RESUMO
The chordae tendineae, described as fibro-collagenous structures, support the leaflets of the atrioventricular valves of the heart in various ways. The chordae tendineae are composed of collagen and elastic fibers. They connect to the ventricular side of the valve leaflets' free border and hinder the leaflets from swinging back into the atrial cavity during systole. Mitral valve chordae tendineae have been classified using a variety of classification systems. To our knowledge, we report a variant chordae tendinea that has yet to be described in the literature. The variant, present only on the mitral anterior papillary muscle, did not show the characteristic appearance of the chorda tendineae. Muscular fibers were observed extending from a larger than usual mitral anterior papillary muscle, inserting into the rough zone of the anterior leaflet. Several tendinous primary and secondary true leaflet chordae emerge from the apical portion of the anterior papillary muscle, inserting into the anterior leaflet's free edge and rough zone. Contraction of this muscular chorda during systole could disrupt the mechanics of valvular closure and result in possible regurgitation across the mitral valve. Additionally, this structure may be subject to rupture during myocardial infarction, leading to valvular dysfunction. The developmental connection between the chordae and papillary muscles could explain the anomalous muscularization of the chordae tendineae observed in this case.
Assuntos
Cordas Tendinosas , Valva Mitral , Músculos Papilares , Humanos , Músculos Papilares/anormalidades , Músculos Papilares/anatomia & histologia , Cordas Tendinosas/anormalidades , Cordas Tendinosas/anatomia & histologia , Valva Mitral/anormalidades , Masculino , Variação Anatômica , Feminino , Cadáver , IdosoRESUMO
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.
Assuntos
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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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.
Assuntos
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
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.
Assuntos
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
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.
Assuntos
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.
Assuntos
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.
Assuntos
Proteínas de Ligação ao Cálcio/metabolismo , Interleucina-6/metabolismo , Cirrose Hepática/metabolismo , Animais , Cardiomiopatias/induzido quimicamente , Cardiomiopatias/metabolismo , Cardiomiopatias/patologia , Cardiomiopatias/fisiopatologia , Cirrose Hepática/induzido quimicamente , Cirrose Hepática/patologia , Cirrose Hepática/fisiopatologia , Masculino , Contração Miocárdica/fisiologia , Miocárdio/metabolismo , Miocárdio/patologia , Fosforilação/efeitos dos fármacos , Distribuição Aleatória , Ratos , Ratos Wistar , Tioacetamida/administração & dosagemRESUMO
BACKGROUND/AIMS: Aortic stenosis-induced chronic pressure overload leads to cardiac dysfunction and congestive heart failure. The pathophysiological mechanisms of the myocardial impairment are multifactorial and include maladaptive ß-adrenergic signaling. Exercise training (ET) has been used as a non-pharmacological therapy for heart failure management. The present study tested the hypothesis that exercise training attenuates diastolic dysfunction through ß-adrenergic signaling preservation. METHODS: Wistar rats were submitted to ascending aortic stenosis (AS) surgery, and after 18 weeks, a moderate aerobic exercise training protocol was performed for ten weeks. RESULTS: ET attenuated diastolic dysfunction, evaluated by echocardiogram and isolated papillary muscle (IPM) assay. Also, ET reduced features of heart failure, cross-sectional cardiomyocyte area, and exercise intolerance, assessed by treadmill exercise testing. The ß2 adrenergic receptor protein expression was increased in AS rats independently of exercise. Interestingly, ET restored the protein levels of phosphorylated phospholamban at Serine 16 and preserved the ß-adrenergic receptor responsiveness as visualized by the lower myocardial compliance decline and time to 50% tension development and relaxation during ß-adrenergic stimulation in the IPM than untrained rats. Additionally, AS rats presented higher levels of TNFα and iNOS, which were attenuated by ET. CONCLUSION: Moderate ET improves exercise tolerance, reduces heart failure features, and attenuates diastolic dysfunction. In the myocardium, ET decreases the cross-sectional area of the cardiomyocyte and preserves the ß-adrenergic responsiveness, which reveals that the adjustments in ß-adrenergic signaling contribute to the amelioration of cardiac dysfunction by mild exercise training in aortic stenosis rats.
