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Sin financiación 6.975 JCR (2021) Q1, 33/143 Cardiac & Cardiovascular Systems 0.407 SJR (2021) Q3, 205/356 Cardiology and Cardiovascular Medicine No data IDR 2021 UEM

Sin financiación No data JCR 2021 0.385 SJR (2021) Q3, 1499/2489 Medicine (miscellaneous) No data IDR 2021 UEM

Fil: Soni, Sanjeev Kumar. Banaras Hindu University. Institute of Sciences. Department of Zoology. Chronobiology Laboratory; India Fil: Basu, Priyoneel. Banaras Hindu University. Institute of Sciences. Department of Zoology. Chronobiology Laboratory; India Fil: Singaravel, Muniyandi. Banaras Hindu University. Institute of Sciences. Department of Zoology. Chronobiology Laboratory; India Fil: Sharma, Ramaswamy. UT Health San Antonio. Department of Cell Systems and Anatomy; Estados Unidos Fil: Pandi Perumal, Seithikurippu R. Somnogen Canada; Canadá Fil: Cardinali, Daniel Pedro. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina Fil: Cardinali, Daniel Pedro. Pontificia Universidad Católica Argentina. Facultad de Ciencias Médicas. Instituto de Investigaciones Biomédicas; Argentina Abstract: Chronic disruption of circadian rhythms which include intricate molecular transcription-translation feedback loops of evolutionarily conserved clock genes has serious health consequences and negatively affects cardiovascular physiology. Sirtuins (SIRTs) are nuclear, cytoplasmic and mitochondrial histone deacetylases that influence the circadian clock with clock-controlled oscillatory protein, NAMPT, and its metabolite NAD+. Sirtuins are linked to the multi-organ protective role of melatonin, particularly in acute kidney injury and in cardiovascular diseases, where melatonin, via upregulation of SIRT1 expression, inhibits the apoptotic pathway. This review focuses on SIRT1, an NAD+-dependent class III histone deacetylase which counterbalances the intrinsic histone acetyltransferase activity of one of the clock genes, CLOCK. SIRT1 is involved in the development of cardiomyocytes, regulation of voltage-gated cardiac sodium ion channels via deacetylation, prevention of atherosclerotic plaque formation in the cardiovascular system, protection against oxidative damage and anti-thrombotic actions. Overall, SIRT1 has a see-saw effect on cardioprotection, with low levels being cardioprotective and higher levels leading to cardiac hypertrophy.

AimsThe aim of this study was to determine whether arterial stiffness assessed with the biochemical parameter active matrix metalloproteinase (MMP)-9 and the clinical parameters pulse pressure (PP) and pulse wave velocity predicts the response to spironolactone in resistant hypertension (RH).Methods and resultsAmbulatory blood pressure (BP) and active MMP-9 (measured by zymography and ELISA) were measured at baseline, and patients were classified as having pseudo-RH or RH. Patients with RH received spironolactone and the response was determined after 8 weeks by ambulatory BP monitoring: those who achieved BP goals were considered controlled (CRH) and those who did not were considered uncontrolled (UCRH). Plasma active MMP-9 was significantly higher in patients with RH than with pseudo-RH, and correlated with 24 h systolic BP and PP. Receiver operating characteristic analysis indicated that active MMP-9 could predict the response to spironolactone, and its combination with 24 h PP and pulse wave velocity significantly improved this prediction. Moreover, plasma of patients with UCRH induced the MMP-9 expression pathway.ConclusionWe propose active MMP-9 as a useful biomarker to identify patients with RH who will not respond to spironolactone. Combining MMP-9 activity with classical arterial stiffness parameters improves the prediction of the clinical response to spironolactone and might contribute to guide the most appropriate therapeutic decisions for patients with RH.

Introduction: Nandrolone decanoate is a synthetic testosterone analogue considered one of the most widely used anabolic androgenic steroids (AAS) among adolescents and athletes. Chronic ingestion of AAS increases the incidence of cardiovascular abnormalities in athletes, but the mechanism that causes these changes remains unknown. Objectives: The purpose of this study is to verify the possible effects of the use of anabolic androgenic steroids (AAS) on the morphology and oxidative metabolism of the heart in exercised and sedentary rats. Methods: This is a comparative prospective level II study. Twenty-four Wistar rats were distributed in groups that performed voluntary (TG) and sedentary (SG) running exercises, and used AAS: the Anabolic Training Group (ATG), and the Anabolic Sedentary Group (ASG). During the three months of the running protocol, the animals received an intramuscular injection of 5 mg/kg b.p. of AAS. After the training period, the rats were euthanized and the hearts were removed for evaluation of lipid peroxidation and antioxidant capacity, and for morphometric analysis. Results: The anabolic groups, ASG (0.3072 ± 0.0531) and ATG (0.2732 ± 0.0413), presented higher lipid peroxidation when compared to the non-anabolic groups SG (0.1705 ± 0.0224) and TG (0.1785 ± 0.0340). Conclusion: There was no change in total antioxidant capacity or in the thickness of the interventricular septum and left ventricular wall. Thus, the use of anabolic androgenic steroids did not cause morphological changes in the myocardium. However it did alter the oxidative metabolism. It was also verified that aerobic exercise had no protective effect against lipid peroxidation in the myocardium caused by the use of AAS. Level of evidence II; Prospective comparative study. RESUMO Introdução: O decanoato de nandrolona é um análogo sintético da testosterona, considerado um dos esteroides anabólicos androgênicos (EAA) mais utilizados entre adolescentes e atletas. Sua ingestão crônica aumenta a incidência de anormalidades cardiovasculares em atletas, porém o mecanismo que causa essas alterações ainda permanece desconhecido. Objetivos: O estudo teve como objetivo verificar os possíveis efeitos do uso de esteroides anabólicos androgênicos (EAA) na morfologia e no metabolismo oxidativo do coração de ratos treinados e sedentários. Métodos: Trata-se de um estudo prospectivo comparativo nível II. Vinte e quatro ratos Wistar foram distribuídos em grupos que realizaram exercícios de corrida voluntária (GT) e sedentários (GS) e faziam uso dos EAA, Grupo Treinado com Anabolizante (GTA) e Grupo Sedentário com Anabolizante (GSA). Durante os três meses do protocolo de corrida, os animais receberam injeção intramuscular de 5 mg/kg p.c. de EAA. Após o período de treinamento, houve a eutanásia e remoção do coração dos ratos para avaliação da peroxidação lipídica e capacidade antioxidante, além da análise morfométrica. Resultados: Verificaram-se que os grupos anabolizantes, GSA (0,3072 ± 0,0531) e GTA (0,2732 ± 0,0413), apresentaram maior peroxidação lipídica quando comparados aos grupos não anabolizantes GS (0,1705 ± 0,0224) e GT (0,1785 ± 0,0340). Conclusões: Não houve alteração na capacidade antioxidante total, assim como não houve alteração na espessura do septo interventricular e da parede ventricular esquerda. Portanto, o uso de esteroides anabólicos androgênicos não provocou alterações morfológicas no miocárdio, contudo alterou o metabolismo oxidativo. Verificou-se também que a prática de exercício aeróbico não teve efeito protetor contra a peroxidação lipídica no miocárdio provocada pelo uso dos EAA. Nível de evidência II; Estudo prospectivo comparativo. RESUMEN Introducción: El decanoato de nandrolona es un análogo sintético de la testosterona considerado uno de los esteroides anabólicos androgénicos (EAA) más utilizados entre los adolescentes y atletas. Su ingestión crónica aumenta la incidencia de anomalías cardiovasculares en atletas, aunque el mecanismo que causa esas alteraciones sigue siendo desconocido. Objetivos: El estudio tuvo como objetivo verificar los posibles efectos del uso de esteroides anabólicos androgénicos (EAA) en la morfología y en el metabolismo oxidativo del corazón de ratones entrenados y sedentarios. Métodos: Se trata de un estudio prospectivo comparativo nivel II. Fueron distribuidos 24 ratones Wistar en grupos que realizaron ejercicios de carrera voluntaria (GE) y sedentarios (GS), y hacían uso de los EAA, Grupo Entrenado con Anabolizante (GEA) y Grupo Sedentario con Anabolizante (GSA). Durante los tres meses del protocolo de carrera, los animales recibieron inyección intramuscular de 5 mg/kg p.c. de EAA. Después del período de entrenamiento, hubo la eutanasia y remoción del corazón de los ratones, para evaluación de la peroxidación lipídica y capacidad antioxidante, además del análisis morfométrico. Resultados: Se verificó que los grupos anabolizantes, GSA (0,3072 ± 0,0531) y GEA (0,2732 ± 0,0413), presentaron mayor peroxidación lipídica cuando comparados a los grupos no anabolizantes GS (0,1705 ± 0,0224) y GE (0,1785 ± 0,0340). Conclusiones: No hubo alteración en la capacidad antioxidante total, así como no hubo alteración en el espesor del septo interventricular y de la pared ventricular izquierda. Por lo tanto, el uso de esteroides anabólicos androgénicos no provocó alteraciones morfológicas en el miocardio, aunque alteró el metabolismo oxidativo. Se verificó también que la práctica de ejercicio aeróbico no tuvo efecto protector contra la peroxidación lipídica en el miocardio provocada por el uso de EAA. Nivel de evidencia II; Estudio prospectivo comparativo.

