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1.
Methods Mol Biol ; 2235: 89-117, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33576972

RESUMO

The brain's high energy requirements drive the need for close coupling of local neuronal activity to blood supply. Capillaries have been shown to dilate before arterioles in response to sensory stimulation, pointing to a key role for microvascular pericytes in mediating cerebrovascular dynamics. However, many aspects of these cells' function remain unknown and even controversial, from their identification, to the mechanism and regulation of their contractility in physiology and disease. Investigating how pericytes regulate vascular diameter is therefore likely to be the subject of many future experiments. Here we provide protocols for three different techniques (ex vivo slice imaging, in vivo imaging, and immunohistochemistry) that are highly valuable for performing such experiments.


Assuntos
Circulação Cerebrovascular/fisiologia , Imagem Óptica/métodos , Pericitos/metabolismo , Animais , Arteríolas/fisiopatologia , Encéfalo/fisiopatologia , Isquemia Encefálica/fisiopatologia , Capilares/fisiopatologia , Humanos , Neurônios/metabolismo , Acoplamento Neurovascular/fisiologia , Pericitos/citologia
2.
Respir Res ; 22(1): 28, 2021 Jan 21.
Artigo em Inglês | MEDLINE | ID: mdl-33478493

RESUMO

BACKGROUND: Risk stratification is essential to assess mortality risk and guide treatment in patients with precapillary pulmonary hypertension (PH). We herein compared the accuracy of different currently used PH risk stratification tools and evaluated the significance of particular risk parameters. METHODS: We conducted a retrospective longitudinal observational cohort study evaluating seven different risk assessment approaches according to the current PH guidelines. A comprehensive assessment including multi-parametric risk stratification was performed at baseline and 4 yearly follow-up time-points. Multi-step Cox hazard analysis was used to analyse and refine risk prediction. RESULTS: Various available risk models effectively predicted mortality in patients with precapillary pulmonary hypertension. Right-heart catheter parameters were not essential for risk prediction. Contrary, non-invasive follow-up re-evaluations significantly improved the accuracy of risk estimations. A lack of accuracy of various risk models was found in the intermediate- and high-risk classes. For these patients, an additional evaluation step including assessment of age and right atrium area improved risk prediction significantly. DISCUSSION: Currently used abbreviated versions of the ESC/ERS risk assessment tool, as well as the REVEAL 2.0 and REVEAL Lite 2 based risk stratification, lack accuracy to predict mortality in intermediate- and high-risk precapillary pulmonary hypertension patients. An expanded non-invasive evaluation improves mortality risk prediction in these individuals.


Assuntos
Capilares/diagnóstico por imagem , Capilares/fisiopatologia , Hipertensão Pulmonar/diagnóstico por imagem , Hipertensão Pulmonar/fisiopatologia , Idoso , Idoso de 80 Anos ou mais , Estudos de Coortes , Feminino , Seguimentos , Humanos , Hipertensão Pulmonar/mortalidade , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Mortalidade/tendências , Estudos Retrospectivos , Medição de Risco
3.
Nature ; 585(7823): 91-95, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32788726

RESUMO

Signalling between cells of the neurovascular unit, or neurovascular coupling, is essential to match local blood flow with neuronal activity. Pericytes interact with endothelial cells and extend processes that wrap capillaries, covering up to 90% of their surface area1,2. Pericytes are candidates to regulate microcirculatory blood flow because they are strategically positioned along capillaries, contain contractile proteins and respond rapidly to neuronal stimulation3,4, but whether they synchronize microvascular dynamics and neurovascular coupling within a capillary network was unknown. Here we identify nanotube-like processes that connect two bona fide pericytes on separate capillary systems, forming a functional network in the mouse retina, which we named interpericyte tunnelling nanotubes (IP-TNTs). We provide evidence that these (i) have an open-ended proximal side and a closed-ended terminal (end-foot) that connects with distal pericyte processes via gap junctions, (ii) carry organelles including mitochondria, which can travel along these processes, and (iii) serve as a conduit for intercellular Ca2+ waves, thus mediating communication between pericytes. Using two-photon microscope live imaging, we demonstrate that retinal pericytes rely on IP-TNTs to control local neurovascular coupling and coordinate light-evoked responses between adjacent capillaries. IP-TNT damage following ablation or ischaemia disrupts intercellular Ca2+ waves, impairing blood flow regulation and neurovascular coupling. Notably, pharmacological blockade of Ca2+ influx preserves IP-TNTs, rescues light-evoked capillary responses and restores blood flow after reperfusion. Our study thus defines IP-TNTs and characterizes their critical role in regulating neurovascular coupling in the living retina under both physiological and pathological conditions.


