Quantification of the flexural rigidity of peripheral arterial endovascular catheters and sheaths.
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ABSTRACT:
SUBMITTER: Hartquist CM
PROVIDER: S-EPMC8802324 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:In vertebrate eyes, the rod photoreceptor has a modified cilium with an extended cylindrical structure specialized for phototransduction called the outer segment (OS). The OS has numerous stacked membrane disks and can bend or break when subjected to mechanical forces. The OS exhibits axial structural variation, with extended bands composed of a few hundred membrane disks whose thickness is diurnally modulated. Using high-resolution confocal microscopy, we have observed OS flexing and disruption in live transgenic Xenopus rods. Based on the experimental observations, we introduce a coarse-grained model of OS mechanical rigidity using elasticity theory, representing the axial OS banding explicitly via a spring-bead model. We calculate a bending stiffness of ?10(5) nN??m2, which is seven orders-of-magnitude larger than that of typical cilia and flagella. This bending stiffness has a quadratic relation to OS radius, so that thinner OS have lower fragility. Furthermore, we find that increasing the spatial frequency of axial OS banding decreases OS rigidity, reducing its fragility. Moreover, the model predicts a tendency for OS to break in bands with higher spring number density, analogous to the experimental observation that transgenic rods tended to break preferentially in bands of high fluorescence. We discuss how pathological alterations of disk membrane properties by mutant proteins may lead to increased OS rigidity and thus increased breakage, ultimately contributing to retinal degeneration.
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Project description:OBJECTIVE:The aim of this study was to determine whether endovascular or open revascularization provides an advantageous approach to symptomatic peripheral arterial disease (PAD) over the longer term. SUMMARY OF BACKGROUND DATA:The optimal revascularization strategy for symptomatic lower extremity PAD is not established. METHODS:We evaluated amputation-free survival, overall survival, and relative rate of subsequent vascular intervention after endovascular or open lower extremity revascularization for propensity-score matched cohorts of Medicare beneficiaries with PAD from 2006 through 2009. RESULTS:Among 14,685 eligible patients, 5928 endovascular and 5928 open revascularization patients were included in matched analysis. Patients undergoing endovascular repair had improved amputation-free survival compared with open repair at 30 days (7.4 vs 8.9%, P = 0.002). This benefit persisted over the long term: At 4 years, 49% of endovascular patients had died or received major amputation compared with 54% of open patients (P < 0.001). An endovascular procedure was associated with a risk-adjusted 16% decreased risk of amputation or death compared with open over the study period (hazard ratio: 0.84; 95% confidence interval, 0.79-0.89; P < 0.001). The amputation-free survival benefit associated with an endovascular revascularization was more pronounced in patients with congestive heart failure or ischemic heart disease than in those without (P = 0.021 for interaction term). The rate of subsequent intervention at 30 days was 7.4% greater for the endovascular vs the open revascularization cohort. At 4 years, this difference remained stable at 8.6%. CONCLUSIONS:Using population-based data, we demonstrate that an endovascular approach is associated with improved amputation-free survival over the long term with only a modest relative increased risk of subsequent intervention.
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Project description:The cooperation of physicians, engineers and other sciences results in a steady launching of effective tools for vascular treatment, which further support the dominating position of endovascular therapy in the field of PAD. Parallel to the treatment options, non-radiation based image guidance is another area, where innovation helps to reduce radiation burden for patient and staff members without losing procedural quality and despite a growing number of radiation based procedures. Meanwhile, the available portfolio of endovascular tools allows to treat every vessel segment with results comparable to or even better then open surgery. This survey presents new techniques, tools and recently published results from related trials, which will probably have further influence on PAD treatment in the coming years.