El ácido alfa lipoico (AAL) ha sido caracterizado como un antioxidante eficiente. Se ha propuesto como un agente terapéutico potencial en el tratamiento o prevención de diferentes alteraciones que pueden estar relacionadas con un desequilibrio del estado celular oxidoreductor. El objetivo de este trabajo fue analizar la sensibilidad a la peroxidación no enzimática (PNE) (ascorbato-Fe⁺⁺ dependiente) en mitocondrias de corazón y cerebro de ratas incubadas con una solución de AAL. La PNE fue evaluada por el método de quimioluminiscencia (QL). Cuando se compararon las muestras control (sin el agregado del ascorbato-Fe⁺⁺) con las muestras ascorbato-Fe⁺⁺ dependientes, se observó un incremento significativo en la emisión lumínica. Simultáneamente, se incubaron las mitocondrias de ambos órganos con diferentes concentraciones de AAL (0,05, 0,15 y 0,25mg/ml) observándose una protección diferencial. Las mitocondrias de cerebro de rata incubadas con dosis de 0,15 y 0,25 mg/ml de AAL fueron protegidas de los efectos de la PNE, mientras que, en las mitocondrias cardíacas, solo se observó protección con la dosis más alta de AAL (0,25 mg/ml). El análisis de QL indicó que las mitocondrias de cerebro fueron protegidas de manera más eficiente que las mitocondrias de corazón de rata. En este último caso, será necesario probar nuevas dosis de AAL para demostrar los efectos en estas membranas. En conclusión, AAL actuó como un antioxidante protector de las membranas de ambos órganos contra el daño peroxidativo., Alphalipoc acid (ALA) has been characterized as an efficient antioxidant. It has been proposed as a potential therapeutic agent in the treatment or prevention of different pathologies that may be related to an imbalance of the oxido reductive cell state. The objective of this work was to analyze the sensitivity to non-enzymatic peroxidation (NEP) (ascorbate-Fe⁺⁺ dependent) in heart and brain mitochondria of rats incubated with an ALA solution. NEP was evaluated by the chemiluminescence method (CL). When the control samples (without the addition of ascorbate-Fe⁺⁺) were compared with the ascorbate-Fe⁺⁺ dependent samples, a significant increase in the light emission. Simultaneously, the mitochondria of both organs were incubated with different concentrations of ALA (0.05, 0,15 and 0,25 mg/ml), observing a differential protection. Rat brain mitochondria incubated with doses of 0.15 and 0,25 mg/ml of ALA were protected from the effects of NEP, while in cardiac mitochondria, protection was only observed with the highest dose of ALA (0,25 mg/ml). The CL analysis indicated that rat brain mitochondria were protected more efficiently than rat heart mitochondria. In the latter case, it will be necessary to test new doses of ALA to demonstrate the effects on these membranes. In conclusion, ALA acted as a protective antioxidant of the membranes of both organs against peroxidative damage., Facultad de Ciencias Veterinarias

Introduction The structural and mechanical adaptations of the right ventricular (RV) myocytes in response to hypertension associated with low-intensity endurance training (LIET) have not been studied in experimental models. Objective To determine the effects of LIET on the structural and mechanical properties of RV myocytes in spontaneously hypertensive rats (SHRs). Methods Male SHRs and normotensive Wistar rats (age: 16 weeks) were allocated to groups (n=7): WIS (Wistar Controls); SHR-C (SHR Controls) and SHR-T (SHR Trained; 60 min/day, 50-60% of maximal exercise capacity, 5 days/week for 8 weeks). Systolic arterial pressure (SAP), isolated RV myocyte dimensions, contractility, intracellular Ca2+ transient ([Ca2+]i), and ventricular Ca2+ regulatory proteins were measured. The statistical analysis was performed by one-way ANOVA followed by the Tukey post hoc test (α=5%). Results LIET reduced the SAP in SHR animals (SHR-C, 164 ± 2 mmHg vs. SHR-T, 152 ± 4 mmHg; P0.05). LIET did not change the cell dimensions in the SHR-T. Neither hypertension nor LIET affected myocyte contractility or the expression of Ca2+ regulatory proteins in the RV of the SHR-C and SHR-T groups. Hypertension did not affect the amplitude of the [Ca2+]i transient or the time to half resting level (P>0.05), but increased the time to peak (WIS, 58 ± 1 ms vs. SHR-C, 79 ± 2 ms; P 0,05). O TABI não alterou as dimensões celulares nos SHR-T. Nem a hipertensão nem o TABI afetaram a contratilidade dos miócitos ou a expressão das proteínas reguladoras do Ca2+ no VD dos grupos SHR-C e SHR-T. A hipertensão não afetou a amplitude do transiente de [Ca2+]i e o tempo até a metade do nível de repouso (P > 0,05), mas aumentou o tempo até o pico (WIS, 58 ± 1 msvs. SHR-C, 79 ± 2 ms; P < 0,05). O TABI aumentou a amplitude do transiente de [Ca2+]i (WIS, 2,28 ± 0,07 F/F0 e SHR-C, 2,48 ± 0,08 F/F0 vs. SHR-T, 2,87 ± 0,08 F/F0 P < 0,05), mas não alterou os tempos até o pico e a metade do nível de repouso. Conclusão O TABI não teve efeito sobre as propriedades estruturais e mecânicas de miócitos do VD de SHR, embora tenha aumentado a amplitude do transiente de [Ca2+]i e reduzido a PAS. Nível de evidência I, Estudos terapêuticos – Investigação dos resultados do tratamento. RESUMEN Introducción Las adaptaciones estructurales y mecánicas de los miocitos del ventrículo derecho (VD) en respuesta a la hipertensión asociada al entrenamiento de resistencia de baja intensidad (ERBI) no se han estudiado en modelos experimentales de ratas. Objetivo Determinar los efectos del ERBI sobre las propiedades estructurales y mecánicas de los miocitos del VD en ratas espontáneamente hipertensas (SHR). Métodos Ratas SHR y ratas Wistar machos y normotensas (edad: 16 semanas) fueron distribuidas en grupos (n = 7): WIS (Wistar controle); SHR-C (SHR controle) y SHR-T (SHR entrenado; 60 min/día, el 50% a 60% de la capacidad máxima de ejercicio, 5 días/semana por 8 semanas). Se midieron presión arterial sistólica (PAS), dimensiones de los miocitos aislados del VD, contractilidad, transitorio intracelular de Ca2+ ([Ca2+]i) y proteínas reguladoras de Ca2+. El análisis estadístico se realizó mediante ANOVA one-way seguida por la prueba de Tukey post hoc (α = 5%). Resultados El ERBI redujo la PAS en los animales SHR (SHR-C, 164 ± 2 mmHg contra SHR-T 152 ± 4 mmHg, P < 0,05). La hipertensión aumentó la longitud de la célula (WIS, 156,8 ± 2,7 μm, SHR-C, 166,6 ± 3,1 μm; P < 0,05), pero no afectó el ancho o el volumen (P > 0,05). El ERBI no alteró las dimensiones de la célula en SHR-T. Ni la hipertensión y ni el ERBI afectaron la contractilidad de los miocitos o la expresión de proteínas reguladoras de Ca2+ en el VD de los grupos SHR-C y SHR-T. La hipertensión no afectó la amplitud del transitorio de [Ca2+]i y el tiempo hasta la mitad del nivel de reposo (P > 0,05), pero aumentó tiempo hasta el pico (WIS, 58 ± 1 ms contra SHR-C, 79 ± 2 ms; P < 0,05). El ERBI aumentó la amplitud del transitorio de [Ca2+]i (WIS, 2,28 ± 0,07 F/F0 y SHR-C, 2,48 ± 0,08 F/F0 contra SHR-T, 2,87 ± 0,08 F/F0 P < 0,05), pero no alteró los tiempos hasta el pico y la mitad del nivel de reposo. Conclusión El ERBI no tuvo efecto sobre las propiedades estructurales y mecánicas de los miocitos del VD de SHR, aunque aumentó la amplitud del transitorio de [Ca2+]i y redujo la PAS. Nivel de Evidencia I, Estudios terapéuticos - Investigación de los resultados del tratamiento.