Assuntos
Nanotubos , Acoplamento Neurovascular , Pericitos/metabolismo , Animais , Isquemia Encefálica/metabolismo , Isquemia Encefálica/patologia , Cálcio/metabolismo , Sinalização do Cálcio , Capilares/fisiopatologia , Capilares/efeitos da radiação , Comunicação Celular , Feminino , Junções Comunicantes/metabolismo , Hemodinâmica , Masculino , Camundongos , Mitocôndrias/metabolismo , Acoplamento Neurovascular/fisiologia , Pericitos/citologia , Pericitos/patologia , Retina/citologia , Retina/patologia
4.
Microvasc Res ; 132: 104064, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-32841626

RESUMO

Veno-Venous Extracorporeal Membrane Oxygenation (VV-ECMO) is a rescue treatment for severe acute respiratory failure refractory to conventional ventilation. We examined the alterations of sublingual microcirculation in patients with SARS-CoV-2 during VV-ECMO treatment and assessed the relationship between microvascular parameters and ventilation, hemodynamics, and laboratory tests. Nine patients were included in the study and the following microcirculatory parameters were estimated: TVD 16.81 (14.46-18.6) mm/mm2; PVD 15.3 (14.09-17.96) mm/mm2; PPV 94.85% (93.82%-97.79%); MFI 2.5 (2.5-2.92); HI 0.4 (0.18-0.4). TVD and PVD were inversely related to D-dimer levels (rho = -0.667, p = 0.05 and rho = -0.733, p = 0.025 respectively), aspartate aminotransferase (AST) (rho = -0.886, p = 0.019 and rho = -0.886, p = 0.019 respectively) and alanine aminotransferase (ALT) (rho = -0.829, p = 0.042 and rho = -0.829, p = 0.042 respectively). Our results showed an altered sublingual microcirculation in patients receiving VV-ECMO for severe SARS-CoV-2 and suggest a potential contribution of endothelia dysfunction to determine microvascular alteration.


Assuntos
Infecções por Coronavirus/sangue , Infecções por Coronavirus/terapia , Oxigenação por Membrana Extracorpórea/métodos , Microcirculação , Soalho Bucal/irrigação sanguínea , Pneumonia Viral/sangue , Pneumonia Viral/terapia , Betacoronavirus , Capilares/fisiopatologia , Endotélio Vascular/fisiopatologia , Feminino , Produtos de Degradação da Fibrina e do Fibrinogênio/análise , Hemodinâmica , Humanos , Masculino , Microscopia de Vídeo , Pessoa de Meia-Idade , Pandemias , Estudos Retrospectivos , Veias
5.
Paediatr Respir Rev ; 35: 20-24, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32653469

RESUMO

Since the initial description in 2019, the novel coronavirus SARS-Cov-2 infection (COVID-19) pandemic has swept the globe. The most severe form of the disease presents with fever and shortness of breath, which rapidly deteriorates to respiratory failure and acute lung injury (ALI). COVID-19 also presents with a severe coagulopathy with a high rate of venous thromboembiolism. In addition, autopsy studies have revealed co-localized thrombosis and inflammation, which is the signature of thromboinflammation, within the pulmonary capillary vasculature. While the majority of published data is on adult patients, there are parallels to pediatric patients. In our experience as a COVID-19 epicenter, children and young adults do develop both the coagulopathy and the ALI of COVID-19. This review will discuss COVID-19 ALI from a hematological perspective with discussion of the distinct aspects of coagulation that are apparent in COVID-19. Current and potential interventions targeting the multiple thromboinflammatory mechanisms will be discussed.


Assuntos
Lesão Pulmonar Aguda/sangue , Infecções por Coronavirus/sangue , Inflamação/sangue , Pneumonia Viral/sangue , Trombose/sangue , Lesão Pulmonar Aguda/tratamento farmacológico , Lesão Pulmonar Aguda/imunologia , Lesão Pulmonar Aguda/fisiopatologia , Anticoagulantes/uso terapêutico , Antitrombinas/uso terapêutico , Betacoronavirus , Transtornos da Coagulação Sanguínea/sangue , Transtornos da Coagulação Sanguínea/imunologia , Transtornos da Coagulação Sanguínea/fisiopatologia , Capilares/imunologia , Capilares/fisiopatologia , Infecções por Coronavirus/tratamento farmacológico , Infecções por Coronavirus/imunologia , Infecções por Coronavirus/fisiopatologia , Endotélio Vascular/imunologia , Endotélio Vascular/fisiopatologia , Inibidores do Fator Xa/uso terapêutico , Humanos , Inflamação/tratamento farmacológico , Inflamação/imunologia , Inflamação/fisiopatologia , Pandemias , Ativação Plaquetária , Inibidores da Agregação de Plaquetas/uso terapêutico , Pneumonia Viral/tratamento farmacológico , Pneumonia Viral/imunologia , Pneumonia Viral/fisiopatologia , Embolia Pulmonar/sangue , Embolia Pulmonar/imunologia , Embolia Pulmonar/fisiopatologia , Trombina/imunologia , Trombina/metabolismo , Trombose/tratamento farmacológico , Trombose/imunologia , Trombose/fisiopatologia
6.
Invest Ophthalmol Vis Sci ; 61(3): 50, 2020 03 09.
Artigo em Inglês | MEDLINE | ID: mdl-32232345

