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.

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.

Cuidados paliativos y su influencia en la calidad de vida de pacientes con insuficiencia cardíaca / Palliative care and its influence on the quality of life of patients with heart failure

La insuficiencia cardíaca congestiva es parte importante de la morbimortalidad mundial. Estos pacientes pierden calidad de vida de manera considerable, particularmente por su trayecto impredecible. Los cuidados paliativos representan una oportunidad para mejorar el control sintomático y prevenir reingresos hospitalarios, especialmente en las fases avanzadas de la enfermedad (New York Heart Association III-IV). El objetivo de esta revisión es determinar la influencia de los cuidados paliativos en la calidad de vida de los pacientes con insuficiencia cardíaca en enfermedad avanzada, puesto que se ha demostrado que sufren múltiples hospitalizaciones: 84% tendrá ≥1 en sus últimos 12 meses de vida, y el reingreso hospitalario a los 30 días posteriores al alta circunda 20-50 %. En general, reciben menos cuidados paliativos que los pacientes oncológicos, y al recibirlos lo hacen presentando una menor funcionalidad (p<0,001). Al implementar los cuidados paliativos aumenta la calidad de vida (p=0,03) y mejoran la depresión (p=0,02), la ansiedad (p=0,048) y la frecuencia de reingresos hospitalarios en comparación con el manejo usual, 33,63 % vs. 61 %, y visitas a emergencias, 35,0 % vs. 60,0 %. Múltiples evidencias señalan que la mortalidad no es influenciada (p>0,19, p>0,22). Según la bibliografía, se concluye que los cuidados paliativos deben ser implementados desde el diagnóstico de esta patología, puesto que ofrecen una mayor calidad de vida, especialmente en enfermedad avanzada

Congestive heart failure is an important part of global morbidity and mortality. These patients lose quality of life considerably, particularly due to their unpredictable path. Palliative care represents an opportunity to improve symptom control and prevent hospital readmissions, especially in the advanced stages of the disease (New York Heart Association III-IV). The objective of this review is to determine the influence of palliative care on the quality of life of patients with heart failure in advanced disease, since it has been shown that they suffer multiple hospitalizations: 84% will have ≥1 in their last 12 months of life, and hospital readmission 30 days after discharge is around 20-50%. In general, they receive less palliative care than cancer patients, and when they receive it they do so with less functionality (p<0.001). When implementing palliative care, quality of life increases (p=0.03) and depression (p=0.02), anxiety (p=0.048) and the frequency of hospital readmissions improve compared to usual management, 33 .63%vs. 61%, and ER visits, 35.0% vs. 60.0%. Multiple pieces of evidence indicate that mortality is not influenced (p>0.19, p>0.22). According to the bibliography, it is concluded that palliative care should be implemented from the diagnosis of this pathology, since it offers a better quality of life, especially in advanced disease

Impacto cardiovascular, conducta diagnóstica y terapéutica del feocromocitoma como causa de hipertensión arterial / Cardiovascular impact, diagnostic and therapeutic management of pheochromocytoma as a cause of arterial hypertension

INTRODUCCIÓN. Los feocromocitomas son tumores que provienen de las células neuroendócrinas de la médula adrenal y producen alta secreción de catecolaminas. Generan complicaciones cardiovasculares graves que suelen asociarse con crisis hipertensivas. Es importante valorar el impacto cardiovascular de esta entidad. OBJETIVO. Realizar una revisión exhaustiva de las diversas manifestaciones de los feocromocitomas como causa de hipertensión arterial, su impacto cardiovascular, conducta diagnóstica y terapéutica. MATERIALES Y MÉTODOS. Revisión bibliográfica y análisis de 141 artículos científicos que incluyeron temas sobre el impacto cardiovascular, conducta diagnóstica y terapéutica del feocromocitoma como causa de hipertensión arterial. Se usó bases de datos: Medline, Embase, Scopus, Pubmed, Google Académico. Criterios de búsqueda en DECS, MeSH: "pheochromocytoma OR hypertension arterial AND cardiomyopathy", en inglés- español. Fueron seleccionados: 13 publicaciones de texto completo, 10 artículos retrospectivos, 2 guías de práctica clínica y 1 revisión. Se excluyeron 128 artículos científicos. RESULTADOS. Se realizó una revisión de las manifestaciones clínicas de los feocromocitomas como causa de hipertensión arterial y el impacto cardiovascular se relacionó con la producción de catecolaminas. Para el diagnóstico, la sensibilidad de la resonancia magnética es del 93-100%; la especificidad de resonancia magnética o tomografía computarizada en combinación con gammagrafía con metayodobencilguanidina con 123I es cercana al 100%. La resección del feocromocitoma tiene potencial curativo. CONCLUSIÓN. Los feocromocitomas presentan variabilidad clínica, se asocian a complicaciones cardiovasculares y cerebrovasculares graves por producción de catecolaminas. El diagnóstico oportuno y eficaz debe realizarse mediante resonancia magnética y gammagrafía en caso de alta sospecha clínica. El tratamiento quirúrgico es de elección.

