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.

Absceso en miocardio secundario a neumonía adquirida en la comunidad por Pseudomona aeruginosa en lactante inmunocompetente: reporte de caso / Myocardial abscess secondary to community acquired Pseudomona aeruginosa pneumonia in an immunocompetent infant: case report

La Pseudomona aeruginosa es una causa importante de infecciones asociadas a la atención de la salud y en las neumonías adquiridas en la comunidad, rara vez se identifica como el agente patógeno, siendo estas de progresión rápida y de mal pronóstico. Se trata de un menor de un año de edad inmunocompetente el cual fallece en casa una semana después de una lesión en la planta del pie derecho que según familiares le sacaron "pus", tratado con antinflamatorios y analgésicos. Se le realizó necropsia que evidenció cicatriz en planta de pie derecho sin lesiones traumáticas. Pulmones de consistencia indurada, con adherencias y áreas que impresionan necróticas, asociada a efusión pleural. El estudio histológico reportó un proceso infeccioso pulmonar agudo abscedado que se diseminó por continuidad a tejido cardiaco y en estudios microbiológicos de pulmón y bazo se reportó Pseudomona aeruginosa.

Pseudomona aeruginosa is an important cause of health care-associated infections and in community-acquired pneumonias, it is rarely identified as the pathogenic agent, being of rapid progression and poor prognosis. This is a one-year-old immunocompetent minor who died at home one week after a lesion in the sole of the right foot which, according to family members, caused "pus", treated with anti-inflammatory and analgesic drugs. A necropsy was performed, which showed a scar on the sole of the right foot with no traumatic lesions. Lungs of indurated consistency, with adhesions and areas that appear necrotic, associated with pleural effusion. The histological study reported an abscessed acute pulmonary infectious process that spread by continuity to cardiac tissue and microbiological studies of lung and spleen reported Pseudomona aeruginosa.

Chronic Obstructive Pulmonary Disease: The Role of Myocardial Deformation Indices and Right Ventricle Three-Dimensional Echocardiography

Abstract Background: Right ventricular dysfunction is a major complication in chronic obstructive pulmonary disease (COPD) and, despite its prognostic implications, is rarely considered in routine clinical analysis. Objectives: To compare RV function variables with standard and advanced echocardiographic techniques in patients with stable COPD and controls. Methods: Twenty COPD patients classified as GOLD ≥ II (13 men aged 68.4 ± 8.3 years) and 20 matched controls were compared. Myocardial strain/strain rate indices were obtained by tissue Doppler and two-dimensional speckle tracking echocardiography. Right ventricular ejection fraction was obtained with three-dimensional software. Free wall myocardial thickness (FWMT) and tricuspid annular systolic excursion (TAPSE) were also measured. Numerical variables were compared between groups with Student's t-test or the Mann-Whitney test. Associations between categorical variables were determined with Fisher's exact test. P-values < 0.05 were considered statistically significant. Results: All myocardial deformation indices, particularly global longitudinal strain (-17.2 ± 4.4 vs -21.2: ± 4.4 = 0.001) and 3D right ventricular ejection fraction (40.8 ± 9.3% vs 51.1 ± 6.4% p <0.001) were reduced in COPD patients. These patients presented higher right ventricular FWMT and lower TAPSE values than controls. Conclusion: Myocardial deformation indices, either tissue Doppler or speckle tracking echocardiography and 3D right ventricular ejection fraction, are robust markers of right ventricular dysfunction in patients with stable COPD. Assessing global longitudinal strain by speckle tracking echocardiography is a more practical and reproducible method.

The Role of the Immune System on the Cardiac Complications Observed in SARS-CoV-2

Abstract An acute respiratory syndrome caused by SARS-CoV2 was declared a pandemic by the World Health Organization. Current data in the world and in Brazil show that approximately 40% of patients who died have some type of cardiac comorbidity. There are also robust reports showing an increase in IL-6 / IL-1B / TNF-alpha and the presence of lymphopenia in patients with COVID-19. Our team and others have shown that increased cytokines are the link between arrhythmias/Left ventricular dysfunction and the immune system in different diseases. In addition, it has been well demonstrated that lymphopenia can not only be a good marker, but also a factor that causes heart failure. Thus, the present review focused on the role of the immune system upon the cardiac alterations observed in the SARS-CoV2 infection. Additionally, it was well described that SARS-CoV-2 is able to infect cardiac cells. Therefore, here it will be reviewed in deep.

