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The use of cardioprotective strategies as adjuvants of cardioplegic solutions has become an ideal alternative for the improvement of post-surgery heart recovery. The choice of the optimal cardioplegia, as well as its distribution mechanism, remains controversial in the field of cardiovascular surgery. There is still a need to search for new and better cardioprotective methods during cardioplegic procedures. New techniques for the management of cardiovascular complications during cardioplegia have evolved with new alternatives and additives, and each new strategy provides a tool to neutralize the damage after ischemia/reperfusion events. Researchers and clinicians have committed themselves to studying the effect of new strategies and adjuvant components with the potential to improve the cardioprotective effect of cardioplegic solutions in preventing myocardial ischemia/reperfusion-induced injury during cardiac surgery. The aim of this review is to explore the different types of cardioplegia, their protection mechanisms, and which strategies have been proposed to enhance the function of these solutions in hearts exposed to cardiovascular pathologies that require surgical alternatives for their corrective progression.

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The meninges shield the nervous system from diverse, rather harmful stimuli and pathogens from the periphery. This tissue is composed of brain endothelial cells (BECs) that express diverse ion channels and chemical-transmitter receptors also expressed by neurons and glial cells to communicate with each other. However, information about the effects of ATP and angiotensin II on BECs is scarce, despite their essential roles in blood physiology. This work investigated in vitro if BECs from the meninges from rat forebrain respond to ATP, angiotensin II and high extracellular potassium, with intracellular calcium mobilizations and its second messenger-associated pathways. We found that in primary BEC cultures, both ATP and angiotensin II produced intracellular calcium responses linked to the activation of inositol trisphosphate receptors and ryanodine receptors, which led to calcium release from intracellular stores. We also used RT-PCR to explore what potassium channel subunits are expressed by primary BEC cultures and freshly isolated meningeal tissue, and which might be linked to the observed effects. We found that BECs mainly expressed the inward rectifier potassium channel subunits Kir1.1, Kir3.3, Kir 4.1 and Kir6.2. This study contributes to the understanding of the functions elicited by ATP and angiotensin II in BECs from rat meninges. SIGNIFICANCE OF THE STUDY: Brain endothelial cells (BECs) express diverse ion channels and membrane receptors, which they might use to communicate with neurons and glia. This work investigated in vitro, if BECs from the rat forebrain respond to angiotensin II and ATP with intracellular calcium mobilizations. We found that these cells did respond to said substances with intracellular calcium mobilizations linked to inositol trisphosphate and ryanodine receptor activation, which led to calcium release from intracellular stores. These findings are important because they might uncover routes of active communication between brain cells and endothelial cells.

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Un nuevo coronavirus hace su aparición en China a fines del año 2019, produciendo infección respiratoria aguda y falla respiratoria. Debido a su similitud clínica y microbiológica con el agente del síndrome respiratorio agudo grave (SARS por sus siglas en inglés), el SARS-CoV1, que afecto a China en el año 2003, fue bautizado como SARS-CoV2, y la enfermedad que produce como COVID-19 (COronaVIrus Disease 2019). Desde su identificación el mundo médico se vio inundado de reportes estadísticos, tablas y cifras que hacen al comportamiento epidemiológico del SARSCoV2, pero pocos autores han focalizado su investigación en los mecanismos patogénicos y si lo han hecho sus artículos han sido diluidos por la vorágine de datos estadísticos. El objetivo del presente trabajo es profundizar en los aspectos fisiopatológicos de la infección por SARS-CoV2 para lo cual realicé una revisión de la literatura desde el inicio de la actual pandemia hasta el mes de junio de 2020, utilizando para la búsqueda Mendeley y PubMed, centrado sobre todo en la capacidad del virus de alterar el delicado balance entre la angiotensina II y sus antagonistas, analizar las posibles razones de la peor evolución en un subgrupo de pacientes y proponer medidas terapéuticas enfocadas en estos hallazgos. El SARS-CoV2 infecta células que expresan el receptor primario para el virus, la enzima ACE2, presente en epitelio intestinal y respiratorio, así como en endotelio. Genera inicialmente hipoxia por lesión alveolar para luego generar disfunción endotelial por lesión directa, lesión mediada por anticuerpos, tormenta de citoquinas y alteración del balance entre la angiotensina II y sus antagonistas funcionales, con eventual trombosis en territorio pulmonar y sistémico, así como hemólisis angiopática y por hiperactividad macrofágica. La retroalimentación positiva entre hipoxia, inflamación y angiotensina II potencian el desarrollo de un síndrome de distrés y fallo multiorgánico, con escalada de la mortalidad. El análisis de la fisiopatología probable en la infección por SARS-CoV2 permite sacar algunas conclusiones siendo las centrales que el endotelio es uno de los actores centrales en la patogenia de la enfermedad y que los pacientes con mayor riesgo de complicaciones son aquellos con disfunción endotelial previa debida a la presencia de obesidad, diabetes mellitus o hipertensión, así como que existen diferentes fases o estadios, cada uno con una posible intervención terapéutica particular, es decir, que la COVID-19 es diferente entre pacientes y en el mismo paciente es diferente en el tiempo, con cada momento requiriendo una intervención terapéutica particular.

