Morphological and Functional Analysis of Cardiac Ameliorations in Elderly Rats Supplemented with a Magnolol Extract Complex / Análisis Morfológico y Funcional de las Mejoras Cardíacas en Ratas Ancianas Suplementadas con un Complejo de Extracto de Magnolol

SUMMARY: Magnolia bark extract supplementation has an anti-oxidative role in mammalians. However, its role in physiological aged-associated heart insufficiency is not known yet. Therefore, we investigated the effects of a magnolia bark complex, including magnolol and honokiol components (MAHOC), in elderly rat hearts (24-month-old aged group). One group of aged rats was supplemented with MAHOC (400 mg/kg/d, for 12 weeks) besides the standard rat diet while the second group of elderly rats and adult rats (to 6-month- old adult-group) were only fed with the standard rat diet. The morphological analysis using light microscopy has shown marked myofibrillar losses, densely localized fibroblasts, vacuolizations, infiltrated cell accumulations, and collagen fibers in the myocardium of the elderly rats compared to the adults. We also detected a markedly increased amount of degenerated cardiomyocytes including the euchromatic nucleus. The MAHOC supplementation of the elderly rats provided marked ameliorations in these abnormal morphological changes in the heart tissue. Furthermore, electrophysiological analysis of electrocardiograms (ECGs) in the supplemented group showed significant attenuations in the prolonged durations of P-waves, QRS-complexes, QT-intervals, and low heart rates compared to the unsupplemented elderly group. The biochemical analysis also showed significant attenuations in the activity of arylesterase and total antioxidant status in the myocardium of the supplemented group. We further determined significant attenuations in the activity of a mitochondrial enzyme succinate dehydrogenase, known as a source of reactive oxygen species (ROS), and the decreased level of ATP/ADP in the heart homogenates of the supplemented group. Moreover, under in vitro conditions by using an aging-mimicked cardiac cell line induced by D-galactose, we demonstrated that MAHOC treatment could provide prevention of depolarization in mitochondria membrane potential and high-level ROS production. Overall, our data presented significant myocardial ameliorations in physiological aging-associated morphological alterations parallel to the function and biochemical attenuations with MAHOC supplementation, at most, through recoveries in mitochondria.

La suplementación con extracto de corteza de magnolia tiene un papel antioxidante en los mamíferos, sin embargo, su rol en la insuficiencia cardíaca asociada al envejecimiento fisiológico aún no se conoce. Por lo anterior, investigamos los efectos de un complejo de corteza de magnolia, incluidos los componentes magnolol y honokiol (MAHOC), en corazones de ratas seniles (grupo de edad de 24 meses). La alimentación de grupo de ratas seniles se complementó con MAHOC (400 mg/kg/d, durante 12 semanas) además de la dieta estándar, mientras que el segundo grupo de ratas seniles y ratas adultas (hasta el grupo de adultos de 6 meses) solo recibió la dieta estándar para ratas. El análisis morfológico mediante microscopía óptica ha mostrado marcadas pérdidas miofibrilares, fibroblastos densamente localizados, vacuolizaciones, acumulaciones de células infiltradas y fibras de colágeno en el miocardio de las ratas seniles en comparación con las adultas. También detectamos una cantidad notablemente mayor de cardiomiocitos degradados, incluido el núcleo eucromático. La suplementación con MAHOC de las ratas seniles proporcionó mejoras marcadas en estos cambios morfológicos anormales en el tejido cardiaco. Por otra parte, el análisis de los electrocardiogramas (ECG) en el grupo suplementado mostró atenuaciones significativas en las duraciones prolongadas de las ondas P, los complejos QRS, los intervalos QT y las frecuencias cardíacas bajas, en comparación con el grupo de ratas seniles sin suplementación alimenticia. El análisis bioquímico también mostró atenuaciones significativas en la actividad de la arilesterasa y el estado antioxidante total en el miocardio del grupo suplementado. Determinamos además atenuaciones significativas en la actividad de la enzima mitocondrial succinato deshidrogenasa, conocida como fuente de especies reactivas de oxígeno (ROS), y la disminución del nivel de ATP/ADP en los homogeneizados de corazón del grupo suplementado. Además, en condiciones in vitro mediante el uso de una línea de células cardíacas, imitando el envejecimiento inducido por D- galactosa, demostramos que el tratamiento con MAHOC podría prevenir la despolarización en el potencial de membrana de las mitocondrias y la producción de ROS de alto nivel. En general, nuestros datos presentaron mejoras miocárdicas significativas en alteraciones morfológicas asociadas con el envejecimiento fisiológico paralelas a la función y atenuaciones bioquímicas con la suplementación con MAHOC, como máximo, a través de recuperaciones en las mitocondrias.

Microcirculatory changes as a hallmark of aging in the heart and kidney / Cambios microcirculatorios como sello distintivo del envejecimiento en el corazón y riñón

SUMMARY: Changes in the microcirculation of multiple tissues and organs have been implicated as a possible mechanism in physiological aging. In particular, vascular endothelial growth factor is a secretory protein responsible for regulating angiogenesis via altering endothelial proliferation, survival, migration, extracellular matrix degradation and cell permeability. The aim of the present study was to evaluate the role of vascular endothelial growth factor in the progression of morphological alterations caused by physiological aging in the heart and kidney and to examine its relation to changes in capillary density. We used two age groups of healthy Wistar rats - 6- and 12-month- old. The expression of vascular endothelial growth factor was examined through immunohistochemistry and immunofluorescence and assessed semi-quantitatively. Changes in capillary density were evaluated statistically and correlated with the expression of vascular endothelial growth factor. We reported stronger immunoreactivity for vascular endothelial growth factor in the left compared to the right ventricle and also observed an increase in its expression in both ventricles in older animals. Contrasting results were reported for the renal cortex and medulla. Capillary density decreased statistically in all examined structures as aging progressed. The studied correlations were statistically significant in the two ventricles in 12-month-old animals and in the renal cortex of both age groups. Our results shed light on some changes in the microcirculation that take place as aging advances and likely contribute to impairment in the function of the examined organs.