Calcificación miocárdica de etiología multifactorial / Myocardial calcification with multifactorial etiology

En el presente trabajo se describe un caso de muerte súbita en una mujer de 70 años que fallece 20 días después de ser dada de alta tras ingreso por infección urinaria secundaria a litiasis renal complicada con shock séptico e insuficiencia renal y respiratoria. En el corazón se identificó una cardiopatía isquémica crónica y extensas áreas de miocardio calcificado. Además, se exponen los tipos de calcificaciones del miocardio existentes y sus causas; y se analizan aquellos factores que en el caso presentado han podido causar la calcificación del miocardio(AU)

In the present report, we describe a case of sudden death in a 70-year-old woman who died 20 days after been discharged after admission for urinary infection secondary to renal lithiasis complicated with septic shock and renal and respiratory failure. It has been identified chronic ischemic heart disease and extensive areas of calcified myocardium. Also, we review myocardial calfications subtypes and its causes, and we analyze the specifics of the presented case(AU)

Acompanhamento a longo prazo de paciente do sexo masculino com fibroma cardíaco assintomático / Long-Term follow-up of an asymptomatic man with a cardiac fibroma

Descreve-se o caso de um homem de 19 anos assintomático com fibroma de ventrículo esquerdo em acompanhamento por 15 anos, sem tratamento.(AU)

Here we describe a case of a 19-year-old asymptomatic man with a left ventricular fibroma on follow-up for 15 years with no treatment required.(AU)

Fatores associados a anormalidades na cintilografia de perfusão miocárdica de pacientes diabéticos / Factors associated with abnormalities on myocardial perfusion scintigraphy in diabetic patients

O diabetes melito é o maior fator de risco para doença arterial coronariana. Além da longa duração de diabetes, outros fatores, como presença de doença arterial periférica e tabagismo são fortes preditores para anormalidades na cintilografia de perfusão do miocárdio. O objetivo deste estudo foi avaliar o impacto dos fatores de risco de pacientes diabéticos nos resultados da cintilografia de perfusão do miocárdio e comparar com os resultados de pacientes não diabéticos em uma clínica de medicina nuclear. Foi realizado um estudo transversal retrospectivo por meio da análise de prontuários de pacientes que realizaram cintilografia miocárdica no período de 2010 a 2019. Foram avaliados 34.736 prontuários. Analisando a fase de estresse da cintilografia de perfusão do miocárdio, os portadores de diabetes melito precisaram receber estímulo farmacológico duas vezes mais que os não diabéticos para sua realização. Também foram avaliados fatores que tivessem impacto negativo no resultado da cintilografia de perfusão do miocárdio, e foi visto que o diabetes melito (33,6%), a insulinoterapia (18,1%), a hipertensão arterial sistêmica (69,9%), a dislipidemia (53%), o sedentarismo (83,1%), o uso de estresse farmacológico (50,6%), a dor torácica típica (8,5%) e a angina limitante durante o teste (1,7%) estiveram associados significativamente (p<0,001) a anormalidades neste exame. (AU)

Diabetes mellitus (DM) is the greatest risk factor for coronary artery disease. In addition to a long duration of diabetes, the presence of peripheral arterial disease and smoking are strong predictors of abnormalities on myocardial perfusion scintigraphy (MPS). This study aimed to assess the impact of risk factors in diabetic patients on MPS results and compare them with those of non-diabetic patients in a nuclear medicine clinic. A retrospective cross-sectional study was performed through the analysis of the medical records of patients who underwent MPS in 2010­2019. A total of 34,736 medical records were evaluated. Analyzing the stress phase of MPS, DM patients required two-fold more pharmacological stimulation than non-diabetic patients for MPS. Factors that negatively impact the MPS results were also evaluated, and DM (33.6%), insulin therapy (18.1%), systemic arterial hypertension (69.9%), dyslipidemia (53%), sedentary lifestyle (83.1%), use of pharmacological stress (50.6%), typical chest pain (8.5%), and limiting angina during the test (1.7%) were significantly associated (p < 0.001) with test abnormalities. (AU)

Infección por SARS-CoV-2 y miocarditis / SARS-CoV-2 infection and myocarditis

COVID-19 es una enfermedad infecciosa respiratoria aguda, causada por el SARS-CoV-2, un nuevo coronavirus, que se extendió rápidamente por todo el mundo, dando como resultado una pandemia. Los pacientes presentan un amplio espectro de manifestaciones clínicas, entre ellas, la miocarditis, y de manera alterna, algunos pacientes sin síntomas de enfermedad cardíaca, tienen anomalías en las pruebas, como elevación de la troponina y arritmias cardíacas en el electrocardiograma, o anomalías en las imágenes cardíacas. La patogenia del compromiso miocárdico no es clara, pero las dos principales teorías prevén un papel directo de la enzima convertidora de angiotensina 2, que funciona como el receptor viral, y una respuesta hiperinmune, que también puede conducir a una presentación aislada. El estándar de oro del diagnóstico es la biopsia endomiocárdica, la cual no está disponible en la mayoría de los escenarios. En esta revisión, se pretende brindar al lector pautas para identificar las manifestaciones clínicas, ayudas diagnósticas y manejo de los pacientes con sospecha de miocarditis por COVID-19

