Abnormalities of the lymphatic system and impaired fluid clearance in patients with heart failure with preserved ejection fraction

Background Coronary and skeletal muscle microvascular dysfunction have been proposed as main factors in the pathogenesis of Heart Failure with Preserved Ejection Fraction (HFpEF). However, assessment of systemic arterial function has only been indirect thus far; most importantly, no direct link between systemic microvasculature and congestion, one of the core characteristics of the syndrome, has yet been investigated. Purpose To provide direct functional and anatomical characterisation of the systemic microvasculature and to explore in vivo parameters of capillary fluid extravasation and lymphatic clearance in HFpEF. Methods In 16 patients with HFpEF and 16 age- and sex-matched healthy controls (72±6 and 68±5 years, respectively) we determined peripheral microvascular filtration coefficient (proportional to vascular permeability and area) and isovolumetric pressure (above which lymphatic drainage cannot compensate for fluid extravasation) by venous occlusion plethysmography and collected a skin biopsy for vascular immunohistochemistry and gene expression analysis (TaqMan). Additionally, we measured brachial flow-mediated dilatation (FMD) and assessed by wire myography the vascular function of resistance arteries isolated from gluteal subcutaneous fat biopsies. Results Skin biopsies in patients with HFpEF showed rarefaction of small blood vessels (82±31 vs 112±21 vessels/mm2; p=0.003) and in ex-vivo analysis (n=6/group) we found defective relaxation of peripheral resistance arteries (p<0.001). Accordingly, post-ischaemic hyperaemic response (fold-change vs baseline, 4.6±1.6 vs 6.7±1.7; p=0.002) and FMD (3.9±2.1 vs 5.6±1.5%; p=0.014) were found to be reduced in patients with HFpEF compared to controls. In the skin of patients with HFpEF we also observed a reduced number (85±27 vs 130±60 vessels/mm2; p=0.012) but larger average diameter of lymphatic vessels (42±19 vs 26±9 μm2; p=0.007) compared to control subjects. These changes were paralleled by reduced expression of LYVE1 (p<0.05) and PROX1 (p<0.001), key determinants of lymphatic differentiation and function. Whilst patients with HFpEF had reduced peripheral capillary fluid extravasation compared to controls (microvascular filtration coefficient, leg 33.1±13.3 vs 48.4±15.2, p<0.01; trend for arm 49.9±20.5 vs 66.3±30.1, p=0.09), they had lower lymphatic clearance (isovolumetric pressure: leg 22±4 vs 16±4 mmHg, p<0.005; arm 25±5 vs 17±4 mmHg, p<0.001). Conclusions We provide direct evidence of systemic dysfunction and rarefaction of small blood vessels in patients with HFpEF. Despite a reduced microvascular filtration coefficient, which is in keeping with microvascular rarefaction, the clearance of extravasated fluid in HFpEF is limited by an anatomically and functionally defective lymphatic system. Funding Acknowledgement Type of funding source: Foundation. Main funding source(s): British Heart Foundation Centre of Research Excellence Award

FORMALIZATION CONCEPT OF A CAPILLARY OF THE CIRCULAR TRANSVERSE SECTION TAKING INTO ACCOUNT THE CONTACT WETTING ANGLE

Расчеты процессов распределения и переноса жидкости в пористых средах основаны на учете ее капиллярных свойств в поровом пространстве. От степени заполнения капиллярной жидкостью порового пространства зависит интенсивность протекающих в нем процессов. Капиллярной жидкостью заполняются поры только малого размера. Поры большего размера остаются незаполненными. Однако отсутствует аналитическое обоснование величины поперечного размера поры с учетом краевого угла смачивания, больше которого она не может заполняться жидкостью за счет капиллярных сил. С этих позиций рассмотрено понятие предельного поперечного размера капилляра в условиях его смачивания жидкостью. Получена расчетная формула наибольшего поперечного размера модельных пор круглого поперечного сечения, относящего их к капиллярам, с учетом величины краевого угла смачивания. Предложено использовать параметр, названный удельным поверхностным натяжением λ, для оценки влияния комплекса физических констант жидкостей на величину предельного поперечного размера капилляра. Параметр λ представляет отношение коэффициента поверхностного натяжения жидкости к силе тяжести ее единичного объема. По полученной формуле для ряда жидкостей выполнены расчеты капилляров предельных размеров как функций углов смачивания. Результаты исследований могут быть использованы для повышения эффективности расчетов тепломассообмена в пористых средах в пищевых производствах и других аналогичных задач. The calculations of the processes of saturation and transfer of fluid in porous media are based on taking into account of its capillary properties in the pore space. The intensity of the processes occurring in the pore space depends on the degree of filling of it by capillary liquid. Only small pores are filled with capillary fluid. Larger pores remain unfilled. However, there is no analytical justification for the transverse pore size taking into account the wetting angle of the meniscus, more than which the pore cannot be filled with liquid by capillary forces. With this in mind, the concept of the limiting transverse size of a capillary for a liquid is considered. The calculated formula for the largest transverse size of model pores of circular transverse section, which relates them to capillaries, taking into account the value of the contact wetting angle, is obtained. It is proposed to use a parameter called specific surface tension λ to evaluate the effect of a complex of physical constants of liquids on the value of the maximum transverse size of the capillary. The parameter λ represents the ratio of the surface tension coefficient of a liquid to the gravity of its unit volume. According to the obtained formula for a number of liquids, calculations of capillaries of limit sizes as functions of contact wetting angles are performed. The research results can be used to improve the efficiency of calculations of heat and mass transfer in porous media in food production and other similar tasks.