Introducción y objetivos: Analizar el impacto del lactato sérico en receptores de trasplante cardiaco urgente en asistencia circulatoria mecánica de corta duración preoperatoria. Métodos: Se realizó un subanálisis de un registro multicéntrico español basado en pacientes incluidos en «urgencia grado 0» para trasplante cardiaco con asistencia circulatoria mecánica preoperatoria de corta duración entre 2010 y 2015. Se seleccionó a los receptores de trasplante con cifras preoperatorias de lactato conocidas. El desenlace principal fue la supervivencia 1 año tras el trasplante. Resultados: Se estudió a 177 receptores de trasplante cardiaco urgente, de los que 90 necesitaron asistencia preoperatoria con oxigenador extracorpóreo de membrana venoarterial, 51 con asistencia ventricular izquierda y 36 con asistencia biventricular. De ellos, 44 (25%) presentaban hiperlactatemia antes del trasplante (≥ 2 mmol/l). En el análisis multivariable, la cifra de lactato sérico resultó predictora independiente de mortalidad tras el trasplante (cada 0,1 mmol/l, HR ajustada = 1,02; IC95%, 1,01-1,03; p = 0,007). La supervivencia estimada al año del trasplante cardiaco fue del 53,1% (IC95%, 45,3-60,9) en los pacientes con hiperlactactemia preoperatoria y el 75,6% (IC95%, 71,8-79,4) en los pacientes sin hiperlactatemia (HR ajustada = 1,94; IC95%, 1,04-3,63; p = 0,039). El impacto pronóstico de la hiperlactatemia fue significativo en los pacientes asistidos con oxigenador extracorpóreo de membrana venoarterial, pero no en aquellos con dispositivos de asistencia ventricular. Conclusiones: Los valores preoperatorios de ácido láctico son un potente factor pronóstico independiente en receptores de trasplante cardiaco urgente. Introduction and objectives: To study the prognostic value of serum lactate in patients under temporary preoperative mechanical circulatory support who underwent urgent heart transplant. Methods: We conducted a subanalysis of a Spanish multicenter registry recording data on patients under temporary mechanical circulatory support listed for highly urgent heart transplant from 2010 to 2015. Participants selected for the present study were those who received a transplant and who had known preoperative serum lactate levels. The main study outcome was 1-year survival after transplant. Results: A total of 177 heart transplant recipients were studied; preoperatively, 90 were supported on venoarterial extracorporeal membrane oxygenation, 51 on temporary left ventricular assist devices, and 36 on temporary biventricular assist devices. Preoperative hyperlactatemia (≥ 2 mmol/L) was present in 44 (25%) patients. On multivariable analysis, pretransplant serum lactate was identified as an independent predictor of 1-year posttransplant survival (adjusted HR per 0.1 mmol/L, 1.02; 95%CI, 1.01-1.03; P = .007). One-year posttransplant survival was 53.1% (95%CI, 45.3-60.9) in patients with preoperative hyperlactatemia and 75.6% (95%CI, 71.8-79.4) in those without preoperative hyperlactatemia (adjusted HR, 1.94; 95%CI, 1.04-3.63; P = .039). Preoperative hyperlactatemia correlated with adverse outcomes in patients supported with extracorporeal membrane oxygenation, but not in patients supported on ventricular assist devices. Conclusions: Preoperative serum lactate is a strong independent predictor of worse outcomes in patients undergoing urgent heart transplant on short-term mechanical circulatory support. Sin financiación 4.642 JCR (2019) Q1, 30/138 Cardiac & Cardiovascular Systems 0.473 SJR (2019) Q3, 196/362 Cardiology and Cardiovascular Medicine No data IDR 2019 UEM

Sin financiación 6.975 JCR (2021) Q1, 33/143 Cardiac & Cardiovascular Systems 0.407 SJR (2021) Q3, 205/356 Cardiology and Cardiovascular Medicine No data IDR 2021 UEM

Digital, Acquired tuberculosis continues to be a challenge worldwide. Although tuberculosis has been considered a global public health emergency, it remains poorly controlled in many countries. Despite being primarily a pulmonary disease, tu-berculosis could involve the heart. This systematic review is part of the "Neglected Tropical Diseases and Other Infectious Diseases Involving the Heart" (the NET-Heart Project) initiative from the Interamerican Society of Cardiology. This project aims to review the cardiovascular involvement of these heterogeneous diseases, advancing original algorithms to help healthcare providers diagnose and manage cardiovascular complications. In tuberculosis, pericardium involvement is relatively common, especially in AIDS, and tuberculosis is the most common cause of constrictive pericarditis in endemic countries. Myocarditis and aortitis by tuberculosis are rare. Clinical manifestations of cardiovascular involvement by tuberculosis differ from those typically found for bacteria or viruses. Prevailing systemic symptoms and the pericarditis diagnostic index should be taken into account. An echocardiogram is the first step for diagnosing cardiovascular involvement; however, several image modalities can be used, depending on the suspected site of infection. Adenosine deaminase levels, gamma interferon, or polymerase chain reaction testing could be used to confirm tuberculosis infection; each has a high diagnostic performance. Antituberculosis chemotherapy and corticosteroids are treatment mainstays that significantly reduce mortality, constriction, and hospitaliza-tions, especially in patients with HIV. In conclusion, tuberculosis cardiac involvement is frequent and could lead to heart failure, constrictive pericarditis, or death. Early detection of complications should be a cornerstone of overall management., Ciencias Médicas y de la Salud

Sin financiación No data JCR 2021 0.385 SJR (2021) Q3, 1499/2489 Medicine (miscellaneous) No data IDR 2021 UEM

The validation of reference genes is an essential step for any RT-qPCR analysis. In this way, the present paper aimed to identify and validate reference genes for RT-qPCR in cardiac tissue of rats of the Rattus norvegicus albinus specie, submitted to obesity associated or not to type 2 diabetes mellitus. For this, the metabolic changes were induced at the 42nd day of life and the euthanasia was performed on the 70th day. The heart apexes were collected and destinates for RNA extraction. The RT-qPCR technique was performed in own thermocycler, the efficiency of the primers found by the LinReg software and the stability of the expression of the reference genes in the samples was analyzed by the RefFinder algorithm. The candidates for reference genes were GAPDH, POLR2A, RPL32, and RPL4 and the target gene used to verify the differences in gene expression of candidates for reference genes was CMA1. The obese animals showed a decrease in CMA1 gene expression when compared to the two most stable reference genes. The opposite occurs when it is compared to the two less stable reference genes. The GAPDH and POLR2A genes are the best to normalize the reactions with the samples in question. There is no universal reference gene for all situations, which requires systematic validation for each situation. The use of unvalidated reference genes may compromise the interpretation of the expression of the target genes, which would prevent the reflection of the actual situation. La validación de genes de referencia es un paso fundamental para análisis de RT-qPCR. El presente trabajo tuvo como objetivo identificar y validar genes de referencia para RT-qPCR en tejido cardíaco de ratas de la especie Rattus norvegicus albinus, sometidas a obesidad asociada o no a diabetes mellitus tipo 2. Fueran introducidos los cambios metabólicos a los 42 días de vida y se realizó la eutanasia a los 70 días. Los ápices del corazón fueran destinados a la extracción de RNA. La técnica RT-qPCR se realizó en termociclador propio, la eficiencia de los cebadores encontrados por el software LinReg y la estabilidad de la expresión de los genes de referencia en las muestras se analizó mediante el algoritmo RefFinder. Los candidatos a genes de referencia fueron GAPDH, POLR2A, RPL32 y RPL4, y el gen diana utilizado para verificar las diferencias en la expresión génica de los candidatos a genes de referencia fue CMA1. Los animales obesos mostraron una disminución en la expresión del gen CMA1 en comparación con los dos genes de referencia más estables. Lo contrario ocurre cuando se compara con los dos genes de referencia menos estables. Los genes GAPDH y POLR2A son los mejores para normalizar las reacciones con las muestras en cuestión. No existe un gen de referencia universal, lo que requiere una validación sistemática para cada situación. El uso de genes de referencia no validados puede comprometer la interpretación de la expresión de los genes diana, lo que evitaría el reflejo de la situación real. A validação dos genes de referência é uma etapa essencial para qualquer análise de RT-qPCR. Dessa forma, o presente trabalho teve como objetivo identificar e validar genes de referência para RT-qPCR em tecido cardíaco de ratos da espécie Rattus norvegicus albinus, submetidos à obesidade associada ou não ao diabetes mellitus tipo 2. Para isso, as alterações metabólicas foram induzidas no 42º dia de vida e a eutanásia foi realizada no 70º dia. Os ápices cardíacos foram coletados e destinam-se à extração de RNA. A técnica de RT-qPCR foi realizada em termociclador próprio, a eficiência dos primers encontrados pelo software LinReg e a estabilidade da expressão dos genes de referência nas amostras foram analisadas pelo algorítmo RefFinder. Os candidatos a genes de referência foram GAPDH, POLR2A, RPL32 e RPL4 e o gene alvo usado para verificar as diferenças na expressão gênica dos candidatos a genes de referência foi CMA1. Os animais obesos apresentaram uma diminuição na expressão do gene CMA1 quando comparados aos dois genes de referência mais estáveis. O oposto ocorre quando comparado aos dois genes de referência menos estáveis. Os genes GAPDH e POLR2A são os melhores para normalizar as reações com as amostras em questão. Não há gene de referência universal para todas as situações, o que requer validação sistemática para cada situação. O uso de genes de referência não validados pode comprometer a interpretação da expressão dos genes alvo, o que impediria a reflexão da situação real.