INTRODUCTION. Pheochromocytomas are tumors arising from the neuroendocrine cells of the adrenal medulla and produce high secretion of catecholamines. They generate severe cardiovascular complications that are often associated with hypertensive crises. It is important to assess the cardiovascular impact of this entity. OBJECTIVE. To perform an exhaustive review of the various manifestations of pheochromocytomas as a cause of arterial hypertension, their cardiovascular impact, diagnostic and therapeutic conduct. MATERIALS AND METHODS. Bibliographic review and analysis of 141 scientific articles that included topics on the cardiovascular impact, diagnostic and therapeutic behavior of pheochromocytoma as a cause of arterial hypertension. The following databases were used: Medline, Embase, Scopus, Pubmed, Google Scholar. Search criteria in DECS, MeSH: "pheochromocytoma OR hypertension arterial AND cardiomyopathy", in English-Spanish. The following were selected: 13 full-text publications, 10 retrospective articles, 2 clinical practice guidelines, and 1 review. A total of 128 scientific articles were excluded. RESULTS. A review of the clinical manifestations of pheochromocytoma as a cause of arterial hypertension was performed and the cardiovascular impact was related to catecholamine production. For diagnosis, the sensitivity of MRI is 93-100%; the specificity of MRI or computed tomography in combination with 123I-methiodobenzylguanidine scintigraphy is close to 100%. Resection of pheochromocytoma has curative potential. CONCLUSION. Pheochromocytomas present clinical variability, are associated with severe cardiovascular and cerebrovascular complications due to catecholamine production. Timely and effective diagnosis should be made by MRI and scintigraphy in case of high clinical suspicion. Surgical treatment is the treatment of choice.

Efeitos do Exercício Aeróbico Tardio na Remodelação Cardíaca de Ratos com Infarto do Miocárdio Pequeno / Effects of Late Aerobic Exercise on Cardiac Remodeling of Rats with Small-Sized Myocardial Infarction

Resumo Fundamento: O exercício físico tem sido considerado uma importante terapia não farmacológica para a prevenção e tratamento das doenças cardiovasculares. No entanto, seus efeitos na remodelação cardíaca leve não são claros. Objetivo: Avaliar a influência do exercício aeróbico sobre a capacidade funcional, estrutura cardíaca, função ventricular esquerda (VE) e expressão gênica das subunidades da NADPH oxidase em ratos com infarto do miocárdio pequeno (IM). Métodos: Três meses após a indução do IM, ratos Wistar foram divididos em três grupos: Sham; IM sedentário (IM-SED); e IM exercício aeróbico (IM-EA). Os ratos se exercitaram em uma esteira três vezes por semana durante 12 semanas. Um ecocardiograma foi realizado antes e após o treinamento. O tamanho do infarto foi avaliado por histologia e a expressão gênica por RT-PCR. O nível de significância para análise estatística foi estabelecido em 5%. Resultados: Ratos com IM menor que 30% da área total do VE foram incluídos no estudo. A capacidade funcional foi maior no IM-EA do que nos ratos Sham e IM-SED. O tamanho do infarto não diferiu entre os grupos. Ratos infartados apresentaram aumento do diâmetro diastólico e sistólico do VE, diâmetro do átrio esquerdo e massa do VE, com disfunção sistólica. A espessura relativa da parede foi menor no grupo IM-SED do que nos grupos IM-EA e Sham. A expressão gênica das subunidades NADPH oxidase NOX2, NOX4, p22phox e p47phox não diferiu entre os grupos. Conclusão: Infarto do miocárdio pequeno altera a estrutura cardíaca e a função sistólica do VE. O exercício aeróbico tardio pode melhorar a capacidade funcional e a remodelação cardíaca por meio da preservação da geometria ventricular esquerda. A expressão gênica das subunidades da NADPH oxidase não está envolvida na remodelação cardíaca, nem é modulada pelo exercício aeróbico em ratos com infarto do miocárdio pequeno.

