Your browser doesn't support javascript.
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 238
Filtrar
1.
Biomed Instrum Technol ; 54(1): 37-43, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31961742

RESUMO

Hydrophilic polymer coatings on intravascular devices lower friction between the device and vasculature, thereby reducing trauma during interventional procedures. Polymer coating embolism-the detachment and downstream embolism of polymer particles-has been reported as an iatrogenic complication of coated interventional devices affecting the vasculature and various organs. The Food and Drug Administration (FDA) acknowledges this complication and continues to work with stakeholders to close gaps in performance testing and standards related to polymer coating integrity. Recent innovations within interventional technologies have led to development of new hydrophilic-coated devices with expanded indications for use. The 2018 FDA draft guidance for intravascular guidewires expands the application of particulate generation testing to most devices and recommends labeling changes to increase industry awareness. This article highlights current procedural trends where the phenomenon of polymer coating embolism may be more prevalent. It describes the mechanisms of polymer separation, reported clinical sequelae, and risk factors for relevant indications. These procedural trends and associated risk factors articulate the need for particulate testing and support the FDA's draft guidance recommendations for performance testing of applied coatings. If standardized, particulate assessments may allow characterization and comparisons of coating integrity among devices from various manufacturers, and are an important foundation for setting particulate limits. As hydrophilic coatings enable endovascular treatment for a range of patient populations, setting particulate limits or finding alternative solutions without compromise to device function may be essential. Particulate testing is relevant to physicians, regulators, and manufacturers for the purposes of product development and quality improvement of interventional devices.


Assuntos
Embolia , Materiais Revestidos Biocompatíveis , Humanos , Interações Hidrofóbicas e Hidrofílicas , Polímeros , Estados Unidos , United States Food and Drug Administration
2.
Plast Reconstr Surg ; 144(4): 608e-618e, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31568296

RESUMO

BACKGROUND: A critical barrier to successful limb replantation and allotransplantation is the maximum allowable limb ischemia time of 4 to 6 hours. The current gold standard is to preserve amputated limbs on an ice slurry. Experimental machine perfusion has yielded promising results as an alternative. In particular, hypothermic acellular perfusion has enabled preservation of amputated limbs for up to 12 hours thus far. METHODS: Amputated forelimbs of Yorkshire pigs were preserved on static cold storage at 4°C for 4 hours (static cold storage group) or perfused at 8°C for 24 hours (perfusion group) with oxygenated modified STEEN Solution perfusate before replantation. Animals were followed up for 7 days after replantation. RESULTS: Eight animals underwent replantation (cold storage group, n = 4; perfusion group, n = 4). Seventy-five and 100 percent of animals in the static cold storage and perfusion groups survived for 7 days, respectively. Glycogen and adenosine triphosphate remained stable throughout perfusion. Heart and respiratory rate after replantation were increased in the static cold storage group. There was increased damage in muscle biopsy specimens obtained from animals in the static cold storage group after 7 days when compared with those from animals in the perfusion group. CONCLUSIONS: Hypothermic acellular ex vivo perfusion of limbs for up to 24 hours enables tissue preservation comparable to that obtained with conventional static cold storage for 4 hours and may reduce muscle damage and systemic reactions on limb replantation. Translation to human limbs may help improve limb replantation and allotransplantation outcomes.


Assuntos
Membro Anterior/cirurgia , Perfusão/métodos , Reimplante/métodos , Preservação de Tecido/métodos , Animais , Feminino , Distribuição Aleatória , Soluções/administração & dosagem , Suínos , Fatores de Tempo
3.
Sci Transl Med ; 11(509)2019 Sep 11.
Artigo em Inglês | MEDLINE | ID: mdl-31511424