Aging is a major risk for cardiovascular diseases (CVD). Age-related disorders include oxidative stress, mitochondria dysfunction, and exacerbation of the NF- B/NLRP3 innate immune response pathways. Some of the molecular mechanisms underlying these processes, however, remain unclear. This study tested the hypothesis that NLRP3 inflammasome plays a role in cardiac aging and melatonin is able to counteract its e ects. With the aim of investigating the impact of NLRP3 inflammasome and the actions and target of melatonin in aged myocardium, we analyzed the expression of proteins implied in mitochondria dynamics, autophagy, apoptosis, Nrf2-dependent antioxidant response and mitochondria ultrastructure in heart of wild-type and NLRP3-knockout mice of 3, 12, and 24 months-old, with and without melatonin treatment. Our results showed that the absence of NLRP3 prevented age-related mitochondrial dynamic alterations in cardiac muscle with minimal e ects in cardiac autophagy during aging. The deficiency of the inflammasome a ected Bax/Bcl2 ratio, but not p53 or caspase 9. The Nrf2-antioxidant pathway was also una ected by the absence of NLRP3. Furthermore, NLRP3-deficiency prevented the drop in autophagy and mice showed less mitochondrial damage than wild-type animals. Interestingly, melatonin treatment recovered mitochondrial dynamics altered by aging and had few e ects on cardiac autophagy. Melatonin supplementation also had an anti-apoptotic action in addition to restoring Nrf2-antioxidant capacity and improving mitochondria ultrastructure altered by aging., Instituto de Salud Carlos III (Ministerio de Economia y Competitividad, Spain) PI16-00519 PI19-01372 CB16-10-00238, European Regional Development Fund/European Social Fund "Investing in your future", Junta de Andalucía CTS-101, German Research Foundation (DFG)

The cardiac plexus is a vast network of neurons grouped into ganglia distributed throughout the myocardium. The epicardial adipose tissue covers the heart performing important functions, such as, lipid storage. However, its exaggerated expression might represent a risk factor, which can be prevented by the practice of physical activities that improves the heart contractile propulsive capacity. Insulin has been used in association with physical exercise so as to increase muscle mass and improve physical performance. Both insulin and exercise have been evidenced due to their neurotrophic effects. The purpose of this study was to ascertain whether insulin associated with resistance training could structurally modify the cardiac plexus and epicardial adipose tissue. Four groups (n = 6) of male Swiss mice were used: non-trained saline, non-trained insulin; trained saline; trained insulin. The training was performed on a vertical ladder at 90% of the maximum load, 3 times/week for 8 consecutive weeks. After the experimental period, the hearts of the animals were removed, and 5-μm sections were stained with Hematoxylin/Eosin, Giemsa and Picrossirius in order to evaluate the structures of the cardiac plexus. There was no significant difference with regard to the area and the total number of neurons, nor to the area with collagen. However, whereas insulin administration hypertrophied the adipocytes and predisposed an inflammatory environment, physical exercise played an anti-inflammatory role. As a conclusion, it is worth mentioning that resistance training did not change the cardiac plexus, however the epicardial adipose tissue was reduced, an effect antagonized by insulin. El plexo cardíaco es una vasta red de neuronas agrupadas en ganglios distribuidos por todo el miocardio. El tejido adiposo epicárdico cubre el corazón y realiza funciones importantes, como el almacenamiento de lípidos. Sin embargo, su exagerada expresión podría representar un factor de riesgo, que puede prevenirse mediante la práctica de actividades físicas que mejoren la capacidad de propulsión contráctil del corazón. La insulina se ha utilizado en asociación con el ejercicio físico para aumentar la masa muscular y mejorar el rendimiento físico. Tanto la insulina como el ejercicio se han evidenciado por sus efectos neurotróficos. El propósito de este estudio fue determinar si la insulina asociada con el entrenamiento de resistencia podría modificar estructuralmente el plexo cardíaco y el tejido adiposo epicárdico. Se utilizaron cuatro grupos (n = 6) de ratones suizos machos: solución salina no adiestrada, insulina no adiestrada; solución salina adiestrada; insulina entrenada. El entrenamiento se realizó en escalera vertical al 90% de la carga máxima, 3 veces / semana durante 8 semanas consecutivas. Después del período experimental, se extrajeron los corazones de los animales y se tiñeron secciones de 5 μm con Hematoxilina / Eosina, Giemsa y Picrossirius para evaluar las estructuras del plexo cardíaco. No hubo diferencia significativa con respecto al área y el número total de neuronas, ni al área con colágeno. Sin embargo, mientras que la administración de insulina hipertrofió los adipocitos y predispuso un ambiente inflamatorio, el ejercicio físico jugó un papel antiinflamatorio. Como conclusión, cabe mencionar que el entrenamiento de resistencia no cambió el plexo cardíaco, sin embargo el tejido adiposo epicárdico se redujo, efecto antagonizado por la insulina. O plexo cardíaco é uma vasta rede de neurônios agrupados em gânglios distribuídos por todo o miocárdio. O tecido adiposo epicárdico cobre o coração desempenhando funções importantes, como o armazenamento de lipídios. No entanto, sua expressão exagerada pode representar um fator de risco, que pode ser prevenido pela prática de atividades físicas que aumentem a capacidade propulsiva contrátil do coração. A insulina tem sido utilizada em associação com exercícios físicos para aumentar a massa muscular e melhorar o desempenho físico. Tanto a insulina quanto os exercícios foram evidenciados devido aos seus efeitos neurotróficos. O objetivo deste estudo foi verificar se a insulina associada ao treinamento de resistência poderia modificar estruturalmente o plexo cardíaco e o tecido adiposo epicárdico. Quatro grupos (n = 6) de camundongos Swiss machos foram usados: não treinado salina, não treinado insulina; treinado; treinado insulina. O treinamento foi realizado em escada vertical a 90% da carga máxima, 3 vezes / semana durante 8 semanas consecutivas. Após o período experimental, os corações dos animais foram retirados e cortes de 5 μm foram corados com Hematoxilina / Eosina, Giemsa e Picrossírius para avaliação das estruturas do plexo cardíaco. Não houve diferença significativa em relação à área e ao número total de neurônios, nem à área com colágeno. No entanto, enquanto a administração de insulina hipertrofiou os adipócitos e predispôs um ambiente inflamatório, o exercício físico exerceu papel antiinflamatório. Como conclusão, vale ressaltar que o treinamento resistido não alterou o plexo cardíaco, porém o tecido adiposo epicárdico foi reduzido, efeito antagonizado pela insulina.

Introduction Advanced interatrial block (IAB) on a 12‐lead electrocardiogram (ECG) is a predictor of stroke, incident atrial fibrillation (AF), and AF recurrence after catheter ablation. The objective of this study was to determine which features of IAB structural remodeling is associated with left atrium (LA) magnetic resonance imaging structure and function. Methods/Results We included 152 consecutive patients (23% nonparoxysmal AF) who underwent preprocedural ECG and cardiac magnetic resonance (CMR) in sinus rhythm before catheter ablation of AF. IAB was defined as P‐wave duration ≥120 ms, and was considered partial if P‐wave was positive and advanced if P‐wave had a biphasic morphology in inferior leads. From cine CMR and late gadolinium enhancement, we derived LA maximum and minimum volume indices, strain, LA fibrosis, and LA dyssynchrony. A total of 77 patients (50.7% paroxysmal) had normal P‐wave, 52 (34.2%) partial IAB, and 23 (15.1%) advanced IAB. Patients with advanced IAB had significantly higher LA minimum volume index (25.7 vs 19.9 mL/m2, P = .010), more LA fibrosis (21.9% vs 13.1%, P = .020), and lower LA maximum strain rate (0.99 vs 1.18, P = .007) than those without. Advanced IAB was independently associated with LA (minimum [P = .032] and fibrosis [P = .009]). P‐wave duration was also independently associated with LA fibrosis (β = .33; P = .049) and LA mechanical dyssynchrony (β = 2.01; P = .007). Conclusion Advanced IAB is associated with larger LA volumes, lower emptying fraction, and more fibrosis. Longer P‐wave duration is also associated with more LA fibrosis and higher LA mechanical dyssynchrony. Sin financiación 2.871 JCR (2020) Q3, 79/142 Cardiac & Cardiovascular Systems 1.193 SJR (2020) Q1, 72/349 Cardiology and Cardiovascular Medicine No data IDR 2020 UEM

The fragile heart is a British miniseries, released in 1996. Since this medical drama offers, among others, a variety of possibilities for debate on deontological and attitudinal features for physicians in particular and professionals in health area in general is more than recommended appreciating the various readings it allows./nThe aim of this paper is to address it and present some of those possibilities. El corazón frágil es una miniserie británica, estrenada en 1996. Dado que este drama médico ofrece, entre otras, una variedad de posibilidades de debate sobre facetas deontológicas y actitudinales para médicos en particular y profesionales del área de la salud en general resulta más que recomendable apreciar las varias lecturas que permite./nEl objetivo de este trabajo es abordarla y presentar algunas de tales posibilidades.

Background The criteria applied for diagnosis of left atrial (LA) abnormality using electrocardiogram (ECG) have high specificity but low sensitivity. In fact, some authors have suggested classifying P‐wave anomalies associated with LA abnormality and interatrial block as “atrial abnormalities.” The most widely known ECG criteria for LA abnormality include P‐wave duration, morphology and voltage of P wave in inferior leads, presence of P‐wave terminal force in V1 (PtfV1), and P‐wave axis and area. PtfV1 has also been reported to vary according to misplacement of the V1 and V2 electrodes. Methods The objective of this observational cohort study is to determine the degree of correlation between ECG criteria for LA abnormality and left atrium volume and functionality, as determined by speckle tracking echocardiography. The study also aims to investigate the correlation between these echocardiographic parameters and PtfV1 value by placing the V1 and V2 electrodes in the second, third, and fourth intercostal spaces. Results and Conclusions Our results could help to clarify whether the decrease in left atrial deformity, which is currently considered a surrogate target of fibrosis, correlates better with ECG criteria for LA abnormality than atrial volumes. Sin financiación 1.468 JCR (2020) Q4, 130/142 Cardiac & Cardiovascular Systems 0.494 SJR (2020) Q3, 190/349 Cardiology and Cardiovascular Medicine No data IDR 2020 UEM

