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1.
Nature ; 628(8008): 612-619, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38509366

RESUMO

There is increasing interest in how immune cells in the meninges-the membranes that surround the brain and spinal cord-contribute to homeostasis and disease in the central nervous system1,2. The outer layer of the meninges, the dura mater, has recently been described to contain both innate and adaptive immune cells, and functions as a site for B cell development3-6. Here we identify organized lymphoid structures that protect fenestrated vasculature in the dura mater. The most elaborate of these dural-associated lymphoid tissues (DALT) surrounded the rostral-rhinal confluence of the sinuses and included lymphatic vessels. We termed this structure, which interfaces with the skull bone marrow and a comparable venous plexus at the skull base, the rostral-rhinal venolymphatic hub. Immune aggregates were present in DALT during homeostasis and expanded with age or after challenge with systemic or nasal antigens. DALT contain germinal centre B cells and support the generation of somatically mutated, antibody-producing cells in response to a nasal pathogen challenge. Inhibition of lymphocyte entry into the rostral-rhinal hub at the time of nasal viral challenge abrogated the generation of germinal centre B cells and class-switched plasma cells, as did perturbation of B-T cell interactions. These data demonstrate a lymphoid structure around vasculature in the dura mater that can sample antigens and rapidly support humoral immune responses after local pathogen challenge.


Assuntos
Dura-Máter , Imunidade Humoral , Tecido Linfoide , Veias , Administração Intranasal , Antígenos/administração & dosagem , Antígenos/imunologia , Medula Óssea/imunologia , Sistema Nervoso Central/irrigação sanguínea , Sistema Nervoso Central/imunologia , Dura-Máter/irrigação sanguínea , Dura-Máter/imunologia , Centro Germinativo/citologia , Centro Germinativo/imunologia , Vasos Linfáticos/imunologia , Tecido Linfoide/irrigação sanguínea , Tecido Linfoide/imunologia , Plasmócitos/imunologia , Crânio/irrigação sanguínea , Linfócitos T/imunologia , Veias/fisiologia , Humanos , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Animais , Camundongos , Idoso de 80 Anos ou mais
2.
J Physiol Sci ; 74(1): 21, 2024 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-38555424

RESUMO

Mean circulatory filling pressure, venous return curve, and Guyton's graphical analysis are basic concepts in cardiovascular physiology. However, some medical students may not know how to view and interpret or understand them adequately. To deepen students' understanding of the graphical analysis, in place of having to perform live animal experiments, we developed an interactive cardiovascular simulator, as a self-learning tool, as a web application. The minimum closed-loop model consisted of a ventricle, an artery, resistance, and a vein, excluding venous resistance. The simulator consists of three modules: setting (parameters and simulation modes), calculation, and presentation. In the setting module, the user can interactively customize model parameters, compliances, resistance, Emax of the ventricular contractility, total blood volume, and unstressed volume. The hemodynamics are calculated in three phases: filling (late diastole), ejection (systole), and flow (early diastole). In response to the user's settings, the simulator graphically presents the hemodynamics: the pressure-volume relations of the artery, vein, and ventricle, the venous return curves, and the stroke volume curves. The mean filling pressure is calculated at approximately 7 mmHg at the initial setting. The venous return curves, linear and concave, are dependent on the venous compliance. The hemodynamic equilibrium point is marked on the crossing point of venous return curve and the stroke volume curve. Users can interactively do discovery learning, and try and confirm their interests and get their questions answered about hemodynamic concepts by using the simulator.


Assuntos
Hemodinâmica , Veias , Animais , Humanos , Veias/fisiologia , Volume Sistólico , Pressão Sanguínea/fisiologia , Débito Cardíaco/fisiologia
4.
Adv Physiol Educ ; 47(1): 97-116, 2023 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-36476117

RESUMO

Vascular diseases of the legs are highly prevalent and constitute an important part of medical curricula. The understanding of these diseases relies on strongly interwoven aspects of vascular physiology and vascular medicine. We aimed to connect these within a horizontally integrated laboratory class on vascular physiology of the leg that was designed in cooperation between the departments of physiology and vascular surgery. Conceptually, we applied examination techniques of vascular medicine to visualize physiological parameters that are altered by the most frequent diseases. This facilitates integrative discussions on malfunctions, trains diagnostic skills, and bridges to vascular medicine. In four experiments, we use oscillometry and impedance venous occlusion plethysmography to address key aspects of the arterial and venous system of the legs: 1) arterial pulse wave, 2) arterial systolic blood pressure, 3) venous capacitance and venous outflow, and 4) reactive hyperemia. After the experiments, physiological vascular function, the associated diseases, their impact on the recorded parameters, and diagnostic options are discussed. To allow reproduction, we describe the course structure and the experimental setup in detail. We present the experimental data of a cohort of medical students and document learning success and student satisfaction. All experiments were feasible and provided robust data on physiologically and clinically relevant vascular functions. The activity was perceived positively by the students and led to a substantial improvement of knowledge. With this work, we offer a template for reproduction or variation of a proven concept of horizontally integrated teaching of vascular physiology of the leg.NEW & NOTEWORTHY This article presents an integrative laboratory class on vascular physiology bridging to vascular medicine. The four experiments rely on oscillometry and venous occlusion plethysmography. We describe in detail this new class regarding structure, experimental setup, and experimental procedure, and we give insight into the applied materials. Moreover, we present the experimental data of 74 students and a quantitative evaluation of the students' learning success and acceptance.