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Estenose Aórtica Supravalvular/metabolismo , Insuficiência Cardíaca Diastólica/terapia , Miócitos Cardíacos/metabolismo , Condicionamento Físico Animal/fisiologia , Receptores Adrenérgicos beta/metabolismo , Animais , Estenose Aórtica Supravalvular/terapia , Proteínas de Ligação ao Cálcio/metabolismo , Ecocardiografia , Teste de Esforço , Masculino , Miocárdio/metabolismo , Miócitos Cardíacos/fisiologia , Óxido Nítrico Sintase Tipo II/metabolismo , Músculos Papilares/fisiologia , Fosforilação , Ratos , Ratos Wistar , Receptores Adrenérgicos beta/fisiologia , Transdução de Sinais/fisiologia , Fator de Necrose Tumoral alfa/metabolismoRESUMO
Severe food restriction (FR) impairs cardiac performance, although the causative mechanisms remain elusive. Since proteins associated with calcium handling may contribute to cardiac dysfunction, this study aimed to evaluate whether severe FR results in alterations in the expression and activity of Ca2+-handling proteins that contribute to impaired myocardial performance. Male 60-day-old Wistar-Kyoto rats were fed a control or restricted diet (50% reduction in the food consumed by the control group) for 90 days. Body weight, body fat pads, adiposity index, as well as the weights of the soleus muscle and lung, were obtained. Cardiac remodeling was assessed by morphological measures. The myocardial contractile performance was analyzed in isolated papillary muscles during the administration of extracellular Ca2+ and in the absence or presence of a sarcoplasmic reticulum Ca2+-ATPase (SERCA2a) specific blocker. The expression of Ca2+-handling regulatory proteins was analyzed via Western Blot. Severe FR resulted in a 50% decrease in body weight and adiposity measures. Cardiac morphometry was substantially altered, as heart weights were nearly twofold lower in FR rats. Papillary muscles isolated from FR hearts displayed mechanical dysfunction, including decreased developed tension and reduced contractility and relaxation. The administration of a SERCA2a blocker led to further decrements in contractile function in FR hearts, suggesting impaired SERCA2a activity. Moreover, the FR rats presented a lower expression of L-type Ca2+ channels. Therefore, myocardial dysfunction induced by severe food restriction is associated with changes in the calcium-handling properties in rats.
Assuntos
Sinalização do Cálcio , Cálcio/metabolismo , Restrição Calórica , Cardiopatias/etiologia , Desnutrição/complicações , Mitocôndrias Cardíacas/metabolismo , Contração Miocárdica , Miócitos Cardíacos/metabolismo , Músculos Papilares/metabolismo , Adiposidade , Animais , Canais de Cálcio Tipo L/metabolismo , Modelos Animais de Doenças , Cardiopatias/metabolismo , Cardiopatias/patologia , Cardiopatias/fisiopatologia , Masculino , Desnutrição/metabolismo , Desnutrição/patologia , Desnutrição/fisiopatologia , Mitocôndrias Cardíacas/patologia , Miócitos Cardíacos/patologia , Músculos Papilares/patologia , Músculos Papilares/fisiopatologia , Ratos Endogâmicos WKY , ATPases Transportadoras de Cálcio do Retículo Sarcoplasmático/metabolismo , Redução de PesoRESUMO
BACKGROUND: Increased reactive oxygen species (ROS) generation in diabetes mellitus (DM) is an important mechanism leading to diabetic cardiomyopathy. Apocynin, a drug isolated from the herb Picrorhiza kurroa, is considered an antioxidant agent by inhibiting NADPH oxidase activity and improving ROS scavenging. This study analyzed the influence of apocynin on cardiac remodeling in diabetic rats. METHODS: Six-month-old male Wistar rats were assigned into 4 groups: control (CTL, n = 15), control + apocynin (CTL + APO, n = 20), diabetes (DM, n = 20), and diabetes + apocynin (DM + APO, n = 20). DM was induced by streptozotocin. Seven days later, apocynin (16 mg/kg/day) or vehicle was initiated and maintained for 8 weeks. Left ventricular (LV) histological sections were used to analyze interstitial collagen fraction. NADPH oxidase activity was evaluated in LV samples. Comparisons between groups were performed by ANOVA for a 2 × 2 factorial design followed by the Bonferroni post hoc test. RESULTS: Body weight (BW) was lower and glycemia higher in diabetic animals. Echocardiogram showed increased left atrial diameter, LV diastolic diameter, and LV mass indexed by BW in both diabetic groups; apocynin did not affect these indices. LV systolic function was impaired in DM groups and unchanged by apocynin. Isovolumic relaxation time was increased in DM groups; transmitral E/A ratio was higher in DM + APO compared to DM. Myocardial functional evaluation through papillary muscle preparations showed impaired contractile and relaxation function in both DM groups at baseline conditions. After positive inotropic stimulation, developed tension (DT) was lower in DM than CTL. In DM + APO, DT had values between those in DM and CTL + APO and did not significantly differ from either group. Myocardial interstitial collagen fraction was higher in DM than CTL and did not differ between DM + APO and CTL + APO. Serum activity of antioxidant enzymes glutathione peroxidase, superoxide dismutase (SOD), and catalase was lower in DM than CTL; apocynin restored catalase and SOD levels in DM + APO. Myocardial NADPH oxidase activity did not differ between groups. CONCLUSION: Apocynin restores serum antioxidant enzyme activity despite unchanged myocardial NADPH oxidase activity in diabetic rats.
