquitous in today's healthcare environment enabling effective delivery of fluids and medications directly into a patient's vasculature. However, complications related ...to their use, such as short peripheral catheter thrombophlebitis (SPCT), affect up to 80% of hospitalized patients. While indwelling within the vein, the catheters exert prolonged constant pressure upon the endothelium which can trigger inflammation processes. We have developed and studied an in-vitro model of cultured endothelial cells subjected to mechanical compression of modular self-designed weights, and explored their inflammatory response by quantification of two key biomarkers- vWF and IL-8. Evaluation was performed by ELISA immunoassay and processing of vWF-labeled immunofluorescence images. We found that application of weights correspond to 272 Pa yielded increased release of vWF and IL-8 up to 150% and 250% respectively, comparing to the exertion of 136 Pa. Analyses of the immunofluorescence images revealed significantly longer and more extracellular vWF-strings as well as higher intensity stained-pixels in cells exposed to elevated pressures. The release of both factors found to be significantly dependent on the extent of the exerted pressure. The research shed a light on the relationship between induced mechanical compression and the pathogenesis of SPCT. Minimizing, let alone eliminating the contact between the catheter and the vein wall will mitigate the pressure acting on the endothelium, thereby reducing the secretion of inflammatory factors and lessen the incidence of SPCT.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Arterial tortuosity manifests in many conditions, including hypertension, genetic mutations predisposing to thoracic aortopathy, and vascular aging. Despite evidence that tortuosity disrupts ...efficient blood flow and that it may be an important clinical biomarker, underlying mechanisms remain poorly understood but are widely appreciated to be largely biomechanical. Many previous studies suggested that tortuosity may arise via an elastic structural buckling instability, but the novel experimental-computational approach used here suggests that tortuosity arises from mechanosensitive, cell-mediated responses to local aberrations in the microstructural integrity of the arterial wall. In particular, computations informed by multimodality imaging show that aberrations in elastic fiber integrity, collagen alignment, and collagen turnover can lead to a progressive loss of structural stability that entrenches during the development of tortuosity. Interpreted in this way, microstructural defects or irregularities of the arterial wall initiate the condition and hypertension is a confounding factor.
Medial deterioration leading to thoracic aortic aneurysms arises from multiple causes, chief among them mutations to the gene that encodes fibrillin-1 and leads to Marfan syndrome. Fibrillin-1 ...microfibrils associate with elastin to form elastic fibers, which are essential structural, functional, and instructional components of the normal aortic wall. Compromised elastic fibers adversely impact overall structural integrity and alter smooth muscle cell phenotype. Despite significant progress in characterizing clinical, histopathological, and mechanical aspects of fibrillin-1 related aortopathies, a direct correlation between the progression of microstructural defects and the associated mechanical properties that dictate aortic functionality remains wanting. In this paper, age-matched wild-type,
, and
mouse models were selected to represent three stages of increasing severity of the Marfan aortic phenotype.
multiphoton imaging and biaxial mechanical testing of the ascending and descending thoracic aorta under physiological loading conditions demonstrated that elastic fiber defects, collagen fiber remodeling, and cell reorganization increase with increasing dilatation. Three-dimensional microstructural characterization further revealed radial patterns of medial degeneration that become more uniform with increasing dilatation while correlating strongly with increased circumferential material stiffness and decreased elastic energy storage, both of which comprise aortic functionality.
Malignant ureteral obstruction may lead to impaired renal function and requires drainage by a percutaneous nephrostomy tube or an internal ureteric stent. Usage of stiff tandem ureteral stents may ...decrease stent failure rates. In this paper we combined computational and in vitro models to examine the flow in a malignant ureteral obstruction (MUO) managed by 4 methods of drainage: single soft stent, single stiff stent, soft tandem ureteral stents, and stiff tandem ureteral stents. Pressure at the renal pelvis was the primary outcome of the computational and in vitro models. Different drainage modalities were compared using ANCOVA. Results of computational and in vitro models agreed completely. Drainage by stiff tandem ureteral stents provides lower renal pelvis pressure levels compared with single and soft stents (p < 0.001), especially for high levels of external pressure. Usage of stiff tandem ureteral stents may decrease stent-failure rates and postpone the need for percutaneous nephrostomy tube insertion.
Transmural failure of the aorta is responsible for substantial morbidity and mortality; it occurs when mechanical stress exceeds strength. The aortic root and ascending aorta are susceptible to ...dissection and rupture in Marfan syndrome, a connective tissue disorder characterized by a progressive reduction in elastic fiber integrity. Whereas competent elastic fibers endow the aorta with compliance and resilience, cross-linked collagen fibers confer stiffness and strength. We hypothesized that postnatal reductions in matrix cross-linking increase aortopathy when turnover rates are high.
We combined ex vivo biaxial mechanical testing with multimodality histological examinations to quantify expected age- and sex-dependent structural vulnerability of the ascending aorta in
Marfan versus wild-type mice without and with 4-week exposures to β-aminopropionitrile, an inhibitor of lysyl oxidase-mediated cross-linking of newly synthesized elastic and collagen fibers.