Assuntos
Cardiologia , Fisiologia , Humanos , Pletismografia/métodos , Veias/fisiologia , Pressão Sanguínea
5.
PLoS Genet ; 18(11): e1010534, 2022 11.
Artigo em Inglês | MEDLINE | ID: mdl-36449521

RESUMO

Tissue factor (TF) is an evolutionarily conserved protein necessary for initiation of hemostasis. Zebrafish have two copies of the tissue factor gene (f3a and f3b) as the result of an ancestral teleost fish duplication event (so called ohnologs). In vivo physiologic studies of TF function have been difficult given early lethality of TF knockout in the mouse. We used genome editing to produce knockouts of both f3a and f3b in zebrafish. Since ohnologs arose through sub- or neofunctionalization, they can unmask unknown functions of non-teleost genes and could reveal whether mammalian TF has developmental functions distinct from coagulation. Here we show that a single copy of either f3a or f3b is necessary and sufficient for normal lifespan. Complete loss of TF results in lethal hemorrhage by 2-4 months despite normal embryonic and vascular development. Larval vascular endothelial injury reveals predominant roles for TFa in venous circulation and TFb in arterial circulation. Finally, we demonstrate that loss of TF predisposes to a stress-induced cardiac tamponade independent of its role in fibrin formation. Overall, our data suggest partial subfunctionalization of TFa and TFb. This multigenic zebrafish model has the potential to facilitate study of the role of TF in different vascular beds.


Assuntos
Duplicação Gênica , Hemostasia , Tromboplastina , Animais , Camundongos , Larva , Tromboplastina/genética , Tromboplastina/fisiologia , Peixe-Zebra/genética , Peixe-Zebra/metabolismo , Proteínas de Peixe-Zebra/genética , Hemostasia/genética , Veias/fisiologia , Artérias/fisiologia
6.
J Vasc Surg ; 75(1): 230-237, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-34314831

RESUMO

OBJECTIVE: Immature arteriovenous fistula (AVF) is a critical problem in patients with chronic kidney disease (CKD) after creation. Exercise with 30% maximum voluntary contraction (MVC) encourages vascular functions in other populations. It is unknown which exercise type is superior on maturation in the CKD population. We compare effects of isometric (ISM) and isotonic (IST) hand exercise training, both at 30% MVC, on AVF maturation and grip strength in patients with CKD. METHODS: Fifty patients with CKD were randomized into the ISM program or IST program (25 per group). Each group performed exercise program at intensity of 30% MVC every day for 10 weeks. Cephalic vein (CV) and brachial artery diameters, brachial blood flows, and grip strength were measured at weeks 0, 2, 6, and 10 of the program. The number of patients meeting clinical and ultrasound maturation were evaluated at weeks 2, 6, and 10. RESULTS: At weeks 6 and 10 of the programs, the ISM group had greater CV diameters (week 6, 7.1 ± 1.2 vs 6.2 ± 1.0 mm; week 10, 7.1 ± 1.0 vs 6.2 ± 1.1 mm) than the IST group. Compared with the IST group, the ISM group had a higher number of patients meeting ultrasound maturation at weeks 2 (IST/ISM, 8/2), 6 (IST/ISM, 16/8), and 10 (IST/ISM, 21/12), and clinical maturation at week 10 (IST/ISM, 25/18). No adverse events were observed throughout the study. CONCLUSIONS: At 30% MVC, ISM is more effective at promoting increases in CV diameter and maturation than IST. Both exercise types are feasible and safe for patients with CKD after AVF creation.


