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SUMMARY: Papillary muscles in the left ventricle present multiple anatomic expressions that are relevant for medical fields focusing on the understanding of clinical events involving these structures. Here, the aim was to perform a morphological characterization of the left ventricle papillary muscles in a sample of Colombian population. In the study were included eighty-two hearts from male individuals who underwent autopsy at the Institute of Legal Medicine and Forensic Sciences in Bucaramanga, Colombia. In each heart was carefully performed a longitudinal incision on the obtuse margin to visualize the papillary muscles. Data set was registered, and analysis of the continuous and categorical variables was carried out. Single anterior papillary muscle was observed in 74 samples (90.2 %) whereas this represented only 48 specimens (58.5 %) for the posterior papillary muscle (p = 0.3). Mean length and breadth of the anterior muscle were 29.9 ± 4.94 and 11.74 ± 2.75 mm, and those for the posterior muscle were 27.42 ± 7.08 and 10.83 ± 4.08 mm. Truncated apical shape was the most frequent type observed on the papillary muscles, anterior 41 (50 %) and posterior 37 (45.1 %), followed by flat-topped in the anterior 25 (30.5 %) and bifurcated in posterior muscle 14 (17.1 %). A mean of 9.04 ± 2.75 chordae raised from the anterior and 7.50 ± 3.3 from posterior papillary muscle. In our study we observed a higher incidence of single papillary muscles and slightly larger dimensions than information reported in the literature. The anatomic diversity of the papillary muscles should be considered for the correct image interpretation, valve implantation and performance evaluation on myocardial ischemic events.
Los músculos papilares del ventrículo izquierdo presentan múltiples expresiones anatómicas que son relevantes para las áreas médicas que se centran en la comprensión de los eventos clínicos que involucran estas estructuras. El objetivo fue realizar una caracterización morfológica de los músculos papilares del ventrículo izquierdo en una muestra de población colombiana. En el estudio se incluyeron ochenta y dos corazones de individuos masculinos a los que se les realizó autopsia en el Instituto de Medicina Legal y Ciencias Forenses de Bucaramanga, Colombia. En cada corazón se realizó cuidadosamente una incisión longitudinal en el margen obtuso para visualizar los músculos papilares. Se registró el conjunto de datos y se realizó el análisis de las variables continuas y categóricas. Se observó un solo músculo papilar anterior en 74 muestras (90,2 %), mientras que este rasgo se presentó en 48 muestras (58,5 %) para el músculo papilar posterior (p = 0,3). La longitud y anchura media del músculo anterior fueron 29,9 ± 4,94 y 11,74 ± 2,75 mm, y las del músculo posterior fueron 27,42 ± 7,08 y 10,83 ± 4,08 mm. La forma apical truncada fue el tipo más frecuente observado en los músculos papilares, anterior 41 (50 %) y posterior 37 (45,1 %), seguido de la forma plana en los 25 anteriores (30,5 %) y bifurcada en el músculo posterior 14 (17,1 %). Una media de 9,04 ± 2,75 cuerdas elevadas desde el músculo papilar anterior y 7,50 ± 3,3 desde posterior. En nuestro estudio observamos una mayor incidencia de músculos papilares únicos y dimensiones ligeramente mayores que la información reportada en la literatura. La diversidad anatómica de los músculos papilares debe ser considerada para la correcta interpretación de imágenes, implantación valvular y evaluación del desempeño en eventos isquémicos miocárdicos.