Abstract Background: Physical exercise has been considered an important non-pharmacological therapy for the prevention and treatment of cardiovascular diseases. However, its effects on minor cardiac remodeling are not clear. Objective: To evaluate the influence of aerobic exercise on the functional capacity, cardiac structure, left ventricular (LV) function, and gene expression of NADPH oxidase subunits in rats with small-sized myocardial infarction (MI). Methods: Three months after MI induction, Wistar rats were divided into three groups: Sham; sedentary MI (MI-SED); and aerobic exercised MI (MI-AE). The rats exercised on a treadmill three times a week for 12 weeks. An echocardiogram was performed before and after training. The infarction size was evaluated by histology, and gene expression was assessed by RT-PCR. The significance level for statistical analysis was set at 5%. Results: Rats with MI lower than 30% of the LV total area were included in the study. Functional capacity was higher in MI-AE than in Sham and MI-SED rats. The infarction size did not differ between groups. Infarcted rats had increased LV diastolic and systolic diameter, left atrial diameter, and LV mass, with systolic dysfunction. Relative wall thickness was lower in MI-SED than in the MI-AE and Sham groups. Gene expression of the NADPH oxidase subunits NOX2, NOX4, p22phox, and p47phox did not differ between groups. Conclusion: Small-sized MI changes cardiac structure and LV systolic function. Late aerobic exercise is able to improve functional capacity and cardiac remodeling by preserving the left ventricular geometry. NADPH oxidase subunits gene expression is not involved in cardiac remodeling or modulated by aerobic exercise in rats with small-sized MI.

Acciones cardiovasculares directas del paracetamol / Direct cardiovascular actions of paracetamol

Introducción: El paracetamol es uno de los antiinflamatorios no esteroideos con efecto analgésico y antipirético más utilizados a nivel mundial. Pocos estudios se enfocan en esclarecer los mecanismos de acción a nivel cardiovascular. Objetivos: Evaluar la acción del paracetamol sobre la fuerza de contracción de anillos de aorta torácica y sobre la actividad eléctrica y contráctil de corazones aislados y perfundidos de ratas Wistar. Métodos: Se midieron los efectos del paracetamol sobre anillos de aorta de rata denudados de su endotelio vascular. Se estudiaron las acciones del fármaco sobre los corazones aislados y perfundidos de las ratas por el método de Langendorff. Se evaluó la amplitud de la fuerza de contracción cardiaca y los intervalos QT, QTc, QRS y RR del electrocardiograma. Las condiciones (control y presencia de paracetamol) fueron comparadas con una prueba t de Student para muestras pareadas (p < 0,05), previa comprobación de la normalidad de los datos. Resultados: El paracetamol no tuvo efectos sobre el músculo liso vascular de los anillos aórticos ni sobre los intervalos QT, QTc, QRS y RR del electrocardiograma bajo ninguna de las concentraciones empleadas. Por otra parte, mostró efecto inotrópico negativo estadísticamente significativo en los corazones aislados, de forma dependiente de la concentración del fármaco. La IC50 estimada para la inhibición de la fuerza de contracción cardiaca fue de 17,15 ± 5,33 µmol/L. Conclusiones: Las acciones cardiovasculares directas del paracetamol son modestas, lo cual contribuye al buen margen de seguridad para su uso en clínica, en pacientes sin enfermedad cardiovascular(AU)