RESUMO

Aortic stenosis (AS) management is classically guided by symptoms and valvular metrics. However, the natural history of AS is dictated by coupling of the left ventricle, aortic valve, and vascular system. We investigated whether metrics of ventricular and vascular state add to the appreciation of AS state above valve gradient alone. Seventy patients with severe symptomatic AS were prospectively followed from baseline to 30 days after transcatheter aortic valve replacement (TAVR). Quality of life (QOL) was assessed using the Kansas City Cardiomyopathy Questionnaire. Left ventricular stroke work (SWLV) and vascular impedance spectrums were calculated noninvasively using in-house models based on central blood pressure waveforms, along with hemodynamic parameters from echocardiograms. Patients with higher preprocedural SWLV and lower vascular impedance were more likely to experience improved QOL after TAVR. Patients fell into two categories: those who did and those who did not exhibit increase in blood pressure after TAVR. In patients who developed hypertension (19%), vascular impedance increased and SWLV remained unchanged (impedance at zeroth harmonic: Z 0, from 3964.4 to 4851.8 dyne·s/cm3, P = 0.039; characteristic impedance: Z c, from 376.2 to 603.2 dyne·s/cm3, P = 0.033). SWLV dropped only in patients who did not develop new hypertension after TAVR (from 1.58 to 1.26 J; P < 0.001). Reduction in valvular pressure gradient after TAVR did not predict change in SWLV (r = 0.213; P = 0.129). Reduction of SWLV after TAVR may be an important metric in management of AS, rather than relying solely on the elimination of transvalvular pressure gradients.

4.
J Control Release ; 310: 94-102, 2019 Sep 28.
Artigo em Inglês | MEDLINE | ID: mdl-31430500

RESUMO

Paclitaxel coated balloons (PCBs) are a promising non-implantable alternative to drug-eluting stents, whereby drug is delivered to the arterial wall in solid form as a semi-continuous solid coating or as micro drug depots. To date, it has been impossible to predict or even infer local tissue dosing levels and persistence, making it difficult to compare in vivo performance of different devices in healthy animals or to extrapolate such data to diseased human arteries. Here we derive and analyze a coupled reaction diffusion model that accounts for coating dissolution and tissue distribution, and predicts the concentration of dissolved drug in the tissue during and post dissolution. Time scale analysis and numerical simulations based on estimated diffusion coefficients in healthy animal and diseased human arteries both imply that dissolution of crystalline paclitaxel coating is mass transfer coefficient-limited, and can therefore be solved for independently of the tissue transport equations. Specifically, coating retention is predicted to follow piecewise linear kinetics, reflecting the differential and faster dissolution of lumenal versus tissue-embedded coating owing to a disparity in convective forces. This prediction is consistent with published data on a range of PCBs and allowed for the estimation of the associated dissolution rate-constants and the maximal soluble drug concentration in the tissue during coating dissolution. Maximal soluble drug concentration in the tissue scales as the product of the solubility and ratio of the dissolution and diffusion rate-constants. Thus, coatings characterized by micromolar solubilities give rise to nanomolar soluble concentrations in healthy animal arteries and ~0.1 micromolar in calcified atherosclerotic arteries owing to slower tissue diffusion. During dissolution, retention in porcine iliofemoral arteries is predicted to be dominated by solid coating, whereas post dissolution it is dominated by receptor-bound drug (3.7 ng receptors/g tissue). Paclitaxel coating dissolution and dosing kinetics can now be modeled based upon accepted principles of surface dissolution and tissue transport to provide insights into the dependence of clinical efficacy on device properties and the interplay of lesion complexity and procedural parameters.

5.
Biomaterials ; 221: 119414, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31419654

RESUMO

The performance of biodegradable magnesium alloy stents (BMgS) requires special attention to non-uniform residual stress distribution and stress concentration, which can accelerate localized degradation after implantation. We now report on a novel concept in stent shape optimization using a finite element method (FEM) toolkit. A Mg-Nd-Zn-Zr alloy with uniform degradation behavior served as the basis of our BMgS. Comprehensive in vitro evaluations drove stent optimization, based on observed crimping and balloon inflation performance, measurement of radial strength, and stress condition validation via microarea-XRD. Moreover, a Rapamycin-eluting polymer coating was sprayed on the prototypical BMgS to improve the corrosion resistance and release anti-hyperplasia drugs. In vivo evaluation of the optimized coated BMgS was conducted in the iliac artery of New Zealand white rabbit with quantitative coronary angiography (QCA), optical coherence tomography (OCT) and micro-CT observation at 1, 3, 5-month follow-ups. Neither thrombus or early restenosis was observed, and the coated BMgS supported the vessel effectively prior to degradation and allowed for arterial healing thereafter. The proposed shape optimization framework based on FEM provides an novel concept in stent design and in-depth understanding of how deformation history affects the biomechanical performance of BMgS. Computational analysis tools can indeed promote the development of biodegradable magnesium stents.