RESUMO

Purpose: To investigate the microvascular changes in macular retina and choriocapillaris (CC) in diabetic eyes without retinopathy using swept-source optical coherence tomography angiography (SS-OCTA). Methods: A commercial SS-OCTA system was used to collect 6 × 6-mm macular scans from patients. Three depth-resolved retinal slabs and a CC slab were segmented by a validated semiautomated algorithm. Retinal vessel area density, vessel skeleton density, and nonperfusion area were calculated on segmented retinal slabs. Foveal avascular zone was automatically measured based on en face image of the whole retinal layer. For CC quantification, the percentage of flow deficits (FD%) and the flow deficit (FD) sizes were measured. Results: Sixteen eyes from 16 diabetic patients without clinically detectable retinopathy and 16 eyes from 16 age-matched nondiabetic controls were included. There was no significant difference between the two groups in all retinal vessel quantitative parameters (all P > 0.05). However, the mean FD% and mean FD sizes were significantly increased in CC in the central 1.0-mm disk (P = 0.011 and P = 0.017, respectively), the central 1.5-mm rim (P = 0.003 and P = 0.009, respectively), the central 2.5-mm rim (P = 0.018 and P = 0.020, respectively), and the entire 5.0-mm disk (P = 0.009 and P = 0.008, respectively) in diabetic eyes compared with controls. Conclusions: CC perfusion in the macula is decreased in diabetic patients without retinopathy as compared to age-matched normal controls. Decreased CC perfusion in the macula may be an early indicator of otherwise clinically undetectable diabetic vasculopathy.


Assuntos
Corioide/irrigação sanguínea , Diabetes Mellitus/fisiopatologia , Vasos Retinianos/fisiopatologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Algoritmos , Capilares/fisiopatologia , Diabetes Mellitus/diagnóstico por imagem , Retinopatia Diabética/fisiopatologia , Feminino , Angiofluoresceinografia , Humanos , Masculino , Pessoa de Meia-Idade , Fluxo Sanguíneo Regional , Vasos Retinianos/diagnóstico por imagem , Estudos Retrospectivos , Tomografia de Coerência Óptica , Adulto Jovem
7.
PLoS One ; 15(4): e0231962, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32324828

RESUMO

Vascular deficits are a fundamental contributing factor of diabetes-associated diseases. Although previous studies have demonstrated that the pro-angiogenic phase of wound healing is blunted in diabetes, a comprehensive understanding of the mechanisms that regulate skin revascularization and capillary stabilization in diabetic wounds is lacking. Using a mouse model of diabetic wound healing, we performed microCT analysis of the 3-dimensional architecture of the capillary bed. As compared to wild type, vessel surface area, branch junction number, total vessel length, and total branch number were significantly decreased in wounds of diabetic mice as compared to WT mice. Diabetic mouse wounds also had significantly increased capillary permeability and decreased pericyte coverage of capillaries. Diabetic wounds exhibited significant perturbations in the expression of factors that affect vascular regrowth, maturation and stability. Specifically, the expression of VEGF-A, Sprouty2, PEDF, LRP6, Thrombospondin 1, CXCL10, CXCR3, PDGFR-ß, HB-EGF, EGFR, TGF-ß1, Semaphorin3a, Neuropilin 1, angiopoietin 2, NG2, and RGS5 were down-regulated in diabetic wounds. Together, these studies provide novel information about the complexity of the perturbation of angiogenesis in diabetic wounds. Targeting factors responsible for wound resolution and vascular pruning, as well those that affect pericyte recruitment, maturation, and stability may have the potential to improve diabetic skin wound healing.


Assuntos
Vasos Sanguíneos/patologia , Vasos Sanguíneos/fisiopatologia , Diabetes Mellitus Experimental/patologia , Diabetes Mellitus Experimental/fisiopatologia , Neovascularização Patológica , Cicatrização , Animais , Vasos Sanguíneos/diagnóstico por imagem , Vasos Sanguíneos/metabolismo , Capilares/metabolismo , Capilares/fisiopatologia , Diabetes Mellitus Experimental/diagnóstico por imagem , Diabetes Mellitus Experimental/metabolismo , Feminino , Camundongos , Camundongos Endogâmicos C57BL , Pericitos/patologia , Permeabilidade , Microtomografia por Raio-X
8.
Am J Physiol Regul Integr Comp Physiol ; 318(5): R894-R900, 2020 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-32209023

RESUMO

The goal of this investigation was to compare the effects of chronic (4 wk) transverse aortic constriction (TAC) in Sprague-Dawley rats and C57BL/6J mice. TAC, after 1 day, induced similar left ventricular (LV) pressure gradients in both rats (n = 7) and mice (n = 7) (113 ± 5.4 vs. 103 ± 11.5 mmHg), and after 4 wk, the percent increase in LV hypertrophy, as reflected by LV/tibial length (51% vs 49%), was similar in rats (n = 12) and mice (n = 12). After 4 wk of TAC, LV systolic and diastolic function were preserved in TAC rats. In contrast, in TAC mice, LV ejection fraction decreased by 31% compared with sham, along with increases in LV end-diastolic pressure (153%) and LV systolic wall stress (86%). Angiogenesis, as reflected by Ki67 staining of capillaries, increased more in rats (n = 6) than in mice (n = 6; 10 ± 2 vs. 6 ± 1 Ki67-positive cells/field). Myocardial blood flow fell by 55% and coronary reserve by 28% in mice with TAC (n = 4), but they were preserved in rats (n = 4). Myogenesis, as reflected by c-kit-positive myocytes staining positively for troponin I, is another mechanism that can confer protection after TAC. However, the c-kit-positive cells in rats with TAC were all negative for troponin I, indicating the absence of myogenesis. Thus, rats showed relative tolerance to severe pressure overload compared with mice, with mechanisms involving angiogenesis but not myogenesis.