Assuntos
Acetofenonas/farmacologia , Diabetes Mellitus Experimental/tratamento farmacológico , Cardiomiopatias Diabéticas/prevenção & controle , Sequestradores de Radicais Livres/farmacologia , Ventrículos do Coração/efeitos dos fármacos , Estreptozocina , Função Ventricular Esquerda/efeitos dos fármacos , Remodelação Ventricular/efeitos dos fármacos , Animais , Catalase/sangue , Colágeno , Diabetes Mellitus Experimental/sangue , Diabetes Mellitus Experimental/induzido quimicamente , Diabetes Mellitus Experimental/complicações , Cardiomiopatias Diabéticas/sangue , Cardiomiopatias Diabéticas/etiologia , Cardiomiopatias Diabéticas/fisiopatologia , Glutationa Peroxidase/sangue , Ventrículos do Coração/metabolismo , Ventrículos do Coração/fisiopatologia , Masculino , NADPH Oxidases/metabolismo , Ratos Wistar , Superóxido Dismutase/sangueRESUMO
Cardiac remodeling is defined as changes in shape and function of the heart in response to aggression (pressure overload). The sarcoplasmic reticulum calcium ATPase cardiac isoform 2a (SERCA2a) is a known factor that influences function. A wide spectrum of studies report a decrease in SERCA2a in heart failure, but none evaluate it's the role in early isolated diastolic dysfunction in supravalvular aortic stenosis (AoS). Our hypothesis was that SERCA2a participates in such dysfunction. Thirty-day-old male Wistar rats (60-80 g) were divided into AoS and Sham groups, which were submitted to surgery with or without aorta clipping, respectively. After 6 weeks, the animals were submitted to echocardiogram and functional analysis by isolated papillary muscle (IPM) in basal condition, hypoxia, and SERCA2a blockage with cyclopiazonic acid at calcium concentrations of 0.5, 1.5, and 2.5 mM. Western-blot analyses were used for SERCA2a and phospholamban detection. Data analysis was carried out with Student's t-test and ANOVA. AoS enhanced left atrium and E and A wave ratio, with preserved ejection fraction. Basal condition in IPM showed similar increases in developed tension (DT) and resting tension (RT) in AoS, and hypoxia was similar between groups. After cyclopiazonic acid blockage, final DT was equally decreased and RT was similar between groups, but the speed of relaxation was decreased in the AoS group. Western-blot was uniform in all evaluations. The hypothesis was confirmed, since functional parameters regarding SERCA2a were changed in the AoS group.