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Project description:ObjectivePeripheral arterial disease (PAD) is a significant age-related medical condition with limited pharmacologic options. Severe PAD, termed critical limb ischemia, can lead to amputation. Skeletal muscle is the end organ most affected by PAD, leading to ischemic myopathy and debility of the patient. Currently, there are not any therapeutics to treat ischemic myopathy, and proposed biologic agents have not been optimized owing to a lack of preclinical models of PAD. Because a large animal model of ischemic myopathy may be useful in defining the optimal dosing and delivery regimens, the objective was to create and to characterize a swine model of ischemic myopathy that mimics patients with severe PAD.MethodsYorkshire swine (N = 8) underwent acute right hindlimb ischemia by endovascular occlusion of the external iliac artery. The effect of ischemia on limb function, perfusion, and degree of ischemic myopathy was quantified by weekly gait analysis, arteriography, hindlimb blood pressures, femoral artery duplex ultrasound scans, and histologic examination. Animals were terminated at 5 (n = 5) and 6 (n = 3) weeks postoperatively. Ossabaw swine (N = 8) fed a high-fat diet were used as a model of metabolic syndrome for comparison of arteriogenic recovery and validation of ischemic myopathy.ResultsThere was persistent ischemia in the right hindlimb, and occlusion pressures were significantly depressed compared with the untreated left hindlimb out to 6 weeks (systolic blood pressure, 31 ± 21 vs 83 ± 15 mm Hg, respectively; P = .0007). The blood pressure reduction resulted in a significant increase of ischemic myopathy in the gastrocnemius muscle in the treated limb. Gait analysis revealed a functional deficit of the right hindlimb immediately after occlusion that improved rapidly during the first 2 weeks. Peak systolic velocity values in the right common femoral artery were severely diminished throughout the entire study (P < .001), and the hemodynamic environment after occlusion was characterized by low and oscillatory wall shear stress. Finally, the internal iliac artery on the side of the ischemic limb underwent significant arteriogenic remodeling (1.8× baseline) in the Yorkshire but not in the Ossabaw swine model.ConclusionsThis model uses endovascular technology to produce the first durable large animal model of ischemic myopathy. Acutely (first 2 weeks), this model is associated with impaired gait but no tissue loss. Chronically (2-6 weeks), this model delivers persistent ischemia, resulting in ischemic myopathy similar to that seen in PAD patients. This model may be of use for testing novel therapeutics including biologic therapies for promoting neovascularization and arteriogenesis.
| S-EPMC5374046 | biostudies-literature
Project description: Not available
| S-EPMC8674611 | biostudies-literature
Project description:A significant proportion of patients with severe lower limb peripheral arterial disease require revascularization. Over the past decade, an endovascular-first approach even for complex disease has gained widespread use among vascular specialists. An important limitation of percutaneous transluminal balloon angioplasty or stenting remains the occurrence of restenosis. Drug-coated balloons have emerged as an exciting technology developed to overcome the limitations of standard balloon angioplasty and stenting. Drug-eluting devices inhibit neointimal growth of vascular smooth muscle cells with the potential of preventing restenosis. This review provides a synopsis of the up-to-date evidence on the role of drug-coated balloons in the treatment of lower limb peripheral arterial disease. Bibliographic searches were conducted using MEDLINE, EMBASE, and the Cochrane Library electronic database. Eleven randomized clinical trials, two systematic reviews, and a published registry providing the best available evidence were identified. Current evidence suggests that angioplasty with drug-coated balloon is reliable, safe, and efficient in increasing patency rates and reducing target lesion revascularization and restenosis. However, it remains unknown whether these improved results can translate into beneficial clinical outcomes, as current randomized clinical trials have failed to demonstrate a significant benefit in limb salvage and mortality. Further randomized trials focusing on clinical and functional outcomes of drug-eluting balloons and on cost versus clinical benefit are required.
| S-EPMC4868867 | biostudies-other
Project description:Motile cilia and flagella are whiplike cellular organelles that bend actively to propel cells or move fluid in passages such as airways, brain ventricles, and the oviduct. Efficient motile function of cilia and flagella depends on coordinated interactions between active forces from an array of motor proteins and passive mechanical resistance from the complex cytoskeletal structure (the axoneme). However, details of this coordination, including axonemal mechanics, remain unclear. We investigated two major mechanical parameters, flexural rigidity and interdoublet shear stiffness, of the flagellar axoneme in the unicellular alga Chlamydomonas reinhardtii. Combining experiment, theory, and finite element models, we demonstrate that the apparent flexural rigidity of the axoneme depends on both the intrinsic flexural rigidity (EI) and the elastic resistance to interdoublet sliding (shear stiffness, ks). We estimated the average intrinsic flexural rigidity and interdoublet shear stiffness of wild-type Chlamydomonas flagella in vivo, rendered immotile by vanadate, to be EI = 840 ± 280 pN??m(2) and ks = 79.6 ± 10.5 pN/rad, respectively. The corresponding values for the pf3; cnk11-6 double mutant, which lacks the nexin-dynein regulatory complex (N-DRC), were EI = 1011 ± 183 pN·?m(2) and ks = 39.3 ± 6.0 pN/rad under the same conditions. Finally, in the pf13A mutant, which lacks outer dynein arms and inner dynein arm c, the estimates were EI = 777 ± 184 pN·?m(2) and ks = 43.3 ± 7.7 pN/rad. In the two mutant strains, the flexural rigidity is not significantly different from wild-type (p > 0.05), but the lack of N-DRC (in pf3; cnk11-6) or dynein arms (in pf13A) significantly reduces interdoublet shear stiffness. These differences may represent the contributions of the N-DRCs (?40 pN/rad) and residual dynein interactions (?35 pN/rad) to interdoublet sliding resistance in these immobilized Chlamydomonas flagella.