6.
Hypertension ; 74(3): 546-554, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31303108

RESUMO

Radiofrequency renal denervation is under investigation for treatment of hypertension with variable success. We developed preclinical models to examine the dependence of ablation biomarkers on renal denervation treatment parameters and anatomic variables. One hundred twenty-nine porcine renal arteries were denervated with an irrigated radiofrequency catheter with multiple helically arrayed electrodes. Nerve effects and ablation geometries at 7 days were characterized histomorphometrically and correlated with associated renal norepinephrine levels. Norepinephrine exhibited a threshold dependence on the percentage of affected nerves across the range of treatment durations (30-60 s) and power set points (6-20 W). For 15 W/30 s treatments, norepinephrine reduction and percentage of affected nerves tracked with number of electrode treatments, confirming additive effects of helically staggered ablations. Threshold effects were only attained when ≥4 electrodes were powered. Histomorphometry and computational modeling both illustrated that radiofrequency treatments directed at large neighboring veins resulted in subaverage ablation areas and, therefore, contributed suboptimally to efficacy. Account for measured nerve distribution patterns and the annular geometry of the artery revealed that, regardless of treatment variables, total ablation area and circumferential coverage were the prime determinants of renal denervation efficacy, with increased efficacy at smaller diameters.


Assuntos
Ablação por Cateter/métodos , Hipertensão/cirurgia , Rim/inervação , Norepinefrina/sangue , Artéria Renal/cirurgia , Simpatectomia/métodos , Animais , Biópsia por Agulha , Modelos Animais de Doenças , Eletrodos , Feminino , Humanos , Hipertensão/fisiopatologia , Imuno-Histoquímica , Masculino , Distribuição Aleatória , Valores de Referência , Suínos , Resultado do Tratamento
7.
Circulation ; 140(2): 147-163, 2019 Jul 09.
Artigo em Inglês | MEDLINE | ID: mdl-31146585

RESUMO

BACKGROUND: The cells that form the arterial wall contribute to multiple vascular diseases. The extent of cellular heterogeneity within these populations has not been fully characterized. Recent advances in single-cell RNA-sequencing make it possible to identify and characterize cellular subpopulations. METHODS: We validate a method for generating a droplet-based single-cell atlas of gene expression in a normal blood vessel. Enzymatic dissociation of 4 whole mouse aortas was followed by single-cell sequencing of >10 000 cells. RESULTS: Clustering analysis of gene expression from aortic cells identified 10 populations of cells representing each of the main arterial cell types: fibroblasts, vascular smooth muscle cells, endothelial cells (ECs), and immune cells, including monocytes, macrophages, and lymphocytes. The most significant cellular heterogeneity was seen in the 3 distinct EC populations. Gene set enrichment analysis of these EC subpopulations identified a lymphatic EC cluster and 2 other populations more specialized in lipoprotein handling, angiogenesis, and extracellular matrix production. These subpopulations persist and exhibit similar changes in gene expression in response to a Western diet. Immunofluorescence for Vcam1 and Cd36 demonstrates regional heterogeneity in EC populations throughout the aorta. CONCLUSIONS: We present a comprehensive single-cell atlas of all cells in the aorta. By integrating expression from >1900 genes per cell, we are better able to characterize cellular heterogeneity compared with conventional approaches. Gene expression signatures identify cell subpopulations with vascular disease-relevant functions.