Assuntos
Hipertrofia Ventricular Esquerda/fisiopatologia , Disfunção Ventricular Esquerda/fisiopatologia , Função Ventricular Esquerda , Pressão Ventricular , Remodelação Ventricular , Animais , Aorta/fisiopatologia , Aorta/cirurgia , Capilares/metabolismo , Capilares/fisiopatologia , Circulação Coronária , Modelos Animais de Doenças , Hipertrofia Ventricular Esquerda/etiologia , Hipertrofia Ventricular Esquerda/metabolismo , Antígeno Ki-67/metabolismo , Ligadura , Camundongos Endogâmicos C57BL , Desenvolvimento Muscular , Miócitos Cardíacos/metabolismo , Neovascularização Fisiológica , Proteínas Proto-Oncogênicas c-kit/metabolismo , Ratos Sprague-Dawley , Transdução de Sinais , Especificidade da Espécie , Fatores de Tempo , Troponina I/metabolismo , Disfunção Ventricular Esquerda/etiologia , Disfunção Ventricular Esquerda/metabolismo
9.
Microvasc Res ; 129: 103971, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-31899168

RESUMO

Diabetes is associated with micro- and macrovascular complications. The aim of the study was to investigate microvascular parameters (glycocalyx dimensions, perfused and total capillary density) in vivo in patients with type 1 and type 2 diabetes mellitus. In vivo sublingual videomicroscopy using sidestream darkfield - derived imaging was performed in 36 patients with diabetes mellitus (type 1: n = 20, type 2: n = 16) and compared to a control group of 36 healthy volunteers. Patients with HbA1c levels ≥ 8% had a significantly higher perfused boundary region (PBR; signifying the loss of glycocalyx dimensions) compared to patients with HbA1c levels < 8%, which was more pronounced in type 1 diabetes (2.08 µm [1.95-2.16 µm] vs.1.9 µm [1.66-1.94 µm], p = .029). Capillary density did not differ significantly between patients with diabetes and healthy controls. PBR was inversely related to RBC filling percentage and perfused capillary density in diabetic patients (r = -0.754, p < .001 and r = -0.505, p = .002, respectively) as well as in healthy volunteers (r = -0.701, p < .001 and r = -0.150, p = n.s.) signifying the association between glycocalyx dimensions and microvessel perfusion. Renal parameters were associated with microvascular perfusion in patients with type 2 diabetes (correlation between eGFR and perfused capillary density: r = 0. 568, p = .027/RBC filling percentage: r = 0.657, p = .008). In addition, the ratio of perfused/total capillary density correlated with CRP levels in type 2 diabetes (r = 0.682, p = .021). In conclusion, diabetes is associated with loss of glycocalyx density.


Assuntos
Capilares/patologia , Diabetes Mellitus Tipo 1/patologia , Diabetes Mellitus Tipo 2/patologia , Angiopatias Diabéticas/patologia , Glicocálix/patologia , Mucosa Bucal/irrigação sanguínea , Adulto , Idoso , Idoso de 80 Anos ou mais , Glicemia/metabolismo , Capilares/fisiopatologia , Estudos de Casos e Controles , Estudos Transversais , Diabetes Mellitus Tipo 1/sangue , Diabetes Mellitus Tipo 1/fisiopatologia , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/fisiopatologia , Angiopatias Diabéticas/sangue , Angiopatias Diabéticas/fisiopatologia , Feminino , Hemoglobina A Glicada/metabolismo , Humanos , Masculino , Microcirculação , Pessoa de Meia-Idade , Projetos Piloto , Adulto Jovem
10.
Microvasc Res ; 129: 103970, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-31891718

RESUMO

BACKGROUND: Nailfold capillaroscopy is a highly sensitive, inexpensive, simple, safe, and noninvasive technique used in the investigation of the microcirculation. However, the diseases having a vasculitic component can cause changes in the nailfold capillaries like viral hepatitis, the microvascular characteristics of the nailfold area in HBV and HCV infected individuals have not been systematically investigated. In this study, we investigated possible dermoscopic differences in the vascular appearance of the nailfold capillaries and their association with the disease's clinical status. METHOD: A hundred and forty-seven patients and 147 healthy controls were enrolled in this study. The patients' group consisted of chronic viral hepatitis B (CHB: 54 cases), chronic hepatitis C (CHC: 36 cases) and carrier of hepatitis B virus infection (CRHB: 57 cases). Nailfold capillaroscopy was performed using a digital dermoscope (Molemax II, X30). All capillaroscopy images were evaluated for capillary density, capillary loop enlargement, capillary tortuosities, branching vessels, micro hemorrhages, avascular areas and splinter hemorrhages, and routine laboratory examinations of all patients were performed. RESULTS: Statistical differences in all of the categories of capillary morphology were prominent between the capillary abnormalities of Hepatitis B and the control group, also the capillary abnormality was significant between hepatitis C and the control group (p < 0.01). None of the 147 healthy control had any nailfold capillary changes. There was a significant difference between the CHB-Control and CRHB-Control groups in all of the capillaroscopic changes (p < 0.01). The avascular area was also the most common finding in Hepatitis C and Hepatitis B infected individuals, and capillary dilatation (CD), capillary tortuosity (CT) and capillary enlargement (CE) were the major nailfold capillary changes in both of two diseases. CONCLUSION: Nailfold capillary abnormalities are one of the extrahepatic dermatologic finding which could be a sign of the endothelial tissue damage in chronic viral hepatitis, we do not have any data about the effects of these two usual infections on the nailfold capillary morphology. This is the first study evaluating the microvasculature abnormalities of the nailfold capillaries in hepatitis B and hepatitis C infected individuals by capillaroscopic examination.