Assuntos
Derivação Arteriovenosa Cirúrgica/reabilitação , Terapia por Exercício/métodos , Mãos/fisiologia , Diálise Renal/métodos , Insuficiência Renal Crônica/terapia , Idoso , Mãos/irrigação sanguínea , Força da Mão , Humanos , Masculino , Pessoa de Meia-Idade , Artéria Radial/diagnóstico por imagem , Artéria Radial/fisiologia , Artéria Radial/cirurgia , Resultado do Tratamento , Ultrassonografia Doppler , Grau de Desobstrução Vascular/fisiologia , Veias/diagnóstico por imagem , Veias/fisiologia , Veias/cirurgia
7.
Anesthesiology ; 135(6): 1027-1041, 2021 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-34731241

RESUMO

BACKGROUND: Previous studies have established the role of various tissue compartments in the kinetics of inhaled anesthetic uptake and elimination. The role of normal lungs in inhaled anesthetic kinetics is less understood. In juvenile pigs with normal lungs, the authors measured desflurane and sevoflurane washin and washout kinetics at three different ratios of alveolar minute ventilation to cardiac output value. The main hypothesis was that the ventilation/perfusion ratio (VA/Q) of normal lungs influences the kinetics of inhaled anesthetics. METHODS: Seven healthy pigs were anesthetized with intravenous anesthetics and mechanically ventilated. Each animal was studied under three different VA/Q conditions: normal, low, and high. For each VA/Q condition, desflurane and sevoflurane were administered at a constant, subanesthetic inspired partial pressure (0.15 volume% for sevoflurane and 0.5 volume% for desflurane) for 45 min. Pulmonary arterial and systemic arterial blood samples were collected at eight time points during uptake, and then at these same times during elimination, for measurement of desflurane and sevoflurane partial pressures. The authors also assessed the effect of VA/Q on paired differences in arterial and mixed venous partial pressures. RESULTS: For desflurane washin, the scaled arterial partial pressure differences between 5 and 0 min were 0.70 ± 0.10, 0.93 ± 0.08, and 0.82 ± 0.07 for the low, normal, and high VA/Q conditions (means, 95% CI). Equivalent measurements for sevoflurane were 0.55 ± 0.06, 0.77 ± 0.04, and 0.75 ± 0.08. For desflurane washout, the scaled arterial partial pressure differences between 0 and 5 min were 0.76 ± 0.04, 0.88 ± 0.02, and 0.92 ± 0.01 for the low, normal, and high VA/Q conditions. Equivalent measurements for sevoflurane were 0.79 ± 0.05, 0.85 ± 0.03, and 0.90 ± 0.03. CONCLUSIONS: Kinetics of inhaled anesthetic washin and washout are substantially altered by changes in the global VA/Q ratio for normal lungs.


Assuntos
Desflurano/administração & dosagem , Desflurano/sangue , Sevoflurano/administração & dosagem , Sevoflurano/sangue , Relação Ventilação-Perfusão/fisiologia , Anestésicos Inalatórios/administração & dosagem , Anestésicos Inalatórios/sangue , Animais , Animais Recém-Nascidos , Artérias/efeitos dos fármacos , Combinação de Medicamentos , Feminino , Cinética , Masculino , Suínos , Veias/efeitos dos fármacos , Veias/fisiologia , Relação Ventilação-Perfusão/efeitos dos fármacos
8.
Sci Rep ; 11(1): 22108, 2021 11 11.
Artigo em Inglês | MEDLINE | ID: mdl-34764362

RESUMO

A method motivated by the eye's aqueous veins is described for the imaging and strain calculation within soft biological tissues. A challenge to the investigation of the biomechanics of the aqueous vein-perilimbal sclera tissue complex is resolution of tissue deformations as a function of intraocular pressure and the subsequent calculation of strain (a normalized measure of deformation). The method involves perfusion of the eye with a contrast agent during conduction of non-invasive, optical resolution photoacoustic microscopy. This imaging technique permits three-dimensional displacement measurements of tracked points on the inner walls of the veins which are used in a finite element model to determine the corresponding strains. The methods are validated against two standard strain measurement methods. Representative porcine globe perfusion experiments are presented that demonstrate the power of the method to determine complex strain fields in the veins dependent on intraocular pressure as well as vein anatomy. In these cases, veins are observed to move radially outward during increases in intraocular pressure and to possess significant spatial strain variation, possibly influenced by their branching patterns. To the authors' knowledge, these are the only such quantitative, data driven, calculations of the aqueous vein strains available in the open literature.