Introduction: Paracetamol is among the non-steroidal anti-inflammatory, analgesic and antipyretic drugs most commonly used worldwide. Few studies have focused on clarifying its mechanisms of action on a cardiovascular level. Objectives: Evaluate the action of paracetamol on the force of contraction of thoracic aortic rings and on the electrical and contractile activity of isolated perfused Wistar rat hearts. Methods: Measurements were taken of the effects of paracetamol on rat aortic rings denuded of their vascular endothelium. Analysis was performed of the actions of the drug on the isolated perfused rat hearts using the Langendorff method. Evaluation was conducted of the amplitude of the force of cardiac contraction and of intervals QT, QTc, QRS and RR of the electrocardiogram. The conditions (control and presence of paracetamol) were compared with a paired samples Student's t-test (p < 0.05) upon verification of the normality of the data. Results: Paracetamol had no effects on the vascular smooth muscle of aortic rings or on intervals QT, QTc, QRS and RR of the electrocardiogram at none of the concentrations used. On the other hand, it displayed a statistically significant negative inotropic effect on the isolated hearts dependent on drug concentration. The IC50 estimated for inhibition of the force of cardiac contraction was 17.15 ± 5.33 µmol/L. Conclusions: The direct cardiovascular actions of paracetamol are modest, which contributes to a good safety margin for its clinical use in patients without cardiovascular disease(AU)

Manejo del Infarto Agudo de Miocardio con elevación de ST en pacientes adultos de la Unidad Técnica de Cardiología del HECAM / Management of ST elevation Acute Myocardial Infarction in adult patients of the Technical Unit of Cardiology of HECAM

INTRODUCCIÓN: La enfermedad isquémica cardiaca es la pri-mera causa de muerte a nivel mundial. A pesar de no tener estadísticas certeras, Amé-rica Latina incurre en la tendencia de un au-mento en la mortalidad por enfermedad car-diovascular; una de las probables causas es la rápida urbanización que ha sido asociada a mayor exposición de riesgo cardiovas-cular1. Es sabido que la única medida efec-tiva para preservar la función ventricular y disminuir la mortalidad, reinfarto y acci-dente cerebrovascular es la apertura rápida de la arteria culpada para reestablecer el flujo coronario2.

INTRODUCTION: Ischemic heart disease is the leading cause of death worldwide. Despite not having ac-curate statistics, Latin America incurs the trend of an increase in mortality from car-diovascular disease; one of the probable causes is rapid urbanization that has been associated with greater exposure to car-diovascular risk1. It is known that the only effective measure to preserve ventricular function and reduce mortality, reinfarction and stroke is the rapid opening of the culprit artery to reestablish coronary flow2.

Celebración del Día Mundial del Corazón en época de pandemia / Celebrating World Heart Day in a time of pandemic

La Federación Mundial del Corazón, con el apoyo de la Organización Mundial de la Salud (OMS) y La Organización de las Naciones Unidas para la Educación, la Ciencia y la Cultura (UNESCO), han designado desde el año 2000, el día 29 de septiembre como el "Día Mundial del Corazón". Esto obedece a la necesidad sentida de dar a conocer a la comunidad, en forma general y masiva, la importancia de las enfermedades cardiovasculares y su impacto en la salud mundial, e incentivar estrategias para su prevención, control y tratamiento. Desde entonces, en colaboración con la OMS, la Federación Mundial del Corazón organiza cada año en más de cien países, eventos que ayudan a adquirir conciencia sobre enfermedades cardiovasculares, como infarto agudo del miocardio, accidente cerebrovascular, hipertensión arterial y otras condiciones que afecten el miocardio y las arterias, ya que son, infortunadamente, las más mortíferas del mundo, pues no en vano generan 17,8 millones de muertes al año.

Unusual hydatid cysts: cardiac and pelvic-ilio femoral hydatid cyst case reports and literature review