We found a strong β-aminopropionitrile-associated sexual dimorphism in aortic dilatation in Marfan mice and aortic rupture in wild-type mice, with dilatation correlating with compromised elastic fiber integrity and rupture correlating with compromised collagen fibril organization. A lower incidence of rupture of β-aminopropionitrile-exposed Marfan aortas associated with increased lysyl oxidase, suggesting a compensatory remodeling of collagen that slows disease progression in the otherwise compromised
aorta.
Collagen fiber structure and function in the Marfan aorta are augmented, in part, by increased lysyl oxidase in female and especially male mice, which improves structural integrity, particularly via fibrils in the adventitia. Preserving or promoting collagen cross-linking may represent a therapeutic target for an otherwise vulnerable aorta.
Coronary artery obstruction (CAO), a fatal complication of transcatheter aortic valve replacement (TAVR), is commonly found after Valve-in-Valve implantation inside a degenerated bioprosthetic valve. ...Leaflet laceration (BASILICA technique) has been proposed to prevent CAO and to potentially reduce the risk of leaflet thrombosis. We have previously demonstrated that this technique can reduce the anchorage forces of the TAVR device, which may lead to future complications. In this short communication, we hypothesize that the anchorage force reduction can be minimized by implanting a TAVR with a larger diameter, if two sizes are clinically recommended. We evaluated this hypothesis by employing finite element models of the deployments of the Evolut 26 and 29 mm inside a 27 mm Mitroflow valve, with and without leaflet lacerations. The results show that a laceration substantially decreases the contact area between the Evolut stent and the Mitroflow valve. The larger Evolut has a larger contact area and stronger anchorage forces. Additionally, the anchorage forces are less sensitive to additional lacerations in the larger Evolut (29 case). The results suggest that a larger self-expending device can ensure stronger anchorage and can lower the risk of possible migration, when TAVR is performed in a lacerated bioprosthesis.
Understanding the hemodynamics surrounding the venous valve environment is of a great importance for prosthetic valves design. The present study aims to evaluate the effect of leaflets’ stiffening ...process on the venous valve hemodynamics, valve’s failure on the next proximal valve hemodynamics and valve’s failure in a secondary daughter vein on the healthy valve hemodynamics in the main vein when both of these valves are distal to a venous junction. Fully coupled, two-way fluid–structure interaction computational models were developed and employed. The sinus pocket region experiences the lowest fluid shear stress, and the base region of the sinus side of the leaflet experiences the highest tissue stress. The leaflets’ stiffening increases the tissue stress the valve is experiencing in a very low fluid shear region. A similar effect occurs with the proximal healthy valve as a consequence of the distal valve’s failure and with the mother vein valve as a consequence of daughter vein valve’s failure. Understanding the described mechanisms may be helpful for elucidating the venous valve stiffness–function relationship in nature, the reasons for a retrograde development of reflux and the relationship between venous valves located near venous junctions, and for designing better prosthetic valves and for improving their positioning.
Collagen is the most abundant protein in mammals; it exhibits a hierarchical organization and provides structural support to a wide range of soft tissues, including blood vessels. The architecture of ...collagen fibrils dictates vascular stiffness and strength, and changes therein can contribute to disease progression. While transmission electron microscopy (TEM) is routinely used to examine collagen fibrils under normal and pathological conditions, computational tools that enable fast and minimally subjective quantitative assessment remain lacking. In the present study, we describe a novel semi-automated image processing and statistical modeling pipeline for segmenting individual collagen fibrils from TEM images and quantifying key metrics of interest, including fibril cross-sectional area and aspect ratio. For validation, we show first-of-their-kind illustrative results for adventitial collagen in the thoracic aorta from three different mouse models.
Thoracic aortopathy associates with extracellular matrix remodeling and altered biomechanical properties. We sought to quantify the natural history of thoracic aortopathy in a common mouse model and ...to correlate measures of wall remodeling such as aortic dilatation or localized mural defects with evolving microstructural composition and biomechanical properties of the wall.
We combined a high-resolution multimodality imaging approach (panoramic digital image correlation and optical coherence tomography) with histopathologic examinations and biaxial mechanical testing to correlate spatially, for the first time, macroscopic mural defects and medial degeneration within the ascending aorta with local changes in aortic wall composition and mechanical properties.
Findings revealed strong correlations between local decreases in elastic energy storage and increases in circumferential material stiffness with increasing proximal aortic diameter and especially mural defect size. Mural defects tended to exhibit a pronounced biomechanical dysfunction that is driven by an altered organization of collagen and elastic fibers.
While aneurysmal dilatation is often observed within particular segments of the aorta, dissection and rupture initiate as highly localized mechanical failures. We show that wall composition and material properties are compromised in regions of local mural defects, which further increases the dilatation and overall structural vulnerability of the wall. Identification of therapies focused on promoting robust collagen accumulation may protect the wall from these vulnerabilities and limit the incidence of dissection and rupture.
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