Assuntos
Imageamento Tridimensional/métodos , Técnicas Fotoacústicas/métodos , Esclera/fisiologia , Veias/fisiologia , Animais , Fenômenos Biomecânicos/fisiologia , Biofísica/métodos , Análise de Elementos Finitos , Pressão Intraocular/fisiologia , Disco Óptico/fisiologia , Estresse Mecânico , Suínos , Tonometria Ocular/métodos
9.
Biomech Model Mechanobiol ; 20(6): 2227-2245, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34535857

RESUMO

The flow patterns of red blood cells through the spleen are intimately linked to clearance of senescent RBCs, with clearance principally occurring within the open flow through the red pulp and slits of the venous sinus system that exists in humans, rats, and dogs. Passage through interendothelial slits (IESs) of the sinus has been shown by MacDonald et al. (Microvasc Res 33:118-134, 1987) to be mediated by the caliber, i.e., slit opening width, of these slits. IES caliber within a given slit of a given sinus section has been shown to operate in an asynchronous manner. Here, we describe a model and simulation results that demonstrate how the supporting forces exerted on the sinus by the reticular meshwork of the red pulp, combined with asymmetrical contractility of stress fibers within the endothelial cells comprising the sinus, describe this vital and intriguing behavior. These results shed light on the function of the sinus slits in species such as humans, rats, and dogs that possess sinusoidal sinuses. Instead of assuming a passive mechanical filtering mechanism of the IESs, our proposed model provides a mechanically consistent explanation for the dynamically modulated IES opening/filtering mechanism observed in vivo. The overall perspective provided is also consistent with the view that IES passage serves as a self-protective mechanism in RBC vesiculation and inclusion removal.


Assuntos
Células Endoteliais/fisiologia , Eritrócitos/fisiologia , Hemorreologia , Baço/irrigação sanguínea , Veias/fisiologia , Simulação por Computador , Células Endoteliais/ultraestrutura , Eritrócitos/ultraestrutura , Humanos , Cinética , Modelos Biológicos , Pressão , Baço/ultraestrutura , Estresse Mecânico , Veias/ultraestrutura
10.
Sci Rep ; 11(1): 17256, 2021 08 26.
Artigo em Inglês | MEDLINE | ID: mdl-34446823

RESUMO

Defining the hemodynamic response to volume therapy is integral to managing critically ill patients with acute circulatory failure, especially in the absence of cardiac index (CI) measurement. This study aimed at investigating whether changes in central venous-to-arterial CO2 difference (Δ-ΔPCO2) and central venous oxygen saturation (ΔScvO2) induced by volume expansion (VE) are reliable parameters to define fluid responsiveness in sedated and mechanically ventilated septic patients. We prospectively studied 49 critically ill septic patients in whom VE was indicated because of circulatory failure and clinical indices. CI, ΔPCO2, ScvO2, and oxygen consumption (VO2) were measured before and after VE. Responders were defined as patients with a > 10% increase in CI (transpulmonary thermodilution) after VE. We calculated areas under the receiver operating characteristic curves (AUCs) for Δ-ΔPCO2, ΔScvO2, and changes in CI (ΔCI) after VE in the whole population and in the subgroup of patients with an increase in VO2 (ΔVO2) ≤ 10% after VE (oxygen-supply independency). Twenty-five patients were fluid responders. In the whole population, Δ-ΔPCO2 and ΔScvO2 were significantly correlated with ΔCI after VE (r = - 0.30, p = 0.03 and r = 0.42, p = 0.003, respectively). The AUCs for Δ-ΔPCO2 and ΔScvO2 to define fluid responsiveness (increase in CI > 10% after VE) were 0.76 (p < 0.001) and 0.68 (p = 0.02), respectively. In patients with ΔVO2 ≤ 10% (n = 36) after VE, the correlation between ΔScvO2 and ΔCI was 0.62 (p < 0.001), and between Δ-ΔPCO2 and ΔCI was - 0.47 (p = 0.004). The AUCs for Δ-ΔPCO2 and ΔScvO2 were 0.83 (p < 0.001) and 0.73 (p = 0.006), respectively. In these patients, Δ-ΔPCO2 ≤ -37.5% after VE allowed the categorization between responders and non-responders with a positive predictive value of 100% and a negative predictive value of 60%. In sedated and mechanically ventilated septic patients with no signs of tissue hypoxia (oxygen-supply independency), Δ-ΔPCO2 is a reliable parameter to define fluid responsiveness.


Assuntos
Artérias/fisiologia , Biomarcadores/análise , Dióxido de Carbono/metabolismo , Hidratação/métodos , Choque Séptico/terapia , Veias/fisiologia , Idoso , Estado Terminal/terapia , Feminino , Hemodinâmica/fisiologia , Humanos , Masculino , Pessoa de Meia-Idade , Avaliação de Resultados em Cuidados de Saúde/métodos , Consumo de Oxigênio/fisiologia , Pressão Parcial , Estudos Prospectivos
11.
J Tissue Eng Regen Med ; 15(10): 818-830, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34318614