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Humanos , Masculino , Músculos Papilares/anatomia & histologia , Ventrículos do Coração/anatomia & histologia , Autopsia , Estudos Transversais , Colômbia , Coração/anatomia & histologiaRESUMO
BACKGROUND: Sodium-glucose cotransporter (SGLT)2 inhibitors have displayed beneficial effects on the cardiovascular system in diabetes mellitus (DM) patients. As most clinical trials were performed in Type 2 DM, their effects in Type 1 DM have not been established. OBJECTIVE: To evaluate the influence of long-term treatment with SGLT2 inhibitor dapagliflozin on cardiac remodeling, myocardial function, energy metabolism, and metabolomics in rats with Type 1 DM. METHODS: Male Wistar rats were divided into groups: Control (C, n = 15); DM (n = 15); and DM treated with dapagliflozin (DM + DAPA, n = 15) for 30 weeks. DM was induced by streptozotocin. Dapagliflozin 5 mg/kg/day was added to chow. STATISTICAL ANALYSIS: ANOVA and Tukey or Kruskal-Wallis and Dunn. RESULTS: DM + DAPA presented lower glycemia and higher body weight than DM. Echocardiogram showed DM with left atrium dilation and left ventricular (LV) hypertrophy, dilation, and systolic and diastolic dysfunction. In LV isolated papillary muscles, DM had reduced developed tension, +dT/dt and -dT/dt in basal condition and after inotropic stimulation. All functional changes were attenuated by dapagliflozin. Hexokinase (HK), phosphofructokinase (PFK) and pyruvate kinase (PK) activity was lower in DM than C, and PFK and PK activity higher in DM + DAPA than DM. Metabolomics revealed 21 and 5 metabolites positively regulated in DM vs. C and DM + DAPA vs. DM, respectively; 6 and 3 metabolites were negatively regulated in DM vs. C and DM + DAPA vs. DM, respectively. Five metabolites that participate in cell membrane ultrastructure were higher in DM than C. Metabolites levels of N-oleoyl glutamic acid, chlorocresol and N-oleoyl-L-serine were lower and phosphatidylethanolamine and ceramide higher in DM + DAPA than DM. CONCLUSION: Long-term treatment with dapagliflozin attenuates cardiac remodeling, myocardial dysfunction, and contractile reserve impairment in Type 1 diabetic rats. The functional improvement is combined with restored pyruvate kinase and phosphofructokinase activity and attenuated metabolomics changes.
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BACKGROUND AND AIMS: Fabry disease (FD) is an X-linked genetic lysosomal disease, in which a deficit in the alpha-galactosidase A enzyme results in lysosomal build-up of globotriaosylceramide in several organs, causing cardiac, renal and cerebrovascular complications. The aim of this study was to assess the prevalence of papillary muscle hypertrophy (PMH) in patients with FD. METHODS: A group of 63 patients with FD and a positive genetic diagnosis were studied and were divided into two groups: one included 24 patients with FD and LVH and another group included 39 patients with FD and without LVH. Papillary muscles were measured from the left parasternal short axis view, defining PMH as a diastolic thickness greater than 11 mm in any diameter. RESULTS: Patients with FD and LVH had a high prevalence of anterolateral PMH (66.6%), and such prevalence was lower for the posteromedial PMH (33.3%). However, patients who had not yet developed LVH had a high prevalence of anterolateral PMH (33.3%). CONCLUSIONS: Patients with FD in the pre-clinical stage (without LVH) have a high prevalence of PMH, especially involving the anterolateral papillary muscle. This finding could be an early marker for the development of LVH, allowing to suspect the disease during its early stages, and begin enzyme replacement therapy in the appropriate patients.