Assuntos
Capilares/patologia , Dermoscopia , Hepatite B Crônica/patologia , Hepatite C Crônica/patologia , Angioscopia Microscópica , Unhas/irrigação sanguínea , Idoso , Capilares/fisiopatologia , Estudos de Casos e Controles , Feminino , Hepatite B Crônica/fisiopatologia , Hepatite C Crônica/fisiopatologia , Humanos , Masculino , Microcirculação , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Prognóstico
11.
J Glaucoma ; 29(3): 168-174, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-31917720

RESUMO

PRéCIS:: In primary open-angle glaucoma (POAG), unlogged mean macular hemifield visual field sensitivity correlates significantly better with superficial capillary vessel density (VD) than with ganglion cell complex (GCC) thickness of the opposite macular hemifield. PURPOSE: The aim of this study was to compare the relationship of the spatially corresponding superficial retinal capillary VD and retinal thickness parameters with the corresponding visual field sensitivity, for the superior and inferior macula, and the superotemporal and inferotemporal peripapillary sectors, respectively. PATIENTS AND METHODS: One eye of 27 POAG, 14 ocular hypertensive, and 9 healthy participants were subjected to optical coherence tomography angiography imaging with the Angiovue optical coherence tomography and Octopus G2 perimetry on the same day. Superior and inferior unlogged hemifield average macular sensitivity was correlated with the opposite macular hemifield VD and GCC thickness, respectively. Correlation of visual field cluster unlogged average sensitivity with the spatially corresponding sector VD and sector retinal nerve fiber layer thickness were compared for the superotemporal and inferotemporal peripapillary sector, respectively. RESULTS: For all participants and the glaucoma population, the correlations for macular hemifield GCC were strong or very strong (r: 0.554 to 0.737, P<0.01). In these groups, the correlations for macular hemifield VD were all very strong (r: 0.823 to 0.838, P<0.0001) and significantly higher than the corresponding correlations for hemifield GCC (P≤0.050). No significant difference between the corresponding correlations was found in the combined normal and ocular hypertensive group for the macular hemifields, or in either population for the peripapillary sectors. CONCLUSION: Our results suggest that, in contrast to superotemporal and inferotemporal peripapillary sectors in which the thickness-function and VD-function relationships are similar, in POAG, for the macular hemifields, the VD-function relationship is stronger than the thickness-function relationship.


Assuntos
Glaucoma de Ângulo Aberto/fisiopatologia , Disco Óptico/irrigação sanguínea , Vasos Retinianos/fisiopatologia , Idoso , Angiografia , Capilares/fisiopatologia , Feminino , Glaucoma de Ângulo Aberto/diagnóstico por imagem , Voluntários Saudáveis , Humanos , Pressão Intraocular/fisiologia , Masculino , Pessoa de Meia-Idade , Fibras Nervosas/patologia , Hipertensão Ocular/fisiopatologia , Células Ganglionares da Retina/patologia , Vasos Retinianos/diagnóstico por imagem , Tomografia de Coerência Óptica/métodos , Testes de Campo Visual , Campos Visuais/fisiologia
12.
Br J Ophthalmol ; 104(4): 473-479, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-31337609

RESUMO

BACKGROUND/AIMS: To assess foveal avascular zone (FAZ) morphology and parafoveal capillary perfusion in patients with various stages of sickle cell retinopathy (SCR) using optical coherence tomography angiography (OCT-A). METHODS: This is a multi-institutional retrospective study of patients with various stages of SCR compared with healthy controls. Parafoveal OCT-A images obtained using a commercial spectral domain-OCT system were reviewed. Foveal-centred 3×3 mm full vascular slab OCT-As were used for image processing and data analysis. FAZ area, perimeter, and acircularity index were determined on the OCT-A image after manual delineation of the FAZ border. Quadrant-based parafoveal capillary density and per cent area deviating from normal distribution were also measured. RESULTS: Fifty-two patients with SCR (33 non-proliferative and 19 proliferative) and 20 age and race-matched healthy controls were included. One randomly selected eye per study participant was analysed. FAZ perimeter and acircularity index were significantly greater in SCR eyes when compared with the controls. While parafoveal capillary density was significantly lower, per cent area deviated from normal distribution was significantly higher in SCR eyes than that of the control. However, no statistically significant difference between the two SCR stages was observed. In quadrant-based analysis, the temporal quadrant showed greater parafoveal capillary dropout due to SCR, with the most profound effect in patients with proliferative SCR. CONCLUSIONS: Abnormal FAZ morphology and altered parafoveal capillary perfusion were found in patients with SCR. Our customised OCT-A image analysis method uniquely highlights significant quantitative alterations in perfusion density mapping in a qualitative display, with minimal obscuration of OCT-A image detail.