RESUMO

Personalized tissue engineered vascular grafts are a promising advanced therapy medicinal product alternative to autologous or synthetic vascular grafts utilized in blood vessel bypass or replacement surgery. We hypothesized that an individualized tissue engineered vein (P-TEV) would make the body recognize the transplanted blood vessel as autologous, decrease the risk of rejection and thereby avoid lifelong treatment with immune suppressant medication as is standard with allogenic organ transplantation. To individualize blood vessels, we decellularized vena cava from six deceased donor pigs and tested them for cellular removal and histological integrity. A solution with peripheral blood from the recipient pigs was used for individualized reconditioning in a perfusion bioreactor for seven days prior to transplantation. To evaluate safety and functionality of the individualized vascular graft in vivo, we transplanted reconditioned porcine vena cava into six pigs and analyzed histology and patency of the graft at different time points, with three pigs at the final endpoint 4-5 weeks after surgery. Our results showed that the P-TEV was fully patent in all animals, did not induce any occlusion or stenosis formation and we did not find any signs of rejection. The P-TEV showed rapid recellularization in vivo with the luminal surface covered with endothelial cells. In summary, the results indicate that P-TEV is functional and have potential for use as clinical transplant grafts.


Assuntos
Prótese Vascular , Estudo de Prova de Conceito , Engenharia Tecidual , Veias/fisiologia , Animais , Suínos , Grau de Desobstrução Vascular , Veias/transplante , Veias/ultraestrutura
12.
Cell Rep ; 36(3): 109395, 2021 07 20.
Artigo em Inglês | MEDLINE | ID: mdl-34289351

RESUMO

Arteries and veins form in a stepwise process that combines vasculogenesis and sprouting angiogenesis. Despite extensive data on the mechanisms governing blood vessel assembly at the single-cell level, little is known about how collective cell migration contributes to the organization of the balanced distribution between arteries and veins. Here, we use an endothelial-specific zebrafish reporter, arteriobow, to label small cohorts of arterial cells and trace their progeny from early vasculogenesis throughout arteriovenous remodeling. We reveal that the genesis of arteries and veins relies on the coordination of 10 types of collective cell dynamics. Within these behavioral categories, we identify a heterogeneity of collective cell motion specific to either arterial or venous remodeling. Using pharmacological blockade, we further show that cell-intrinsic Notch signaling and cell-extrinsic blood flow act as regulators in maintaining the heterogeneity of collective endothelial cell behavior, which, in turn, instructs the future territory of arteriovenous remodeling.


Assuntos
Artérias/fisiologia , Rastreamento de Células , Células Endoteliais/citologia , Remodelação Vascular/fisiologia , Veias/fisiologia , Animais , Animais Geneticamente Modificados , Células Clonais , Células Endoteliais/metabolismo , Genes Reporter , Receptores Notch/metabolismo , Fluxo Sanguíneo Regional , Reologia , Transdução de Sinais , Peixe-Zebra
13.
Transfus Apher Sci ; 60(5): 103198, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34187772

RESUMO

BACKGROUND: This study aims to determine the phlebotomy and procedural outcomes using a vein assessment tool (VAT) in Double Dose Platelet (DDP) collections by apheresis. METHODS: VAT was based on assessing vein visibility, palpation and size with maximum score of 12 and the least being 0 and the scores were graded as adequate and inadequate. A vein-viewer was used for studying cubital vein patterns (type 1-5). Phlebotomy outcome was defined based on need for re-puncture. Procedural outcomes in terms of target yield attained and RBC reinfusion completed. Chi square test and Mann- Whitney U test were used to assess the vein score and pattern against phlebotomy and procedural outcome. RESULTS: Out of 200 DDP collections, the phlebotomy was successful in 88 % with good procedural outcome in 94 % donations. The cut off in VAT scores for successful phlebotomy was ≥8 (AUC: 70 %). Median vein scores of the arm selected for phlebotomy was 9 and graded adequate in 154 (77 %) donations.Odds for successful phlebotomy was 3.7 times higher when donors had an adequate VAT grades(p = 0.003). Procedural outcomes was favourable when at least one arm had adequate VAT grade when compared to both arms being inadequate (98 % vs 82 %; p < 0.001). Phlebotomy failure was more with first time apheresis donors than repeat apheresis donors (p = 0.014). CONCLUSION: This study indicated that a VAT score with a cut off of ≥8 had better phlebotomy and procedural outcomes in DDP collections and that donor with at least one arm having the VAT score of ≥8 are preferred for DDP collections.