A new coronavirus makes its appearance in China in late 2019, causing acute respiratory infection and respiratory failure. Due to its clinical and microbiological similarity to the agent of severe acute respiratory syndrome (SARS), SARS-CoV1, which affected China in 2003, was named SARS-CoV2, and the disease it produces as COVID-19 (COronaVIrus Disease 2019). Since its identification, the medical world has been flooded with statistical reports, tables and figures regarding the epidemiological behavior of SARS-CoV2, but few authors have focused their research on pathogenic mechanisms and if they have, their articles have been diluted by the maelstrom of statistical data. The objective of the present work is to delve into the pathophysiological aspects of SARS-CoV2 infection, for which I carried out a literature review from the start of the current pandemic until June 2020, using Mendeley and PubMed for the search, focused above all on the ability of the virus to alter the delicate balance between angiotensin II and its antagonists, to analyze the possible reasons for the worse evolution in a subgroup of patients and to propose therapeutic measures focused on these findings. SARS-CoV2 infects cells that express the primary receptor for the virus, the enzyme ACE2, present in the intestinal and respiratory epithelium, as well as the endothelium. Initially, it generates hypoxia due to alveolar injury and then generates endothelial dysfunction due to direct injury, antibody-mediated injury, cytokine storm and alteration of the balance between angiotensin II and its functional antagonists, with eventual thrombosis in pulmonary and systemic territory, as well as angiopathic hemolysis and due to macrophage hyperactivity. The positive feedback between hypoxia, inflammation and angiotensin II potentiates the development of a distress syndrome and multi-organ failure, with an increase in mortality. The analysis of the probable pathophysiology in SARS-CoV2 infection allows us to draw some conclusions, the main ones being that the endothelium is one of the central actors in the pathogenesis of the disease and that the patients with the highest risk of complications are those with previous endothelial dysfunction, due to the presence of obesity, diabetes mellitus or hypertension, as well as that there are different phases or stages, each with a possible particular therapeutic intervention, that is, that COVID-19 is different between patients and in the same patient it is different in time, with each moment requiring a particular therapeutic intervention.

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Resumen: El Congreso Europeo de Cardiología constituye uno de los eventos más relevantes de la comunidad cardiológica mundial. Fue realizado entre el 31 de agosto y el 4 de setiembre en el corazón de París, siendo el tema central la salud cardiovascular global. Como es habitual, contó con la presencia de más de 30.000 profesionales y destacados invitados. Se presentaron actualizaciones de varias guías de práctica clínica e importantes trabajos científicos que sin duda impactarán en el tratamiento de los pacientes con patología cardiovascular. A continuación realizaremos un breve resumen de algunos de los trabajos presentados: - A trial to evaluate the effect of the sodium-glucose cotransporter 2 inhibitor dapagliflozin in patients with heart failure and reduced left ventricular ejection fraction: DAPA-HF - Complete revascularization with multivessel PCI for myocardial infarction: the COMPLETE Trial - Angiotensin-neprylysin inhibition in heart failure with preserved ejection fraction: the PARAGON-HF - Antithrombotic therapy for atrial fibrillation with stable coronary disease: the AFIRE Investigators - Ticagrelor or prasugrel in patients with acute coronary syndromes: the ISAR-REACT 5 Trial

Summary: The European Congress of Cardiology is one of the most relevant events of the world cardiology community. It was held from August 31 to September 4 in the heart of Paris, France, the central theme being global cardiovascular health. As usual, it was attended by more than 30,000 professionals and prominent guests. Updates of several clinical practice guides and important scientific papers were presented. These undoubtedly will impact in the treatment of patients with cardiovascular pathology. Below we present a brief summary of some of the trials presented: - A trial to evaluate the effect of the sodium-glucose cotransporter 2 inhibitor dapagliflozin in patients with heart failure and reduced left ventricular ejection fraction: DAPA-HF - Complete revascularization with multivessel PCI for myocardial infarction: the COMPLETE Trial - Angiotensin-neprylysin inhibition in heart failure with preserved ejection fraction: the PARAGON-HF - Antithrombotic therapy for atrial fibrillation with stable coronary disease: the AFIRE Investigators - Ticagrelor or prasugrel in patients with acute coronary syndromes: the ISAR-REACT 5 Trial