Los cambios en la microcirculación de múltiples tejidos y órganos se han implicado como un posible mecanismo en el envejecimiento fisiológico. En particular, el factor de crecimiento endotelial vascular es una proteína secretora responsable de regular la angiogénesis mediante la alteración de la proliferación endotelial, la supervivencia, la migración, la degradación de la matriz extracelular y la permeabilidad celular. El objetivo del presente estudio fue evaluar el papel del factor de crecimiento del endotelio vascular en la progresión de las alteraciones morfológicas causadas por el envejecimiento fisiológico en el corazón y riñón y examinar su relación con los cambios en la densidad capilar. Utilizamos dos grupos de ratas Wistar sanas: 6 y 12 meses de edad. La expresión del factor de crecimiento del endotelio vascular se examinó mediante inmunohistoquímica e inmunofluorescencia y se evaluó semicuantitativamente. Los cambios en la densidad capilar se evaluaron estadísticamente y se correlacionaron con la expresión del factor de crecimiento del endotelio vascular. Informamos una inmunorreactividad más fuerte para el factor de crecimiento endotelial vascular en el ventrículo izquierdo en comparación con el derecho y también observamos un aumento en su expresión en ambos ventrículos en animales mayores. Se informaron resultados contrastantes para la corteza renal y la médula. La densidad capilar disminuyó estadísticamente en todas las estructuras examinadas a medida que avanzaba el envejecimiento. Las correlaciones estudiadas fueron estadísticamente significativas en los dos ventrículos en animales de 12 meses y en la corteza renal de ambos grupos de edad. Nuestros resultados arrojan luz sobre algunos cambios en la microcirculación que tienen lugar a medida que avanza el envejecimiento y probablemente contribuyan a un deterioro en la función de los órganos examinados.

Single-cell analysis reveals an Angpt4-initiated EPDC-EC-CM cellular coordination cascade during heart regeneration

Mammals exhibit limited heart regeneration ability, which can lead to heart failure after myocardial infarction. In contrast, zebrafish exhibit remarkable cardiac regeneration capacity. Several cell types and signaling pathways have been reported to participate in this process. However, a comprehensive analysis of how different cells and signals interact and coordinate to regulate cardiac regeneration is unavailable. We collected major cardiac cell types from zebrafish and performed high-precision single-cell transcriptome analyses during both development and post-injury regeneration. We revealed the cellular heterogeneity as well as the molecular progress of cardiomyocytes during these processes, and identified a subtype of atrial cardiomyocyte exhibiting a stem-like state which may transdifferentiate into ventricular cardiomyocytes during regeneration. Furthermore, we identified a regeneration-induced cell (RIC) population in the epicardium-derived cells (EPDC), and demonstrated Angiopoietin 4 (Angpt4) as a specific regulator of heart regeneration. angpt4 expression is specifically and transiently activated in RIC, which initiates a signaling cascade from EPDC to endocardium through the Tie2-MAPK pathway, and further induces activation of cathepsin K in cardiomyocytes through RA signaling. Loss of angpt4 leads to defects in scar tissue resolution and cardiomyocyte proliferation, while overexpression of angpt4 accelerates regeneration. Furthermore, we found that ANGPT4 could enhance proliferation of neonatal rat cardiomyocytes, and promote cardiac repair in mice after myocardial infarction, indicating that the function of Angpt4 is conserved in mammals. Our study provides a mechanistic understanding of heart regeneration at single-cell precision, identifies Angpt4 as a key regulator of cardiomyocyte proliferation and regeneration, and offers a novel therapeutic target for improved recovery after human heart injuries.

Is the Wistar Rat a more Suitable Normotensive Control for SHR to Test Blood Pressure and Cardiac Structure and Function?

Abstract Background: There are divergences in the literature regarding the experimental model (Wistar-WIS or Wistar Kyoto-WKY) to be used as a Spontaneously Hypertensive Rat (SHR) control. The characterization of these models in terms of cardiovascular parameters provides researchers with important tools at the time of selection and application in scientific research. Objective: The aim of this study was to evaluate the use of WIS and WKY as a Spontaneously Hypertensive Rat (SHR) control by assessing the long-term behavior of blood pressure and cardiac structure and function in these strains. Methods: To this end, WIS, WKY, and SHR underwent longitudinal experiments. Blood pressure and body mass were measured every two weeks from the 8th to the 72nd. Echocardiographic analysis was performed in all groups with 16, 48, and 72 weeks of life. After having applied the normality test, the Two-Way ANOVA of repeated measures followed by the Tukey post hoc test was used. A significance level of 5% was established. Results: The WIS group showed higher body mass (p<0.05), while the WKY and SHR presented higher body mass variation over time (p<0.05). SHR exhibited increased values of systolic, diastolic, and mean blood pressure when compared to WKY and WIS, whereas the WKY generally showed higher values than WIS (p<0.05). Regarding the cardiac function, SHR showed reduced values, while the WKY presented an early decrease when compared to WIS with aging (p<0.05). Conclusion: WIS is a more suitable normotensive control for SHR than WKY in experiments to test blood pressure and cardiac structure and function.