Assuntos
Remoção de Componentes Sanguíneos/métodos , Plaquetas/citologia , Plaquetoferese/instrumentação , Plaquetoferese/métodos , Veias/anatomia & histologia , Veias/fisiologia , Adulto , Transfusão de Componentes Sanguíneos/instrumentação , Transfusão de Componentes Sanguíneos/métodos , Doadores de Sangue , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Razão de Chances , Flebotomia , Estudos Prospectivos , Resultado do Tratamento , Adulto Jovem
14.
Am J Physiol Heart Circ Physiol ; 321(1): H77-H111, 2021 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-33989082

RESUMO

The measurement of vascular function in isolated vessels has revealed important insights into the structural, functional, and biomechanical features of the normal and diseased cardiovascular system and has provided a molecular understanding of the cells that constitutes arteries and veins and their interaction. Further, this approach has allowed the discovery of vital pharmacological treatments for cardiovascular diseases. However, the expansion of the vascular physiology field has also brought new concerns over scientific rigor and reproducibility. Therefore, it is appropriate to set guidelines for the best practices of evaluating vascular function in isolated vessels. These guidelines are a comprehensive document detailing the best practices and pitfalls for the assessment of function in large and small arteries and veins. Herein, we bring together experts in the field of vascular physiology with the purpose of developing guidelines for evaluating ex vivo vascular function. By using this document, vascular physiologists will have consistency among methodological approaches, producing more reliable and reproducible results.


Assuntos
Artérias/fisiologia , Vasoconstrição/fisiologia , Vasodilatação/fisiologia , Veias/fisiologia , Animais , Endotélio Vascular/fisiologia , Microscopia/métodos , Miografia/métodos , Reprodutibilidade dos Testes
15.
FASEB J ; 35(6): e21643, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-33977574

RESUMO

The endothelial glycocalyx is a dynamic structure integral to blood vessel hemodynamics and capable of tightly regulating a range of biological processes (ie, innate immunity, inflammation, and coagulation) through dynamic changes in its composition of the brush structure. Evaluating the specific roles of the endothelial glycocalyx under a range of pathophysiologic conditions has been a challenge in vitro as it is difficult to generate functional glycocalyces using commonly employed 2D cell culture models. We present a new multi-height microfluidic platform that promotes the growth of functional glycocalyces by eliciting unique shear stress forces over a continuous human umbilical vein endothelial cell monolayer at magnitudes that recapitulate the physical environment in arterial, capillary and venous regions of the vasculature. Following 72 hours of shear stress, unique glycocalyx structures formed within each region that were distinct from that observed in short (3 days) and long-term (21 days) static cell culture. The model demonstrated glycocalyx-specific properties that match the characteristics of the endothelium in arteries, capillaries and veins, with respect to surface protein expression, platelet adhesion, lymphocyte binding and nanoparticle uptake. With artery-to-capillary-to-vein transition on a continuous endothelial monolayer, this in vitro platform is an improved system over static cell culture for more effectively studying the role of the glycocalyx in endothelial biology and disease.


Assuntos
Artérias/fisiologia , Capilares/fisiologia , Glicocálix/química , Glicocálix/metabolismo , Células Endoteliais da Veia Umbilical Humana/fisiologia , Estresse Mecânico , Veias/fisiologia , Hemodinâmica , Células Endoteliais da Veia Umbilical Humana/citologia , Humanos , Microfluídica , Resistência ao Cisalhamento
16.
Sci Rep ; 11(1): 7975, 2021 04 12.
Artigo em Inglês | MEDLINE | ID: mdl-33846433

RESUMO

Extracorporeal membrane oxygenation (ECMO) support has a high incidence of both bleeding and thrombotic complications. Despite clear differences in patient characteristics and pathologies between veno-venous (VV) and veno-arterial (VA) ECMO support, anticoagulation practices are often the same across modalities. Moreover, there is very little data on their respective coagulation profiles and comparisons of thrombin generation in these patients. This study compares the coagulation profile and thrombin generation between patients supported with either VV and VA ECMO. A prospective cohort study of patients undergoing VA and VV ECMO at an Intensive care department of a university hospital and ECMO referral centre. In addition to routine coagulation testing and heparin monitoring per unit protocol, thromboelastography (TEG), multiplate aggregometry (MEA), calibrated automated thrombinography (CAT) and von-Willebrand's activity (antigen and activity ratio) were sampled second-daily for 1 week, then weekly thereafter. VA patients had significantly lower platelets counts, fibrinogen, anti-thrombin and clot strength with higher d-dimer levels than VV patients, consistent with a more pronounced consumptive coagulopathy. Thrombin generation was higher in VA than VV patients, and the heparin dose required to suppress thrombin generation was lower in VA patients. There were no significant differences in total bleeding or thrombotic event rates between VV and VA patients when adjusted for days on extracorporeal support. VA patients received a lower median daily heparin dose 8500 IU [IQR 2500-24000] versus VV 28,800 IU [IQR 17,300-40,800.00]; < 0.001. Twenty-eight patients (72%) survived to hospital discharge; comprising 53% of VA patients and 77% of VV patients. Significant differences between the coagulation profiles of VA and VV patients exist, and anticoagulation strategies for patients of these modalities should be different. Further research into the development of tailored anticoagulation strategies that include the mode of ECMO support need to be completed.