Abstract Introduction: Hydatid cyst is a parasitic disease caused by Echinococcus granulosus, most commonly seen in the liver and lungs. The hydatid cyst is rarely seen in the heart and iliofemoral region, representing less than 2% of all cases. In this article, we report our cases of hydatid cysts in unusual loci. Methods: Between 2015 and 2018, 6 rare cases of hydatid cysts were diagnosed at the Cardiovascular Surgery Department of Harran University. Four of these patients had cardiac localization and two patients had their cysts located in the iliofemoral region, extending to the pelvic zone. All patients were female. Three patients had no other organ involvement. One patient with cardiac hydatid cyst underwent normothermic cardiopulmonary bypass + total pericystectomy + Cooley-like aneurysmectomy. Total pericystectomy was performed in three other patients with intrathoracic locus by normothermic cardiopulmonary bypass. Two patients who were referred to our clinic with palpable iliofemoral mass were evaluated with appropriate imaging methods and diagnosed accordingly. Multiple iliofemoral cysts were managed with pericystectomy and drainage by a single incision made over the inguinal ligament. Conclusion: Hydatid cyst disease can develop in cardiac chambers and inguinal region with or without hepatic or pneumatic involvement. Normothermic cardiopulmonary bypass can be safely used in patients with cardiac hydatid cysts, and capitonnage similar to ventricular aneurysm repair in patients with a widely involved cystic lesion can be very useful for the protection of ventricular functions.

Three-dimensional printing: is it useful for cardiac surgery?

Abstract Introduction: The medical use of three-dimensional (3-D) images has been a topic in the literature since 1988, but 95% of papers on 3-D printing were published in the last six years. The increase in publications is the result of advances in 3-D printing methods, as well as of the increasing availability of these machines in different hospitals. This paper sought to review the literature on 3-D printing and to discuss thoughtful ideas regarding benefits and challenges to its incorporation into cardiothoracic surgeons' routines. Methods: A comprehensive and systematic search of the literature was performed in PubMed and included material published as of March 2020. Results: Using this search strategy, 9,253 publications on 3-D printing and 497 on "heart" 3-D printing were retrieved. Conclusion: 3 -D printed models are already helping surgeons to plan their surgeries, helping patients and their families to understand complex anatomy, helping fellows and residents to practice surgery, even for rare cases, and helping nurses and other health care staff to better understand some conditions, such as heart diseases.

Hidroxicloroquina: Mensajes desde la cardiología en tiempos de pandemia por Coronavirus / Hydroxychloroquine. Cardiology's viewpoint in times of coronavirus pandemic

Ante la pandemia de COVID-19 (del inglés coronavirus disease 2019), uno de los fármacos propuesto para su tratamiento es la hidroxicloroquina. Se revisan aquí aspectos cardiológicos del uso de cloroquina e hidroxicloroquina. Se realizó una revisión no sistemática en la literatura médica orientada a la búsqueda de información acerca de su seguridad y eficacia como antimaláricos y antivirales, así como en el tratamiento prolongado de enfermedades reumatológicas. Se halló un efecto antiinflamatorio con reducción de eventos cardiovasculares a largo plazo, una cardiopatía muy infrecuente por un efecto lisosomal del fármaco, y a nivel hemodinámico hipotensión, taquicardia, y prolongación del intervalo QT, exacerbado si se combina con azitromicina. Sin embargo, la tasa de eventos adversos cardíacos de la hidroxicloroquina y la cloroquina fue baja.

Due to the coronavirus disease 2019 (COVID-19) pandemic, a wide number of compounds are under scrutiny regarding their antiviral activity, one of them being hydroxychloroquine. Cardiac aspects of the use of chloroquine and hydroxychloroquine are reviewed in this manuscript. A non-systematic review of the medical literature was performed. Information about their safety and efficacy as antimalarials, antivirals, as well as in the long-term treatment of rheumatic diseases was collected. We found an anti-inflammatory effect with reduction of long-term cardiovascular events, a very infrequent heart disease due to a lysosomal effect of the drug, and at the hemodynamic level hypotension, tachycardia, and QT interval prolongation, exacerbated when combined with azithromycin. However, the rate of adverse cardiac events of hydroxychloroquine (and chloroquine) was low.

O Coração e a COVID-19: O que o Cardiologista Precisa Saber / The Heart and COVID-19: What Cardiologists Need to Know

Resumo Frente à pandemia da doença causada pelo novo coronavírus (COVID-19), o manejo do paciente com fator de risco e/ou doença cardiovascular é desafiador nos dias de hoje. As complicações cardiovasculares evidenciadas nos pacientes com COVID-19 resultam de vários mecanismos, que vão desde lesão direta pelo vírus até complicações secundárias à resposta inflamatória e trombótica desencadeada pela infecção. O cuidado adequado do paciente com COVID-19 exige atenção ao sistema cardiovascular em busca de melhores desfechos.