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Doença de Fabry , Humanos , Doença de Fabry/diagnóstico , Doença de Fabry/epidemiologia , Doença de Fabry/genética , Músculos Papilares/diagnóstico por imagem , Prevalência , Hipertrofia/epidemiologia , RimRESUMO
Aerobic exercise training (AET) has been used to manage heart disease. AET may totally or partially restore the activity and/or expression of proteins that regulate calcium (Ca2+) handling, optimize intracellular Ca2+ flow, and attenuate cardiac functional impairment in failing hearts. However, the literature presents conflicting data regarding the effects of AET on Ca2+ transit and cardiac function in rats with heart failure resulting from aortic stenosis (AoS). This study aimed to evaluate the impact of AET on Ca2+ handling and cardiac function in rats with heart failure due to AoS. Wistar rats were distributed into two groups: control (Sham; n = 61) and aortic stenosis (AoS; n = 44). After 18 weeks, the groups were redistributed into: non-exposed to exercise training (Sham, n = 28 and AoS, n = 22) and trained (Sham-ET, n = 33 and AoS-ET, n = 22) for 10 weeks. Treadmill exercise training was performed with a velocity equivalent to the lactate threshold. The cardiac function was analyzed by echocardiogram, isolated papillary muscles, and isolated cardiomyocytes. During assays of isolated papillary muscles and isolated cardiomyocytes, the Ca2+ concentrations were evaluated. The expression of regulatory proteins for diastolic Ca2+ was assessed via Western Blot. AET attenuated the diastolic dysfunction and improved the systolic function. AoS-ET animals presented an enhanced response to post-rest contraction and SERCA2a and L-type Ca2+ channel blockage compared to the AoS. Furthermore, AET was able to improve aspects of the mechanical function and the responsiveness of the myofilaments to the Ca2+ of the AoS-ET animals. AoS animals presented an alteration in the protein expression of SERCA2a and NCX, and AET restored SERCA2a and NCX levels near normal values. Therefore, AET increased SERCA2a activity and myofilament responsiveness to Ca2+ and improved the cellular Ca2+ influx mechanism, attenuating cardiac dysfunction at cellular, tissue, and chamber levels in animals with AoS and heart failure.
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Estenose da Valva Aórtica , Insuficiência Cardíaca , Ratos , Animais , Cálcio/metabolismo , Ratos Wistar , Insuficiência Cardíaca/etiologia , Insuficiência Cardíaca/terapia , Insuficiência Cardíaca/metabolismo , Miócitos Cardíacos/metabolismo , Cálcio da Dieta/metabolismo , Estenose da Valva Aórtica/metabolismo , Exercício Físico , ATPases Transportadoras de Cálcio do Retículo Sarcoplasmático/metabolismoRESUMO
Resumen La ablación con catéter se ha convertido en un enfoque práctico para el tratamiento de las arritmias cardiacas, sobre todo cuando el manejo farmacológico óptimo no logra controlarlas. De esta manera se reduce la readmisión hospitalaria y se mejora la calidad de vida de los pacientes, incluso de aquellos en quienes no se logra la resolución completa de la arritmia. Hasta la fecha se han utilizado varias modalidades entre las que se incluyen la radiofrecuencia y la crioablación. Los principios de la criobiología se establecieron por primera vez con investigaciones sobre la congelación de los tumores y datos actuales sugieren que es necesaria una temperatura entre -30 a -40 °C para inducir muerte celular, ya sea por mecanismos inmediatos, como ruptura celular, lesión hipotérmica o daño vascular, o tardíos, como apoptosis. Se presenta el primer caso en Colombia de mapeo de alta densidad y crioablación como estrategias combinadas para el tratamiento efectivo de un paciente con alta carga de arritmia ventricular sintomática originada en el músculo papilar anterolateral, sin recurrencia de la arritmia en el tiempo de seguimiento.
Abstract Catheter ablation has become a practical approach for the treatment of cardiac arrhythmias, especially when optimal pharmacological management does not achieve adequate control of it, thus reducing hospital readmission and improving quality of life, even in patients in whom the complete resolution of the arrhythmia is not achieved. To date, a variety of modalities have been used, including radiofrequency and cryoablation. The principles of cryobiology were established for the first time with research on the freezing of tumors and current data suggest that a temperature of -30 to -40 °C is necessary to induce cell death either by immediate or delayed mechanisms; immediate as cellular rupture or hypothermic injury as well as vascular damage or apoptosis among the late. The first case in Colombia of high-density mapping and cryoablation is presented as combined strategies for the effective treatment of a patient with a high load of symptomatic ventricular arrhythmia originating in the anterolateral papillary muscle, without recurrence of the arrhythmia at the time of follow-up with symptoms, so it was to successful cryoablation, as the first case with this technique.