Assuntos
Animais , Masculino , Estenose Aórtica Supravalvular/complicações , Hipertrofia Ventricular Esquerda/fisiopatologia , ATPases Transportadoras de Cálcio do Retículo Sarcoplasmático/fisiologia , Disfunção Ventricular Esquerda/fisiopatologia , Estenose Aórtica Supravalvular/metabolismo , Proteínas de Ligação ao Cálcio/análise , Colágeno/análise , Diástole/fisiologia , Modelos Animais de Doenças , Ecocardiografia , Ventrículos do Coração/patologia , Ventrículos do Coração/fisiopatologia , Hipertrofia Ventricular Esquerda/etiologia , Hipertrofia Ventricular Esquerda/metabolismo , Hipóxia/metabolismo , Hipóxia/fisiopatologia , Indóis , Contração Miocárdica/fisiologia , Ratos Wistar , ATPases Transportadoras de Cálcio do Retículo Sarcoplasmático/análise , ATPases Transportadoras de Cálcio do Retículo Sarcoplasmático/metabolismo , Fatores de Tempo , Disfunção Ventricular Esquerda/etiologia , Disfunção Ventricular Esquerda/metabolismo , Remodelação Ventricular/fisiologiaRESUMO
Iron intoxication is related to reactive oxygen species (ROS) production and organic damage including the cardiovascular system, and is a leading cause of poisoning deaths in children. In this study we examined whether a range of ferrous iron (Fe(2+)) concentrations can interfere differently on the myocardial mechanics, investigating the ROS-mediated effects. Developed force of isolated rat papillary muscles was depressed with a concentration- and time-dependency by Fe(2+) 100-1000µM. The contractile response to Ca(2+) was reduced, but it was partially reversed by co-incubation with catalase and DMSO, but not TEMPOL. In agreement, in situ detection of OH was increased by Fe(2+) whereas O2(-) was unchanged. The myosin-ATPase activity was significantly decreased. Contractions dependent on the sarcolemal Ca(2+) influx were impaired only by Fe(2+) 1000µM, and antioxidants had no effect. In skinned fibers, Fe(2+) reduced the pCa-force relationship, and pCa50 was right-shifted by 0.55. In conclusion, iron overload can acutely impair myocardial contractility by reducing myosin-ATPase activity and myofibrillar Ca(2+) sensitivity. These effects are mediated by local production of OH and H2O2. Nevertheless, in a such high concentration as 1000µM, Fe(2+) appears to depress force also by reducing Ca(2+) influx, probably due to a competition at Ca(2+) channels.
Assuntos
Compostos Ferrosos/farmacologia , Contração Miocárdica/efeitos dos fármacos , Músculos Papilares/efeitos dos fármacos , Animais , Cálcio/metabolismo , Técnicas In Vitro , Sobrecarga de Ferro/metabolismo , Sobrecarga de Ferro/fisiopatologia , Contração Isométrica/efeitos dos fármacos , Masculino , Miosinas/metabolismo , Músculos Papilares/metabolismo , Músculos Papilares/fisiologia , Ratos Wistar , Espécies Reativas de Oxigênio/metabolismoRESUMO
Myocardial stretch is an established signal that leads to hypertrophy. Myocardial stretch induces a first immediate force increase followed by a slow force response (SFR), which is a consequence of an increased Ca(2+) transient that follows the NHE1 Na(+)/H(+) exchanger activation. Carbonic anhydrase II (CAII) binds to the extreme COOH terminus of NHE1 and regulates its transport activity. We aimed to test the role of CAII bound to NHE1 in the SFR. The SFR and changes in intracellular pH (pHi) were evaluated in rat papillary muscle bathed with CO2/HCO3(-) buffer and stretched from 92% to 98% of the muscle maximal force development length for 10 min in the presence of the CA inhibitor 6-ethoxzolamide (ETZ, 100 µM). SFR control was 120 ± 3% (n = 8) of the rapid initial phase and was fully blocked by ETZ (99 ± 4%, n = 6). The SFR corresponded to a maximal increase in pHi of 0.18 ± 0.02 pH units (n = 4), and pHi changes were blocked by ETZ (0.04 ± 0.04, n = 6), as monitored by epifluorescence. NHE1/CAII physical association was examined in the SFR by coimmunoprecipitation, using muscle lysates. CAII immunoprecipitated with an anti-NHE1 antibody and the CAII immunoprecipitated protein levels increased 58 ± 9% (n = 6) upon stretch of muscles, assessed by immunoblots. The p90(RSK) kinase inhibitor SL0101-1 (10 µM) blocked the SFR of heart muscles after stretch 102 ± 2% (n = 4) and reduced the binding of CAII to NHE1, suggesting that the stretch-induced phosphorylation of NHE1 increases its binding to CAII. CAII/NHE1 interaction constitutes a component of the SFR to heart muscle stretch, which potentiates NHE1-mediated H(+) transport in the myocardium.