COVID-19 is an acute respiratory infectious disease caused by a new coronavirus, SARS-CoV-2 virus, that spread rapidly around the world, resulting in a pandemic. Patients present with a wide spectrum of clinical manifestations, including myocarditis, and alternately, some patients without symptoms of heart disease have abnormalities in tests, such as elevated troponin, arrhythmias in the ECG orabnormalities in cardiac imaging testing. The pathogenesis of myocardial involvement is not completely clear, but the two main theories suggest a direct role of the angiotensin-converting enzyme, which functions as the virus receptor, and a hyperimmune response, which can also lead to an isolated presentation. The gold standard for the diagnosis is the endomyocardial biopsy, which is not available in most settings. In this review, we intend to provide the reader with guidelines to identify the clinical manifestations, diagnostic tools, and management of patients with suspected COVID-19 myocarditis

Estratificação da Insuficiência Cardíaca Clínica através do Mapa T1 Nativo: Experiência de um Serviço de Referência / Clinical Heart Failure Stratification Through Native T1 Mapping: Experience of a Referral Service

Resumo Fundamento: Fibrose cardíaca difusa é fator importante na avaliação prognóstica dos pacientes com disfunção ventricular. Mapeamento T1 nativo pela ressonância magnética cardíaca (RMC) apresenta elevada sensibilidade e é considerado preditor independente de mortalidade por todas as causas e desenvolvimento de insuficiência cardíaca (IC) nos pacientes com cardiomiopatia. Objetivos: Avaliar aplicabilidade da avaliação com mapa T1 nativo em pacientes com IC em um hospital de referência de cardiologia e sua associação com parâmetros estruturais e perfil funcional. Métodos: Estudo transversal com pacientes adultos com IC classes funcionais NYHA I e II, isquêmicos e não isquêmicos, acompanhados em hospital de referência, que realizaram RMC. Os valores de T1 nativo foram analisados em relação a parâmetros estruturais, comorbidades, etiologia e categorização da IC pela fração de ejeção do ventrículo esquerdo (FEVE). Análises foram realizadas com nível de significância de 5%. Resultados: Analisados 134 pacientes. Valores de T1 nativo elevados foram encontrados em pacientes com maior dilatação (1004,9 vs 1042,7ms, p=0,001), volume (1021,3 vs 1050,3ms, p<0,01) e disfunção ventricular (1010,1 vs 1053,4ms, p<0,001), mesmo quando analisados isoladamente os não isquêmicos. Pacientes classificados com IC com fração de ejeção reduzida apresentaram maiores valores T1 em relação aos com IC e fração de ejeção preservada (ICFEP) (992,7 vs 1054,1ms, p<0,001). Dos com ICFEP, 55,2% apresentavam T1 elevado. Conclusões: Mapeamento T1 por RMC é factível para avaliação da IC clínica. Houve associação direta entre maior valor nativo de T1 e menor fração de ejeção, maiores diâmetros e volumes do VE, independentemente da etiologia da IC.

Abstract Background: Diffuse cardiac fibrosis is an important factor in the prognostic assessment of patients with ventricular dysfunction. Cardiovascular magnetic resonance imaging (CMR) native T1 mapping is highly sensitive and considered an independent predictor of all-cause mortality and heart failure (HF) development in patients with cardiomyopathy. Objectives: To evaluate the feasibility of native T1 mapping assessment in patients with HF in a cardiology referral hospital and its association with structural parameters and functional profile. Methods: Cross-sectional study with adult patients with HF NYHA functional classes I and II, ischemic and non-ischemic, followed in a referral hospital, who underwent CMR. Native T1 values were analyzed for structural parameters, comorbidities, etiology, and categorization of HF by left ventricular ejection fraction (LVEF). Analyses were performed with a significance level of 5%. Results: Enrollment of 134 patients. Elevated native T1 values were found in patients with greater dilation (1004.9 vs 1042.7ms, p = 0.001), ventricular volumes (1021.3 vs 1050.3ms, p <0.01) and ventricular dysfunction (1010.1 vs 1053.4ms, p <0.001), also present when the non-ischemic group was analyzed separately. Patients classified as HF with reduced ejection fraction had higher T1 values than those with HF and preserved ejection fraction (HFPEF) (992.7 vs 1054.1ms, p <0.001). Of those with HFPEF, 55.2% had higher T1. Conclusions: CMR T1 mapping is feasible for clinical HF evaluation. There was a direct association between higher native T1 values and lower ejection fraction, and with larger LV diameters and volumes, regardless of the etiology of HF.