Assuntos
Artérias/fisiologia , Coagulação Sanguínea/fisiologia , Oxigenação por Membrana Extracorpórea , Hemostasia/fisiologia , Trombina/metabolismo , Veias/fisiologia , Adulto , Anticoagulantes/farmacologia , Automação , Coagulação Sanguínea/efeitos dos fármacos , Oxigenação por Membrana Extracorpórea/efeitos adversos , Fator Xa/metabolismo , Feminino , Hemorragia/etiologia , Hemostasia/efeitos dos fármacos , Heparina/farmacologia , Humanos , Masculino , Pessoa de Meia-Idade , Tempo de Tromboplastina Parcial , Tromboelastografia
17.
PLoS One ; 16(3): e0248999, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33750977

RESUMO

BACKGROUND: Delayed identification of infiltration and dysfunction of peripheral intravenous (PIV) access can lead to serious consequences during general anesthesia in children. This preliminary study aimed to describe the application of precordial Doppler ultrasound during general anesthesia in children to detect and confirm the correct PIV access and to evaluate the accuracy of this method. METHODS: This was a single-center, preliminary study that was conducted in children (<18 years) who were scheduled for elective surgeries between October 2019 and March 2020. Rater anesthesiologists judged the change in precordial Doppler sound (S test) before and after injection of 0.5 mL/kg of normal saline (NS) via PIV. Blood flow velocity before and after NS injection was recorded, and multiple cutoff points were set to analyze the accuracy of detecting the infiltration and dysfunction of PIV catheter (V test). RESULTS: The total incidence of peripheral infiltration and dysfunction of PIV catheter was 7/512 (1.4%). In the S test, the sensitivity, specificity, positive and negative likelihood ratios, and area under the receiver-operating characteristic curves (AUCs) were 5/7 (71.4%; 95% confidence interval [CI], 29.0%-96.3%), 490/505 (97.0%; 95% CI, 95.1%-98.3%), 24.0, 0.29, and 0.84, respectively. The V test showed that the reasonable threshold of blood flow velocity change was 1.0 m/s, with sensitivity, specificity, positive and negative likelihood ratios, and AUC of 4/7 (57.1%; 95% CI, 18.4%-90.1%), 489/505 (96.8%; 95% CI, 94.9%-98.2%), 18.0 and 0.44, and 0.84, respectively. CONCLUSIONS: This preliminary study demonstrated that precordial Doppler ultrasound is a feasible, easy-to-use, and noninvasive technique with good accuracy to confirm the correct PIV access during general anesthesia in children. However, its accuracy requires further evaluation.


Assuntos
Anestesia Geral , Ultrassonografia Doppler , Veias/fisiologia , Administração Intravenosa , Velocidade do Fluxo Sanguíneo , Criança , Pré-Escolar , Feminino , Cardiopatias Congênitas/sangue , Cardiopatias Congênitas/diagnóstico por imagem , Cardiopatias Congênitas/fisiopatologia , Humanos , Lactente , Masculino , Curva ROC , Fluxo Sanguíneo Regional/fisiologia
18.
J Vis Exp ; (168)2021 02 20.
Artigo em Inglês | MEDLINE | ID: mdl-33682855

RESUMO

Sepsis and septic shock remain the leading cause of death in intensive care units. Despite significant improvements in sepsis management, mortality still ranges between 20 and 30%. Novel treatment approaches in order to reduce sepsis-related multiorgan failure and death are urgently needed. Robust animal models allow for one or multiple treatment approaches as well as for testing their effect on physiological and molecular parameters. In this article, a simple animal model is presented. First, general anesthesia is induced in animals either with the use of volatile or by intraperitoneal anesthesia. After placement of an intravenous catheter (tail vein), tracheostomy, and insertion of an intraarterial catheter (tail artery), mechanical ventilation is started. Baseline values of mean arterial blood pressure, arterial blood oxygen saturation, and heart rate are recorded. The injection of lipopolysaccharides (1 milligram/kilogram body weight) dissolved in phosphate-buffered saline induces a strong and reproducible inflammatory response via the toll-like receptor 4. Fluid corrections as well as the application of norepinephrine are performed based on well-established protocols. The animal model presented in this article is easy to learn and strongly oriented towards clinical sepsis treatment in an intensive care unit with sedation, mechanical ventilation, continuous blood pressure monitoring, and repetitive blood sampling. Also, the model is reliable, allowing for reproducible data with a limited number of animals in accordance with the 3R (reduce, replace, refine) principles of animal research. While animal experiments in sepsis research cannot easily replaced, repetitive measurements allow for a reduction of animals and keeping septic animals anesthetized diminishes suffering.