REPÓRTER RECORD INVESTIGAÇÃO E VIOLÊNCIA DE GÊNERO: VISIBILIDADE DAS RELAÇÕES ASSIMÉTRICAS ENTRE PODERES E SABERES SOBRE MULHERES KALUNGAS | REPORTER RECORD INVESTIGATION AND GENDER VIOLENCE: VISIBILITY OF ASYMMETRIC RELATIONS BETWEEN POWERS AND ...

<p>Objetivamos com esta pesquisa descrever, interpretar e analisar, por meio da reportagem do Programa Repórter Record Investigação, exibida no dia 15 de junho de 2015, como a ordem sócio-histórica contemporânea visibiliza a condição desigual de gênero na contemporaneidade, além de identificar as articulações discursivas com as correntes ideológicas que subjazem suas posições-sujeito. O referencial teórico da Análise do Discurso de linha francesa é mobilizado como metodologia para investigar recortes de imagens da reportagem e transcrições do depoimento de vítimas, agressores e repórteres como corpus de pesquisa. Utilizamos as concepções de discurso de Bakhtin (2006), poder e biopoder em Foucault (2002, 2003, 2016); pesquisas sobre a desigualdade social (IBGE 2009, LEAL, 2015); e estudos sobre gênero (HOOKS, 1995; RAGO, 2008; MUNANGA, 2006).<em> </em>A análise é necessária para a compreensão de acontecimentos discursivos como elementos responsáveis pela construção de uma ordem sócio-histórica, uma vez que os discursos são tomados como práticas sociais, historicamente determinados, que constituem os sujeitos e seus respectivos objetos. Como resultados, constatamos que as violências doméstica e sexual estão entremeadas por significados e constituições identitárias que derivam da articulação entre as dimensões de gênero e de raça. Concluímos que a resistência e a luta das meninas Kalungas demonstram como o poder, conforme a concepção foucaultiana, é capilar, fluido, em relação às práticas de subjetivação dissonantes, e como o discurso feminista possibilita, na contemporaneidade, a espetacularização da condição de inferioridade como valor social, mas para visibilizar, e não para reiterar, as relações assimétricas, com a meta de apagá-las das práticas discursivas opressoras.</p><p><strong>Palavras-chave</strong>: Violência; Poder; Desigualdade de gênero; Quilombo Kalunga.</p><p><strong><em>Abstract:</em></strong><em> The objective of this research is to describe, interpret and analyze, through the report of the Reporter Record Research Program, presented on June 15, 2015, how contemporary socio-historical order visibilizes the unequal gender condition in contemporaneity, in addition to identifying articulations discursives with the ideological currents that underlie their subject-positions. The theoretical reference of the French Speech Analysis is mobilized as a methodology to investigate clippings of reportage images and transcriptions of the testimony of victims, aggressors and reporters as a corpus of research. We use Bakhtin's conceptions of discourse (2006), power and biopower in Foucault (2002, 2003, 2016); research on social inequality (IBGE 2009, LEAL, 2015); and studies on gender (HOOKS, 1995; RAGO, 2008; MUNANGA, 2006). The analysis is necessary for the understanding of discursive events as elements responsible for the construction of a socio-historical order, since the discourses are taken as social practices, historically determined, that constitute the subjects and their respective objects. As results, we find that domestic and sexual violence are interspersed with identity meanings and constitutions that derive from the articulation between the dimensions of gender and race. We conclude that the Kalungas girls' resistance and struggle demonstrate how power, according to the Foucaultian conception, is capillary, fluid, in relation to dissonant subjectivation practices, and how feminist discourse makes it possible in contemporary times to spectacularize the condition of inferiority as social value, but to visualize, not to reiterate, asymmetrical relations, with the goal of erasing them from oppressive discursive practices. </em></p><p><strong><em>Keywords:</em></strong><em> Violence; Power; Gender inequality; Quilombo Kalunga</em></p>