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Resumo Fundamento O remodelamento cardíaco patológico se caracteriza por disfunção diastólica e sistólica, levando à insuficiência cardíaca. Neste contexto, o cenário disfuncional do trânsito de cálcio miocárdico (Ca2+) tem sido pouco estudado. Um modelo experimental de estenose aórtica tem sido extensamente utilizado para aprimorar os conhecimentos sobre os principais mecanismos do remodelamento patológico cardíaco. Objetivo Entender o processo disfuncional dos principais componentes responsáveis pelo equilíbrio do cálcio miocárdico e sua influência sobre a função cardíaca na insuficiência cardíaca induzida pela estenose aórtica. Métodos Ratos Wistar de 21 dias de idade foram distribuídos em dois grupos: controle (placebo; n=28) e estenose aórtica (EaO; n=18). A função cardíaca foi analisada com o ecocardiograma, músculo papilar isolado e cardiomiócitos isolados. No ensaio do músculo papilar, SERCA2a e a atividade do canal de Ca2+ do tipo L foram avaliados. O ensaio de cardiomiócitos isolados avaliou o trânsito de cálcio. A expressão proteica da proteínas do trânsito de cálcio foi analisada com o western blot. Os resultados foram estatisticamente significativos quando p <0,05. Resultados Os músculos papilares e cardiomiócitos dos corações no grupo EaO demonstraram falhas mecânicas. Os ratos com EaO apresentaram menor tempo de pico do Ca2+, menor sensibilidade das miofibrilas do Ca2+, prejuízos nos processos de entrada e recaptura de cálcio pelo retículo sarcoplasmático, bem como disfunção no canal de cálcio do tipo L (CCTL). Além disso, os animais com EaO apresentaram maior expressão de SERCA2a, CCTL e trocador de Na+/Ca2+. Conclusão Insuficiência cardíaca sistólica e diastólica devido à estenose aórtica supravalvular acarretou comprometimento da entrada de Ca2+ celular e inibição da recaptura de cálcio pelo retículo sarcoplasmático devido à disfunção no CCTL e SERCA2a, assim como mudanças no trânsito de cálcio e na expressão das principais proteínas responsáveis pela homeostase de Ca2+ celular.
Abstract Background Maladaptive cardiac remodelling is characterized by diastolic and systolic dysfunction, culminating in heart failure. In this context, the dysfunctional scenario of cardiac calcium (Ca2+) handling has been poorly studied. An experimental model of aortic stenosis has been extensively used to improve knowledge about the key mechanisms of cardiac pathologic remodelling. Objective To understand the dysfunctional process of the major components responsible for Ca2+ balance and its influence on cardiac function in heart failure induced by aortic stenosis. Methods Male 21-day-old Wistar rats were distributed into two groups: control (sham; n= 28) and aortic stenosis (AoS; n= 18). Cardiac function was analysed by echocardiogram, isolated papillary muscle, and isolated cardiomyocytes. In the papillary muscle assay, SERCA2a and L-type Ca2+ channel activity was evaluated. The isolated cardiomyocyte assay evaluated Ca2+ handling. Ca2+ handling protein expression was analysed by western blot. Statistical significance was set at p <0.05. Results Papillary muscles and cardiomyocytes from AoS hearts displayed mechanical malfunction. AoS rats presented a slower time to the Ca2+ peak, reduced Ca2+ myofilament sensitivity, impaired sarcoplasmic reticulum Ca2+ influx and reuptake ability, and SERCA2a and L-type calcium channel (LTCC) dysfunction. Moreover, AoS animals presented increased expression of SERCA2a, LTCCs, and the Na+/Ca2+ exchanger. Conclusion Systolic and diastolic heart failure due to supravalvular aortic stenosis was paralleled by impairment of cellular Ca2+ influx and inhibition of sarcoplasmic reticulum Ca2+ reuptake due to LTCC and SERCA2a dysfunction, as well as changes in Ca2+ handling and expression of the major proteins responsible for cellular Ca2+ homeostasis.