Sumário: O Congresso Europeu de Cardiologia é um dos eventos mais relevantes da comunidade mundial de cardiologia. Foi realizada de 31 de agosto ao 4 de setembro no coração de Paris, na França, o tema central foi a saúde cardiovascular global. Como sempre, participaram mais de 30.000 profissionais e convidados de destaque. Atualizações de vários guias de prática clínica e importantes artigos científicos foram apresentados que, sem dúvida, impactarão o tratamento de pacientes com patologia cardiovascular. Abaixo, faremos um breve resumo de alguns trials apresentados: - A trial to evaluate the effect of the sodium-glucose cotransporter 2 inhibitor dapagliflozin in patients with heart failure and reduced left ventricular ejection fraction: DAPA-HF - Complete revascularization with multivessel PCI for myocardial infarction: the COMPLETE Trial - Angiotensin-neprylysin inhibition in heart failure with preserved ejection fraction: the PARAGON-HF - Antithrombotic therapy for atrial fibrillation with stable coronary disease: the AFIRE Investigators - Ticagrelor or prasugrel in patients with acute coronary syndromes: the ISAR-REACT 5 Trial

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Background: Angiotensin converting enzyme (ACE) polymorphism has been associated with different clinical and echocardiographic parameters in patients with heart failure (HF). However, no studies have been investigated such association with HF caused by Chagas disease. Objectives: To perform a genetic study to evaluate the frequency of ACE polymorphism in patients with HF caused by Chagas disease attending a university hospital in the central-west region and its association with echocardiographic findings. Methods: Descriptive study of ACE polymorphism (I/D) and echocardiographic data of 103 patients with HF caused by Chagas disease. Echocardiographic parameters were compared between the genotypes using the ANOVA test. Results: Genotypic distribution of the ACE polymorphism was 16.5% DD, 57.3% DI and 26.2% II. There was no statistically significant difference in the distribution of genotypes between men and women. The echocardiographic findings were: left ventricular ejection fraction: 43.8 ± 14.8 (DD) vs. 42.3 ± 11.6 (ID) vs. 44.9 ± 13.0 (II), p = 0.664; left ventricular diastolic diameter: 59.2 ± 9.7 (DD) vs. 60.3 ± 7.6 (ID) vs. 59.7 ± 78.1 (II), p = 0.879; left ventricular systolic diameter: 48.6 ± 12.8 (DD) vs. 50.6 ± 9.7 (ID) vs. 49.3 ± 11.9 (II), p = 0.753; and left atrial volume: 44.9 ± 10.1 (DD) vs. 40.9 ± 9.6 (ID) vs. 38.2 ± 7.8 (II), p = 0.068. Significant correlation coefficients were found for gender, age, ethnicity, heart rate and dyslipidemia. Conclusion: ACE polymorphism was not associated with echocardiographic findings in patients with HF caused by Chagas disease

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La fisiopatología de la hipertensión arterial es compleja, pues intervienen múltiples factores que, en su mayoría, tienen una base genética. Se ha podido mostrar que es el sistema renina-angiotensina-aldosterona (SRAA) el que tiene mayor importancia, puesto que condiciona la acción de otros factores humorales y/o neurales, tales como producción de endotelina, la inhibición del óxido nítrico o de la prostaciclina, la acción de catecolaminas o de vasopresina, del factor ouabaína-sensible o FDE, del tromboxano A2 (TxA2) y de diversas sustancias vasopresoras endógenas. Se presenta en este artículo una revisión exhaustiva de lo que conocemos hoy acerca del SRAA. Y se incluye algunas novedades de la investigación del SRAA.

The pathophysiology of hypertension is complex because it involves multiple factors which mostly have a genetic basis. It has been shown that the renin-angiotensinaldosterone system (RAAS) is the most important factor, since it determines the action of other humoral and/or neural factors such as production of endothelin, inhibition of nitric oxide or prostacyclin, action of catecholamines, vasopressin, ouabain-sensitive factor, thromboxane A2 (TxA2) and various vasopressor endogenous agents. In this article, we present a thorough review of what we know today about the RAAS. We also include some new research on this system.