8.
Med Biol Eng Comput ; 57(9): 1861-1874, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31209712

RESUMO

Aortic dissections are challenging for it remains perplexing to determine when surgical, endovascular, or medical therapies are optimal. We studied the effect of the multilayer flow modulator (MFM) device in patients with different forms of type-B aortic dissections. CT scans were performed pre-, immediately post-MFM implantation, and multiple times within a 24-month follow-up. Three-dimensional reconstructions were created from these scans and the multilayer or single-layer mesh device placed virtually into the true lumen. We observed that MFM device can sufficiently restore flow perfusion, reduce the false lumen, eliminate local flow recirculation, and reduce wall shear stress distribution globally. Single-layer devices can reduce false lumen dimensions; however, they generate local disturbance and recirculation zones in selected areas at specific time points. Moreover, in polar extremes of dissection, the MFM device restored flow to vital organs perfusing vessels independent of effects on luminal patency. Management of aortic dissections should focus on modulation of blood flow, suppression of local recirculation, and restoration of vital organ perfusion rather than primarily restoring vascular lumen morphology. While the latter restores the geometry of the true lumen, only the former restores homeostasis. Graphical abstract.


Assuntos
Aneurisma Dissecante , Prótese Vascular , Modelos Cardiovasculares , Adulto , Aneurisma Dissecante/sangue , Aneurisma Dissecante/cirurgia , Velocidade do Fluxo Sanguíneo , Procedimentos Endovasculares/instrumentação , Feminino , Hemodinâmica , Humanos , Masculino , Pessoa de Meia-Idade , Tomografia Computadorizada por Raios X
10.
Sci Transl Med ; 11(489)2019 04 24.
Artigo em Inglês | MEDLINE | ID: mdl-31019024

RESUMO

In this Editorial, co-Chief Scientific Advisors of Science Translational Medicine, Elazer Edelman and Garret FitzGerald, discuss challenges and opportunities for the next decade of translational research.

11.
Artigo em Inglês | MEDLINE | ID: mdl-30703007

RESUMO

OBJECTIVE: Limitations in available diagnostic metrics restrict the efficacy of managing therapies for cardiogenic shock. In current clinical practice, cardiovascular state is inferred through measurement of pulmonary capillary wedge pressure and reliance on linear approximations between pressure and flow to estimate peripheral vascular resistance. Mechanical circulatory support devices residing within the left ventricle and aorta provide an opportunity for both determining cardiac and vascular state and offering therapeutic benefit. We leverage the controllable mode of operation and transvalvular position of an indwelling percutaneous ventricular assist device to assess vascular and, in turn, cardiac state through the effects of device-arterial coupling across different levels of device support. METHODS: Vascular state is determined by measuring changes in the pressure waveforms induced through intentional variation in the device generated blood flow. We evaluate this impact by applying a lumped parameter model to quantify state-specific vascular resistance and compliance and calculate beat-to-beat stroke volume and cardiac output in both animal models and retrospective patient data without external calibration. RESULTS: Vascular state was accurately predicted in patients and animals in both baseline and experimental conditions. In the animal, stroke volume was predicted within a total RMS error of 3.71 mL (n=482). CONCLUSION: We demonstrate that device-arterial coupling is a powerful tool for evaluating patient and state specific parameters of cardiovascular function. SIGNIFICANCE: These insights may yield improved clinical care and support the development of next generation mechanical circulatory support devices that determine and operate in tandem with the supported organ.