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Project description:The mechanical properties of biopolymers can be determined from a statistical analysis of the ensemble of shapes they exhibit when subjected to thermal forces. In practice, extracting information from fluorescence microscopy images can be challenging due to low signal/noise ratios and other artifacts. To address these issues, we develop a suite of tools for image processing and spectral data analysis that is based on a biopolymer contour representation expressed in a spectral basis of orthogonal polynomials. We determine biopolymer shape and stiffness using global fitting routines that optimize a utility function measuring the amount of fluorescence intensity overlapped by such contours. This approach allows for filtering of high-frequency noise and interpolation over sporadic gaps in fluorescence. We use benchmarking to demonstrate the validity of our methods, by analyzing an ensemble of simulated images generated using a simulated biopolymer with known stiffness and subjected to various types of image noise. We then use these methods to determine the persistence lengths of taxol-stabilized microtubules. We find that single microtubules are well described by the wormlike chain polymer model, and that ensembles of chemically identical microtubules show significant heterogeneity in bending stiffness, which cannot be attributed to sampling or fitting errors. We expect these approaches to be useful in the study of biopolymer mechanics and the effects of associated regulatory molecules.
| S-EPMC3296053 | biostudies-literature
Project description:BackgroundMicrotubules (MTs) are highly dynamic tubular cytoskeleton filaments that are essential for cellular morphology and intracellular transport. In vivo, the flexural rigidity of MTs can be dynamically regulated depending on their intracellular function. In the in vitro reconstructed MT-motor system, flexural rigidity affects MT gliding behaviors and trajectories. Despite the importance of flexural rigidity for both biological functions and in vitro applications, there is no clear interpretation of the regulation of MT flexural rigidity, and the results of many studies are contradictory. These discrepancies impede our understanding of the regulation of MT flexural rigidity, thereby challenging its precise manipulation.ResultsHere, plausible explanations for these discrepancies are provided and a new method to evaluate the MT rigidity is developed. Moreover, a new relationship of the dynamic and mechanic of MTs is revealed that MT flexural rigidity decreases through three phases with the growth rate increases, which offers a method of designing MT flexural rigidity by regulating its growth rate. To test the validity of this method, the gliding performances of MTs with different flexural rigidities polymerized at different growth rates are examined. The growth rate-dependent flexural rigidity of MTs is experimentally found to influence the pattern formation in collective motion using gliding motility assay, which is further validated using machine learning.ConclusionOur study establishes a robust quantitative method for measurement and design of MT flexural rigidity to study its influences on MT gliding assays, collective motion, and other biological activities in vitro. The new relationship about the growth rate and rigidity of MTs updates current concepts on the dynamics and mechanics of MTs and provides comparable data for investigating the regulation mechanism of MT rigidity in vivo in the future.
| S-EPMC8287809 | biostudies-literature
Project description:Peripheral arterial disease (PAD) represents one of the most prevalent cardiovascular disease processes and carries a high burden of morbidity and mortality. Patients with chronic limb-threatening ischemia (CLTI), the most severe manifestation of PAD, have the highest rates of cardiovascular morbidity and mortality of the overall PAD population. Patients with below-the-knee (BTK) PAD have an increased propensity toward CLTI due to small-vessel caliber and the frequently comorbid conditions of end-stage renal disease and diabetes mellitus, which tend to affect small artery beds preferentially. For those with BTK PAD with CLTI, the standard of care is revascularization. Early revascularization was performed using surgical bypass. However, endovascular techniques, starting with percutaneous transluminal angioplasty and expanding to the modern armamentarium of adjunctive devices and therapies, have become standard of care for most patients with CLTI due to BTK PAD. In this review, we will discuss the modern surgical and endovascular approaches to revascularization, as well as devices that are currently in development or preapproval study for the treatment of BTK PAD.
| S-EPMC11308828 | biostudies-literature