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Abstract Introduction: It is still unknown how the pharmacological inhibition of the Renin Angiotensin System (RAS) impacts the levels of inflammation and fibrosis biomarkers. Objective: This study sought to evaluate the effect of enalapril, candesartan and aliskiren on urinary levels of cytokines in a model of chronic kidney disease (CKD). Methods: Male Wistar rats were submitted to surgical removal of ¾ of renal parenchyma to induce CKD (¾ nephrectomy), or subjected to sham surgery (control). Animals were then randomized into five groups: Sham surgery receiving vehicle; ¾ Nephrectomy receiving vehicle; ¾ Nephrectomy receiving enalapril (10 mg/kg); ¾ Nephrectomy receiving candesartan (10 mg/kg) and ¾ Nephrectomy receiving aliskiren (10 mg/kg). Urine output, water intake, mean arterial pressure (MAP) and urinary concentrations of creatinine, urea, albuminuria, Na+, K+, interleukin (IL) -1β, IL-6, IL-10 and transforming growth factor beta (TGF-β) were measured. Results: Nephrectomy significantly impaired renal function, increased MAP and altered the levels of all evaluated cytokines in urine. Enalapril, candesartan and aliskiren improved renal function and decreased MAP and IL-6 when compared to vehicle-treated nephrectomized group. Candesartan and aliskiren decreased IL-1β, while only candesartan reduced TGF-β and only aliskiren increased IL-10. Conclusion: Enalapril, candesartan and aliskiren presented similar effects on improving renal function and reducing MAP and urinary levels of IL-6 in rats with CKD. On the other hand, cytokine profile differed according to the treatment, suggesting that differential mechanisms were triggered in response to the site of RAS blockade.

Resumo Introdução: Ainda não se sabe como a inibição farmacológica do Sistema Renina Angiotensina (SRA) afeta os níveis de biomarcadores de inflamação e fibrose. Objetivo: Este estudo pretendeu avaliar o efeito de enalapril, candesartan e alisquireno sobre os níveis urinários de citocinas em um modelo de doença renal crônica (DRC). Métodos: Ratos Wistar machos foram submetidos à remoção cirúrgica de ¾ do parênquima renal para induzir DRC (nefrectomia), ou submetidos à cirurgia fictícia (controle). Animais foram então randomizados em cinco grupos: Cirurgia fictícia recebendo veículo; Nefrectomia recebendo veículo; Nefrectomia recebendo enalapril (10 mg/kg); Nefrectomia recebendo candesartan (10 mg/kg) e Nefrectomia recebendo alisquireno (10 mg/kg). Débito urinário, ingesta hídrica, pressão arterial media (PAM) e concentrações urinárias de creatinina, ureia, albumina, Na+, K+, interleucina (IL) -1β, IL-6, IL-10 e fator de transformação e crescimento beta (TGF-β) foram medidas. Resultados: A nefrectomia comprometeu significativamente a função renal, aumentou a PAM e alterou os níveis de todas as citocinas avaliadas na urina. Enalapril, candesartan e alisquireno melhoraram a função renal e diminuíram a PAM e a IL-6 quando comparado aos grupo de animais nefrectomizados tratados com veículo. Candesartan e alisquireno reduziram IL-1β, enquanto somente candesartan diminuiu o TGF-β e somente alisquireno aumentou a IL-10. Conclusão: Enalapril, candesartan e alisquireno apresentaram efeitos similares em relação à melhora da função renal e redução da PAM e dos níveis urinários de IL-6 em ratos com DRC. Por outro lado, o perfil de citocinas diferiu de acordo com o tratamento, sugerindo que diferentes mecanismos sejam desencadeados em resposta ao local de bloqueio do SRA.