12.
IEEE Trans Med Imaging ; 38(6): 1384-1397, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-30507499

RESUMO

Automated analysis of vascular imaging techniques is limited by the inability to precisely determine arterial borders. Intravascular optical coherence tomography (OCT) offers unprecedented detail of artery wall structure and composition, but does not provide consistent visibility of the outer border of the vessel due to the limited penetration depth. Existing interpolation and surface fitting methods prove insufficient to accurately fill the gaps between the irregularly spaced and sometimes unreliably identified visible segments of the vessel outer border. This paper describes an intuitive, efficient, and flexible new method of 3D surface fitting and smoothing suitable for this task. An anisotropic linear-elastic mesh is fit to irregularly spaced and uncertain data points corresponding to visible segments of vessel borders, enabling the fully automated delineation of the entire inner and outer borders of diseased vessels in OCT images for the first time. In a clinical dataset, the proposed smooth surface fitting approach had great agreement when compared with human annotations: areas differed by just 11 ± 11% (0.93 ± 0.84 mm2), with a coefficient of determination of 0.89. Overlapping and non-overlapping area ratios were 0.91 and 0.18, respectively, with a sensitivity of 90.8 and specificity of 99.0. This spring mesh method of contour fitting significantly outperformed all alternative surface fitting and interpolation approaches tested. The application of this promising proposed method is expected to enhance clinical intervention and translational research using OCT.

13.
Catheter Cardiovasc Interv ; 93(2): 278-285, 2019 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-30244502

RESUMO

OBJECTIVES: Drug-eluting stent (DES) strut fracture (SF) is associated with higher incidence of In-stent restenosis (ISR)-return of blockage in a diseased artery post stenting-than seen with bare metal stents (BMS). We hypothesize that concomitance of drug and SF leads to greater neointimal response. BACKGROUND: Controlled release of therapeutic agents, such as sirolimus and its analogs, or paclitaxel from has reduced tissue based DES failure modes compared to BMS. ISR is dramatically reduced and yet the implications of mechanical device failure is magnified. METHODS: Bilateral Xience Everolimus-eluting stents (EES) were implanted in 20 New Zealand White rabbits on normal (n = 7) or high fat (HF)/high cholesterol (HC) (n = 13) diets. Implanted stents were intact or mechanically fractured. Everolimus concentration was as packaged or pre-eluted. After 21 days, stented vessels were explanted, resin embedded, MicroCT scanned, and analyzed histomorphometrically. RESULTS: Fractured EES were associated with significant (P < 0.05) increases in arterial stenosis and neointimal formation and lower lumen-to-artery area ratios compared to intact EES. Hyperlipidemic animals receiving pre-eluted EES revealed no significant difference between intact and fracture groups. CONCLUSIONS: SF increases intimal hyperplasia, post EES implant, and worse with more advanced disease. Pre-eluted groups, reflective of BMS, did not show significant differences, suggesting a synergistic effect of everolimus and mechanical injury, potentially explaining the lack of SF reports for BMS. Here, we report that ISR has a higher incidence with SF in EES, the clinical implication is that patients with SF after DES implantation merit careful follow-up.

14.
IEEE J Biomed Health Inform ; 23(1): 4-11, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30346296

RESUMO

Computational cardiology is the scientific field devoted to the development of methodologies that enhance our mechanistic understanding, diagnosis and treatment of cardiovascular disease. In this regard, the field embraces the extraordinary pace of discovery in imaging, computational modeling, and cardiovascular informatics at the intersection of atherogenesis and vascular biology. This paper highlights existing methods, practices, and computational models and proposes new strategies to support a multidisciplinary effort in this space. We focus on the means by that to leverage and coalesce these multiple disciplines to advance translational science and computational cardiology. Analyzing the scientific trends and understanding the current needs we present our perspective for the future of cardiovascular treatment.


Assuntos
Técnicas de Imagem Cardíaca , Biologia Computacional , Informática Médica , Cardiologia/organização & administração , Cardiologia/estatística & dados numéricos , Doenças Cardiovasculares/diagnóstico por imagem , Humanos , Aprendizado de Máquina , Publicações/estatística & dados numéricos
15.
Am J Physiol Cell Physiol ; 316(2): C210-C222, 2019 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-30566394