Assuntos
Endotoxinas/toxicidade , Unidades de Terapia Intensiva , Anestesia , Animais , Artérias/fisiologia , Modelos Animais de Doenças , Masculino , Monitorização Fisiológica , Ratos Wistar , Reprodutibilidade dos Testes , Sepse/patologia , Traqueostomia , Veias/fisiologia
19.
J Physiol Anthropol ; 40(1): 5, 2021 Feb 10.
Artigo em Inglês | MEDLINE | ID: mdl-33568227

RESUMO

BACKGROUND: Circulating fatty acid-binding protein 4 (FABP4) is a marker for various diseases. It would be highly useful to have simple and less invasive techniques for the assessment of FABP4 concentrations in the clinical research setting. The purpose of the present study was to assess the concordance of circulating FABP4 concentrations in venous and capillary blood both at rest and immediately after acute exercise in healthy young males. RESULTS: Thirty-eight healthy young male adults aged from 19 to 25 years (mean age, 20.8 ± 1.2 years) were recruited. Paired blood samples were taken from the cubital vein (venous) and fingertip (capillary) blood at rest (resting state) and immediately after incremental exercise (exercising state). Blood samples were analyzed to determine the circulating FABP4 concentration using an enzyme-linked immunosorbent assay. Pearson's correlation coefficients for circulating FABP4 concentrations between venous and capillary blood samples indicated a strong positive correlation in both the resting and exercising state (resting state: r = 0.982, exercising state: r = 0.989, both p < 0.001). The mean FABP4 concentration was similar between venous and capillary blood in the resting state (p = 0.178), whereas it was significantly higher in capillary blood than in venous blood in the exercising state (p < 0.001). Furthermore, Bland-Altman plots showed a non-significant bias (- 0.07 ± 0.61 ng/mL, p = 0.453) in the resting state, whereas a significant bias (- 0.45 ± 0.61 ng/mL, p < 0.001) was observed in the exercising state. CONCLUSIONS: These results indicate that capillary blood sampling can slightly overestimate circulating FABP4 concentrations under a physiologically dynamic state. However, the association between the venous and capillary blood in terms of FABP4 concentration was very strong, suggesting that capillary blood sampling can detect changes in FABP4 concentration in both physiologically steady and dynamic states.


Assuntos
Exercício Físico/fisiologia , Proteínas de Ligação a Ácido Graxo/sangue , Adulto , Análise Química do Sangue/normas , Coleta de Amostras Sanguíneas/métodos , Capilares/fisiologia , Humanos , Masculino , Veias/fisiologia , Adulto Jovem
20.
J Plast Reconstr Aesthet Surg ; 74(9): 2042-2049, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-33455872

RESUMO

INTRODUCTION: The consequences on the cervicofacial venous circulation of major cervicofacial vein ligations are poorly known. We aimed to highlight by using Doppler Ultrasound flow differences in the cervicofacial venous network in the case of unilateral or bilateral ligation of main venous collector trunks (external jugular vein [EJV] and internal jugular vein [IJV]) METHODS: A Doppler ultrasound was performed on 10 healthy volunteers, 8 patients with previous bilateral ligation of the EJV, 8 with a unilateral ligation of the EJV, and 8 with a unilateral ligation of the EJV and IJV, after modified radical neck dissection. The diameter, the flow direction and the peak systolic velocity (PSV) of the superficial temporal vein, the facial vein (FV) and the IJV were measured. RESULTS: Healthy patients had a similar right and left PSV for all the veins studied, with always antegrade flows. Patients with previous ligations had some significant right/left differences and retrograde flows. CONCLUSION: A redistribution of venous blood flow on the contralateral side of the face and neck seems to take place in the case of unilateral ligation of the EJV and/or IJV. Retrograde flows are sometimes observed in the case of previous ligation of the EJV and/or IJV and might compromise the success of venous microanastomoses.


Assuntos
Face/irrigação sanguínea , Veias Jugulares/fisiologia , Veias Jugulares/cirurgia , Ligadura , Microcirurgia/métodos , Pescoço/irrigação sanguínea , Procedimentos Cirúrgicos Vasculares/métodos , Adulto , Veias Cerebrais/diagnóstico por imagem , Veias Cerebrais/fisiologia , Face/cirurgia , Feminino , Neoplasias de Cabeça e Pescoço/cirurgia , Humanos , Veias Jugulares/diagnóstico por imagem , Masculino , Pescoço/cirurgia , Esvaziamento Cervical , Fluxo Sanguíneo Regional , Carcinoma de Células Escamosas de Cabeça e Pescoço/cirurgia , Ultrassonografia Doppler em Cores , Veias/diagnóstico por imagem , Veias/fisiologia
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