Abstract In face of the pandemic of the novel coronavirus disease 2019 (COVID-19), the management of patients with cardiovascular risk factors and/or disease is challenging. The cardiovascular complications evidenced in patients with COVID-19 derive from several mechanisms, ranging from direct viral injury to complications secondary to the inflammatory and thrombotic responses to the infection. The proper care of patients with COVID-19 requires special attention to the cardiovascular system aimed at better outcomes.

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.

Future Directions in Coronary CT Angiography: CT-Fractional Flow Reserve, Plaque Vulnerability, and Quantitative Plaque Assessment

Coronary computed tomography angiography (CCTA) is a well-validated and noninvasive imaging modality for the assessment of coronary artery disease (CAD) in patients with stable ischemic heart disease and acute coronary syndromes (ACSs). CCTA not only delineates the anatomy of the heart and coronary arteries in detail, but also allows for intra- and extraluminal imaging of coronary arteries. Emerging technologies have promoted new CCTA applications, resulting in a comprehensive assessment of coronary plaques and their clinical significance. The application of computational fluid dynamics to CCTA resulted in a robust tool for noninvasive assessment of coronary blood flow hemodynamics and determination of hemodynamically significant stenosis. Detailed evaluation of plaque morphology and identification of high-risk plaque features by CCTA have been confirmed as predictors of future outcomes, identifying patients at risk for ACSs. With quantitative coronary plaque assessment, the progression of the CAD or the response to therapy could be monitored by CCTA. The aim of this article is to review the future directions of emerging applications in CCTA, such as computed tomography (CT)-fractional flow reserve, imaging of vulnerable plaque features, and quantitative plaque imaging. We will also briefly discuss novel methods appearing in the coronary imaging scenario, such as machine learning, radiomics, and spectral CT.

CD36 (SR-B2) as a Target to Treat Lipid Overload-Induced Cardiac Dysfunction

The heart faces the challenge of adjusting the rate of fatty acid uptake to match myocardial demand for energy provision at any given moment, avoiding both too low uptake rates, which could elicit an energy deficit, and too high uptake rates, which pose the risk of excess lipid accumulation and lipotoxicity. The transmembrane glycoprotein cluster of differentiation 36 (CD36), a scavenger receptor (B2), serves many functions in lipid metabolism and signaling. In the heart, CD36 is the main sarcolemmal lipid transporter involved in the rate-limiting kinetic step in cardiac lipid utilization. The cellular fatty acid uptake rate is determined by the presence of CD36 at the cell surface, which is regulated by subcellular vesicular recycling from endosomes to the sarcolemma. CD36 has been implicated in dysregulated fatty acid and lipid metabolism in pathophysiological conditions, particularly high-fat diet-induced insulin resistance and diabetic cardiomyopathy. Thus, in conditions of chronic lipid overload, high levels of CD36 are moved to the sarcolemma, setting the heart on a route towards increased lipid uptake, excessive lipid accumulation, insulin resistance, and eventually contractile dysfunction. Insight into the subcellular trafficking machinery of CD36 will provide novel targets to treat the lipid-overloaded heart. A screen for CD36-dedicated trafficking proteins found that vacuolar-type H⁺-ATPase and specific vesicle-associated membrane proteins, among others, were uniquely involved in CD36 recycling. Preliminary data suggest that these proteins may offer clues on how to manipulate myocardial lipid uptake, and thus could be promising targets for metabolic intervention therapy to treat the failing heart.

Composition of Ophiopogon Polysaccharide, Notoginseng Total Saponins and Rhizoma Coptidis Alkaloids Inhibits the Myocardial Apoptosis on Diabetic Atherosclerosis Rabbit / 中国结合医学杂志