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Animais , Masculino , Ratos , Estenose da Valva Aórtica/patologia , Insuficiência Cardíaca/patologia , Músculos Papilares , Cálcio/metabolismo , Ratos Wistar , Miócitos Cardíacos/patologia , ATPases Transportadoras de Cálcio do Retículo Sarcoplasmático/metabolismo , Contração Miocárdica/fisiologiaAssuntos
COVID-19/diagnóstico , Ruptura Cardíaca/diagnóstico , Insuficiência da Valva Mitral/diagnóstico , Insuficiência da Valva Mitral/terapia , Infarto do Miocárdio/diagnóstico , Idoso , COVID-19/complicações , COVID-19/fisiopatologia , COVID-19/terapia , Diagnóstico Tardio , Diagnóstico Diferencial , Feminino , Ruptura Cardíaca/fisiopatologia , Ruptura Cardíaca/terapia , Humanos , Insuficiência da Valva Mitral/genética , Insuficiência da Valva Mitral/fisiopatologia , Infarto do Miocárdio/complicações , Infarto do Miocárdio/fisiopatologia , Infarto do Miocárdio/terapia , Valor Preditivo dos Testes , Resultado do TratamentoRESUMO
Hypercaloric low-protein diet may lead to a state of malnutrition found in the low-income population of Northeastern Brazil. Although malnutrition during critical periods in the early life is associated with cardiovascular diseases in adulthood, the mechanisms of cardiac dysfunction are still unclear. Here we studied the effects of post-weaning malnutrition due to low protein intake induced by a regional basic diet on the cardiac contractility of young adult rats. In vivo arterial hemodynamic and in vitro myocardial contractility were evaluated in 3-month-old rats. Additionally, protein content of the sarcoplasmic reticulum Ca(2+)-ATPase (SERCA), total phospholamban (PLB) and phosphorylated at serine 16 (p-Ser(16)-PLB), α2-subunit of the Na(+)/K(+)-ATPase (α2-NKA), and Na(+)/Ca(2+) exchanger (NXC) and in situ production of superoxide anion (O2(-)) were measured in the heart. Blood pressure and heart rate increased in the post-weaning malnourished (PWM) rats. Moreover, malnutrition decreased twitch force and inotropic responses of the isolated cardiac muscle. Protein expression of SERCA, PLB/SERCA, and p-Ser(16)-PLB/PLB ratios and α2-NKA were decreased without changing NCX. The contraction dependent on transsarcolemmal calcium influx was unchanged but responsiveness to Ca(2+) and tetanic peak contractions were impaired in the PWM group. Myocardial O2(-) production was significantly increased by PWM. Our data demonstrated that this hypercaloric low-protein diet in rats is associated with myocardial dysfunction, altered expression of major calcium handling proteins, and increased local oxidative stress. These findings reinforce the attention needed for pediatric care, since chronic malnutrition in early life is related to increased cardiovascular risk in adulthood. Graphical Abstract.