“Estudio anidado al proyecto de investigación “Valor pronóstico de los polimorfismos de la Metaloproteinasa de Matriz extracelular-9 (MMP-9: SNP-1562C/T), su inhibidor tisular endógeno (TIMP-1: SNP-372T/C), MMP-2 (– 1575 A/G) y de la Acuaporina 5 (AQP5: SNP-1364A/C) en pacientes sépticos.” Introducción: La disfunción cardiovascular asociada a la sepsis tiene un papel fundamental a nivel diagnóstico y pronóstico. Varios biomarcadores se han estudiado para objetivar la disfunción cardiovascular en la sepsis tales como la troponina, péptidos natriuréticos y parámetros ecocardiográficos. Se han encontrado moléculas como las acuaporinas y su polimorfismo AQP-5 SNP- 1364A/C que se han asociado a la fisiopatología de la sepsis y que impactan en la mortalidad. Objetivo: Determinar la asociación entre polimorfismo de la AQP-5 SNP-1364A/C con la disfunción cardiovascular en pacientes adultos con sepsis. Materiales y Métodos: Estudio analítico de corte transversal anidado a la cohorte del estudio “Valor pronóstico de los polimorfismos de la Metaloproteinasa de Matriz extracelular-9 (MMP-9: SNP-1562C/T), su inhibidor tisular endógeno (TIMP-1: SNP- 372T/C), MMP-2 (– 1575 A/G) y de la Acuaporina 5 (AQP5: SNP-1364 A/C) en pacientes sépticos.” Se calculó la asociación del NT pro BNP, troponina I disfunción sistólica /diastólicas medidas por variables ecocardiográficas con el polimorfismo AQP-5 -SNP1364A/C en pacientes con sepsis. Resultados: Se analizó 540 registros. La mediana de edad de los pacientes fue de 59 años con un rango de edad entre 45-74 años. La mediana de NT-pro BNP fue 762 (RIQ: 215.5-3284), de la troponina I 0.1 (RIQ: 0.1- 0.1). El origen más frecuente de la sepsis fue tracto urinario (34.4%). El 14.63% de los pacientes fallecieron. La disfunción sistólica estuvo presente en 29.64 %, la disfunción diastólica 66.1%. El 76.67% fueron manejados en unidad de cuidados intensivo, 22.04% presentaron choque séptico. La asociación entre el polimorfismo de la AQP-5 -SNP1364A/C con la disfunción sistólica (RP:0.94; IC 95%= 0.64- 1.3 Valor P: 0.4503), disfunción diastólica, (RP: 0.93; IC 95%= 0 .75- 1.14 Valor P: 0.2909) Troponina I (RP: 1.2; IC 95%= 0 .75- 2.1 Valor P: 0.2006 ) y NT-proBNP (RP: 1.0; IC 95%= 0 .90- 1.15 Valor P: 0.4169). Conclusiones: No se encontró una asociación estadísticamente significativa entre el polimorfismo AQP-5 -SNP1364A/C con los biomarcadores de lesión miocárdica y variables ecocardiográficas en pacientes con sepsis. A partir de los hallazgos, la metodología de análisis y la evidencia es necesario reorientar las estrategias de investigación alrededor, de la relacion polimorfismo de la AQP-5 -SNP1364A/C con la disfunción cardiovascular incluyendo más pacientes para evaluar su asociación. RESUMEN 9 SUMMARY 11 INTRODUCCIÓN 12 PLANTEAMIENTO DEL PROBLEMA Y JUSTIFICACIÓN 15 MARCO TEÓRICO Y ESTADO DEL ARTE 18 Definición y epidemiologia de la Sepsis 18 Fisiopatología de la sepsis: 22 Disfunción cardiaca asociada a la sepsis 29 Disfunción cardiaca asociada a la sepsis, fisiopatología: 31 Alteraciones hemodinámicas en miocardiopatía séptica 34 Definición de cardiomiopatía séptica 35 Métodos diagnósticos de cardiomiopatía séptica: 37 Biomarcadores de origen cardiogénico 38 Manifestaciones ecocardiográficas 40 Acuaporinas conceptos generales 42 Acuaporinas de origen cardiaco: 43 Acuaporinas cardiacas asociada a la sepsis: 45 OBJETIVOS 47 Objetivos específicos 47 METODOLOGÍA PROPUESTA 48 Tipo de estudio: 48 Población 48 Muestra 49 Recolección de la información 50 Procesamiento y control de calidad 52 Procesamiento y análisis estadístico 52 CONSIDERACIONES ÉTICAS 54 RESULTADOS 56 Características de base 56 Desenlaces primarios 57 Asociación entre el polimorfismo de la AQP-5 -SNP1364A/C con la disfunción sistólica medida por ecocardiograma. 57 Asociación entre el polimorfismo de la AQP-5 -SNP1364A/C con la disfunción diastólica medida por ecocardiograma. 57 Asociación entre el polimorfismo de la AQP-5 -SNP1364A/C con la troponina I.................................................................................................................................................. 58 Asociación entre el polimorfismo de la AQP-5 -SNP1364A/C con el NT- pro BNP. .................................................................................................................................................. 58 DISCUSIÓN 59 CONCLUSIONES 66 BIBLIOGRAFÍA 67 TABLAS 78 FIGURAS 82 ANEXOS 83 CRONOGRAMA 85 CARTAS AUTORIZACIÓN 86 Especialización Background: Cardiovascular dysfunction associated with sepsis plays a fundamental role at a diagnostic and prognostic level. Various cardiac biomarkers have been studied to identify the cardiovascular dysfunction in sepsis such as troponin, natriuretic peptides and echocardiographic parameters. Molecules have been found such as aquaporins and its polymorphism AQP-5 SNP-136A/C that have been associated to the pathophysiology of sepsis that impact mortality. Objective: An association was determined between polymorphism of the AQP-5 SNP-1364A/C molecule with cardiovascular dysfunction in adult patients with sepsis Methods: Analytic study in a transversal cut added to the cohort of study “Prognostic value of polymorphisms of Extracellular Matrix Metalloproteinase-9 (MMP-9: SNP- 1562C / T), its endogenous tissue inhibitor (TIMP-1: SNP-372T / C), MMP-2 (- 1575 A / G ) and Aquaporin 5 (AQP5: SNP-1364 A / C) in septic patients.” An association was calculated of the NT pro BNP, troponin I dysfunction systolic/diastolic measurements through echocardiographic variables with the polymorphism AQP-5-SNP1364A/C in patients with sepsis. Results: 540 charts were reviewed. The average age of the patients was 59 years with a range of age between 45-74 years. The average NT-pro BNP was 762 (RIQ: 215.5-3284), and the average of troponin I was 0.1 (RIQ: 0.1- 0.1). The most frequent origin of sepsis was via the urinary tract (34.4%). 14.63% of patients expired. Systolic dysfunction was present in 29.64% and diastolic dysfunction was 66.1%. 76.67% were managed in the intensive care unit, 22.04% presented with septic shock. The association between polymorphism of AQP-5 SNP-1364A/C with systolic dysfunction (RP:0.94; IC 95%= 0.64- 1.3; P Value: 0.4503), diastolic dysfunction, (RP: 0.93; IC 95%= 0 .75- 1.14; P value: 0.2909), Troponin I (RP: 1.2; IC 95%= 0 .75- 2.1; P Value: 0.2006) and NT-proBNP (RP: 1.0; IC 95%= 0 .90- 1.15;P Value: 0.4169). Conclusions: There was not a stadistically significant association found between polymorphism AQP-5 SNP-136A/C with the biomarkers of myocardial injury and echocardiographic variables in patients with sepsis. As a result of these findings, the methodology of analysis and evidence is necessary to reorient the strategies of research surrounding the relation between AQP-5 -SNP1364A/C with cardiovascular dysfunction including more patients to assess their association.

Despite strong scientific evidence supporting the benefits of regular exercise for the prevention and management of cardiovascular disease (CVD), physical inactivity is highly prevalent worldwide. In addition to merely changing well-known risk factors for systemic CVD, regular exercise can also improve cardiovascular health through non-traditional mechanisms. Understanding the pathways through which exercise influences different physiological systems is important and might yield new therapeutic strategies to target pathophysiological mechanisms in CVD. This Review includes a critical discussion of how regular exercise can have antiatherogenic effects in the vasculature, improve autonomic balance (thereby reducing the risk of malignant arrhythmias), and induce cardioprotection against ischaemia–reperfusion injury, independent of effects on traditional CVD risk factors. This Review also describes how exercise promotes a healthy anti-inflammatory milieu (largely through the release of muscle-derived myokines), stimulates myocardial regeneration, and ameliorates age-related loss of muscle mass and strength, a frequently overlooked non-traditional CVD risk factor. Finally, we discuss how the benefits of exercise might also occur via promotion of a healthy gut microbiota. We argue, therefore, that a holistic view of all body systems is necessary and useful when analysing the role of exercise in cardiovascular health. Sin financiación 17.420 JCR (2018) Q1, 4/136 Cardiac & Cardiovascular Systems 4.882 SJR (2018) Q1, 8/365 Cardiology and Cardiovascular Medicine No data IDR 2018 UEM

Since the outbreak of the COVID-19 pandemic, much has been learned regarding its clinical course, prognostic inflammatory markers, disease complications, and mechanical ventilation strategy. Clinically, three stages have been identified based on viral infection, pulmonary involvement with inflammation, and fibrosis. Moreover, low and high elastance phenotypes can be distinguished in mechanically ventilated patients, based on lung mechanics, ventilation-to-perfusion ratio, and CT scans; these two phenotypes have presumed differences in their underlying pathophysiology. Although essential for therapeutic guidance, the pathophysiology of COVID-19 is poorly understood. Here, we systematically reviewed published case reports and case series in order to increase our understanding of COVID-19 pathophysiology by constructing a timeline and correlating histopathological findings with clinical stages of COVID-19. Using PRISMA-IPD guidelines, 42 articles reporting 198 individual cases were included in our analysis. In lung samples (n = 131 cases), we identified three main histological patterns: epithelial (n = 110, 85%), with reactive epithelial changes and DAD; vascular (n = 76, 59%) with microvascular damage, (micro)thrombi, and acute fibrinous and organizing pneumonia; and fibrotic (n = 28, 22%) with interstitial fibrosis. The epithelial and vascular patterns can present in all stages of symptomatic COVID-19, whereas the fibrotic pattern presents starting at ~3 weeks. Moreover, patients can present with more than one pattern, either simultaneously or consecutively. These findings are consistent with knowledge regarding clinical patterns of viral infection, development of hyperinflammation and hypercoagulability, and fibrosis. Close collaboration among medical staff is necessary in order to translate this knowledge and classification of pathophysiological mechanisms into clinical stages of disease in individual patients. Moreover, further research, including histopathological studies, is warranted in order to develop reliable, clinically relevant biomarkers by correlating these pathological findings with laboratory results and radiological findings, thus, increasing our understanding of COVID-19 and facilitating the move to precision medicine for treating patients.