OBJECTIVE@#To investigate the effects of Composition of Ophiopogon polysaccharide, Notoginseng total saponins and Rhizoma Coptidis alkaloids (CONR) on myocardial apoptosis of diabetic atherosclerosis (DA) rabbits METHODS: Sixty male New Zealand white rabbits were randomly divided into 6 groups [control group, model group, CONR high-dose group (450 mg/kg), CONR medium-dose group (150 mg/kg), CONR low-dose group (50 mg/kg), and simvastatin group] by using a completely random method, 10 in each group. DA model was established by intravenously injected alloxan combined with high-fat diet and abdominal aortic balloon injury. After mediation for 10 weeks, fasting blood glucose (FBG), glycosylated hemoglobin (GHB), glycosylated serum protein (GSP), fructoseamine (FRA), aldose reductase (AR), advanced glycation end products (AGEs) in serum were measured by enzyme linked immunosorbent assay (ELISA) method; the expression of receptor of AGEs (RAGE) in myocardial tissue were observed by immunohistochemical method; and p-Jun N-terminal kinase (p-JNK), caspase-3, B-cell lymphoma-2 (bcl-2) protein expression in myocardial tissue were measured by Western blotting. The myocardial apoptosis was detected by TdT-mediated dUTPnick-end labeling (TUNEL) method, and apoptosis index (AI) was calculated.@*RESULTS@#Compared with the control group, serum FBG, GHB, GSP, FRA, AR, AGEs and the expression of myocardium RAGE, p-JNK, caspase-3 proteins, as well as apoptosis index (AI) were significantly increased and bcl-2 protein was significantly decreased in the model group (P<0.01). Compared with the model group, the levels of serum FBG, GHB, GSP, FRA and AR showed a significant decline in CONR high- and medium-dose groups (P<0.01). FBG and GHB showed a significant decline in CONR low-dose group (P<0.01). Compared with the model group, the expression of serum AGEs and myocardium RAGE, p-JNK and caspase-3 protein as well as AI were significantly decreased and bcl-2 protein was significantly up-regulated in all treatment groups (P<0.01); high-dose CONR had the most significant effect on abovementioned indices compared with other treatment groups (P<0.01). Middle-dose CONR had better effect on serum AGEs compared with the low-dose group (P<0.01); middle-dose CONR and simvastatin groups had better effect on the expression of caspase-3, bcl-2 protein, myocardium apoptosis compared with the CONR low-dose group (P<0.01).@*CONCLUSION@#CONR may effectively inhibit myocardial apoptosis on DA rabbits by intervening AGEs-RAGE and JNK, caspase-3, and bcl-2 protein expressions.

Effects of electroacupuncture pretreatment on cardiac function and immune inflammatory response in mice with acute myocardial ischemia / 中国针灸

OBJECTIVE@#To observe the effects of electroacupuncture (EA) pretreatment on the cardiac ejection fraction (EF), the number of macrophages in spleen and heart, and the expression of nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3) and interleukin-1β (IL-1β) in myocardium in mice with acute myocardial ischemia, and to explore the possible mechanism of EA pretreatment on promoting myocardial protection.@*METHODS@#A total of 30 male C57BL/6J mice were randomly divided into a control group, a model group and an EA pretreatment group, 10 rats in each group. The acute myocardial ischemia model was established by ligating the left anterior descending branch of the coronary artery in the model group and EA pretreatment group, while threading but no ligating at left anterior descending branch of the coronary artery was applied in the control group. In the EA pretreatment group, mice were intervented with EA at bilateral "Neiguan" (PC 6), disperse-dense wave, frequency of 2 Hz/15 Hz, intensity of 2 mA; each EA treatment last for 20 min, once a day, and 3-day treatment was given before model establishment. The EF value was evaluated by ultrasonic cardiogram; the number of macrophages in spleen and heart was measured by flow cytometry; the expression level of NLRP3 and IL-1β in myocardium was measured by Western blot.@*RESULTS@#Compared with the control group, the EF value was decreased in the model group (<0.001), the number of macrophages in the heart and spleen was increased (<0.001), and the expression level of NLRP3 and IL-1β in the myocardium was increased (<0.001, <0.01). Compared with the model group, the EF value was increased in the EA pretreatment group (<0.01), the number of macrophages in the heart and spleen was decreased (<0.01), and the expression level of NLRP3 and IL-1β in the myocardium was decreased (<0.01, <0.05).@*CONCLUSION@#EA pretreatment could reduce the number of macrophages in spleen and heart, down-regulate the expression of NLRP3 and IL-1β in myocardial tissue in mice with acute myocardial ischemia, which could relieve the local inflammatory response and achieve the myocardial protective effect.