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Cálcio/metabolismo , Dieta com Restrição de Proteínas/efeitos adversos , Miocárdio/metabolismo , Desnutrição Proteico-Calórica/metabolismo , Trocador de Sódio e Cálcio/metabolismo , Animais , Animais Recém-Nascidos , Pressão Sanguínea/fisiologia , Proteínas de Ligação ao Cálcio/genética , Proteínas de Ligação ao Cálcio/metabolismo , Regulação da Expressão Gênica , Frequência Cardíaca/fisiologia , Masculino , Contração Miocárdica/fisiologia , Miocárdio/patologia , Estresse Oxidativo , Desnutrição Proteico-Calórica/etiologia , Desnutrição Proteico-Calórica/genética , Desnutrição Proteico-Calórica/fisiopatologia , Ratos , Ratos Wistar , Espécies Reativas de Oxigênio/metabolismo , Retículo Sarcoplasmático/metabolismo , ATPases Transportadoras de Cálcio do Retículo Sarcoplasmático/genética , ATPases Transportadoras de Cálcio do Retículo Sarcoplasmático/metabolismo , Trocador de Sódio e Cálcio/genética , ATPase Trocadora de Sódio-Potássio/genética , ATPase Trocadora de Sódio-Potássio/metabolismo , DesmameRESUMO
Background: The exact geometric pathogenesis of leaflet tethering in ischemic mitral regurgitation (IMR) and the relative contribution of each component of the mitral valve complex (MVC) remain largely unknown. In this study, we sought to further elucidate mitral valve (MV) leaflet remodeling and papillary muscle dynamics in an ovine model of IMR with magnetic resonance imaging (MRI) and 3-dimensional echocardiography (3DE). Methods: Multimodal imaging combining 3DE and MRI was used to analyze the MVC at baseline, 30 minutes post-myocardial infarction (MI), and 12 weeks post-MI in ovine IMR models. Advanced 3D imaging software was used to trace the MVC from each modality, and the tracings were verified against resected specimens. Results: 3DE MV remodeling was regionally heterogenous and observed primarily in the anterior leaflet, with significant increases in surface area, especially in A2 and A3. The posterior leaflet was significantly shortened in P2 and P3. Mean posteromedial papillary muscle (PMPM) volume was decreased from 1.9 ± 0.2 cm3 at baseline to 0.9 ± 0.3 cm3 at 12 weeks post-MI (P < .05). At 12 weeks post-MI, the PMPM was predominately displaced horizontally and outward along the intercommissural axis with minor apical displacement. The subvalvular contribution to tethering is a combination of unilateral movement, outward displacement, and degeneration of the PMPM. These findings have led to a proposed new framework for characterizing PMPM dynamics in IMR. Conclusions: This study provides new insights into the complex interrelated and regionally heterogenous valvular and subvalvular mechanisms involved in the geometric pathogenesis of IMR tethering.
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BACKGROUND: Decreased cardiac contractility has been observed in cirrhosis, but the mechanisms that initiate and maintain cardiac dysfunction are not entirely understood. AIM OF THE STUDY: We test the hypothesis that cirrhotic cardiomyopathy is related to deterioration of myocardial contractility due to alterations in calcium-handling proteins expression. In addition, we evaluated whether cardiac pro-inflammatory cytokine levels are associated with this process. METHODS: Cirrhosis was induced by thioacetamide (TAA, 100 mg/kg/i.p., twice weekly for eight weeks). The myocardial performance was evaluated in isolated left ventricle papillary muscles under basal conditions and after inotropic challenge. The cardiac calcium handling protein expression was detected by Western blotting. Cardiac TNF-α and IL-6 levels were measured by ELISA. RESULTS: Thioacetamide induced liver cirrhosis, which was associated with cirrhotic cardiomyopathy characterized by in vivo left ventricular diastolic and systolic dysfunction as well as cardiac hypertrophy. In vitro baseline myocardial contractility was lower in cirrhosis. Also, myocardial responsiveness to post-rest contraction stimulus was declined. Protein expression for RYR2, SERCA2, NCX, pPBL Ser16 and L-type calcium channel was quantitatively unchanged; however, pPBL Thr17 was significantly lower while IL-6 was higher. CONCLUSIONS: Our study demonstrates that cirrhotic cardiomyopathy is associated with decreased cardiac contractility with alteration of phospholamban phosphorylation in association with higher cardiac pro-inflammatory IL-6 levels. These findings provided molecular and functional insights about the effects of liver cirrhosis on cardiac function.