Sin financiación 7.598 JCR (2020) Q1, 6/36 Critical Care Medicine 3.002 SJR (2020) Q1, 3/88 Critical Care and Intensive Care Medicine No data IDR 2020 UEM

Introduction: The study of the effects of different types of physical exercise on cardiovascular physiology is increasing in the literature. The many mechanisms of hemodynamic control include the atrial release of natriuretic peptides. Although extensive evidence demonstrates their acute effects and the increase in their plasma concentration, it is not known whether both atria respond in a similar way to both types of natriuretic peptide in response to different types of exercise. Objective: To compare the acute responses of different exercise types in the atrial (ANP) and brain (BNP) natriuretic peptides of both atrial cardiomyocytes of Wistar rats. Methods: Animals were divided into control (CG), aerobic (AG), resistance (RG) and combined (ARG). The RG performed six climbs, with a load equivalent to 60% of body weight. The AG ran on a treadmill at a speed of 12m/min for 60 minutes. The ARG exercise consisted of three consecutive ladder climbs, followed by 30 minutes of running. Results: First, the right atrium released more ANP and BNP during all types of exercise; second, the resistance exercise released the most ANP and BNP in both atria; third, in the right atrium, aerobic and combined workouts released more small and medium ANP granules while resistance exercise released larger BNP granules; and fourth, in the left atrium, aerobic exercise released more ANP granules while resistance and combined exercise released larger ANP and BNP granules. Conclusion: All types of exercise induce partial release of natriuretic peptide granules, with greater response to resistance exercise. Furthermore, a particular and different response could be seen in both types of atria in the release of ANP and BNP. Level of evidence II; Therapeutic studies - Investigation of treatment results.

OBJECTIVES To investigate the potential clinical benefit of an intra-aortic balloon pump (IABP) in patients supported with venoarterial extracorporeal membrane oxygenation (VA-ECMO) as a bridge to heart transplantation (HT). METHODS We studied 169 patients who were listed for urgent HT under VA-ECMO support at 16 Spanish institutions from 2010 to 2015. The clinical outcomes of patients under simultaneous IABP support (n = 73) were compared to a control group of patients without IABP support (n = 96). RESULTS There were no statistically significant differences between the IABP and control groups with regard to the cumulative rates of transplantation (71.2% vs 81.2%, P = 0.17), death during VA-ECMO support (20.6% vs 14.6%, P = 0.31), transition to a different mechanical circulatory support device (5.5% vs 5.2%, P = 0.94) or weaning from VA-ECMO support due to recovery (2.7% vs 0%, P = 0.10). There was a higher incidence of bleeding events in the IABP group (45.2% vs 25%, P = 0.006; adjusted odds ratio 2.18, 95% confidence interval 1.02–4.67). In-hospital postoperative mortality after HT was 34.6% in the IABP group and 32.5% in the control group (P = 0.80). One-year survival after listing for urgent HT was 53.3% in the IABP group and 52.2% in the control group (log rank P = 0.75). Multivariate adjustment for potential confounders did not change this result (adjusted hazard ratio 0.94, 95% confidence interval 0.56–1.58). CONCLUSIONS In our study, simultaneous IABP therapy in transplant candidates under VA-ECMO support did not significantly reduce morbidity or mortality. Sin financiación 1.675 JCR (2019) Q3, 98/138 Cardiac & Cardiovascular Systems, 123/210 Surgery; Q4, 53/64 Respiratory System 0.660 SJR (2019) Q2, 137/362 Cardiology and Cardiovascular Medicine, 63/147 Pulmonary and Respiratory Medicine, 138/451 Surgery No data IDR 2019 UEM

Sin financiación 4.045 JCR (2019) Q2, 40/138 Cardiac & Cardiovascular Systems 2.053 SJR (2019) Q1, 9/107 Physiology (medical), 37/362 Cardiology and Cardiovascular Medicine No data IDR 2019 UEM

Background: The impact of high exercise loads on a previously healthy heart remains controversial. We examined the consequences of decades of strenuous endurance exercise at the highest competition level on heart dimensions and volumes as well as on serum biomarkers of cardiac fibrosis/remodeling. Methods and results: We compared echocardiographic measurements and serum biomarkers of cardiac fibrosis/remodeling [troponin I, galectin-3, matrix metallopeptidase-2 and -9, N-terminal pro-brain natriuretic peptide, carboxy-terminal propeptide of type I procollagen, and soluble suppressor of tumorigenicity-2 (sST-2)/interleukin(IL)-1R4] in 53 male athletes [11 former professional ('elite') and 42 amateur-level ('sub-elite') cyclists or runners, aged 40-70 years] and 18 aged-matched controls. A subset of 15 subjects (5 controls, 3 sub-elite and 7 elite athletes) also underwent cardiac magnetic resonance imaging (cMRI). Elite and sub-elite athletes had greater echocardiography-determined left ventricular myocardial mass indexed to body surface area than controls (113 +/- 22, 115.2 +/- 23.1 and 94.8 +/- 21 g/m(2), respectively, p = 0.008 for group effect), with similar results for left (50.5 +/- 4.4, 48.2 +/- 4.3 and 46.4 +/- 5.2 mm, p = 0.008) and right (38.6 +/- 3.8, 41.1 +/- 5.5 and 34.7 +/- 4.3 mm, p < 0.001) ventricular end-diastolic diameter, and cMRI-determined left atrial volume indexed to body surface area (62.7 +/- 8.1, 56.4 +/- 16.0 and 39.0 +/- 14.1 ml/m(2), p = 0.026). Two athletes showed a non-coronary pattern of small, fibrotic left ventricular patches detected by late gadolinium enhancement. No group effect was noted for biomarkers. Conclusions: Regardless of their competition level at a younger age, veteran endurance athletes showed an overall healthy, non-pathological pattern of cardiac remodeling. Nonetheless, the physiopathology of the ventricular fibrotic patches detected warrants further investigation. (C) 2016 Elsevier Ireland Ltd. All rights reserved.

a Research Institute of Hospital 12 de Octubre (‘i+12’), Madrid, Spain b GIDFYS, European University Miguel de Cervantes, Department of Health Sciences, Valladolid, Spain c School of Health Sciences, University of Leon, Leon, Spain d European University of Madrid, Madrid, Spain e IRyS group, School of Physical Education, Pontificia Universidad Catolica de Valparaiso, Valparaiso, Chile f Universidad Autonoma de Chile, Temuco, Chile g Facultad de Ciencias de la Salud y del Deporte, Universidad de Zaragoza, Huesca, Spain

Sin financiación 5.166 JCR (2017) Q1, 26/128 Cardiac and Cardiovacular Systems UEM