A Remodelação do Sistema Nervoso Autônomo Cardíaco pode Desempenhar um Papel na Fibrilação Atrial: Um Estudo do Sistema Nervoso Autônomo e Receptores Miocárdicos / Cardiac Autonomic Nervous System Remodeling May Play a Role in Atrial Fibrillation: A Study of the Autonomic Nervous System and Myocardial Receptors

Resumo Fundamento Alterações do substrato elétrico e anatômico do coração são fatores que originam e perpetuam a fibrilação atrial (FA), porém, os mecanismos envolvidos não foram totalmente elucidados ainda. Objetivo: Avaliar o papel do remodelamento do sistema nervoso cardíaco intrínseco (SNCI), incluindo fibras nervosas e receptores muscarínicos e β-adrenérgicos, na FA permanente humana. Métodos Foram avaliadas 4 amostras em átrios de 13 corações obtidos em necrópsias de pacientes com doença cardíaca e FA permanente, e em 13 controles com as mesmas doenças, porém, sem FA. Utilizando imunoperoxidase e histomorfometria, quantificamos a densidade das fibras do SNCI, bem como a porcentagem positiva de miocárdio para receptores β-adrenérgicos 1, 2 e 3, receptor quinase 5 acoplado à proteína G (GRK-5), e receptores muscarínicos 1 a 5. Os resultados foram comparados usando ANOVA e ANOVA hierarquizada e ajustados pelo volume do átrio esquerdo e, para avaliação da expressão de receptores β e GRK-5, pelo uso de β-bloqueadores. Adotamos como significativo α = 0,05. Resultados Houve aumento na densidade das fibras ( p <0,01), especialmente nas fibras simpáticas ( p =0,02). Quanto aos receptores muscarínicos, só houve diferença nos M1, que estavam aumentados (5,87±4,52 vs 2,85±2,40; p =0,03). Quanto aos componentes do sistema adrenérgicos analisados, houve expressão aumentada de β-3 (37,41 vs 34,18, p =0,04) e GRK-5 (51,16 vs 47,66; p<0,01). O uso de β-bloqueadores não teve impacto na expressão de receptores beta. Conclusão O aumento na inervação do SNCI e a alteração na expressão de receptores em regiões suscetíveis de desencadear FA podem ter um papel na fibrilação atrial permanente.

Abstract Background The primary factors that originate and perpetuate atrial fibrillation (AF) are electrical and anatomical substrate alterations. However, the central mechanisms governing AF perpetuation have not been elucidated yet, which is reflected on the modest results of the treatment in patients with long persistent AF. Objective To evaluate if human intrinsic cardiac autonomic nervous system (ICANS) remodeling, including nervous system fibers and muscarinic and β-adrenergic receptors, play a role in permanent AF. Methods Heart necropsy samples from thirteen patients with heart disease and permanent AF and thirteen controls without AF were used. By using immunoperoxidase and histomorphometry quantification, we identified the following: the density of all fibers of the ICANS, sympathetic and parasympathetic fibers; and the percentage of myocardium positive for β-adrenergic receptors 1, 2 and 3; G protein-coupled receptor kinase-5 (GRK-5); and muscarinic receptors M1 to M5. The results were compared using ANOVA and nested ANOVA and were adjusted according to the left atrium volume for all variables, and β-blocker use to evaluate the expression of β-receptors and GRK-5. Results There was an overall increase in the density of fibers of the ICANS (p=0.006), especially in atrial sympathetic nerve fibers (p=0.017). Only M1 muscarinic receptors were increased (5.87 vs 2.35, p=0.032). For adrenergic receptors, the results were positive for increased expression of β-3 (37.41 vs 34.18, p=0.039) and GRK-5 (51.16 vs 47.66; p<0.001). β-blocker use had no impact on β-receptor expression. Conclusion Increased ICANS innervation and remodeling receptor expression in regions prone to triggering AF may play a role in permanent AF.

IInvestigation of possible oxidative damage caused by formaldehyde exposure in the rat's heart and aorta tissue / Investigación de posible daño oxidativo causado por la exposición al formaldehído en el corazón de la rata y tejido de la aorta