Assuntos
Anemia Falciforme/fisiopatologia , Capilares/fisiopatologia , Fóvea Central/irrigação sanguínea , Isquemia/patologia , Doenças Retinianas/fisiopatologia , Vasos Retinianos/patologia , Adulto , Idoso , Anemia Falciforme/diagnóstico por imagem , Capilares/diagnóstico por imagem , Feminino , Angiofluoresceinografia , Humanos , Isquemia/diagnóstico por imagem , Masculino , Pessoa de Meia-Idade , Doenças Retinianas/diagnóstico por imagem , Vasos Retinianos/diagnóstico por imagem , Estudos Retrospectivos , Tomografia de Coerência Óptica , Acuidade Visual , Adulto Jovem
13.
Invest Ophthalmol Vis Sci ; 60(15): 4985-4990, 2019 12 02.
Artigo em Inglês | MEDLINE | ID: mdl-31791062

RESUMO

Purpose: Swept-source optical coherence tomography angiography (SS-OCTA) was used to investigate if the clinical stage of dry age-related macular degeneration (AMD) was correlated with global and regional macular choriocapillaris (CC) perfusion. Methods: In this retrospective, cross-sectional study, 6 × 6-mm SS-OCTA images from eyes with early, intermediate, and advanced dry AMD (56 eyes, 41 patients) were analyzed using algorithms described in the literature to assess regional flow deficit percentage (FD%) and average flow deficit size. Regions were defined by concentric areas centered on the fovea: a 1-mm-diameter area, 3-mm-diameter ring, 5-mm-diameter area, 5-mm-diameter ring, and 6 × 6-mm whole image. Data were modeled using the generalized estimating equations approach. Results: The relationship between age and CC FD% and average flow deficit size was statistically significant (P ≤ 0.05) in all regions of analysis by linear modeling. The relationship between dry AMD stage and FD% was statistically significant by linear modeling in the 5-mm ring, and between dry AMD stage and average flow deficit size in the 3-mm ring, 5-mm area, 5-mm ring, and 6 × 6-mm whole image. Conclusions: Linear modeling suggests a statistically significant relationship between dry AMD stage and CC perfusion, most prominent in the more peripheral regions of the macula.


Assuntos
Capilares/fisiopatologia , Corioide/irrigação sanguínea , Angiofluoresceinografia/métodos , Atrofia Geográfica/diagnóstico , Macula Lutea/irrigação sanguínea , Fluxo Sanguíneo Regional/fisiologia , Tomografia de Coerência Óptica/métodos , Idoso , Idoso de 80 Anos ou mais , Capilares/patologia , Corioide/patologia , Estudos Transversais , Feminino , Fundo de Olho , Atrofia Geográfica/fisiopatologia , Humanos , Macula Lutea/patologia , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos
15.
J Transl Med ; 17(1): 368, 2019 11 12.
Artigo em Inglês | MEDLINE | ID: mdl-31718666

RESUMO

BACKGROUND: Hypertension often presents with microvascular rarefaction (MVR), which is closely associated with impaired angiogenesis. Early detection of MVR is essential for systemic assessment in patient with hypertension. We aimed to determine the systemic MVR through both optical coherence tomography angiography (OCTA) and intravital capillaroscopy, and to investigate their respective efficacies and related mechanisms associated with late endothelial progenitor cells (LEPCs) dysfunction. METHODS: Seventy-one hypertensive and sixty-nine age-match normotensive subjects were included in this study. All subjects received intravital capillaroscopy for skin capillary density (SCD) and OCTA for retinal capillary density (RCD) and non-perfused areas (R-NPA). Subsequently, correlation of LEPCs activities and microvascular rarefaction were examined. RESULTS: Compared with normotensive subjects, hypertensive patients had significantly lower RCD [(52.9 ± 2.9)% vs. (57.8 ± 1.6)%, P < 0.01] and higher R-NPA [(0.12 ± 0.07) mm2 vs. (0.053 ± 0.020) mm2, P < 0.01]. SCD correlated positively with RCD but negatively with R-NPA [(RCD: OR = 0.40, 95% CI 0.25-0.67, P < 0.01); (R-NPA: OR = 0.39, 95% CI - 0.0029 to 0.0011, P < 0.01)]. The discriminative powers of RCD performed best (AUC 0.79 versus SCD AUC 0.59, P < 0.001) followed by R-NPA (AUC 0.73 versus SCD AUC 0.59, P < 0.001) for systolic blood pressure. Similar pattern is also found for diastolic blood pressure (RCD AUC 0.80 versus SCD AUC 0.54, P < 0.001; R-NPA AUC 0.77 versus SCD AUC 0.54, P < 0.001). Furthermore, LEPCs tube formation was impaired in hypertensive patients (36.8 ± 2.3 vs. 28 ± 3.7, P < 0.01). After multivariate adjustments, positive correlation existed between RCD or R-NPA with LEPCs tube formation (RCD: ß = 0.64, 95% CI 0.34-0.91, P < 0.01; R-NPA: ß = - 24.67, 95% CI - 43.14 to - 4.63, P < 0.05) but not with SCD (ß = 0.082, 95% CI 0.01-0.18, P = 0.085). CONCLUSION: Compared to intravital capillaroscopy, OCTA is a more precise technique for early detection of hypertensive microvascular rarefaction, which is associated with the fall in LEPC-mediated angiogenesis. Both of OCTA and LEPCs function can help identify hypertension-related capillary abnormality. Trail Registration The trial is a substudy of EXCAVATION-CHN1, registered at clinicaltrials.gov as NCT02817204 (June 26, 2016).