Introduction and objectives In Spain, intra-aortic balloon pump (IABP) has been used frequently as a bridge to urgent heart transplant (HT). We sought to analyze the clinical outcomes of this strategy. Methods We conducted a case-by-case, retrospective review of clinical records of 281 adult patients listed for urgent HT under IABP support in 16 Spanish institutions from 2010 to 2015. Pre- and post-transplant survival and adverse clinical events were analyzed. Results A total of 194 (69%, 95%CI, 63.3-74.4) patients were transplanted and 20 (7.1%, 95%CI, 4.4-10.8) died during a mean period of IABP support of 10.9 ± 9.7 days. IABP support was withdrawn before an organ became available in 32 (11.4%) patients. Thirty-five (12.5%, 95%CI, 8.8-16.9) patients transitioned from IABP to full-support mechanical devices. Mean urgent waiting list time increased from 5.9 ± 6.3 days in 2010 to 15 ± 11.7 days in 2015 (P = .001). Post-transplant survival rates at 30-days, 1-year, and 5-years were 88.1% (95%CI, 85.7-90.5), 76% (95%CI, 72.9-79.1), and 67.8% (95%CI, 63.7-71.9), respectively. The incidence rate of major adverse clinical outcomes—device dysfunction, stroke, bleeding or infection—during IABP support was 26 (95%CI, 20.6-32.4) episodes per 1000 patient-days. The incidence rate of IABP explantation due to complications was 7.2 (95%CI, 4.5-10.8) cases per 1000 patient-days. Conclusions In a setting of short waiting list times, IABP can be used to bridge candidates to urgent HT with acceptable postoperative results, but there were significant rates of adverse clinical events during support. Introducción y objetivos En España, el balón de contrapulsación intraaórtico (BCIA) se ha usado frecuentemente como puente al trasplante cardiaco (TxC) urgente. El propósito es analizar los resultados de esta estrategia. Métodos Se realizó una revisión retrospectiva caso por caso de los registros clínicos de 281 pacientes adultos listados para TxC urgente asistidos con BCIA en 16 hospitales españoles entre 2010 y 2015. Se analizaron la supervivencia antes y después del trasplante y la incidencia de eventos adversos. Resultados Se trasplantó a 194 pacientes (69%; IC95%, 63,3-74,4) y 20 (7,1%; IC95%, 4,4-10,8) fallecieron durante la asistencia, cuya duración media fue de 10,9 ± 9,7 días. El BCIA se explantó antes de obtener un órgano a 32 pacientes (11,4%). En 35 pacientes (12,5%; IC95%, 8,8-16,9) se implantó un dispositivo de asistencia circulatoria mecánica completa. El tiempo en la lista de espera urgente se incrementó desde 5,9 ± 6,3 días en 2010 hasta 15 ± 11,7 días en 2015 (p = 0,001). La supervivencia a 30 días y a 1 y 5 años tras el TxC fue del 88,1% (IC95%, 85,7-90,5), 76% (IC95%, 72,9-79,1) y 67,8% (IC95%, 63,7-71,9) respectivamente. La tasa de incidencia de eventos adversos mayores —disfunción del BCIA, ictus, hemorragia o infección— durante la asistencia fue de 26 (IC95%, 20,6-32,4) eventos/1.000 pacientes-día. La tasa de incidencia de explante del BCIA por complicaciones fue de 7,2 (IC95%, 4,5-10,8) casos/1.000 pacientes-día. Conclusiones En el contexto de listas de espera cortas, el BCIA puede utilizarse como puente al TxC urgente con resultados aceptables. Esta estrategia conlleva una incidencia significativa de eventos adversos. Sin financiación 4.642 JCR (2019) Q1, 30/138 Cardiac & Cardiovascular Systems 0.473 SJR (2019) Q3,196/362 Cardiology and Cardiovascular Medicine No data IDR 2019 UEM

Frailty reflects a state of decreased physiological reserve and vulnerability to stressors. Its prevalence among patients with cardiovascular disease is as high as 60%. Frailty is associated with a poor prognosis for patients with heart failure, increasingly frequent hospitalization, and death. The recent published listing criteria for heart transplantation of the International Society for Heart and Lung Transplantation recommend assessing frailty (class IIb recommendation, level of evidence C). However, this recommendation is not based on prospective studies, and frailty scores have only been validated in patients age > 65 years. The aim of the FELICITAR registry (Frailty Evaluation After List Inclusion, Characteristics and Influence on Transplantation and Results) is to assess the impact of frailty on prognosis before and after heart transplantation. A series of 100 patients from 3 Spanish centers will be included as soon as they are added to the national heart transplantation waiting list. Frailty will be evaluated again every 3 months until heart transplantation and at 3, 6, and 12 months thereafter. Depression, cognitive assessment, and quality of life also will be analyzed. The 2 primary endpoints are all‐cause mortality and prevalence of frailty assessed using the Fried frailty index. Results from this study may show that frailty is frequent in patients with advanced heart failure listed for heart transplantation and is associated with a poor prognosis both before and after surgery. The findings may contribute to a better understanding of the characteristics of the optimal candidate for heart transplantation. Grant 2017 of the Spanish Society of Cardiology, Heart Failure and Heart Transplantation Section Cátedra ASISA‐Universidad Europea de Madrid 2017/UEM31 2.455 JCR (2018) Q2, 67/136 Cardiac & Cardiovascular Systems 1.219 SJR (2018) Q1, 75/365 Cardiology and Cardiovascular Medicine, 389/2844 Medicine (miscellaneous) No data IDR 2018 UEM

The advanced interatrial block (A‐IAB) (P ≥ 120 ms plus ± pattern in II, III and aVF) corresponds at atrial level, to right or left advanced bundle branch block at ventricular level, and it is well known that these patterns may be seen transiently in relation to taquicardia or bradycardia (tachycardia or bradycardia dependent right or left bundle branch block). We present for the first time, the same phenomenon at atrial level. In one case, the A‐IAB appears in relation to tachycardization and in the other disappears during a pause induced by ventricular premature complex. Sin financiación 1.235 JCR (2018) Q4, 117/136 Cardiac & Cardiovascular Systems 0.526 SJR (2018) Q2, 1251/2844; Q3, 184/365 Cardiology and Cardiovascular Medicine, 67/108 Physiology (medical) No data IDR 2018 UEM

[Background]: Profound disturbances in mineral metabolism are closely linked to the progression of chronic kidney disease. However, increasing clinical and experimental evidence indicates that alterations in phosphate homoeostasis could have an even stronger impact on the heart., [Aim]: The aim of this review is to provide the reader with an update of how alterations in mineral metabolism are related to direct and indirect cardiotoxic effects beyond the nephrology setting., [Results]: Evidence exists that alterations in mineral metabolism that are related to changes in parathyroid hormone (PTH), vitamin D, and the FGF‐23–klotho axis have direct pathological consequences for the heart. Alterations in plasma PTH levels are associated with cardiac dysfunction and detrimental cardiac remodelling. Several clinical studies have associated vitamin D deficiency with the prevalence of cardiovascular disease (CV) and its risk factors. Recent evidences support deleterious direct and nonphosphaturic effects of FGF‐23 on the heart as hypertrophy development. In contrast, reduced systemic klotho levels are related to CV damage, at least when advanced age is present. In addition, we discuss how these mineral metabolism molecules can counteract each other in some situations, in the context of failed clinical trials on cardiac protection as is the case of vitamin D supplementation., [Conclusions]: Among all mineral components, an increase in systemic FGF‐23 levels is considered to have the greatest CV impact and risk. However, it is quite possible that many intracellular mechanisms mediated by FGF‐23, especially those related to cardiomyocyte function, remain to be discovered., The authors acknowledge the support from the Spanish Institute of Health, Carlos III (PIE13/00045, PI14/01841, PI14/01078, CP15/00129, MSII16/00047, PI17/01093, PI17/01193, PI17/01344), Ministerio de Economía Industria y Competitividad (SAF‐2014‐57190R), Fundación SENEFRO/Sociedad Española de Nefrología (SEN), Sociedad Española de Cardiología (SEC), Fundación Íñigo Álvarez de Toledo (FRIAT) and CIBER de Enfermedades Cardiovasculares (CIBERCV) and Fondos FEDER.

Cell-based therapy is a promising approach for many diseases, including ischemic heart disease. Cardiac mesoangioblasts are committed vessel-associated progenitors that can restore to a significant, although partial, extent, heart structure and function in a murine model of myocardial infarction. Low-intensity pulsed ultrasound (LIPUS) is a non-invasive form of mechanical energy that can be delivered into biological tissues as acoustic pressure waves, and is widely used for clinical applications including bone fracture healing. We hypothesized that the positive effects of LIPUS on bone and soft tissue, such as increased cell differentiation and cytoskeleton reorganization, could be applied to increase the therapeutic potential of mesoangioblasts for heart repair. In this work, we show that LIPUS stimulation of cardiac mesoangioblasts isolated from mouse and human heart results in significant cellular modifications that provide beneficial effects to the cells, including increased malleability and improved motility. Additionally, LIPUS stimulation increased the number of binucleated cells and induced cardiac differentiation to an extent comparable with 5′-azacytidine treatment. Mechanistically, LIPUS stimulation activated the BMP-Smad signalling pathway and increased the expression of myosin light chain-2 together with upregulation of β1 integrin and RhoA, highlighting a potentially important role for cytoskeleton reorganization. Taken together, these results provide functional evidence that LIPUS might be a useful tool to explore in the field of heart cell therapy. SAF 2010 3.111 JCR (2015) Q2, 42/124 Medicine, research & experimental; Q3, 14/21 Cell & tissue engineering, 97/187 Cell biology UEM