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BACKGROUND: The renin-angiotensin (Ang) system (RAS) has been reported as an important modulator of inflammatory and immune responses. Evidence suggests an alternative Ang 1-7/Mas receptor axis as counter-regulatory to the classic RAS Ang II/Ang II Type 1 (AT1) receptor axis. It is known that periodontal pathogens elicit host-derived immune response due to release of cytokines such as interleukin (IL)-1ß, and fibroblasts are among the most numerous sentinel cells that contribute to this production. The aim of this study is to determine whether AT1 receptor (AT1R) contributes to production of inflammatory cytokines that are important for periodontal pathogenesis using primary human gingival fibroblasts (HGFs) and human periodontal ligament fibroblasts (HPLFs) stimulated with IL-1ß. METHODS: Through RNA interference or pharmacologic inhibition using AT1R antagonist losartan, HGF and HPLF were stimulated by IL-1ß for 3 (messenger RNA [mRNA]) or 24 (protein) hours. RESULTS: IL-1ß upregulated mRNA expression of AT1R, IL-1ß, IL-6, IL-8, tumor necrosis factor-alpha, and osteoprotegerin (OPG) in HGF and HPLF. AT1R knockdown impaired IL-1ß-induced IL-6 and IL-8 secretion in cultured HGF and HPLF. AT1R silencing also increased OPG gene expression in HGF only. Pharmacologic inhibition of AT1R through losartan modulated mRNA transcription of IL-6 and IL-8 in HPLF but not in HGF. In contrast, IL-1ß-induced secretion of IL-6 and IL-8 was not influenced by losartan in HGF or HPLF. CONCLUSION: These results suggest that AT1R knockdown and AT1R pharmacologic blockade by losartan may differently control balance of inflammatory cytokines, such as IL-6 and IL-8, in primary human periodontal fibroblasts.

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We studied the effects of tempol, an oxygen radical scavenger, on hydrosaline balance in rats with acute sodium overload. Male rats with free access to water were injected with isotonic (control group) or hypertonic saline solution (0.80 mol/l NaCl) either alone (Na group) or with tempol (Na-T group). Hydrosaline balance was determined during a 90 min experimental period. Protein expressions of aquaporin 1 (AQP1), aquaporin 2 (AQP2), angiotensin II (Ang II) and endothelial nitric oxide synthase (eNOS) were measured in renal tissue. Water intake, creatinine clearance, diuresis and natriuresis increased in the Na group. Under conditions of sodium overload, tempol increased plasma sodium and protein levels and increased diuresis, natriuresis and sodium excretion. Tempol also decreased water intake without affecting creatinine clearance. AQP1 and eNOS were increased and Ang II decreased in the renal cortex of the Na group, whereas AQP2 was increased in the renal medulla. Nonglycosylated AQP1 and eNOS were increased further in the renal cortex of the Na-T group, whereas AQP2 was decreased in the renal medulla and was localized mainly in the cell membrane. Moreover, p47-phox immunostaining was increased in the hypothalamus of Na group, and this increase was prevented by tempol. Our findings suggest that tempol causes hypernatremia after acute sodium overload by inhibiting the thirst mechanism and facilitating diuresis, despite increasing renal eNOS expression and natriuresis.

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The venom of marine animals is a rich source of compounds with remarkable selectivity and functional diversity. Scorpaena plumieri is the most venomous fish in the Brazilian fauna and is responsible for relatively frequent accidents involving anglers and bathers. In humans, its venom causes edema, erythema, ecchymoses, anxiety, nausea, vomiting, and syncope. The venom is chemically characterized by Sp-CTx, a enzyme able to generate an initial endothelium-dependent relaxation response, followed by a contraction response. This study sought to investigate the proteolytic activities regarding vasopeptides angiotensin I and II. Both the venom and the epidermal mucus presented angiotensin conversion activity for angiotensin I, as well as a capacity to form Ang 1-7 directly via Ang I and II. Captopril (10 µM) and EDTA (1 mM) were able to abolish the converting activity of the venom and the epidermal mucus, representing the first description of a converting activity in S. plumieri venom and epidermal mucus.

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OBJECTIVE: The aim of this study was to evaluate the role of angiotensin I, II and 1-7 on left ventricular hypertrophy of Wistar and spontaneously hypertensive rats submitted to sinoaortic denervation. METHODS: Ten weeks after sinoaortic denervation, hemodynamic and morphofunctional parameters were analyzed, and the left ventricle was dissected for biochemical analyses. RESULTS: Hypertensive groups (controls and denervated) showed an increase on mean blood pressure compared with normotensive ones (controls and denervated). Blood pressure variability was higher in denervated groups than in their respective controls. Left ventricular mass and collagen content were increased in the normotensive denervated and in both spontaneously hypertensive groups compared with Wistar controls. Both hypertensive groups presented a higher concentration of angiotensin II than Wistar controls, whereas angiotensin 1-7 concentration was decreased in the hypertensive denervated group in relation to the Wistar groups. There was no difference in angiotensin I concentration among groups. CONCLUSION: Our results suggest that not only blood pressure variability and reduced baroreflex sensitivity but also elevated levels of angiotensin II and a reduced concentration of angiotensin 1-7 may contribute to the development of left ventricular hypertrophy. These data indicate that baroreflex dysfunction associated with changes in the renin angiotensin system may be predictive factors of left ventricular hypertrophy and cardiac failure.

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