SUMMARY: Formaldehyde (FA) is a toxic substance used frequently in the field of medicine as well as in many industrial areas. Especially people working in the field of anatomy, histology, and pathology are in high risk group because of the use of the FA. Studies showing the effects of FA on the cardiovascular system are few in number. The purpose of the present study was to investigate the effects of FA exposure, which we believe can cause oxidative stress, on the heart and aorta with various biochemical analyses. A total of 24 Wistar Albino rats were used in our study. We divided the rats into 3 groups as the Control Group (CG), the group exposed to low-dose FA (avg. 1 ppm) (DDG) Group, and the group exposed to high-dose FA (avg. 10 ppm) (YDG). At the end of the subchronic FA exposure, the blood samples, heart and aorta tissues of the rats were taken and subjected to biochemical analyses. As a result of the analyses, statistically significant differences were detected between CG (2.96?0.85 ng/mg), and HDG (2.08?0.77 ng/mg) in aortic tissues in TXNIP analysis (p<0.05). In heart tissues, significant differences were detected between CG (0.73?0.27 ng/mg) and LDG (1.13?0.22 ng/mg) (p<0.05). Statistically significant differences were also detected between CG (1.98?0.31 mM/ml) and YDG (2.43?0.31 mM/ml) in serum MDA analyses (p<0.05). It was shown that subchronic application of FA to LDG rats through inhalation had no effects on apoptosis markers in heart tissues. More studies are required to show FA toxicity and the mechanism of action of pathology on the cardiovascular system. We believe that our study will contribute to clarifying the roles of mild and subchronic exposure of FA in heart and aortic tissues in terms of oxidative stress risk.

RESUMEN: El formaldehído es una sustancia tóxica que se utiliza con frecuencia en el campo de la medicina, así como en muchas áreas industriales. Especialmente las personas que trabajan en el area de la anatomía, y patología se encuentran en el grupo de alto riesgo debido al uso de esta sustancia. Pocos son los estudios que muestran los efectos del formaldehído en el sistema cardiovascular. El propósito del presente estudio fue investigar a través de análisis bioquímicos, los efectos de la exposición a formaldehído, que podría causar estrés oxidativo, en el corazón y la aorta. Se utilizaron un total de 24 ratas Albinas Wistar. Dividimos a las ratas en 3 grupos: grupo control (GC), grupo expuesto a dosis bajas de AG (promedio 1 ppm) (DDG) y grupo expuesto a dosis altas de AG (promedio 10 ppm) (YDG). Al término de la exposición a FA subcrónica, se tomaron muestras de sangre, tejido cardíaco y aorta de las ratas y se sometieron a análisis bioquímicos. Como resultado de los análisis, se detec- taron diferencias estadísticamente significativas entre GC (2,96 ? 0,85 ng / mg) y HDG (2,08 ? 0,77 ng / mg) en los tejidos aórticos en el análisis TXNIP (p <0,05). En los tejidos cardíacos se detectaron diferencias significativas entre GC (0,73 ? 0,27 ng / mg) y LDG (1,13 ? 0,22 ng / mg) (p <0,05). También se detectaron diferencias estadísticamente significativas entre CG (1,98 ? 0,31 mM / ml) y YDG (2,43 ? 0,31 mM / ml) en los análisis de MDA en suero (p <0,05). Se demostró que la aplicación subcrónica de formaldehído a ratas LDG a través de la inhalación no tuvo efectos sobre los marcadores de apoptosis en los tejidos del corazón. Se requieren más estudios para demostrar la toxicidad de los AG y el mecanismo de acción de la patología en el sistema cardiovascular. Creemos que nuestro estudio contribuirá a aclarar las funciones de la exposición leve y subcrónica de formaldehído en los tejidos cardíacos y aórticos en términos de riesgo al estrés oxidativo.

Inhibidores del cotransportador de sodio-glucosa tipo 2: Efecto de los mecanismos moleculares en el miocardio / Sodium-glucose cotransporter 2 inhibitors: Effect of molecular mechanisms on the myocardium

Resumen Los receptores del cotransportador de sodio-glucosa han demostrado una gran relevancia en la función miocárdica. Los receptores tipo 1 se encuentran en el miocardio en valores bajos, sin embargo, se elevan en patologías cardiacas por medio de distintos mecanismos moleculares. Por otra parte, los receptores tipo 2 están ausentes en el miocardio. Los fármacos que inhiben este receptor tienen beneficio cardiovascular evidente en estudios clínicos y experimentales, principalmente en pacientes con diabetes mellitus tipo 2 e insuficiencia cardiaca, en los que se ha demostrado una reducción de la mortalidad por causas cardiovasculares y reducción en hospitalización por insuficiencia cardiaca. Existen interrogantes sobre el mecanismo de acción directo de este grupo antihiperglicemiantes sobre el cardiomiocito y se han desarrollado hipótesis y teorías para explicar este efecto. El objetivo de este artículo es revisar y analizar los diferentes mecanismos metabólicos, estructurales, funcionales y mitocondriales en un contexto molecular de los inhibidores del cotransportador sodio-glucosa tipo 2. La acción fisiopatológica del receptor tipo 1 en el miocardio también es importante y se encuentran en desarrollo estudios clínicos para establecer el efecto de su inhibición a nivel cardíaco.