The objective of this research was to characterise morphologically the right coronary artery and its branches inthe horse. The right coronary arteries of 120 horse hearts were perfused with semi-synthetic resin (85% Palatal GP40L; 15% styrene)and mineral red dye. The morphological and biometric characteristics of the right coronary artery and its branches (digital calibrator)were assessed. The diameter of the right coronary artery was 6.72 ± 2.58 mm. The interventricular subsinusal branch ended at theapex in 94 specimens (78.4%). The right circumflex branch originated at the site of intersection of the subsinnusal interventricularsulcus and the atrioventricular septum, extended along the coronary sulcus with a convoluted trajectory, ended at the obtuse edge ofthe heart or even at the anterior aspect of the left ventricle in 62 hearts (52.5%), and at the middle segment of the left ventricle in 42cases (35.6%), whereas in 14 samples (11.9%) it ended at the adjacent surface of the left ventricle. The right conus branch was foundin 98 specimens (81.6%) and in 2 of them (1.7%) it emerged directly from the right aortic sinus (third coronary artery). The heartsexhibited right coronary dominance in 118 specimens (98.3%) and in 2 specimens (1.7%) the coronary dominance was balanced. Nomyocardial bridges were observed. The high incidence of right coronary dominance observed in this study is consistent with previousstudies. Due to its similarity with the human heart, we may ratify the equine model for procedural and hemodynamic applications., El objetivo de esta investigación fue caracterizar morfológicamente la arteria coronaria derecha del caballo y susramas. En 120 corazones de caballo se perfundieron las arterias coronarias derechas con resina semisintética (palatal GP40L al 85%;estireno al 15%) y color rojo mineral. Se evaluó las características morfológicas y biométricas de la arteria coronaria derecha y susramas (calibrador digital). El diámetro de la arteria coronaria derecha fue 6,72 +/–2,58 mm. La rama interventricular subsinusal finalizóen el ápex en 94 especímenes (78,4%). La rama circunfleja derecha se originó a nivel del sitio de cruce del surco interventricularsubsinusal y el septum atrioventricular, se extendió a lo largo del surco coronario con una trayectoria contorneada y finalizando en elborde obtuso del corazón o incluso en la cara anterior del ventrículo izquierdo en 62 corazones (52,5%) y en el segmento medio delventrículo izquierdo en 42 casos (35,6%), mientras que en 14 muestras (11,9%) esta finalizó en la superficie adyacente del ventrículoizquierdo. La rama derecha del cono, se encontró en 98 especímenes (81,6%) y en 2 corazones (1,7%) emergió directamente del senoaórtico derecho (tercera coronaria). Los corazones presentaron dominancia coronaria derecha en 118 muestras (98,3%) y en 2 casos(1,7%) la dominancia coronaria fue balanceada. No se observó puentes miocárdicos. La alta incidencia de dominancia coronariaderecha observada en este estudio es concordante con estudios previos. Debido a su semejanza con el corazón humano, nos permiteratificar el modelo equino para aplicaciones procedimentales y hemodinámicas.

Fil: Tesan, Fiorella Carla. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Laboratorio de Radioisotopos; Argentina Fil: Portillo, Mariano Gaston. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Laboratorio de Radioisotopos; Argentina Fil: Martinel Lamas, Diego José. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Laboratorio de Radioisotopos; Argentina Fil: Martinel Lamas, Diego José. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina Fil: Martinel Lamas, Diego José. Pontificia Universidad Católica Argentina. Facultad de Ciencias Médicas. Instituto de Investigaciones Biomédicas. Laboratorio de Biología Celular y Molecular; Argentina Fil: Medina, Vanina Araceli. Pontificia Universidad Católica Argentina. Facultad de Ciencias Médicas. Instituto de Investigaciones Biomédicas. Laboratorio de Biología Celular y Molecular; Argentina Fil: Medina, Vanina Araceli. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina Fil: Medina, Vanina Araceli. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Laboratorio de Radioisotopos; Argentina Fil: Salgueiro, Maria Jimena. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Laboratorio de Radioisotopos; Argentina Fil: Zubillaga, Marcela Beatriz. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Laboratorio de Radioisotopos; Argentina Fil: Zubillaga, Marcela Beatriz. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina Abstract: Background: Chemotherapy is one of the most common approaches for cancer treatment. Particularly Doxorubicin has been proven to be effective in the treatment of many soft and solid tumors for locally advanced and metastatic cancer. It is not easy to clinically evaluate the chemotoxic or chemoprotective effect of some drugs, even more when there is a subclinical toxicity. Objective: To determine the usefulness of the hepatobiliary, colloid and cardiac scintigraphies, employing 99mTcdisida, 99mTc-phytate and 99mTc-sestamibi respectively, in the evaluation of the hepato and cardiotoxicity of two chemotherapeutic treatments assessed in rats. Method: Two groups were submitted to doxorubicin (DOX) treatment and one was co-administered with histamine (DOX+HIS). Static 99mTc-phytate and 99mTc-sestamibi scintigraphies as well as a dynamic 99mTc-disida study were performed in a small field of view gamma camera at: 0 weeks (control), 1 week and 2 weeks of treatment. Imagenological parameters were calculated: Liver/Bone Marrow ratio (L/BM), Heart/Background ratio (H/B) and time to the maximum (Tmax) for 99mTc-phytate, 99mTc-sestamibi and 99mTc-disida extraction, respectively. Results: Control (L/BM= 98±3; H/B=2.3±0.4; Tmax=8±3), DOX (L/BM: 85±3, 80±3; H/B, 3.5±0.5, 3.3±0.5 and Tmax 6±1, 4±1) for 1 and 2 weeks respectively and DOX+HIS (L/BM: 99±0.3, 98±1; H/B 2.9±0.5, 2.9±0.5 and Tmax, 8±2, 9±2) for 1 and 2 weeks, respectively. Histological analysis showed cardio and hepatotoxicity induced by doxorubicin. Conclusion: Imagenological parameters showed differences among treated and control groups and between both chemotherapy treatments. Thus, these radiopharmaceutical functional approaches were able to reflect heart and liver toxicity produced by doxorubicin.

Zamorano Gómez, José Luis, codir., Premio Extraordinario de Doctorado de la UAH en el año académico 2016-2017, Es conocido la importancia del ventrículo derecho en varias enfermedades cardiacas, tanto como predictor pronóstico como para su manejo. La presente tesis doctoral supone una línea de investigación sobre el análisis del ventrículo derecho por ecocardiografía, tratando de resolver algunas de cuestiones que son de relevancia en la práctica clínica. Incluye tres puntos principales: Punto 1. Influencia que tienen distintas condiciones de carga sobre la función ventricular derecha. Se incluyeron prospectivamente 32 pacientes con insuficiencia tricúspide funcional significativa y 56 sin insuficiencia tricúspide, ambos grupos con cardiopatía izquierda. La función sistólica del ventrículo derecho se estimó mediante parámetros longitudinales: TAPSE y velocidad pico sistólica del anillo tricúspide, transversales: fracción de acortamiento transversal, y combinados: cambio fraccional de área. Sólo los parámetros longitudinales disminuyeron en los pacientes con insuficiencia tricúspide significativa (TAPSE: 18,3±3,9 vs 22,7±4,4; p-17,3% presentaron menor supervivencia libre de eventos (Log Rank=22,033, p-17,3% (HR=5,341; p

ResumenSon muchos los géneros musicales en todo el orbe que hacen mención a diversos aspectos de la medicina y en especial al corazón como órgano vital en la economía corporal, relacionado de manera metafórica con la expresión y génesis de emociones como el amor, la ira y el odio, no siendo ajeno a ello la música vallenata, oriunda de la costa norte colombiana.ConclusionesEl vallenato, al igual que muchos otros géneros musicales de corte popular, le canta a los médicos y al corazón, concebido este último, en un contexto poético, como depositario de emociones y capaz de enfermar de amor.AbstractThere are many musical genres which cover different aspects of medicine, and especially the heart, as a very important organ in bodily economy, metaphorically related to the expression and genesis of some emotions like love, anger, hate. The Vallenato music, born in the northern Colombian coast, is not an exception.ConclusionsThe Vallenato music, as well as many other popular music genres, sing to the doctors and the heart, this latter being, in a poetic context, a depositary of emotions and capable of making one lovesick.

MRI and CT have become the ideal methods for assessing the complex morphology of the conotruncal region, including the right ventricular outflow tract (RVOT). Detailed information about the embryology and anatomy of the RVOT provides a better understanding of the spectrum of diseases of this region and helps to narrow the differential diagnoses of abnormalities involving this important structure. In this review, we focus on the role of CT and MRI to evaluate morphology in relation to developmental malformation of the RVOT. A spectrum of conotruncal anomalies with abnormally positioned great arteries may arise from a perturbation of RVOT formation. Complications after surgery are common, and many patients need follow-up imaging for diagnosis and surgical planning. In this regard, the spectrum of diseases, differential diagnoses, and postoperative findings are briefly described. With CT and MRI, the relationship of the RVOT to critical structures, such as the coronary arteries, can be revealed. 2.744 JCR (2013) Q2, 32/122 Radiology, nuclear medicine & medical imaging UEM

Reactive oxygen species (ROS) produced by NADPH oxidase 2 (Nox2) function as key mediators of mechanotransduction during both physiological adaptation to mechanical load and maladaptive remodeling of the heart. This is despite low levels of cardiac Nox2 expression. The mechanism underlying the transition from adaptation to maladaptation remains obscure, however. We demonstrate that transient receptor potential canonical 3 (TRPC3), a Ca2+-permeable channel, acts as a positive regulator of ROS (PRROS) in cardiomyocytes, and specifically regulates pressure overload-induced maladaptive cardiac remodeling in mice. TRPC3 physically interacts with Nox2 at specific C-terminal sites, thereby protecting Nox2 from proteasome-dependent degradation and amplifying Ca2+-dependent Nox2 activation through TRPC3-mediated background Ca2+ entry. Nox2 also stabilizes TRPC3 proteins to enhance TRPC3 channel activity. Expression of TRPC3 C-terminal polypeptide abolished TRPC3-regulated ROS production by disrupting TRPC3-Nox2 interaction, without affecting TRPC3-mediated Ca2+ influx. The novel TRPC3 function as a PRROS provides a mechanistic explanation for how diastolic Ca2+ influx specifically encodes signals to induce ROS-mediated maladaptive remodeling and offers new therapeutic possibilities., Article, SCIENTIFIC REPORTS. 6: 37001(2016)