Assuntos
Anidrase Carbônica II/antagonistas & inibidores , Inibidores da Anidrase Carbônica/farmacologia , Etoxzolamida/farmacologia , Fusos Musculares/metabolismo , Músculos Papilares/efeitos dos fármacos , Trocadores de Sódio-Hidrogênio/metabolismo , Animais , Anidrase Carbônica II/metabolismo , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Concentração de Íons de Hidrogênio , Imunoprecipitação , Medições Luminescentes , Masculino , Músculos Papilares/enzimologia , Fosforilação , Ligação Proteica , Domínios e Motivos de Interação entre Proteínas , Mapeamento de Interação de Proteínas/métodos , Inibidores de Proteínas Quinases/farmacologia , Ratos , Ratos Wistar , Proteínas Quinases S6 Ribossômicas 90-kDa/antagonistas & inibidores , Proteínas Quinases S6 Ribossômicas 90-kDa/metabolismo , Trocador 1 de Sódio-Hidrogênio , Fatores de TempoRESUMO
Se realizó un estudio descriptivo de las características anatómicas y biométricas del músculo papilar septal en 30 corazones de individuos adultos chilenos, en edades comprendidas entre 18 y 84 años de edad, de ambos sexos, sin aparente patología cardíaca, pertenecientes a la Unidad de Anatomía Humana Normal del Departamento de Ciencias Básicas de la Universidad de La Frontera. Los resultados mostraron que el músculo papilar septal, se presenta en un 83,3 por ciento de los corazones del estudio. De éstos, el 44,0 por ciento presenta un solo músculo, el 28 por ciento presenta dos músculos y el 28 por ciento tres músculos papilares septales. De los músculos papilares septales encontrados, el 71,1 por ciento correspondió a la forma cono libre, el 24,4 por ciento a la forma cono pegado y el 4,5 por ciento a la forma puente. En cuanto a la longitud de forma cono pegado y cono libre, el rango que se encuentra en mayor porcentaje está entre 4,0 mm 5,99 mm; con un 45,5 por ciento y 42,4 por ciento, respectivamente. Este estudio nos demuestra la importancia de incorporar al músculo papilar septal a la nomenclatura anatómica internacional.
A descriptive research study was carried out on the anatomical and biometric characteristics of the septal papillary muscle in 30 hearts of adult Chilean subjects, between 18 and 84 years of age of both sexes and without apparent cardiac pathology, from the Normal Human Anatomy Unit, Basic Sciences Department of the Universidad de La Frontera. Results show that the septal papillary muscle was present in 83.3 percent of the hearts in the study. Of these 44.0 percent show one muscle only, 28 percent show two muscles and 28 percent show three septal papillary muscles. In the septal papillary muscles found, 71.1 percent are free cone-shaped, 24.4 percent were attached cone-shaped, and 4.5 percent were bridge-shaped. Regarding the length of attached cone and free cone shaped, the highest percentage range was between 4.0 mm and 5.99 mm, with 45.5 percent and 42.4 percent respectively. The present study shows the importance of integrating the septal papillary muscle to the International Anatomical Nomenclature.
Assuntos
Idoso , Músculos Papilares/anatomia & histologia , Músculos Papilares/ultraestrutura , Septos Cardíacos/anatomia & histologia , Septos Cardíacos/embriologia , Septos Cardíacos/ultraestrutura , Anatomia Regional/métodos , ChileRESUMO
Los tejidos cardíacos son capaces de trabajar en un amplio intervalo de frecuencias con el fin de atender las distintas demandas que el organismo impone al sistema cardiovascular. Sin embargo, bajo un régimen de cambios de frecuencia y con ciertas condiciones patológicas, pueden desarrollarse arritmias, como bloqueos, taquicardias, fibrilaciones, etc. de posibles consecuencias fatales. Esto motiva la realización de diversos arreglos experimentales en los cuales se explora el comportamiento del corazón, o de regiones de éste. En este artículo reportamos diversos fenómenos que ocurren en el músculo papilar de cobayo cuando se le estimula eléctricamente, desde una frecuencia basal de un pulso por segundo (pps) hasta frecuencias muy altas, de varias decenas de pps, pero incrementando paulatinamente la frecuencia de estimulación. Describimos que en nuestras condiciones experimentales, el músculo despliega sucesivamente ritmos tipo n:1 (una respuesta cada n estímulos) con n creciente; encontramos también que entre uno y otro de estos ritmos aparecen diversas formas de transición, entre las cuales describimos una totalmente nueva en este sistema, que hemos denominado por "ráfagas"; finalmente mostramos que este sistema exhibe de manera generalizada histéresis en la frecuencia, siendo el primer reporte que se hace para esta especie y además el primer reporte en el que se muestran varias "asas" o regiones de histéresis por frecuencia dentro de una misma excursión experimental. Debido al gran volumen de datos generados, hemos introducido una forma de presentación y análisis concisa y eficiente, basada en los espectros de potencia de los datos obtenidos a través de la transformada rápida de Fourier. Este método también se describe brevemente en el artículo.
Cardiac tissues are able to work within a wide range of frequencies to respond to the changing requirements an organism may have. However, during these frequency variations and under certain pathologic conditions arrhythmias such as blocks, tachycardia, fibrillation, etc, may arise some with fatal consequences. For this reason several experimental procedures have been developed that have shown to be useful in studying whole heart properties, or as an alternative from portions of it when changes in its work rate are imposed. This study reports different phenomena occurring in the papillary muscle of the guinea pig heart when stimulated at very high frequency, of several tens of pps, while analyzing its responses during gradual increments starting at 1 (pulses per second). We found that in our conditions papillary muscles display N:1 rhythms with progressive higher N; further more we found that between one and the next rhythm diverse transition patterns appear, among them a new one that we have named "burst pattern". Finally we show that our system exhibits a generalized process of hysteresis by frequency, being this the first report for guinea pig cardiac tissue and the first one to show also the presence of several hysteresis loops in the same experiment. Due to the large volume of generated data we used a faster and easier way to analyze and display them, based on the fast Fourier transform (FFT). The method is briefly described. (Arch Cardiol Mex 2004; 74:11-24).
Assuntos
Animais , Cobaias , Masculino , Potenciais de Ação/fisiologia , Arritmias Cardíacas/fisiopatologia , Músculos Papilares/fisiologia , Estimulação Elétrica , Eletrocardiografia , Eletrofisiologia , Função VentricularRESUMO
PURPOSE: To evaluate the effects of afterload on peak rate of tension rise (dT/dt) in the isolated muscle. METHODS: Left ventricular papillary muscles from Wistar rats were studied in isometric and isotonic afterloaded contractions. Muscles were analised in Krebs-Henseleit solution with calcium concentration of 2.52mM at 28 degrees C. The resting muscle length (preload) was maintained constant. The peak isometric developed tension (DT) and dT/dt were measured during increases of afterload (25, 50, 75 and 100 from DT). RESULTS: A rise in afterload corresponding to 50, 75 and 100 of DT, did not cause an increase in dT/dt values (p > 0.05). The dT/dt value decreased (p < 0.05) when afterload was changed from 75 to 25 of DT. CONCLUSION: The data suggest that an increase in the afterload from 50 of the DT did not promote changes in the dT/dt
Objetivo - Avaliar a influência da pós-carga sobre a taxa de variação da tensão desenvolvida (dT/dt) em músculo isolado.Métodos - Músculos papilares isolados de ventrículo esquerdo de ratos Wistar foram estudados em contrações isométrica e isotônicas contra pós-carga, em solução de Krebs-Henseleit, com concentração de cálcio de 2,52mM, frequência de estímulos de 0,2Hz e temperatura de 28o C. O comprimento diastólico da fibra (pré-carga) foi mantido constante. A tensão máxima desenvolvida (TD) e dT/dt foram medidas durante elevações progressivas da pós-carga (25, 50, 75 e 100% da TD). Resultados - Não ocorreu variação significante (p> 0,05) na dT/dt entre as alterações de pós-carga correspondentes a 50, 75 e 100% da tensão máxima desenvolvida. O valor da dT/dt foi significantemente menor (p < 0,05) em pós-carga de 25%, comparativamente à de 75% da TD. Conclusão - Os resultados sugerem que elevações isoladas da pós-carga, a partir de 50% da tensão máxima desenvolvida, não acarretam variações nos valores da dT/dt.