Abstract Sodium-glucose cotransporter receptors have demonstrated relevance in myocardial function. Type 1 receptors are found in the myocardium in low values, however, they are elevated in cardiac pathologies by means of different molecular mechanisms. On the other hand, type 2 receptors are absent in the myocardium. The drugs that inhibit this receptor have been shown to have a cardiovascular benefit demonstrated in clinical and experimental studies, mainly in patients with type 2 diabetes mellitus and heart failure, presenting a reduction in mortality due to cardiovascular causes and a reduction in hospitalization due to heart failure. Due to the above, many questions arise about the mechanism of direct action of this antihyperglycemic group on cardiomyocyte, which is why they have been developed from hypotheses and theories to clarify this action by medicines. The objective of this article is to analyze the different metabolic, structural, functional and mitochondrial mechanisms in a molecular context of the inhibitors of the sodium-glucose cotransporter type 2. On the other hand, to analyze the pathophysiological action of the type 1 receptor in the myocardium, since that future clinical studies will be developed to establish the effect with its inhibition at the cardiac level.

Testosterone activates glucose metabolism through AMPK and androgen signaling in cardiomyocyte hypertrophy

BACKGROUND: Testosterone regulates nutrient and energy balance to maintain protein synthesis and metabolism in cardiomyocytes, but supraphysiological concentrations induce cardiac hypertrophy. Previously, we determined that testosterone increased glucose uptake­via AMP-activated protein kinase (AMPK)­after acute treatment in cardiomyocytes. However, whether elevated glucose uptake is involved in long-term changes of glucose metabolism or is required during cardiomyocyte growth remained unknown. In this study, we hypothesized that glucose uptake and glycolysis increase in testosterone-treated cardiomyocytes through AMPK and androgen receptor (AR). METHODS: Cultured cardiomyocytes were stimulated with 100 nM testosterone for 24 h, and hypertrophy was verified by increased cell size and mRNA levels of ß-myosin heavy chain (ß-mhc). Glucose uptake was assessed by 2-NBDG. Glycolysis and glycolytic capacity were determined by measuring extracellular acidification rate (ECAR). RESULTS: Testosterone induced cardiomyocyte hypertrophy that was accompanied by increased glucose uptake, glycolysis enhancement and upregulated mRNA expression of hexokinase 2. In addition, testosterone increased AMPK phosphorylation (Thr172), while inhibition of both AMPK and AR blocked glycolysis and cardiomyocyte hypertrophy induced by testosterone. Moreover, testosterone supplementation in adult male rats by 5 weeks induced cardiac hypertrophy and upregulated ß-mhc, Hk2 and Pfk2 mRNA levels. CONCLUSION: These results indicate that testosterone stimulates glucose metabolism by activation of AMPK and AR signaling which are critical to induce cardiomyocyte hypertrophy.

Sintomas de ansiedade, depressão e ansiedade cardíaca pré-operatórios segundo o tipo de cirurgia cardíaca / Síntomas de ansiedad, depresión y ansiedad cardíaca preoperatoria según el tipo de cirugía cardíaca / Pre-operative anxiety, depression and cardiac anxiety symptoms according to the type of heart surgery

RESUMO Introdução: observando a diferença de perfil dos pacientes submetidos à cirurgia de revascularização do miocárdio daqueles submetidos à correção cirúrgica de valvopatias, considera-se importante a avaliação do estado emocional de acordo com a cirurgia a ser realizada. Objetivo: comparar os sintomas de ansiedade, depressão e ansiedade cardíaca de pacientes no pré-operatório, segundo o tipo de cirurgia cardíaca a ser realizada: revascularização do miocárdio ou cirurgia de correção de valvopatias. Método: estudo observacional, analítico, de corte transversal, realizado nas enfermarias de cirurgia de um hospital universitário do interior paulista. Uma amostra consecutiva e não probabilística foi constituída pelos pacientes maiores de idade que vieram de casa para a internação e cujo agendamento para a realização da cirurgia foi eletivo. Para a avaliação dos sintomas de ansiedade e depressão, foi utilizado o instrumento Hospital Anxiety and Depression Scale; já para a avaliação da ansiedade cardíaca, foi utilizado o "Questionário de Ansiedade Cardíaca". Para a comparação das medidas dos sintomas, segundo o tipo de cirurgia, foi realizado o teste de Mann-Whitney para amostras independentes, com nível de significância de 5%. Resultados: os grupos foram homogêneos entre si, quanto à caracterização sociodemográfica, exceto para idade. Pacientes em pré-operatório de correção de valvopatias apresentaram escore maior para os sintomas de ansiedade cardíaca quando comparados com pacientes em pré-operatório de revascularização do miocárdio, e a diferença encontrada foi estatisticamente significativa (p=0,020). Conclusão: pacientes em pré-operatório de correção de valvopatias apresentaram mais sintomas de ansiedade cardíaca quando comparados com pacientes em pré-operatório de revascularização do miocárdio.