Estratificação de Risco e Avaliação da Atividade Simpática Cardíaca Utilizando Imagem Miocárdica com [123I] MIBG na Denervação Renal / Risk Stratification and Cardiac Sympathetic Activity Assessment Using Myocardial [123I] MIBG Imaging in Renal Denervation

Resumo A hiperativação do sistema nervoso simpático desempenha um papel central na fisiopatologia da hipertensão. O objetivo deste estudo foi avaliar a atividade simpática cardíaca e investigar o papel da cintigrafia miocárdica com metaiodobenzilguanidina com 123I ([123I] MIBG) na estratificação de risco cardiovascular de pacientes com hipertensão resistente tratados com denervação renal (DR). Dezoito pacientes foram incluídos neste estudo prospectivo (média de idade de 56 ± 10 anos, 27,8% mulheres). Ecocardiograma transtorácico, análise geral do sangue e cintilografia miocárdica com [(123I) MIBG] foram realizados antes e seis meses após a DR. Um paciente era considerado respondedor (R) se uma diminuição ≥ 5 mmHg na pressão arterial sistólica (PAS) média ambulatorial fosse observada no seguimento de seis meses. 66,7% dos pacientes foram R (diminuição na PAS de 20,6 ± 14,5 mmHg, vs. menos 8 ± 11,6 mmHg em não-respondedores (NR), p = 0,001). A relação coração-mediastino (RCM) inicial foi significativamente menor na linha basal no grupo R (1,6 ± 0,1 vs. 1,72 ± 0,1, p <0,02), mas semelhante em seis meses. Considerando os dois momentos no tempo, o grupo R teve valores iniciais de RCM mais baixos do que o grupo NR (p <0,05). Tanto o RCM tardio quanto a taxa de washout foram idênticos e nenhuma correlação significativa entre a resposta à DR ou qualquer índice de imagem com MIBG foi encontrada. A denervação renal efetivamente reduziu a pressão arterial na maioria dos pacientes, mas a imagem com [123I] MIBG não foi útil na previsão da resposta. Entretanto, houve evidência de overdrive do sistema nervoso simpático e, tanto a RCM inicial quanto tardia estavam reduzidas em geral, provavelmente colocando essa população em um risco maior de eventos adversos.

Abstract Hyperactivation of the sympathetic nervous system plays a central role in the pathophysiology of hypertension. The aim of this study was to assess cardiac sympathetic activity and investigate the role of myocardial123I-labelled meta-iodo benzyl guanidine ([123I] MIBG) scintigraphy in cardiovascular risk stratification of patients with resistant hypertension treated with renal denervation (RDN). Eighteen patients were included in this prospective study (mean age 56 ± 10 years old, 27.8% females). Transthoracic echocardiogram, general blood analysis and myocardial ([123I] MIBG scintigraphy were performed before and six-months after RDN. A patient was considered a responder (R) if a drop ≥ 5mmHg on mean systolic ambulatory blood pressure (BP) monitoring was observed at the six-month follow-up. 66.7% of patients were R (drop in systolic BP of 20.6 ± 14.5mmHg, vs minus 8 ± 11.6mmHg in non-responders (NR), p=0.001). Early heart-mediastinum ratio (HMR) was significantly lower at baseline in the R group (1.6 ± 0.1 vs 1.72 ± 0.1, p<0.02) but similar at six months. Considering both instants in time, the R group had lower early HMR values than the NR group (p<0.05). Both the late HMR and the washout rate were identical and no significant correlation between response to RDN or any MIBG imaging index was found. Renal denervation effectively lowered blood pressure in the majority of patients but [123I] MIBG was not useful in predicting the response. However, there was evidence of sympathetic overdrive and, both early and late HMR were overall reduced, probably putting this population at a higher risk of adverse events.

Research Progress on Vector Flow Imaging of Cardiac Ultrasound / 中国医疗器械杂志

Echocardiogram is vital for the diagnosis of cardiac disease. The heart has complex hemodynamics requiring an advanced ultrasound imaging mode. Cardiac ultrasound vector flow imaging is capable of measuring the actual magnitude and direction of the blood flow velocity, obtaining the quantitative parameters of hemodynamics, and then providing more information for clinical research and diagnosis. This study mainly reviewed several different vector flow imaging techniques for cardiac flow and presented the implementation difficulties, and proposed a diverging wave based high frame rate cardiac ultrasound vector flow imaging. The study discussed the limitation of current ultrasound technology used in the cardiac flow measurement, analyzed and demonstrated the specific reasons for these implementation difficulties and the potential future development.

Effects of concurrent training and intermittent fasting on structural, functional, and morphological parameters of the heart / Efectos del entrenamiento concurrente y el ayuno intermitente sobre los parámetros estructurales, funcionales y morfológicos del corazón

SUMMARY: Intermittent fasting and concurrent training have been performed frequently to decrease body mass. The aim was to analyze the effects of concurrent training (CT) and intermittent fasting (IF) on cardiac remodeling. In total, 39 adult male Wistar rats were used, divided into four groups: control (C [n = 12]), fasting control (FC [n = 11]), training (T [n = 8]) and fasting training (FT [n = 8]). The CT protocol was composed of 12 sessions, with 30 minutes of aerobic training (AT) in the liquid medium at an intensity of 80 % of the anaerobic threshold, followed by resistance training (RT) with 4 series of 10 aquatic jumps at an corresponding to 50 % of body weight. The IF period was established at 12/12 hours, starting at 9 p.m. and ending at 9 a.m. Echocardiographic analyzes were performed before and after the intervention and, at the end of the experiment, samples of the cardiac tissue were collected to perform the histological analyses. Data analysis was performed using the Shapiro-Wilk tests, Analysis of Variance - ANOVA with Tukey's post-test, and Kruskal- Wallis with Dunn's post-test. All procedures assumed an error of 5 % (p<0.05). Neither group showed alterations in the functional (min. p= 0.12 - max. p= 0.83) and structural parameters of the heart (min. p=0.31 - max. p=0.83). A decrease was observed in the area of cardiomyocytes in the T (p=0.001) and FT groups (p=0.001). The CT and IF did not alter the functional and structural parameters of the heart, but did cause a decrease in the area of the cardiomyocytes.