Assuntos
Células Progenitoras Endoteliais/patologia , Hipertensão/complicações , Hipertensão/fisiopatologia , Rarefação Microvascular/complicações , Rarefação Microvascular/fisiopatologia , Adulto , Pressão Sanguínea , Capilares/patologia , Capilares/fisiopatologia , Feminino , Humanos , Modelos Lineares , Masculino , Microcirculação , Análise Multivariada , Neovascularização Fisiológica , Perfusão , Curva ROC , Retina/patologia , Pele/irrigação sanguínea
16.
Arthritis Res Ther ; 21(1): 253, 2019 11 27.
Artigo em Inglês | MEDLINE | ID: mdl-31775852

RESUMO

BACKGROUND: While microangiopathy is well-documented in systemic sclerosis (SSc), a potential link between SSc and macrovascular disease is highly debated and remains to be established. The aim of the present study is to investigate the association between micro- and macrovascular involvement in the setting of SSc. METHODS: Consecutive, consenting SSc patients were assessed by nailfold video-capillaroscopy (NVC) to evaluate the microcirculation. The number of capillaries per mm2 and the capillaroscopic skin ulcer risk index (CSURI) were measured, and findings were also classified into three scleroderma patterns (i.e., early, active, and late). Carotid intima-media thickness (IMT), aortic augmentation index corrected for a heart rate of 75 beats per minute (AIx-75), carotid-femoral pulse wave velocity (PWV), and central systolic and diastolic blood pressure were also determined to assess macrovascular function. RESULTS: A total of 37 patients were studied. A significant correlation was observed between AIx and the average number of capillaries per mm2 (r = - 0.34, p = 0.047) and between AIx and CSURI (r = 0.35, p = 0.044). Patients with the "early" scleroderma pattern had lower AIx values compared with "active" (20.5 ± 11.4 vs 34.1 ± 11.5%, p = 0.02) and "late" (20.5 ± 11.4 vs 33.4 ± 8.8%, p = 0.05) patterns. No other significant correlations were found between macrovascular biomarkers (PWV, carotid IMT, systolic and diastolic central blood pressure) and the capillaroscopic measurements. CONCLUSIONS: These data suggest that arterial stiffness (as assessed by AIx-75) correlates with microvascular damage in patients with SSc.


Assuntos
Artérias/fisiopatologia , Angioscopia Microscópica/métodos , Escleroderma Sistêmico/fisiopatologia , Rigidez Vascular/fisiologia , Adulto , Idoso , Pressão Sanguínea/fisiologia , Capilares/patologia , Capilares/fisiopatologia , Espessura Intima-Media Carotídea , Estudos de Casos e Controles , Estudos Transversais , Progressão da Doença , Feminino , Humanos , Masculino , Microcirculação , Pessoa de Meia-Idade , Análise de Onda de Pulso , Escleroderma Sistêmico/diagnóstico , Escleroderma Sistêmico/patologia , Úlcera Cutânea/diagnóstico , Úlcera Cutânea/fisiopatologia
17.
Khirurgiia (Mosk) ; (10): 43-49, 2019.
Artigo em Russo | MEDLINE | ID: mdl-31626238

RESUMO

OBJECTIVE: To analyze the effectiveness of complex therapy of necrotizing infection using the original method of stimulation of angiogenesis in patients with chronic arterial insufficiency of the lower extremities. MATERIAL AND METHODS: In 53 patients, operations were performed using the proposed technologies for stimulation of angiogenesis. A control group consisting of 56 patients was formed to compare the results of treatment. They had standard vascular therapy for the correction of ischemia. Morphological studies of the muscles of the lower extremities included assessment of capillary bed density and spatial orientation of the capillaries before and after treatment. Computed angiography of the lower extremities followed by calculation of perfusion index was performed to assess changes in the microvasculature. Clinical evaluation of the results was carried out using R. Rutherford scale. RESULTS: Revascularization resulted significant augmentation of capillary bed density and the number of functioning capillaries in muscular tissue. This was accompanied by increased perfusion index and TcPO2 values. The effect of treatment is observed in 12-14 days after surgery and persists for a long time. The best outcomes are found in patients with ischemia grade IIb-III. Incidence of lower limb amputations was more than 2 times lower in the main group compared with the control group. CONCLUSION: Combined stimulation of angiogenesis including mechanical tunneling of the muscles of the affected limb and administration of platelet rich plasma is effective procedure. This method does not require complex equipment and may be used in the treatment of patients with complications of chronic lower limb ischemia and contraindicated direct arterial reconstruction.