RESUMO

The programmed form of cell death (apoptosis) is essential for normal development of multicellular organisms. Dysregulation of apoptosis has been linked with embryonal death and is involved in the pathophysiology of various diseases. Specifically, endothelial apoptosis plays pivotal roles in atherosclerosis whereas prevention of endothelial apoptosis is a prerequisite for neovascularization in tumors and metastasis. Endothelial biology is intertwined with the composition of subendothelial basement membrane proteins. Apoptosis was induced by addition of tumor necrosis factor-α to cycloheximide-sensitized endothelial cells. Cells were either grown on polystyrene culture plates or on plates precoated with healthy basement membrane proteins (collagen IV, fibronectin, or laminin) or collagen I. Our results reveal that proteins of healthy basement membrane alleviate cytokine-induced apoptosis whereas precoating with collagen type I had no significant effect on apoptosis by addition of tumor necrosis factor-α to cycloheximide-sensitized endothelial cells compared with cells cultured on uncoated plates. Yet, treatment with transforming growth factor-ß1 significantly reduced the rate of apoptosis endothelial cells grown on collagen I. Detailed analysis reveals differences in intracellular signaling pathways for each of the basement membrane proteins studied. We provide additional insights into the importance of basement membrane proteins and the respective cytokine milieu on endothelial biology. Exploring outside-in signaling by basement membrane proteins may constitute an interesting target to restore vascular function and prevent complications in the atherosclerotic cascade.


Assuntos
Aorta/metabolismo , Apoptose/fisiologia , Membrana Basal/metabolismo , Vasos Coronários/metabolismo , Células Endoteliais/metabolismo , Aorta/citologia , Membrana Basal/citologia , Células Cultivadas , Vasos Coronários/citologia , Matriz Extracelular/metabolismo , Humanos
16.
Acta Biomater ; 82: 34-43, 2018 12.
Artigo em Inglês | MEDLINE | ID: mdl-30342288

RESUMO

Polymeric bioresorbable scaffolds (BRS), at their early stages of invention, were considered as a promising revolution in interventional cardiology. However, they failed dramatically compared to metal stents showing substantially higher incidence of device failure and clinical events, especially thrombosis. One problem is that use of paradigms inherited from metal stents ignores dependency of polymer material properties on working environment and manufacturing/deployment steps. Unlike metals, polymeric material characterization experiments cannot be considered identical under dry and submerged conditions at varying rates of operation. We demonstrated different material behaviors associated with variable testing environment and parameters. We, then, have employed extracted material models, which are verified by computational methods, to assess the performance of a full-scale BRS in different working condition and under varying procedural strategies. Our results confirm the accepted notion that slower rate of crimping and inflation can potentially reduce stress concentrations and thus reduce localized damages. However, we reveal that using a universal set of material properties derived from a benchtop experiment conducted regardless of working environment and procedural variability may lead to a significant error in estimation of stress-induced damages and overestimation of benefits procedural updates might offer. We conclude that, for polymeric devices, microstructural damages and localized loss of structural integrity should complement former macroscopic performance-assessment measures (fracture and recoil). Though, to precisely capture localized stress concentration and microstructural damages, context-related testing environment and clinically-relevant procedural scenarios should be devised in preliminary experiments of polymeric resorbable devices to enhance their efficacy and avoid unpredicted clinical events. STATEMENT OF SIGNIFICANCE: Bioresorbable scaffolds (BRS) with the hope to become the next cardiovascular interventional revolution failed in comparison to metal stents. When BRS were characterized using methods for metal stents, designers were misled to seek problem sources at erroneous timeframe and use inefficient indicators, and thus no signal of concern emerged. We demonstrated fundamental flaws associated with applying a universal set of material properties to study device performances in different phases of manufacturing/implantation, and these may be responsible for failure in predicting performance in first-generation BRS. We introduced new criterion for the assessment of structural integrity and device efficacy in next-generation BRS, and indeed all devices using polymeric materials which evolve with the environment they reside in.