RESUMEN Introducción: al observar la diferencia en el perfil de los pacientes sometidos a cirugía de revascularización miocárdica respecto a los sometidos a corrección quirúrgica de valvulopatías, se considera importante evaluar el estado emocional de acuerdo con la cirugía a realizar. Objetivo: comparar los síntomas de ansiedad, depresión y ansiedad cardíaca de los pacientes en el período preoperatorio, según el tipo de cirugía cardíaca a realizar: revascularización miocárdica o cirugía de corrección de valvulopatías. Método: estudio observacional, analítico, transversal, realizado en las salas de recuperación de cirugía de un hospital universitario del interior de São Paulo. Una muestra consecutiva y no probabilística estuvo conformada por pacientes mayores que acudieron a su domicilio para ser hospitalizados y cuya cita para la cirugía fue electiva. Para evaluar los síntomas de ansiedad y depresión se utilizó el instrumento Escala Hospitalaria de Ansiedad y Depresión; para la evaluación de la ansiedad cardíaca se utilizó el "Cuestionario de Ansiedad Cardíaca". Para comparar las medidas de síntomas, según el tipo de cirugía, se realizó la prueba de Mann-Whitney para muestras independientes, con un nivel de significancia del 5%. Resultados: los grupos fueron homogéneos entre sí, encuanto a caracterización sociodemográfica, excepto por edad. Los pacientes en el período preoperatorio para la corrección de valvulopatías tuvieron una puntuación más alta para los síntomas de ansiedad cardíaca en comparación con los pacientes en el período preoperatorio de revascularización miocárdica, y la diferencia encontrada fue estadísticamente significativa (p=0,020). Conclusión: los pacientes en período preoperatorio de corrección de valvulopatías presentaron más síntomas de ansiedad cardíaca en comparación con los pacientes en el período preoperatorio de revascularización miocárdica.

ABSTRACT Introduction: observing the difference in profile of patients undergoing coronary artery bypass graft surgery from those undergoing surgical correction of valvular heart disease, it is considered important to assess the emotional state according to the surgery to be performed. Objective: to compare the symptoms of anxiety, depression, and cardiac anxiety of patients in the preoperative period, according to the type of cardiac surgery to be performed: myocardial revascularization or surgery to correct valvular heart diseases. Method: observational, analytical, cross-sectional study carried out in the surgery wards of a university hospital in the countryside of São Paulo. A consecutive and non-probabilistic sample was made up of older patients who came home for hospitalization and whose appointment for the surgery was elective. To evaluate the symptoms of anxiety and depression, the Hospital Anxiety and Depression Scale instrument was used; for the assessment of cardiac anxiety, the "Heart Anxiety Questionnaire" was used. To compare the measures of symptoms, according to the type of surgery, the Mann-Whitney test was performed for independent samples, with a significance level of 5%. Results: the groups were homogeneous among themselves, in terms of sociodemographic characterization, except for age. Patients in the preoperative period for correction of valvular heart disease had a higher score for the symptoms of cardiac anxiety when compared with patients in the preoperative period of myocardial revascularization, and the difference found was statistically significant (p=0.020). Conclusion: patients in the preoperative period for correction of valvular heart disease presented more symptoms of cardiac anxiety when compared with patients in the preoperative period of myocardial revascularization.

Deformação miocárdica (strain) e fibrose miocárdica na forma cardíaca leve da Doença de Chagas / Myocardial deformation (strain) and myocardial fibrosis in mild cardiac Chagas Disease