Assuntos
Arteriopatias Oclusivas/cirurgia , Capilares/cirurgia , Extremidade Inferior/irrigação sanguínea , Extremidade Inferior/cirurgia , Necrose/cirurgia , Neovascularização Fisiológica , Arteriopatias Oclusivas/fisiopatologia , Capilares/fisiopatologia , Humanos , Infecções/fisiopatologia , Infecções/terapia , Isquemia/fisiopatologia , Isquemia/cirurgia , Extremidade Inferior/fisiopatologia , Microvasos/fisiopatologia , Microvasos/cirurgia , Músculo Esquelético/fisiopatologia , Músculo Esquelético/cirurgia , Necrose/etiologia , Necrose/fisiopatologia , Plasma Rico em Plaquetas/fisiologia , Resultado do Tratamento
18.
Ophthalmic Surg Lasers Imaging Retina ; 50(9): e222-e228, 2019 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-31589762

RESUMO

BACKGROUND AND OBJECTIVE: Geographic atrophy (GA) involves the progressive loss of retinal pigment epithelium (RPE), photoreceptors, and choriocapillaris (CC). CC flow within a GA area is severely impaired in patients with atrophic age-related macular degeneration. The aim of this study was to compare GA area measured on optical coherence tomography angiography (OCTA) (CC nonperfusion area) and on fundus autofluorescence (FAF). PATIENTS AND METHODS: In this prospective, observational, cross-sectional study, OCTA and FAF were performed in patients with GA. On OCTA (CC segmentation), the CC nonperfusion area was measured manually using calipers. On FAF, GA was manually delimited, and the total surface was obtained using Region Finder software. The primary endpoint was to compare the CC nonperfusion area measured on OCTA and on the gold standard method (FAF). RESULTS: Forty eyes of 34 patients with a mean age of 82.63 years ± 9.21 years (range: 66 years to 100 years) were included. The mean GA area measured on FAF and OCTA was, respectively, 2.184 ± 3.045 mm2 and 2.349 ± 3.237 mm2 (P = .035). The mean difference was 0.165 ± 0.290 mm2. A strong correlation was found between both measurements (r = 0.97; P < .0001; confidence interval: 0.98-0.99), although the CC nonperfusion area was larger than the GA area on FAF (P = .035). CONCLUSIONS: In this study, the authors showed that in GA, the CC nonperfusion area correlates linearly with the GA area assessed by FAF. Also, the CC nonperfusion area is larger than the GA area measured by FAF, suggesting that CC degeneration could occur before RPE degeneration in GA. [Ophthalmic Surg Lasers Imaging Retina. 2019;50:e222-e228.].


Assuntos
Angiofluoresceinografia , Atrofia Geográfica/diagnóstico por imagem , Imagem Óptica , Epitélio Pigmentado da Retina/patologia , Tomografia de Coerência Óptica , Idoso , Idoso de 80 Anos ou mais , Capilares/fisiopatologia , Corioide/irrigação sanguínea , Neovascularização de Coroide/diagnóstico por imagem , Estudos Transversais , Feminino , Atrofia Geográfica/fisiopatologia , Humanos , Masculino , Estudos Prospectivos
19.
Invest Ophthalmol Vis Sci ; 60(13): 4310-4318, 2019 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-31622467

RESUMO

Purpose: To evaluate whether retinal capillary nonperfusion is found predominantly adjacent to arteries or veins in eyes with diabetic retinopathy (DR). Methods: Sixty-three eyes from 44 patients with proliferative DR (PDR) or non-PDR (NPDR) were included. Images (12 × 12-mm) foveal-centered optical coherence tomography (OCT) angiography (OCTA) images were taken using the Zeiss Plex Elite 9000. In 37 eyes, widefield montages with five fixation points were also obtained. A semiautomatic algorithm that detects nonperfusion in full-retina OCT slabs was developed, and the percentages of capillary nonperfusion within the total image area were calculated. Retinal arteries and veins were manually traced. Based on the shortest distance, nonperfusion pixels were labeled as either arterial-side or venous-side. Arterial-adjacent and venous-adjacent nonperfusion and the A/V ratio (arterial-adjacent nonperfusion divided by venous-adjacent nonperfusion) were quantified. Results: Twenty-two eyes with moderate NPDR, 16 eyes with severe NPDR, and 25 eyes with PDR were scanned. Total nonperfusion area in PDR (median: 8.93%) was greater than in moderate NPDR (3.49%, P < 0.01). Arterial-adjacent nonperfusion was greater than venous-adjacent nonperfusion for all stages of DR (P < 0.001). The median A/V ratios were 1.93 in moderate NPDR, 1.84 in severe NPDR, and 1.78 in PDR. The A/V ratio was negatively correlated with the total nonperfusion area (r = -0.600, P < 0.0001). The results from the widefield montages showed similar patterns. Conclusions: OCTA images with arteries and veins traced allowed us to estimate the nonperfusion distribution. In DR, smaller nonperfusion tends to be arterial-adjacent, while larger nonperfusion tends toward veins.


Assuntos
Retinopatia Diabética/fisiopatologia , Isquemia/fisiopatologia , Artéria Retiniana/fisiopatologia , Veia Retiniana/fisiopatologia , Idoso , Capilares/fisiopatologia , Estudos Transversais , Diabetes Mellitus Tipo 1/complicações , Diabetes Mellitus Tipo 2/complicações , Retinopatia Diabética/diagnóstico por imagem , Feminino , Angiofluoresceinografia , Humanos , Isquemia/diagnóstico por imagem , Edema Macular/diagnóstico por imagem , Edema Macular/fisiopatologia , Masculino , Pessoa de Meia-Idade , Artéria Retiniana/diagnóstico por imagem , Veia Retiniana/diagnóstico por imagem , Estudos Retrospectivos , Tomografia de Coerência Óptica/métodos
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