RESUMEN: El ayuno intermitente y el entrenamiento concurrente se han realizado frecuentemente para disminuir la masa corporal. El objetivo fue analizar los efectos del entrenamiento concurrente (EC) y el ayuno intermitente (AI) sobre el remodelado cardíaco. En total, se utilizaron 39 ratas Wistar macho adultas, divididas en cuatro grupos: control (C [n = 12]), control en ayunas (AC [n = 11]), entrenamiento (E [n = 8]) y ayuno, entrenamiento [n = 8]). El protocolo de EC estuvo compuesto de 12 sesiones, con 30 minutos de entrenamiento aeróbico (EA) en el medio líquido a una intensidad del 80 % del umbral anaeróbico, seguido de entrenamiento de resistencia (ER) con 4 series de 10 saltos acuáticos correspondiente al 50 % del peso corporal. El período de AI se estableció a las 12/12 horas, a partir de las 21:00 horas. finalizando a las 9 a.m. Se realizaron análisis ecocardiográficos antes y después de la intervención y, al finalizar el experimento, se reco- lectaron muestras del tejido cardíaco para realizar los análisis histológicos. El análisis de los datos se realizó mediante las pruebas de Shapiro-Wilk, Análisis de Varianza - ANOVA con pos test de Tukey y Kruskal-Wallis con postest de Dunn. Todos los procedimientos asumieron un error del 5 % (p <0,05). No se observaron alteraciones funcionales de los grupos (mín. P = 0,12 - máx. P = 0,83) y estructurales del corazón (mín. P = 0,31 - máx. P = 0,83). Se observó una disminución en el área de cardiomiocitos en los grupos E (p = 0,001) y EA (p = 0,001). La EC y la AI no alteraron los parámetros funcionales y estructurales del corazón, pero sí provocaron una disminución del área de los cardiomiocitos.

Trascendencia de los exosomas en la cardiología: heraldos de la cardioprotección / Significance of exosomes in cardiology: heralds of cardioprotection

Resumen Los exosomas tienen un papel clave en la comunicación intercelular. Debido a sus múltiples interacciones, estas estructuras cumplen con el papel de «mensajeros¼ de forma dinámica, transportando su contenido a células blanco específicas y generando nuevas señales celulares. En este artículo se describen algunas de las proteínas, lípidos y ácidos nucleicos que son transportados por estas vesículas y que se han relacionado con cardioprotección, con la finalidad de proporcionar información y generar interés sobre la relevancia de los exosomas como posibles blancos diagnósticos y terapéuticos.

Abstract Exosomes have a key role in intercellular communication. Due to their multiple interactions, these structures fulfill the role of “messengers” in a dynamic way, transporting their content to target-specific cells and generating new cellular signals. This article describes some of the proteins, lipids and nucleic acids that are transported by these vesicles and that have been related to cardioprotection, in order to provide information and generate interest in the relevance of exosomes as possible diagnostic and therapeutic targets.

Efeitos ecocardiográficos da adesão a exercícios físicos em idosos: resultados da coorte AGA@4life / Echocardiographic effects of adherence to physical exercise in older adults: results from the AGA@4life cohort

INTRODUÇÃO: O envelhecimento associa-se a alterações na estrutura e função do coração, havendo benefícios da prática de exercício físico no retardamento dessas alterações. OBJETIVOS: Caracterizar as alterações ecocardiográficas de uma população idosa submetida à intervenção multidisciplinar incluindo programa de exercício físico adaptado e avaliar as diferenças entre os melhores e piores níveis de adesão à atividade física. MÉTODOS: Estudo de intervenção não randomizado com um grupo de idosos da coorte AGA@4life. Realizaram-se duas avaliações ecocardiográficas, uma basal e outra após a implementação de um programa de intervenção multidisciplinar com um componente de exercício físico por três meses consecutivos. Os participantes foram divididos em dois grupos: grupo 1, com baixa adesão ao programa de exercício físico (< 20% das sessões); grupo 2, com elevada adesão ao programa de exercício físico (> 90% das sessões). RESULTADOS: Na avaliação basal, identificaram-se alterações ecocardiográficas associadas ao envelhecimento ­ 89,2% (n = 33) de casos com fibrose aórtica, 73% (n = 27) de casos com fibrose mitral, 51,2% (n = 19) de casos com regurgitação aórtica e 68% (n = 25) de casos com regurgitação mitral. Após a intervenção, verificaram-se variações significativas em diversos parâmetros funcionais no grupo 2, sobretudo nas velocidades máximas das ondas E' (p = 0,016) e S (p = 0,02) da válvula mitral e da onda E' da válvula tricúspide (p = 0,027). Observaram-se ainda modificações estruturais no grupo 2, nomeadamente redução na espessura parietal relativa (p = 0,033) e no diâmetro diastólico (p = 0,041) do ventrículo esquerdo. CONCLUSÕES: O exercício físico adaptado e implementado no âmbito de um programa de intervenção multidisciplinar constitui uma ferramenta não farmacológica útil para a manutenção de função e estrutura cardíacas adequadas no idoso.

INTRODUCTION: Aging is associated with changes in heart structure and function, and there are benefits of physical exercise in delaying these changes. OBJECTIVES: To characterize the heart of a geriatric cohort at a structural and functional level, and to evaluate the potential cardiac benefits of a personalized exercise intervention program. METHODS: Non-randomized intervention study, including a group of old adults from the AGA@4life cohort. Two echocardiographic evaluations were performed, at baseline and 3 months after the implementation of a multidisciplinary intervention program, integrating the practice of adapted physical exercise. Participants were divided into 2 groups: group 1 with low adherence to the exercise program (< 20% of sessions); group 2 with high adherence to the exercise program (> 90% of sessions). RESULTS: Characteristic heart changes were observed at baseline, mainly at the valvular level, with 89.2% (n = 33) cases of aortic fibrosis, 73% (n = 27) cases of mitral fibrosis, 51.2% (n = 19) cases of aortic regurgitation, and 68% (n = 25) cases of mitral regurgitation. After the intervention, significant changes were observed in several functional parameters in group 2, namely in the maximum velocity of the E' (p = 0.01) and S' (p = 0.02) mitral valve waves, and maximum velocity of the E' tricuspid valve wave (p = 0.02). Positive structural changes were also observed in group 2, namely a reduction in relative wall thickness (p = 0.03) and left ventricular diastolic diameter (p = 0.04). CONCLUSION: Personalized physical exercise implemented as part of a multidisciplinary intervention program is a useful non-pharmacological tool for maintaining adequate cardiac function and structure in the old adult.

Analyzing approaches to mathematic modeling of heart sounds

The article introduces the findings of the analysis of the existing approaches to the development of mathematical models of acoustic heart phenomena. The analysis of mathematical methods that can be used to model heart sounds has been performed with the use of reference signals from the 3M Open Library (Littmann Library) and a set of signals obtained by the authors during their previous scientific efforts. The analysis findings have allowed revealing the approaches and methods that are most suitable for developing the mathematical models of human phonocardiograms (normal and pathological) for further research efforts meant to develop methods to single out heart beats against the high level of interference and creating intervalograms to characterize the heart rate at the current moments of time. In addition to the generation of model phonocardiograms, the article reviews the methods to analyze model and real-life phonocardiograms with the assessment of an input from random and deterministic components.

Acute Physical Stress Preconditions the Heart Against Ischemia/Reperfusion Injury Through Activation of Sympathetic Nervous System / Estresse Físico Agudo Precondiciona o Coração Contra a Injúria por Isquemia/Reperfusão Através da Ativação do Sistema Nervoso Simpático

Abstract Background: Stress is defined as a complicated state that related to homeostasis disturbances, over-activity of the sympathetic nervous system and hypothalamus-pituitary-adrenal axis responses. Cardiac preconditioning reduces myocardial damages. Objective: This study was designed to assess the cardioprotective effects of acute physical stress against ischemia/reperfusion (I/R) injury through the activation of the sympathetic nervous system. Methods: Thirty-two male Wistar rats were divided into four groups; (1) IR (n = 8): rats underwent I/R, (2) Acute stress (St+IR) (n = 8): physical stress induced 1-hour before I/R, (3) Sympathectomy (Symp+IR) (n = 8): chemical sympathectomy was done 24-hours before I/R and (4) Sympathectomy- physical stress (Symp+St+IR) (n = 8): chemical sympathectomy induced before physical stress and I/R. Chemical sympathectomy was performed using 6-hydroxydopamine (100 mg/kg, sc). Then, the hearts isolated and located in the Langendorff apparatus to induce 30 minutes ischemia followed by 120 minutes reperfusion. The coronary flows, hemodynamic parameters, infarct size, corticosterone level in serum were investigated. P < 0.05 demonstrated significance. Results: Physical stress prior to I/R could improve left ventricular developed pressure (LVDP) and rate product pressure (RPP) of the heart respectively, (63 ± 2 versus 42 ± 1.2, p < 0.05, 70 ± 2 versus 43 ± 2.6, p < 0.05) and reduces infarct size (22.16 ± 1.3 versus 32 ± 1.4, p < 0.05) when compared with the I/R alone. Chemical sympathectomy before physical stress eliminated the protective effect of physical stress on I/R-induced cardiac damages (RPP: 21 ± 6.6 versus 63 ± 2, p < 0.01) (LVDP: 38 ± 4.5 versus 43 ± 2.6, p < 0.01) (infarct size: 35 ± 3.1 versus 22.16 ± 1.3, p < 0.01). Conclusion: Findings indicate that acute physical stress can act as a preconditional stimulator and probably, the presence of sympathetic nervous system is necessary.

Resumo Fundamento: O estresse é definido como um estado complicado de distúrbios da homeostase, hiperatividade do sistema nervoso simpático e das respostas do eixo hipotálamo-hipófise-adrenal. O pré-condicionamento cardíaco diminui os danos do miocárdio. Objetivo: Esse estudo avaliou os efeitos cardioprotetores do estresse físico agudo contra a lesão por isquemia-reperfusão (I/R) através da ativação do sistema nervoso simpático. Métodos: Trinta e dois ratos machos Wistar foram divididos em quatro grupos; (1) IR (n = 8): ratos submetidos a I/R, (2) Estresse agudo (St+IR) (n = 8): estresse físico induzido 1 hora antes da I/R, (3) Simpatectomia (Symp+IR) (n = 8): a simpatectomia química foi realizada 24 horas antes da I/R e (4) Simpatectomia-estresse físico (Symp+St+IR) (n = 8): simpatectomia induzida antes do estresse físico e da I/R. A simpatectomia química foi realizada com 6-hidroxidopamina (100 mg/kg, SC). Em seguida, os corações foram isolados e colocados em aparato de Lagendorff por 30 minutos para induzir isquemia, seguida de reperfusão por 120 minutos. Os fluxos coronarianos, os parâmetros hemodinâmicos, o tamanho do infarto e os níveis de corticosterona plasmática foram investigados. Valores de p < 0,05 foram considerados significativos. Resultados: O estresse físico anterior à I/R pode melhorar a pressão desenvolvida no ventrículo esquerdo (PDVE) e duplo produto (DP), respectivamente, (63 ± 2 versus 42 ± 1,2, p < 0,05, 70 ± 2 versus 43 ± 2,6, p < 0,05) e reduzir o tamanho do infarto (22,16 ± 1,3 versus 32±1,4, p < 0,05) quando comparado com a I/R isoladamente. A simpatectomia química antes do estresse físico eliminou o efeito protetor do estresse físico sobre os danos cardíacos induzidos pela I/R (DP: 21 ± 6,6 versus 63 ± 2, p < 0,01) (PDVE: 38 ± 4,5 versus 43 ± 2,6, p < 0,01) (tamanho do infarto: 35 ± 3,1 versus 22,16 ± 1,3, p < 0,01). Conclusão: Os achados indicam que o estresse físico agudo pode funcionar como um estimulador pré-condicional e, provavelmente, a presença do sistema nervoso simpático é necessária.

Study of Myocardial Perfusion in Obese Individuals without Known Ischemic Heart Disease / Estudo de Perfusão Miocárdica em Obesos sem Doença Cardíaca Isquêmica Conhecida

Abstract Background: Obesity is associated with an increased risk of type 2 diabetes mellitus (DM), ischemic heart disease (IHD) and cardiovascular mortality. Several studies have demonstrated the diagnostic and prognostic value of single photon computed tomography-myocardial perfusion scintigraphy (SPECT-MPI) in the evaluation of patients with suspected IHD, including in obese population. Data on clinical risk factors and their association with abnormal myocardial perfusion in obese patients are scarce in the Brazilian population. Objective: To determine the factors associated with abnormal myocardial perfusion in obese individuals without known IHD. Methods: We studied obese patients without known IHD who were referred for evaluation through SPECT-MPI between January 2011 and December 2016. Clinical variables and results of SPECT-MPI were obtained systematically. The distribution of continuous variables was assessed using the Shapiro-Wilk and Shapiro-Francia tests. We used the unpaired Student t test to compare the means of continuous variables with normal distribution and the Chi Square test for binomial variables analysis. A p value < 0.05 was considered statistically significant. The association of the clinical variables for the presence of factors associated with abnormal myocardial perfusion was determined by univariate and multivariate logistic regression analysis, and respective odds ratios (OR) and 95% confidence intervals (CI). Results: The study sample consisted of 5,526 obese patients. Mean body mass index (BMI) of our patients was 33.9 ± 3.7 kg/m2, 31% had DM, and myocardial perfusion abnormalities was observed in 23% of the total sample. The factors associated with abnormal myocardial perfusion on multivariate analysis were: age (OR: 1.02, 95% CI 1.01-1.03, p < 0.001), DM (OR: 1.57, 95% CI 1.31-1.88, p < 0.001), typical angina before the test (OR: 2.45, 95% CI: 1.82-3.31, p < 0.001), need for pharmacologic stress test (OR: 1.61, 95% CI: 1.26-2.07, p < 0.001), less physical effort evaluated in metabolic equivalents (METs) during the exercise treadmill test (OR: 0.89, 95% CI: 0.85-0.94, p < 0.001) and a lower post-stress left ventricular ejection fraction after stress (LVEF; OR: 0.989, 95% CI: 0.984-0.994, p < 0.001). Conclusion: The factors associated with abnormal myocardial perfusion in obese patients without known IHD were age, DM, presence of typical angina, ventricular dysfunction, and inability to undergo physical stress as clinical variables, in addition to functional capacity during physical stress.

Resumo Fundamento: A obesidade associa-se a um risco aumentado de diabetes mellitus do tipo 2 (DM), doença cardíaca isquêmica (DCI) e mortalidade cardiovascular. Vários estudos demonstraram o valor diagnóstico e prognóstico da cintilografia de perfusão miocárdica com tomografia computadorizada por fóton único (CPM-SPECT) na avaliação de pacientes com suspeita de DCI, inclusive na população de obesos. Dados sobre fatores de risco clínicos, e sua associação com perfusão miocárdica anormal em obesos, são escassos na população brasileira. Objetivo: Determinar quais são os fatores associados à anormalidade de perfusão miocárdica em obesos sem DCI conhecida. Métodos: Estudamos pacientes obesos sem DCI conhecida que foram encaminhados para avaliação por CPM-SPECT entre janeiro de 2011 até dezembro de 2016. Variáveis clínicas e resultados da CPM-SPECT foram obtidos de forma sistematizada. A distribuição das variáveis contínuas foi avaliada utilizando-se os testes de Shapiro-Wilk e Shapiro-Francia. Utilizou-se o teste t de Student não pareado para comparar as médias das variáveis contínuas com distribuição normal, e o teste do Chi quadrado para análise das variáveis binomiais. Considerou-se o valor de p < 0,05 como estatisticamente significativo. A associação das variáveis clínicas para a presença de anormalidade de perfusão miocárdica foi determinada por análise de regressão logística univariada e multivariada, calculando-se e apresentando-se os respectivos odds ratios (OR) e intervalos de confiança (IC) de 95. Resultados: A amostra do estudo foi de 5.526 pacientes obesos. O índice de massa corporal médio dos nossos pacientes foi de 33,9 ± 3,7 kg/m2, 31% eram portadores de DM, e anormalidades de perfusão foram observadas em 23% do total da amostra. Os fatores associados à anormalidade de perfusão miocárdica, após análise multivariada, foram: idade (OR: 1,02, IC 95%: 1,01-1,03, p < 0,001), DM (OR: 1,57, IC 95%: 1,31-1,88, p < 0,001), presença de angina típica antes do exame (OR: 2,45, IC 95%: 1,82-3,31, p < 0,001), necessidade de utilização de protocolo com estresse farmacológico (OR: 1,61, IC 95%: 1,26-2,07, p < 0,001), menor esforço físico avaliado em equivalentes metabólicos durante o teste ergométrico (OR: 0,89, IC 95%: 0,85-0,94, p < 0,001) e menor fração de ejeção do ventrículo esquerdo após estresse (OR: 0,989, IC 95%: 0,984-0,994, p < 0,001). Conclusão: Os fatores associados à anormalidade de perfusão miocárdica em pacientes obesos sem DCI conhecida foram idade, DM, presença de angina típica, disfunção ventricular e incapacidade para o estresse físico como variáveis clínicas, além da capacidade funcional durante o estresse físico.

Interacciones cardiopulmonares: de la fisiología a la clínica / Cardiopulmonary Interactions: from Physiology to Clinic

Resumen: Las Interacciones Cardiopulmonares (ICP) corresponden al conjunto de interrelaciones entre el sis tema respiratorio y el cardiovascular, durante el ciclo respiratorio y cardíaco. Estas interacciones varían dependiendo de si el paciente se encuentra en ventilación espontánea o mecánica, afectando en distintos grados la precarga y postcarga, tanto del ventrículo derecho e izquierdo. El entender estas interacciones, resulta esencial al momento de manejar pacientes críticamente enfermos, en donde las manipulaciones de la precarga y postcarga, son de especial importancia al momento de optimizar el débito cardíaco y la entrega de oxígeno a los tejidos. En este artículo se presentan los principios fisiológicos que permiten entender las interacciones cardiopulmonares en ventilación espontánea y en ventilación mecánica, aplicadas a situaciones clínicas específicas, lo que nos ayudará a utilizarlas como herramientas en el manejo de los pacientes.

Abstract: Cardiopulmonary Interactions (CPI) refer to the interplay between the respiratory and cardiovascu lar systems during the respiratory and cardiac cycle. These interactions vary depending on whether the patient is in spontaneous or mechanical ventilation and affect the preload and afterload of both ventricles at different levels. Understanding CPI is essential to the management of critically ill pa tients, where preload and afterload manipulations are specialy important to optimize cardiac output and oxygen delivery to the periphery. The present article reviews the physiological principles required to understand CPI in patients both in spontaneous and mechanical ventilation using specific clinical scenarios to facilitate its use as part of day to day clinical practice.

Inappropriate activity of local renin-angiotensin-aldosterone system during high salt intake: impact on the cardio-renal axis / Atividade inadequada do sistema renina-angiotensina-aldosterona local durante período de alta ingestão de sal: impacto sobre o eixo cardiorrenal

ABSTRACT Although there is a general agreement on the recommendation for reduced salt intake as a public health issue, the mechanism by which high salt intake triggers pathological effects on the cardio-renal axis is not completely understood. Emerging evidence indicates that the renin-angiotensin-aldosterone system (RAAS) is the main target of high Na+ intake. An inappropriate activation of tissue RAAS may lead to hypertension and organ damage. We reviewed the impact of high salt intake on the RAAS on the cardio-renal axis highlighting the molecular pathways that leads to injury effects. We also provide an assessment of recent observational studies related to the consequences of non-osmotically active Na+ accumulation, breaking the paradigm that high salt intake necessarily increases plasma Na+ concentration promoting water retention

RESUMO Apesar de haver uma concordância geral sobre a necessidade de redução na ingestão de sal como questão de saúde publica, o mecanismo pelo qual a alta ingesta de sal deflagra efeitos patológicos sobre o eixo cardiorrenal não está ainda completamente elucidado. Cada vez mais evidencias indicam que o sistema renina-angiotensina-aldosterona (SRAA) seja o principal alvo da alta ingesta de Na+. Uma ativação inadequada do SRAA tecidual pode causar hipertensão e dano ao órgão. Nós revisamos o impacto da dieta com alto teor de sódio sobre o eixo cardiorrenal, destacando as vias moleculares que causam a lesão. Também fizemos uma avaliação de recentes estudos observacionais relacionados às consequências do acúmulo de Na+ não osmoticamente ativo, quebrando assim o paradigma de que a alta ingestão de sódio necessariamente aumenta a concentração sérica de Na+, assim promovendo a retenção de água.

Etiología de la insuficiencia cardíaca crónica / Chronic heart failure etiology

La insuficiencia cardiaca es el resultado fisiopatológico de múltiples enfermedades. Además de la patologia isquémica, valvular, de la conducción o hipertensiva existen otras etiologías poco sospechadas. En la mayoría de ocasiones se realizan diagnósticos estructurales basados en la imagenologia como cardiomiopatía dilatada o cardiomiopatía restrictiva, lo que lleva al clínico a tratamientos sintomáticos, dejando de lado tratamientos etiológicos específicos que pudiesen preservar la función cardiaca, revertir el daño miocárdico y mejorar la calidad de vida de estos pacientes. Comprender y reconocer que existen factores nutricionales, hormonales, genéticos, infecciosos, medicamentosos, infiltrativos o autoinmunes en la patogénesis de la insuficiencia cardiaca permitirá optar por mejores tratamientos, mejorando las tasas de sobrevida.

Heart failure is a pathophysiologic result of several diseases and it's not only related to ischemic, valvular, arrhythmias or hypertensive. Most of the times structural diagnoses are made based on imaging, like dilated or restrictive cardiomyopathy, which leads to symptomatic treatments instead directed etiological therapies that could preserve heart function, reverse myocardial damage and improve life quality. Understands and recognize that there are nutritional, hormonal, genetic, infectious, drugs, infiltrative or autoimmune factors that could lead to heart failure would help clinicians to recognize them and propose targeted treatments, improving survival rates

O que o cardiologista precisa saber sobre achados torácicos na tomografia / What cardiologist needs to know about extracardiac findings on tomography

A angiotomografia das artérias coronárias é um método diagnóstico não invasivo que pode ser utilizado para avaliação da doença arterial coronariana em pacientes selecionados e pode fornecer informações quanto às demais estruturas incluídas no campo de visão tomográfico. Por vezes são identificados achados extracardíacos que, em sua maior parte, representam achados incidentais de relevância variável. A adequada detecção, interpretação e comunicação de achados extracardíacos relevantes pode, em última análise, beneficiar pacientes na detecção precoce de doenças das quais não se suspeitava, sem a necessidade de dose adicional de radiação. Revisaremos achados extracardíacos e discutiremos os principais temas deste assunto: nódulos pulmonares; doenças difusas do parênquima pulmonar; alteração das vias aéreas; espaço pleural; aorta; artérias pulmonares; linfonodos; mediastino; fígado; esôfago/estômago; adrenal; mamas; cavidade peritoneal; baço; ossos. Finalmente, a excelência na capacitação, busca, detecção e adequada interpretação dos achados de imagem extracardíacos tem impacto significativo no cuidado com o paciente

Coronary artery angiotomography is a noninvasive diagnostic method that can be used to evaluate coronary artery disease in selected patients, and may provide information on other structures included in the tomographic field of vision. Extracardiac findings are occasionally identified, the majority of which represent incidental findings of varying relevance. Adequate detection, interpretation and reporting of relevant extracardiac findings may ultimately benefit patients through early detection of unsuspected diseases without the need for additional doses of radiation. Extracardiac findings will be reviewed, and main topics of the subject discussed: pulmonary nodules; diffuse pulmonary parenchyma disease; airway disease; pleural space; aorta; pulmonary arteries; lymph nodes; mediastinum; liver; esophagus/stomach; adrenal; breasts; peritoneal cavity; spleen; and bones. Finally, excellence in training, searching, detecting and adequate interpretation of extracardiac imaging findings has a significant impact on patient care

Interacción cardiopulmonar en el paciente pediátrico crítico / Cardiopulmonary interactions in the critical pediatric patient

To optimize the management of critically ill patients, it is essential to understand the principles of cardiopulmonary interaction.The ultimate goal of the interaction between pulmonary and circulatory systems from a physiological point of view is to optimize the delivery of oxygen to tissues in order to meet metabolic demand, especially in situations where normal physiology is altered, as is the case of pediatric critically ill patients. Thus, during a critical illness, if any of these systems fails (together or separately), the end result is an inadequate delivery of O2 to tissues, which can lead to ischemia, progressive organ dysfunction, and if untreated, to death.In this review we will address key physiological concepts involved in cardiopulmonary interactions and how they are affected by the management we perform in the pediatric critically ill patients.

Para optimizar el manejo de los pacientes críticos, es fundamental comprender los principios de la interacción cardiopulmonar. El objetivo úultimo desde el punto de vista fisiológico de la interacción entre los sistemas circulatorio y pulmonar es optimizar la entrega de oxígeno a los tejidos y dar cuenta de la demanda metabólica especialmente en situaciones donde la fisiología normal se ve alterada, como es el caso de los pacientes pediátricos críticamente enfermos. Es así como durante una enfermedad crítica, si alguno de estos dos sistemas falla, (juntos o por separado), el resultado final es una inadecuada entrega de O2 tisular, que puede conducir a isquemia, disfunción orgánica progresiva, y si no se trata, hasta la muerte.En esta revisión intentaremos abordar de forma didáctica los principales conceptos fisiológicos involucrados en las interaccionescardiopulmonares y cómo estos se ven afectados frente a las intervenciones que realizamos en el manejo de los pacientes críticos.

Cardiac Regeneration using Growth Factors: Advances and Challenges / Regeneração Cardíaca com Fatores de Crescimento: Avanços e Desafios

Abstract Myocardial infarction is the most significant manifestation of ischemic heart disease and is associated with high morbidity and mortality. Novel strategies targeting at regenerating the injured myocardium have been investigated, including gene therapy, cell therapy, and the use of growth factors. Growth factor therapy has aroused interest in cardiovascular medicine because of the regeneration mechanisms induced by these biomolecules, including angiogenesis, extracellular matrix remodeling, cardiomyocyte proliferation, stem-cell recruitment, and others. Together, these mechanisms promote myocardial repair and improvement of the cardiac function. This review aims to address the strategic role of growth factor therapy in cardiac regeneration, considering its innovative and multifactorial character in myocardial repair after ischemic injury. Different issues will be discussed, with emphasis on the regeneration mechanisms as a potential therapeutic resource mediated by growth factors, and the challenges to make these proteins therapeutically viable in the field of cardiology and regenerative medicine.

Resumo O infarto do miocárdio representa a manifestação mais significativa da cardiopatia isquêmica e está associado a elevada morbimortalidade. Novas estratégias vêm sendo investigadas com o intuito de regenerar o miocárdio lesionado, incluindo a terapia gênica, a terapia celular e a utilização de fatores de crescimento. A terapia com fatores de crescimento despertou interesse em medicina cardiovascular, devido aos mecanismos de regeneração induzidos por essas biomoléculas, incluindo angiogênese, remodelamento da matriz extracelular, proliferação de cardiomiócitos e recrutamento de células-tronco, dentre outros. Em conjunto, tais mecanismos promovem a reparação do miocárdio e a melhora da função cardíaca. Esta revisão pretende abordar o papel estratégico da terapia, com fatores de crescimento, para a regeneração cardíaca, considerando seu caráter inovador e multifatorial sobre o reparo do miocárdio após dano isquêmico. Diferentes questões serão discutidas, destacando-se os mecanismos de regeneração como recurso terapêutico potencial mediado por fatores de crescimento e os desafios para tornar essas proteínas terapeuticamente viáveis no âmbito da cardiologia e da medicina regenerativa.

Assessment of the left ventricular function in normotensive prediabetics: a tissue Doppler echocardiography study

ABSTRACT Objective Several studies have shown that left ventricular (LV) dysfunction is increased in individuals with diabetes. However, there are scarce data about LV function in prediabetics. This study assessed the early changes in LV diastolic and systolic myocardial function in normotensive prediabetics using tissue Doppler echocardiography (TDE). Subjects and methods We evaluated 94 patients with prediabetes (mean age of 50.8 ± 6.9 years, 78 female) without known cardiovascular diseases and 70 healthy volunteers with similar demographic characteristics. Systolic and diastolic function of the left ventricle was evaluated with transthoracic echocardiography according to the latest consensus recommendations including TDE. Results The mean results of septal and lateral parts of the mitral annulus Pulsed wave TDE showed that myocardial systolic wave (Sm), myocardial early diastolic wave (Em) and Em to atrial peak velocity (Am) ratio were significantly lower whereas early diastolic peak flow velocity (E) to Em ratio, myocardial isovolumetric relaxation time (IVRTm), myocardial isovolumetric contraction time (IVCTm) and myocardial performance index (MPI) values were significantly higher in patients with prediabetes (preDM). In addition, mean left atrium (LA) diameter measured with M-mode echocardiography was significantly higher in prediabetics than controls. Conclusion PreDM is associated with subclinical LV systolic and diastolic dysfunction as evaluated by TDE.