Assuntos
Implantes Absorvíveis , Prótese Vascular , Desenho de Prótese , Stents , Tecidos Suporte/química , Humanos
17.
J Control Release ; 285: 252-257, 2018 09 10.
Artigo em Inglês | MEDLINE | ID: mdl-30078756

RESUMO

The Hebrew word "b'reshith" (בְּרֵאשִׁית) means "in the beginning". It is the first word and title of the Book of Genesis, and it describes a process of creation. The four authors were present at the beginning of Langer labs, and the purpose of this essay is to convey the scientific and technological zeitgeist that existed in the late 1970s and early 1980s, when Bob Langer began his exceptionally creative work. While Langer labs has branched into many other areas, Bob's unique ability to recognize important problems and entice people to look beyond their own disciplines to solve them was evident from the start. We focus on the two areas of most interest to Bob at the time, namely controlled release of macromolecules from polymers, and removal of heparin in order to prevent uncontrolled bleeding during surgery.


Assuntos
Preparações de Ação Retardada/química , Sistemas de Liberação de Medicamentos/métodos , Polímeros/química , Animais , Anticoagulantes/isolamento & purificação , Biotecnologia/história , Biotecnologia/instrumentação , Biotecnologia/métodos , Sistemas de Liberação de Medicamentos/história , Sistemas de Liberação de Medicamentos/instrumentação , Desenho de Equipamento , Hemorragia/induzido quimicamente , Hemorragia/terapia , Heparina/isolamento & purificação , História do Século XX , História do Século XXI , Humanos
18.
Am J Physiol Heart Circ Physiol ; 315(5): H1182-H1193, 2018 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-30095992

RESUMO

Management of aortic dissections (AD) is still challenging, with no universally approved guideline among possible surgical, endovascular, or medical therapies. Approximately 25% of patients with AD suffer postintervention malperfusion syndrome or hemodynamic instability, with the risk of sudden death if left untreated. Part of the issue is that vascular implants may themselves induce flow disturbances that critically impact vital organs. A multilayer mesh construct might obviate the induced flow disturbances, and it is this concept we investigated. We used preintervention and post-multilayer flow modulator implantation (PM) geometries from clinical cases of type B AD. In-house semiautomatic segmentation routines were applied to computed tomography images to reconstruct the lumen. The device was numerically reconstructed and adapted to the PM geometry concentrically fit to the true lumen centerline. We also numerically designed a pseudohealthy case, where the geometry of the aorta was extracted interpolating geometric features of preintervention, postimplantation, and published representative healthy volunteers. Computational fluid dynamics methods were used to study the time-dependent flow patterns, shear stress metrics, and perfusion to vital organs. A three-element Windkessel lumped parameter module was coupled to a finite-volume solver to assign dynamic outlet boundary conditions. Multilayer flow modulator not only significantly reduced false lumen blood flow, eliminated local flow disturbances, and globally regulated wall shear stress distribution but also maintained physiological perfusion to peripheral vital organs. We propose further investigation to focus the management of AD on both modulation of blood flow and restoration of physiologic end-organ perfusion rather than mere restoration of vascular lamina morphology. NEW & NOTEWORTHY The majority of aortic dissection modeling efforts have focused on the maintenance of physiological flow using minimally invasive placed grafts. The multilayer flow modulator is a complex mesh construct of wires, designed to eliminate flow disruptions in the lumen, regulate the physiological wall stresses, and enhance endothelial function and offering the promise of improved perfusion of vital organs. This has never been fully proved or modeled, and these issues we confirmed using a dynamic framework of time-varying arterial waveforms.


Assuntos
Aneurisma Dissecante/cirurgia , Aneurisma Aórtico/cirurgia , Implante de Prótese Vascular/instrumentação , Prótese Vascular , Hemodinâmica , Aneurisma Dissecante/diagnóstico por imagem , Aneurisma Dissecante/fisiopatologia , Aneurisma Aórtico/diagnóstico por imagem , Aneurisma Aórtico/fisiopatologia , Aortografia/métodos , Velocidade do Fluxo Sanguíneo , Angiografia por Tomografia Computadorizada , Humanos , Hidrodinâmica , Modelos Cardiovasculares , Modelagem Computacional Específica para o Paciente , Desenho de Prótese , Interpretação de Imagem Radiográfica Assistida por Computador , Fluxo Sanguíneo Regional , Fatores de Tempo , Resultado do Tratamento
19.
Nano Lett ; 18(9): 5839-5845, 2018 09 12.
Artigo em Inglês | MEDLINE | ID: mdl-30096241