Fundamento: A identificação precoce do dano miocárdico parece ser importante na abordagem do paciente com doença de Chagas. A ecocardiografia com strain obtida por speckle tracking e a avaliação da fibrose miocárdica por meio da ressonância magnética cardíaca podem ser métodos diagnósticos promissores nesse sentido. Objetivo: Avaliar o acometimento miocárdico especificamente na forma crônica cardíaca leve da doença de Chagas por meio do strain por speckle tracking e da fibrose miocárdica pela ressonância magnética cardíaca, além de suas correlações. Método: Estudo de corte transversal que analisou portadores da forma cardíaca crônica leve da doença de Chagas (fração de ejeção preservada) submetidos à ecocardiografia com strain por speckle tracking e à ressonância magnética cardíaca. Resultados: Foram incluídos 21 participantes (mulheres: 62%; idade: 54 ± 5 anos). A prevalência de fibrose miocárdica por meio do realce tardio miocárdico foi de 50%. O strain longitudinal global encontrava-se diminuído em 17 pacientes (81%), com mediana de 14,1% (intervalo interquartil de 12,1 a 16,3). Os valores do mapa T1 encontravam-se, em média, elevados nos portadores de doença de Chagas (993 ± 163 ms). O mapa T1 foi significativamente correlacionado com o strain longitudinal global (r= 0,634; p = 0,015). Além disso, o índice de dispersão mecânica, obtido por strain, estava aumentado (> 55 ms) em 84%, com a maior área sob a curva Característica de Operação do Receptor (área sob a curva de 0,696; intervalo de confiança de 95% de 0,412-0,981) para discriminação de fibrose pelo realce tardio miocárdico. Conclusão: O strain miocárdico e o mapa T1 se comportam como marcadores precoces do dano miocárdico na cardiopatia chagásica crônica leve. O índice de dispersão mecânica estava elevado e foi o parâmetro que melhor se correlacionou com o realce tardio miocárdico. (AU)

Background: The early identification of myocardial damage seems important in the management of patients with Chagas disease. However, it is unknown whether speckle tracking echocardiography strain and cardiac magnetic resonance imaging are promising methods for assessing myocardial involvement and fibrosis, respectively. Objective: To evaluate myocardial involvement in the mild chronic cardiac form of Chagas disease using speckle tracking strain and myocardial fibrosis by cardiac magnetic resonance and assess their correlations. Method: This cross-sectional study analyzed patients with the mild chronic cardiac form of Chagas disease (preserved ejection fraction) using speckle tracking echocardiography and cardiac magnetic resonance. Results: The study included 21 participants (women: 62%; age: 54 ± 5 years). The prevalence of myocardial fibrosis was 50% on delayed myocardial enhancement. The median global longitudinal strain was decreased (14.1%; interquartile range, 12.1­16.3%) in 17 patients (81%). The mean T1 mapping value was high in patients with Chagas disease (993 ± 163 ms). The T1 map was significantly correlated with the global longitudinal strain (r = 0.634; p = 0.015). In addition, the mechanical dispersion index obtained by strain was increased (>55 ms) by 84%, with the largest area under the receiver operating characteristic curve (area under the curve, 0.696; 95% confidence interval, 0.412­0.981) for fibrosis discrimination by delayed myocardial enhancement. Conclusion: Myocardial strain and T1 mapping are early markers of myocardial damage in mild chronic Chagas heart disease. The mechanical dispersion index was high and the most closely correlated with delayed myocardial enhancement. (AU)

Comportamento dos critérios de uso apropriado da cintilografia de perfusão miocárdica na avaliação de assintomáticos de alto risco cardiovascular ou com doença coronária conhecida / Appropriate use of myocardial perfusion scintigraphy criteria for assessing asymptomatic patients with high cardiovascular risk or known coronary disease

Fundamentos: O papel da cintilografia de perfusão miocárdica em pacientes assintomáticos permanece restrito a situações clínicas muito específicas, muitas delas abordadas nos Critérios de Uso Apropriado (AUC) de Cintilografia de Perfusão Miocárdica. Objetivo: Realizar uma análise crítica da aplicação desses critérios nas indicações de exames realizados em pacientes assintomáticos do Instituto Dante Pazzanese de Cardiologia, cuja população é notadamente de alto risco cardiovascular. Métodos: Foram selecionados pacientes assintomáticos que realizaram cintilografia de perfusão miocárdica para pesquisa de isquemia. As indicações dos exames foram classificadas em apropriadas, inapropriadas ou incertas. Hipocaptação fixa, hipocaptação transitória ou dilatação isquêmica transitória foram consideradas exames alterados. Na análise estatística, buscou-se avaliar a correlação entre o grau de recomendação das indicações e a presença de exames alterados. Resultados: A partir de uma seleção inicial de 2.999 prontuários, 490 foram considerados assintomáticos e incluídos conforme critérios de inclusão estabelecidos previamente. Apenas 9,8% das indicações foram inapropriadas, enquanto que 61,4% foram apropriadas, e 28,8% foram incertas. A hipocaptação fixa do radiofármaco ocorreu em 43,5% dos casos e a hipocaptação transitória, em 16,1%. Solicitar o exame de maneira apropriada ou incerta foi fator preditor de exame com resultado alterado nesta população. Conclusão: O uso dos critérios de uso apropriado da cintilografia de perfusão miocárdica mostrou-se eficaz em predizer exames alterados em uma população assintomática de alto risco cardiovascular, especialmente no grupo de pacientes com indicação incerta, o que pode significar que algumas das indicações consideradas incertas talvez sejam apropriadas para uma população de alto risco cardiovascular. (AU)