Morphological Assessment and Possible Clinical Implications of the Left Ventricle Papillary Muscles. Study in a Colombian Population Sample

SUMMARY: Papillary muscles in the left ventricle present multiple anatomic expressions that are relevant for medical fields focusing on the understanding of clinical events involving these structures. Here, the aim was to perform a morphological characterization of the left ventricle papillary muscles in a sample of Colombian population. In the study were included eighty-two hearts from male individuals who underwent autopsy at the Institute of Legal Medicine and Forensic Sciences in Bucaramanga, Colombia. In each heart was carefully performed a longitudinal incision on the obtuse margin to visualize the papillary muscles. Data set was registered, and analysis of the continuous and categorical variables was carried out. Single anterior papillary muscle was observed in 74 samples (90.2 %) whereas this represented only 48 specimens (58.5 %) for the posterior papillary muscle (p = 0.3). Mean length and breadth of the anterior muscle were 29.9 ± 4.94 and 11.74 ± 2.75 mm, and those for the posterior muscle were 27.42 ± 7.08 and 10.83 ± 4.08 mm. Truncated apical shape was the most frequent type observed on the papillary muscles, anterior 41 (50 %) and posterior 37 (45.1 %), followed by flat-topped in the anterior 25 (30.5 %) and bifurcated in posterior muscle 14 (17.1 %). A mean of 9.04 ± 2.75 chordae raised from the anterior and 7.50 ± 3.3 from posterior papillary muscle. In our study we observed a higher incidence of single papillary muscles and slightly larger dimensions than information reported in the literature. The anatomic diversity of the papillary muscles should be considered for the correct image interpretation, valve implantation and performance evaluation on myocardial ischemic events.

Los músculos papilares del ventrículo izquierdo presentan múltiples expresiones anatómicas que son relevantes para las áreas médicas que se centran en la comprensión de los eventos clínicos que involucran estas estructuras. El objetivo fue realizar una caracterización morfológica de los músculos papilares del ventrículo izquierdo en una muestra de población colombiana. En el estudio se incluyeron ochenta y dos corazones de individuos masculinos a los que se les realizó autopsia en el Instituto de Medicina Legal y Ciencias Forenses de Bucaramanga, Colombia. En cada corazón se realizó cuidadosamente una incisión longitudinal en el margen obtuso para visualizar los músculos papilares. Se registró el conjunto de datos y se realizó el análisis de las variables continuas y categóricas. Se observó un solo músculo papilar anterior en 74 muestras (90,2 %), mientras que este rasgo se presentó en 48 muestras (58,5 %) para el músculo papilar posterior (p = 0,3). La longitud y anchura media del músculo anterior fueron 29,9 ± 4,94 y 11,74 ± 2,75 mm, y las del músculo posterior fueron 27,42 ± 7,08 y 10,83 ± 4,08 mm. La forma apical truncada fue el tipo más frecuente observado en los músculos papilares, anterior 41 (50 %) y posterior 37 (45,1 %), seguido de la forma plana en los 25 anteriores (30,5 %) y bifurcada en el músculo posterior 14 (17,1 %). Una media de 9,04 ± 2,75 cuerdas elevadas desde el músculo papilar anterior y 7,50 ± 3,3 desde posterior. En nuestro estudio observamos una mayor incidencia de músculos papilares únicos y dimensiones ligeramente mayores que la información reportada en la literatura. La diversidad anatómica de los músculos papilares debe ser considerada para la correcta interpretación de imágenes, implantación valvular y evaluación del desempeño en eventos isquémicos miocárdicos.

Development, Histological, and Ultrastructural Evaluation of Sheep Hyperimmune Serum Therapy for COVID-19 / Desarrollo, Evaluación Histológica y Ultraestructural de la Terapia con Suero Hiperinmune de Oveja para COVID-19

SUMMARY: In response to the threat posed by new variants of SARS-CoV-2 and the urgent need for effective treatments in the absence of vaccines, the aim of this study was to develop a rapid and cost-effective hyperimmune serum (HS) derived from sheep and assess its efficacy. The utilization of a halal-certified, easily maintained in certain geographic regions, easy-to-handle animal such as sheep could provide a viable alternative to the expensive option of horses. Sheep were immunized with a whole inactivated SARS-CoV- 2 antigen to produce HS, which was evaluated for neutralizing potency using the PRNT50 assay. K18-hACE2 transgenic mice (n=35) were divided into three groups: control, SARS-CoV-2 exposure through inhalation, and SARS-CoV-2 exposed mice treated with HS. HS efficacy was assessed through serum proinflammatory cytokine levels, qRT-PCR analysis, histopathological examination of lungs and hearts, and transmission electron microscopy. Purified HS exhibited significant neutralizing activity (1/24,576). The SARS-CoV-2+HS group showed lower levels of TNF-α, IL-10, and IL-6 (P<0.01) and relatively lower levels of MCP-1 compared to the SARS-CoV-2 group. HS prevented death, reduced viral RNA levels in the lungs and hearts, protected against severe interstitial pneumonia, preserved lung tissue integrity, and prevented myocyte damage, while the SARS-CoV-2 group exhibited viral presence in the lungs. This study successfully developed a sheep-derived HS against the entire SARS-CoV-2 virus, resulting in a significant reduction in infection severity, inflammation, and systemic cytokine production. The findings hold promise for treating severe COVID-19 cases, including emerging viral variants, and immunocompromised patients.

En respuesta a la amenaza que suponen las nuevas variantes del SARS-CoV-2 y la urgente necesidad de tratamientos eficaces en ausencia de vacunas, el objetivo de este estudio fue desarrollar un suero hiperinmune (HS) rápido y rentable derivado de ovejas. y evaluar su eficacia. La utilización de un animal con certificación halal, de fácil mantenimiento en determinadas regiones geográficas y de fácil manejo, como las ovejas, podría proporcionar una alternativa viable a la costosa opción de los caballos. Las ovejas fueron inmunizadas con un antígeno de SARS-CoV-2 completamente inactivado para producir HS, cuya potencia neutralizante se evaluó mediante el ensayo PRNT50. Los ratones transgénicos K18-hACE2 (n = 35) se dividieron en tres grupos: control, exposición al SARS-CoV-2 mediante inhalación y ratones expuestos al SARS-CoV-2 tratados con HS. La eficacia de HS se evaluó mediante niveles de citoquinas proinflamatorias en suero, análisis qRT-PCR, examen histopatológico de pulmones y corazones y microscopía electrónica de transmisión. El HS purificado exhibió una actividad neutralizante significativa (1/24,576). El grupo SARS-CoV-2+HS mostró niveles más bajos de TNF-α, IL-10 e IL-6 (P<0,01) y niveles relativamente más bajos de MCP-1 en comparación con el grupo SARS-CoV-2. HS evitó la muerte, redujo los niveles de ARN viral en los pulmones y el corazón, protegió contra la neumonía intersticial grave, preservó la integridad del tejido pulmonar y evitó el daño de los miocitos, mientras que el grupo SARS-CoV-2 exhibió presencia viral en los pulmones. Este estudio desarrolló con éxito un HS derivado de ovejas contra todo el virus SARS-CoV-2, lo que resultó en una reducción significativa de la gravedad de la infección, la inflamación y la producción sistémica de citocinas. Los hallazgos son prometedores para el tratamiento de casos graves de COVID- 19, incluidas las variantes virales emergentes y los pacientes inmunocomprometidos.

Interleukin-37 has A Promising Cardioprotective Effect on Isoproterenol-Induced Myocardial Infarction / La Interleucina-37 tiene un Efecto Cardioprotector Prometedor sobre el Infarto de Miocardio Inducido por Isoproterenol

SUMMARY: The main cause of mortality and disability globally is myocardial infarction (MI). Isoproterenol (ISO), a β-adrenoceptor agonist, has been used to induce rat myocardial necrosis. Whereas interleukin-37 (IL-37) has anti-inflammatory and cytoprotective properties. The study aimed to investigate the potential protective effects of IL-37 administration on cardiac architecture, oxidative stress, and inflammatory markers during ISO-induced MI in rats. Three groups of adult male rats were used in this study, the normal control group (n=8), ISO-induced MI group (n=8) that received isoproterenol hydrochloride (ISO) (100 mg/kg/day, SC, for the first 2 consecutive days), and IL-37-treated group (ISO+IL-37) (n=8) that received recombinant human IL-37 (40 µg/kg /day, intraperitoneally, for 2 weeks during and after ISO injections. Heart rate (HR.) and ECG changes were monitored. Some oxidative stress markers such as superoxide dismutase (SOD), nitric oxide (NOx), malondialdehyde (MDA), and glutathione (GSH) tissue levels in the tissue homogenate were assayed. Interleukin- 6 (IL-6), tumor necrosis factor- α (TNF-α), caspase-8, P53, and C- reactive protein (CRP) were among the inflammatory markers examined. In addition, serum levels of creatinine kinase (CK-MB) and lactate dehydrogenase (LDH) were analyzed to evaluate the myocardial injury. For histological analysis, tissues were sectioned, fixed in paraffin, and stained with hematoxylin and eosin (H&E), Masson Trichrome and, immunohistochemical against NF-kB, TNF-α, and Caspase-9. IL-37 improved ECG changes, cardiac enzyme markers, and some inflammatory markers of oxidative stress in ISO-induced MI. It also improved the histopathological and immunohistochemical changes in MI. In conclusion: IL-37 might be a promising therapeutic modality in myocardial infarction.

La principal causa de mortalidad y discapacidad a nivel mundial es el infarto de miocardio (IM). El isoproterenol (ISO), un agonista de los receptores adrenérgicos β, se ha utilizado para inducir necrosis miocárdica en ratas. Mientras que la interleucina-37 (IL-37) tiene propiedades antiinflamatorias y citoprotectoras. El estudio tuvo como objetivo investigar los posibles efectos protectores de la administración de IL-37 en la arquitectura cardíaca, el estrés oxidativo y los marcadores inflamatorios durante el infarto de miocardio inducido por ISO en ratas. En este estudio se utilizaron tres grupos de ratas macho adultas, el grupo control normal (n=8), el grupo con IM inducido por ISO (n=8) que recibió clorhidrato de isoproterenol (ISO) (100 mg/kg/día, SC, durante los primeros 2 días consecutivos) y el grupo tratado con IL-37 (ISO+IL- 37) (n=8) que recibió IL-37 humana recombinante (40 µg/kg/día, por vía intraperitoneal, durante 2 semanas durante y después de las inyecciones de ISO. Se monitorearon la frecuencia cardíaca (FC) y los cambios en el ECG. Se analizaron algunos marcadores de estrés oxidativo como la superóxido dismutasa (SOD), el óxido nítrico (NOx), el malondialdehído (MDA) y los niveles tisulares de glutatión (GSH) en el homogeneizado de tejido. La interleucina-6 (IL-6), el factor de necrosis tumoral-α (TNF-α), la caspasa-8, la P53 y la proteína C reactiva (CRP) se encontraban entre los marcadores inflamatorios examinados. Se analizaron los niveles de creatinoquinasa (CK-MB) y lactato deshidrogenasa (LDH) para evaluar la lesión miocárdica; para el análisis histológico se seccionaron los tejidos, se fijaron en parafina y se tiñeron con hematoxilina y eosina (H&E), Tricromo de Masson e inmunohistoquímica contra NF-kB, TNF-α y Caspasa-9. IL-37 mejoró los cambios de ECG, los marcadores de enzimas cardíacas y algunos marcadores inflamatorios de estrés oxidativo en el IM inducido por ISO. Además mejoró los cambios histopatológicos e inmunohistoquímicos en MI. En conclusión: la IL-37 podría ser una modalidad terapéutica prometedora en el infarto de miocardio.

Conservation of Organs (Heart, Brain and Kidney) of Canine by Cold-Temperature Silicone Plastination in an Animal Anatomy Laboratory in Ecuador / Conservación de Órganos (Corazón, Encéfalo y Riñón) de Canino Mediante la Técnica de Plastinación en Silicona al Frío Realizada en Laboratorio de Anatomía Animal en Ecuador

SUMMARY: For the purposes of teaching anatomy, the use of cadaver preparations is considered the most efficient way of ensuring that students retain knowledge. Nevertheless, in Ecuador the use of animal specimens in universities must comply with the internationally accepted principles of replacement, reduction and refinement (3Rs). Plastination is an alternative technique which allows organs to be conserved in the long term and complies with the 3Rs. The object of the present work was to use cold-temperature silicone plastination with Biodur® products to obtain long-lasting, easy-to-handle canine organs for use as tools for the teaching of animal anatomy. Six canine cadavers were obtained from local animal protection charities. The hearts, brains and kidneys of the cadavers were dissected and fixed with formaldehyde 10 %. They were then dehydrated with acetone at -20 °C. The specimens were impregnated with Biodur® S10:S3 (-20 °C) and finally cured with Biodur® S6. We plastinated six hearts, twelve kidneys, four brains and one encephalic slice of canine. The application of cold-temperature plastination to canine organs followed the parameters established for the conventional protocol, enabling us to obtain organs of brilliant appearance, free of odours, in which the anatomical form was preserved. Thus the technique helped us to comply with the 3Rs, as we obtained easy-to-handle teaching models to replace fresh or formaldehyde-fixed samples for the teaching-learning of the canine anatomy.

En la enseñanza de la Anatomía, el uso de preparaciones cadavéricas se considera el método que permite a los estudiantes retener el conocimiento de una forma más eficiente. No obstante, en Ecuador, el uso de especímenes animales en las universidades se debe realizar bajo el principio internacional de reemplazo, reducción y refinamiento (3Rs). La técnica de plastinación es una técnica alternativa que permite preservar órganos a largo plazo y que se adapta al principio de las 3Rs. El objetivo del trabajo fue utilizar la técnica de plastinación en silicona al frío con productos Biodur® para obtener órganos caninos duraderos y manejables útiles como herramienta para la enseñanza de la anatomía animal. Se obtuvieron seis cadáveres de caninos de fundaciones locales para la protección animal. Se realizaron disecciones de corazones, cerebros y riñones de los cadáveres caninos. Los órganos se fijaron con formalina al 10 %. A continuación, se llevó a cabo la deshidratación con acetona a -20 °C. Los especímenes fueron impregnados con S10:S3 Biodur® (-20 °C) y al final fueron curados con Biodur® S6. Se lograron plastinar seis corazones, doce riñones, cinco encéfalos y un tallo encefálico de canino. La técnica de plastinación al frío utilizada para obtener órganos de canino conservó los parámetros empleados en el protocolo convencional y permitió obtener órganos que presentaron aspecto brillante, ausencia de olores y mantuvieron la forma anatómica. Por lo que, la técnica facilitó cumplir con el principio de las 3Rs al obtenerse modelos didácticos fáciles de manipular que pueden reemplazar muestras frescas o formolizadas en el proceso de enseñanza-aprendizaje de la anatomía del canino.

Cardiac Corpuscles: A "New" Morphofunctional Entity? / Corpúsculos Cardíacos: ¿Una "Nueva" Entidad Morfofuncional?

SUMMARY: The existence of "transitional muscular structures" between subendocardial branches (Purkinje fibers) and ventricular working muscle fibers (WF) was first described by the German anatomist, Kurt Goerttler, in 1964. He designated them as "subendocardial nucleus organs." He supposed such fibers functioned as mechanoreceptors, controlling of the intensity of contraction of the ventricular musculature. Brazilian anatomist Ferraz de Carvalho described similar structures in 1993. A thorough literature search failed to identify any other research articles confirming or denying their existence. The objective of this work was to find such structures in subendocardial ventricular walls in human hearts. We collected fifteen formalin-preserved hearts from the Anatomy Department of São Paulo University and sectioned the apical portions on the right and left ventricles according to method used by Goerttler. We utilized conventional histology (light microscopy- LM), scanning electron microscopy (SEM), and a new preservation method called micro- plastination (MP). At the anterior wall of the right ventricle in the subendocardial region between the interventricular septum and moderator band, we found several bundles of fusiform and helicoidal fibers of similar histology to the WF. The bundles measured between 400 and 1150 µm in length and were separated from adjacent muscular fibers by thin collagen fiber, thus acting as a "pseudo capsule." Some structures seemed to be linked to PF and were appeared to be lymphatic and blood vessels and nerves. We called those structures "cardiac corpuscles" (CC). The observation of the previously "unknown" CC in this initial study confirmed the previous descriptions and its discovery may contribute to new perspectives in the study of cardiac muscle structure and function.

La existencia de "estructuras musculares de transición" entre los ramos subendocárdicos (fibras de Purkinje) y las fibras musculares ventriculares activas(FMV) fue descrita por primera vez por el anatomista alemán Kurt Goerttler en 1964, quien las denominó "órganos del núcleo subendocárdico". Supuso que tales fibras funcionaban como mecanoreceptores, controlando la intensidad de la contracción de la musculatura ventricular. El anatomista brasileño Ferraz de Carvalho describió estructuras similares en 1993. Una búsqueda bibliográfica exhaustiva no logró identificar ningún otro artículo de investigación que confirmara o negara su existencia. El objetivo de este trabajo fue encontrar dichas estructuras en las paredes ventriculares subendocárdicas de corazones humanos. Recolectamos 15 corazones conservados en formalina del Departamento de Anatomía de la Universidad de São Paulo y seccionamos las porciones apicales de los ventrículos derecho e izquierdo según el método utilizado por Goerttler. Utilizamos histología convencional (microscopía de luz-LM), microscopía electrónica de barrido (SEM) y un nuevo método de conservación llamado microplastinación (MP). En la pared anterior del ventrículo derecho en la región subendocárdica entre el tabique interventricular y la banda moderadora, encontramos varios haces de fibras fusiformes y helicoidales de histología similar a la FMV. Los haces medían entre 400 y 1150 µm de longitud y estaban separados de las fibras musculares adyacentes por una fina fibra de colágeno, actuando así como una "pseudocápsula". Algunas estructuras parecían estar vinculadas a la fibras de purkinje y parecían ser vasos linfáticos, sanguíneos y nerviosos. Llamamos a esas estructuras "corpúsculos cardíacos" (CC). La observación del CC previamente "desconocido" en este estudio inicial confirmó las descripciones anteriores y su descubrimiento puede contribuir a nuevas perspectivas en el estudio de la estructura y función del músculo cardíaco.

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.

Como eu faço no Coração de Atleta: avaliação dos diferentes tipos de adaptação ao exercício / My approach to "Athlete'S Heart": evaluation of the different types of adaptation to exercise

A prática regular de esportes pode induzir adaptações no coração, sendo essa condição comumente chamada de "coração de atleta". As alterações observadas incluem dilatação das câmaras cardíacas, aumento da espessura miocárdica, melhora do enchimento ventricular, aumento da trabeculação do ventrículo esquerdo (VE), dilatação da veia cava inferior, entre outras. Essas alterações também podem ser observadas em algumas doenças cardíacas, como cardiomiopatia (CMP) dilatada, hipertrófica e outras. Dessa forma, os exames de imagem cardíaca são fundamentais na identificação dessas alterações e na diferenciação entre o "coração de atleta" e uma possível cardiopatia.(AU)

Exercise-induced adaptation may occur in amateur and professional athletes. This condition is commonly named "athlete's heart". The alterations observed include dilation of the heart chambers, increased myocardial thickness, improved ventricular filling, increased left ventricular trabeculation, dilation of the inferior vena cava, among others. These changes can also be observed in some heart diseases, such as dilated, hypertrophic and other cardiomyopathies (CMP). Thus, cardiac imaging tests are fundamental in identifying these alterations and in differentiating between "athlete's heart" and possible heart disease. (AU)

Mecanismos de adaptação do coração em atletas de elite do sexo feminino: comparação com indivíduos sadios e tempo de treinamento / Heart adaptation mechanisms in elite female athletes: comparison with healthy individuals and time of training

Fundamento: O exercício intenso e continuado em atletas provoca fenótipos de remodelamento adaptativo, cujos parâmetros podem ser avaliados pela ecocardiografia convencional, e de deformação miocárdica. Assim, foi comparado o remodelamento miocárdico em atletas do sexo feminino (grupo atletas) com mulheres sedentárias da mesma faixa etária (grupo-controle) e entre atletas com maior e menor tempo de treinamento. Métodos: Foram selecionadas 57 futebolistas femininas (grupo atletas) e 25 mulheres sadias sedentárias (grupocontrole). As atletas foram divididas em dois grupos: grupo principal, com 32 atletas, e grupo sub-17, com 25 atletas. Foram determinadas, através de ecocardiografia, as dimensões, a função sistólica e diastólica das câmaras cardíacas e a deformação miocárdica (strain longitudinal, circunferencial, radial e mecânica rotacional), utilizando a estatística Z com significância de p < 0,05. Resultados: A idade dos grupos atletas, controle, principal e sub-17 foi de 22,1±6,3; 21,2±5,0; 26,5±5,1; e 16,5±0,6, respectivamente. O peso, o índice de massa corporal e a frequência cardíaca foram menores no grupo atletas. A espessura das paredes, o índice de massa do ventrículo esquerdo (VE), o volume do átrio esquerdo (AE), a fração de ejeção e as dimensões do ventrículo direito (VD) foram maiores no grupo atletas, mas dentro de valores normais. A deformação miocárdica mostrou diminuição do strain radial, da rotação basal, da rotação apical e do twist, sugerindo mecanismo de reserva contrátil. Esses parâmetros foram menores no grupo principal, que também apresentava maior espessura das paredes, maior volume do AE e maior tamanho do VD, sugerindo que o aumento da reserva contrátil se relaciona com maior tempo de treinamento. Conclusões: As atletas do sexo feminino com treinamento intenso de longa duração apresentam remodelamento adaptativo das câmaras cardíacas e aumento da reserva contrátil observada em repouso, com esses parâmetros mais acentuados nas atletas com maior tempo de treinamento.(AU)

Background: Intense continuous exercise provokes adaptive remodeling phenotypes in athletes, the parameters of which can be evaluated through conventional echocardiography and myocardial deformation. We compared myocardial remodeling in female athletes (athlete group) with sedentary women of the same age range (control group) and between older and younger athletes. Methods: A total of 57 female soccer players and 25 healthy sedentary women were selected. The athlete group was subdivided into a main group and those under 17 years of age (< 17 group). The dimensions and systolic and diastolic function of the cardiac chambers and myocardial deformation (longitudinal and circumferential, as well as radial strain and rotational mechanics) was determined through echocardiography, using the Z statistic with a significance level of p< 0.05. Results: The mean age of the athlete, control, main, and < 17 groups was 22.1 (SD, 6.3); 21.2 (SD, 5.0); 26.5 (SD, 5.1); 16.5 (SD, 0.6) years, respectively. Weight, body mass index and heart rate were lower in the athlete group. Wall thickness, left ventricular mass index, left atrial (LA) volume, ejection fraction, and right ventricular dimensions were higher in athlete group, but remained within normal ranges. Regarding myocardial deformation, there was decreased radial strain, basal rotation, apical rotation, and twisting in the athlete group, suggesting a contractile reserve mechanism. These parameters were lesser in the main athlete group, who also had greater wall thickness, greater volume in the left atrium (LA) and larger size in the right ventricle (RV), suggesting that increased contractile reserve is related to longer time spent in the sport. Conclusions: In female athletes who had undergone intense long-term training, we observed adaptive remodeling of the cardiac chambers and increased contractile reserve (at rest), and these changes were more pronounced in those with longer involvement in the sport.(AU)

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.

Morphological study in heart of wild Chinese alligator (Alligator sinensis) / Estudio morfológico del corazón del caimán chino salvaje (Alligator sinensis)

SUMMARY: The Chinese alligator (Alligator sinensis) belongs to the genus Alligator, which is a unique crocodile in China. In order to study the macroscopic structure of the heart of Chinese alligator, we performed detailed cardiac anatomy on five specimens. The heart is in the cranial mediastinum. It is caudally involved by the liver cranial margins, and ventrally by the ribs, intercostal muscles, and sternum and dorsally by the lungs. The wild Chinese alligator heart is a typical four-chamber heart, with two (right and left) atria and ventricles, left and right aorta, pulmonary artery and subclavian artery branch from the aorta. Morphology measures the circumference (129.36 mm), weight (44.14 g), and length of the heart from apex to bottom (52.50 mm). Studies have shown that the shape of the wild Chinese alligator's heart is consistent with the anatomy of other crocodiles.

El caimán chino (Alligator sinensis) pertenece al género Alligator, que es un cocodrilo único en China. Para estudiar la estructura macroscópica del corazón del caimán chino, revisamos detalladamente la anatomía cardíaca de cinco especímenes. El corazón está en el mediastino craneal. Está limitado caudalmente por los márgenes craneales del hígado, y ventralmente por las costillas, los músculos intercostales y el esternón, y dorsalmente por los pulmones. El corazón de cocodrilo chino salvaje es un corazón típico de cuatro cámaras, con dos atrios y dos ventrículos (derecho e izquierdo), aortas izquierda y derecha, arteria pulmonar y rama de la arteria subclavia de la aorta. La morfología mide la circunferencia (129,36 mm), el peso (44,14 g) y la longitud del corazón desde el ápice hasta la base (52,50 mm). Los estudios han demostrado que la forma del corazón del caimán chino salvaje es consistente con la anatomía de otros cocodrilos.

Comparative study between suprasternal and apical windows: a user-friendly cardiac output measurement for the anesthesiologist

Abstract Introduction Transthoracic echocardiography is a safe and readily available tool for noninvasive monitoring of Cardiac Output (CO). The use of the suprasternal window situated at the sternal notch can be an alternative approach for estimating blood flow. The present study aimed to compare two methods of CO calculation. We compared the descending aorta Velocity-Time Integral (VTI) measurement from the suprasternal window view with the standard technique to determine CO that uses VTI measurements from the LVOT (Left Ventricular Outflow Tract) view. We also aimed to find out whether after basic training a non-echocardiographer operator can obtain reproducible measurements of VTI using this approach. Methods In the first part of the study, 26 patients without known cardiovascular diseases were evaluated and VTI data were acquired from the suprasternal window by a non-echocardiographer and an echocardiographer. Next, 17 patients were evaluated by an echocardiographer only and VTI and CO measurements were obtained from suprasternal and apical windows. Data were analyzed using the Bland and Altman method (BA), correlation and regression. Results We found a strong correlation between measurements obtained by a non-expert and an expert echocardiographer and detected that an inexperienced trainee can acquire VTI measurements from the suprasternal window view. Regarding agreement between CO measurements, data obtained showed a positive correlation and the Bland and Altman analysis presented a total variation of 38.9%. Conclusion Regarding accuracy, it is likely that TTE (Transthoracic Echocardiogram) measurements of CO from the suprasternal window view are comparable to other minimally invasive techniques currently available. Due to its user-friendliness and low cost, it can be a convenient technique for obtaining perioperative hemodynamic measurements, even by inexperienced operators.

Report on Cardiac Gross Pathologic Measurements of Sudden Cardiac Death in Adults / 法医学杂志

OBJECTIVES@#To analyze the gross pathological data of sudden cardiac death (SCD) with different causes, to provide data support for the identification of sudden cardiac death with unknown causes.@*METHODS@#A total of 167 adult SCD cases in the archive of the Forensic Expertise Institute of Nanjing Medical University from 2010 to 2020 were collected. The gross pathological data of SCD cases were summarized and the characteristics of different causes of death were statistically analyzed.@*RESULTS@#The ratio of male to female SCD cases was 3.4∶1. Coronary heart disease was the leading cause of SCD, and mainly distributed in people over 40 years old. SCD caused by myocarditis was mainly distributed in young people and the mean age of death was (34.00±9.55) years. By analyzing the differences in cardiac pathological parameters of SCD with different causes, it was found that the aortic valve circumference was significantly dilated in the SCD caused by aortic aneurysm or dissection (P<0.05). The heart weight of SCD caused by aortic aneurysm or dissection and combined factors was greater, and both pulmonary and tricuspid valvular rings were dilated in the SCD caused by combined factors in adult males (P<0.05).@*CONCLUSIONS@#Various gross pathological measures of SCD with different causes are different, which has reference value in the cause of death identification of SCD.

ZHANG Wei-hua's clinical experience of Zhenjing Anshen method in treatment of insomnia / 中国针灸

The paper summarizes professor ZHANG Wei-hua's clinical experience in treatment of insomnia with Zhenjing Anshen (calming-down the spirit) method. It is believed that insomnia results from the unstable spirit in pathogenesis of TCM. The basic therapeutic principle is regulating the spirit, in which, stabilizing the primary spirit and tranquilizing the heart spirit are emphasized. Main acupoints are Baihui (GV 20), Sishencong (EX-HN 1) and Yintang (GV 24+) to stabilize the primary spirit, located on the head; and Shenmen (HT 7) located on the wrist to calm-down the heart spirit, as well as Sanyinjiao (SP 6) and Yongquan (KI 1) in the lower extremities to benefit yin and balance yang, and then to house the spirit eventually. The needles are inserted in different depths and to various directions. The external application of herbal plaster is combined at Yongquan (KI 1) and the supplementary acupoints are selected in terms of syndrome differentiation. This therapy is simple in acupoint selection and very effective in treatment of insomnia.

Research progress on image-based calculation of coronary artery fractional flow reserve / 生物医学工程学杂志

Coronary artery fractional flow reserve (FFR) is a critical physiological indicator for assessment of impaired blood flow caused by coronary artery stenosis. The wire-based invasive measurement of blood flow pressure gradient across stenosis is the gold standard for clinical measurement of FFR. However, it has the risk of vascular injury and requires the use of vasodilators, increasing the time and overall cost of interventional examination. Coronary imaging is playing an important role in clinical diagnosis of stenotic lesions, evaluation of severity of lesions, and planning of therapies. In recent years, the computation of FFR based on the physiological information of blood flow obtained from routinely collected coronary image data has become a research focus in this field. This technique reduces the cost of physiological assessment of coronary lesions and the use of pressure wires. It is beneficial to strengthen the physiological guidance in interventional therapy. In order to better understand this emerging technique, this paper highlights its implementation principle and diagnostic performance, analyzes practical problems and current challenges in clinical applications, and discusses possible future development.

UPLC-Q-TOF-MS metabolomic study on improvement of acute myocardial ischemia in rats by Dalbergia cochinchinensis heartwood / 中国中药杂志

This paper aimed to study the effect of Dalbergia cochinchinensis heartwood on plasma endogenous metabolites in rats with ligation of the left anterior descending coronary artery, and to analyze the mechanism of D. cochinchinensis heartwood in improving acute myocardial ischemic injury. The stability and consistency of the components in the D. cochinchinensis heartwood were verified by the establishment of fingerprint, and 30 male SD rats were randomly divided into a sham group, a model group, and a D. cochinchinensis heartwood(6 g·kg~(-1)) group, with 10 rats in each group. The sham group only opened the chest without ligation, while the other groups established the model of ligation. Ten days after administration, the hearts were taken for hematoxylin-eosin(HE) staining, and the content of heart injury indexes in the plasma creatine kinase isoenzyme(CK-MB) and lactate dehydrogenase(LDH), energy metabolism-related index glucose(Glu) content, and vascular endothelial function index nitric oxide(NO) was determined. The endogenous metabolites were detected by ultra-high-performance liquid chromatography-time-of-flight-mass spectrometry(UPLC-Q-TOF-MS). The results showed that the D. cochinchinensis heartwood reduced the content of CK-MB and LDH in the plasma of rats to relieve myocardial injury, reduced the content of Glu in the plasma, improved myocardial energy metabolism, increased the content of NO, cured the vascular endothelial injury, and promoted vasodilation. D. cochinchinensis heartwood improved the increase of intercellular space, myocardial inflammatory cell infiltration, and myofilament rupture caused by ligation of the left anterior descending coronary artery. The metabolomic study showed that the content of 26 metabolites in the plasma of rats in the model group increased significantly, while the content of 27 metabolites decreased significantly. Twenty metabolites were significantly adjusted after the administration of D. cochinchinensis heartwood. D. cochinchinensis heartwood can significantly adjust the metabolic abnormality in rats with ligation of the left anterior descending coronary artery, and its mechanism may be related to the regulation of cardiac energy metabolism, NO production, and inflammation. The results provide a corresponding basis for further explaining the effect of D. cochinchinensis on the acute myocardial injury.

Erythropoietin promotes myocardial infarction repair in mice by improving the function of Sca-1+ stem cells / 生理学报

Myocardial infarction (MI) is one of the leading causes of death in the world. With the improvement of clinical therapy, the mortality of acute MI has been significantly reduced. However, as for the long-term impact of MI on cardiac remodeling and cardiac function, there is no effective prevention and treatment measures. Erythropoietin (EPO), a glycoprotein cytokine essential to hematopoiesis, has anti-apoptotic and pro-angiogenetic effects. Studies have shown that EPO plays a protective role in cardiomyocytes in cardiovascular diseases, such as cardiac ischemia injury and heart failure. EPO has been demonstrated to protect ischemic myocardium and improve MI repair by promoting the activation of cardiac progenitor cells (CPCs). This study aimed to investigate whether EPO can promote MI repair by enhancing the activity of stem cell antigen 1 positive stem cells (Sca-1+ SCs). Darbepoetin alpha (a long-acting EPO analog, EPOanlg) was injected into the border zone of MI in adult mice. Infarct size, cardiac remodeling and performance, cardiomyocyte apoptosis and microvessel density were measured. Lin- Sca-1+ SCs were isolated from neonatal and adult mouse hearts by magnetic sorting technology, and were used to identify the colony forming ability and the effect of EPO, respectively. The results showed that, compared to MI alone, EPOanlg reduced the infarct percentage, cardiomyocyte apoptosis ratio and left ventricular (LV) chamber dilatation, improved cardiac performance, and increased the numbers of coronary microvessels in vivo. In vitro, EPO increased the proliferation, migration and clone formation of Lin- Sca-1+ SCs likely via the EPO receptor and downstream STAT-5/p38 MAPK signaling pathways. These results suggest that EPO participates in the repair process of MI by activating Sca-1+ SCs.

Predictive value of postoperative serum procalcitonin concentration for moderate to severe acute respiratory distress syndrome in patients undergoing cardiopulmonary bypass surgery / 中华危重病急救医学

OBJECTIVE@#To explore the changes of serum procalcitonin (PCT) level in patients with moderate and severe acute respiratory distress syndrome (ARDS) after cardiac surgery under cardiopulmonary bypass (CPB), and try to find out the best cut-off of PCT to predict the progression to moderate and severe ARDS.@*METHODS@#Medical records of patients undergoing cardiac surgery with CPB in Fujian Provincial Hospital from January 2017 to December 2019 were retrospectively analyzed. Adult patients who were admitted in intensive care unit (ICU) for more than 1 day and had PCT values on the first postoperative day were enrolled. Clinical data such as patient demographics, past history, diagnosis, and New York Heart Association (HYHA) classification, and the operation mode, procedure duration, CPB duration, aortic clamp duration, intraoperative fluid balance, calculation of 24 hours postoperative fluid balance and vasoactive-inotropic score (VIS); 24 hours postoperative C-reactive protein (CRP), N-terminal B-type natriuretic peptide precursor (NT-proBNP) and PCT levels were collected. Two clinicians independently made the diagnosis of ARDS according to the Berlin definition, and the diagnosis was established only in patients with a consistent diagnosis. The differences in each parameter were compared between patients with moderate to severe ARDS and those without or with mild ARDS. Analysis of the ability of PCT to predict moderate to severe ARDS was evaluated by receiver operator characteristic curve (ROC curve). Multivariate Logistic regression was conducted to determine the risk factors of the development of moderate to severe ARDS.@*RESULTS@#108 patients were finally enrolled, including 37 patients with mild ARDS (34.3%), 35 patients with moderate ARDS (32.4%), 2 patients with severe ARDS (1.9%), and 34 patients without ARDS. Compared with patients with no or mild ARDS, patients with moderate to severe ARDS were older (years old: 58.5±11.1 vs. 52.8±14.8, P < 0.05), with a higher proportion of combined hypertension [45.9% (17/37) vs. 25.4% (18/71), P < 0.05], longer operative time (minutes: 363.2±120.6 vs. 313.5±97.6, P < 0.05), and higher mortality (8.1% vs. 0, P < 0.05), but there were no differences in the VIS score, incidence of acute renal failure (ARF), CPB duration, aortic clamp duration, and intraoperative bleeding, transfusion volume, and fluid balance between the two groups. Serum PCT and NT-proBNP levels in patients with moderate to severe ARDS at postoperative day 1 were significantly higher than those in patients with no or mild ARDS [PCT (μg/L): 16.33 (6.96, 32.56) vs. 2.21 (0.80, 5.76), NT-proBNP (ng/L): 2 405.0 (1 543.0, 6 456.5) vs. 1 680.0 (1 388.0, 4 667.0), both P < 0.05]. ROC curve analysis showed that the area under the curve (AUC) for PCT to predict the occurrence of moderate to severe ARDS was 0.827 [95% confidence interval (95%CI) was 0.739-0.915, P < 0.05]. When PCT cut-off value was 7.165 μg/L, the sensitivity was 75.7% and the specificity was 84.5%, for differentiating patients who developed moderate to severe ARDS from who did not. Multivariate Logistic regression showed that age and the elevated PCT concentration were independent risk factors for the development of moderate to severe ARDS [age: odds ratio (OR) = 1.105, 95%CI was 1.037-1.177, P = 0.002; PCT: OR = 48.286, 95%CI was 10.282-226.753, P < 0.001].@*CONCLUSIONS@#Patients with moderate to severe ARDS undergoing CPB cardiac surgery have a higher serum concentration of PCT than patients with no or mild ARDS. Serum PCT level may be a promising biomarker to predict the development of moderate to severe ARDS, the cut-off value is 7.165 μg/L.

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.

Perforation of the esophagus: an overlooked cause of chest pain as a complication of esophageal foreign bodies / 浙江大学学报（英文版）（B辑：生物医学和生物技术）

Chest pain is one of the most common complaints in the emergency department. Diseases of the heart, aorta, lungs, esophagus, stomach, mediastinum, pleura, and abdominal viscera can all cause chest discomfort (Gulati et al., 2021; Jiao et al., 2021; Lu et al., 2022). Clinicians in the emergency department are expected to immediately recognize life-threatening chest pain (Jiao et al., 2021). Delayed diagnosis further increases the risk of complications and mortality (Liu et al., 2021). In this case, we present an elderly Chinese female who had a history of myocardial infarction two years previously, with chest pain eventually found to be caused by ingestion of a duck bone.