RESUMO

Fibrosis contributes to ∼45% of all deaths in industrialized nations, but no direct antifibrotic therapeutic interventions exist to date. Graphene-based nanomaterials exhibit excellent versatility in electronics, and emerging trends exploit their properties for biomedical applications, especially for drug and gene delivery. We designed constructs of graphene nanostars linked to PAMAM-G5 dendrimer for the selective targeting and delivery of a plasmid expressing the collagenase metalloproteinase 9 under the CD11b promoter into inflammatory macrophages in cirrhotic livers. Graphene nanostars preferentially accumulated in inflammatory macrophages M1 in less than 3 h in a manner unaffected by covalent linkage to dendrimers. Dendrimer-graphene nanostars efficiently delivered the plasmid encoding for metalloproteinase 9 into macrophages, allowing the synthesis and secretion of the metalloproteinase to digest adjacent collagen fibers. In turn, metalloproteinase 9 overexpression promoted the macrophage switch from inflammatory M1 to pro-regenerative M2 in 3 days. This targeted gene therapy reduced selectively and locally the presence of collagen fibers in fibrotic tracts where inflammatory macrophages accumulated in cirrhotic mice without affecting the activation state of hepatic stellate cells. Overall, this treatment significantly reduced hepatic injury and improved liver restoration in mice with liver cirrhosis treated for 10 days. Graphene-dendrimer nanostars targeted the macrophage overexpression of metalloproteinase 9, selectively reducing hepatic fibrosis, and might be a good treatment for diseases associated with fibrosis and inflammatory macrophage accumulation.


Assuntos
Dendrímeros/química , Grafite/química , Cirrose Hepática/terapia , Macrófagos/metabolismo , Metaloproteinase 9 da Matriz/genética , Nanopartículas/química , Plasmídeos/administração & dosagem , Animais , Técnicas de Transferência de Genes , Terapia Genética , Cirrose Hepática/genética , Camundongos , Camundongos Endogâmicos BALB C , Nanopartículas/ultraestrutura , Plasmídeos/genética , Plasmídeos/uso terapêutico , Regulação para Cima
20.
IEEE J Biomed Health Inform ; 22(4): 1168-1176, 2018 07.
Artigo em Inglês | MEDLINE | ID: mdl-29969405

RESUMO

We present a novel and time-efficient method for intracoronary lumen detection, which produces three-dimensional (3-D) coronary arteries using optical coherence tomographic (OCT) images. OCT images are acquired for multiple patients and longitudinal cross-section (LOCS) images are reconstructed using different acquisition angles. The lumen contours for each LOCS image are extracted and translated to 2-D cross-sectional images. Using two angiographic projections, the centerline of the coronary vessel is reconstructed in 3-D, and the detected 2-D contours are transformed to 3-D and placed perpendicular to the centerline. To validate the proposed method, 613 manual annotations from medical experts were used as gold standard. The 2-D detected contours were compared with the annotated contours, and the 3-D reconstructed models produced using the detected contours were compared to the models produced by the annotated contours. Wall shear stress (WSS), as dominant hemodynamics factor, was calculated using computational fluid dynamics and 844 consecutive 2-mm segments of the 3-D models were extracted and compared with each other. High Pearson's correlation coefficients were obtained for the lumen area (r = 0.98) and local WSS (r = 0.97) measurements, while no significant bias with good limits of agreement was shown in the Bland-Altman analysis. The overlapping and nonoverlapping areas ratio between experts' annotations and presented method was 0.92 and 0.14, respectively. The proposed computer-aided lumen extraction and 3-D vessel reconstruction method is fast, accurate, and likely to assist in a number of research and clinical applications.


Assuntos
Angiografia Coronária/métodos , Imagem Tridimensional/métodos , Tomografia de Coerência Óptica/métodos , Algoritmos , Vasos Coronários/diagnóstico por imagem , Humanos
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA