Type 2 diabetes mellitus in obesity promotes prolongation of cardiomyocyte contractile function, impaired Ca2+ handling and protein carbonylation damage.

AIMS: To investigate whether the obesity associated to T2DM presented cardiomyocyte myocardial contractility dysfunction due to damage in Ca2+ handling, concomitantly with increased biomarkers of oxidative stress. METHODS: Male Wistar rats were randomized into two groups: control (C): fed with standard diet; and obese (Ob) that fed a saturated high-fat. After the characterization of obesity (12 weeks), the Ob animals were submitted to T2DM induction with a single dose of intraperitoneal (i.p.) injection of streptozotocin (30 mg/kg). Thus, remained Ob rats that were characterized as to the presence (T2DMOb; n = 8) and/or absence (Ob; n = 10) of T2DM. Cardiac remodeling was measured by post-mortem morphological, isolated cardiomyocyte contractile function, as well as by intracellular Ca2+-handling analysis. RESULTS: T2DMOb presented a significant reduction of all fat pads, total body fat and adiposity index. T2DMOb group presented a significant increase in protein carbonylation and superoxide dismutase (SOD) activity, respectively. T2DMOb promoted elevations in fractional shortening (15.6 %) and time to 50 % shortening (5.8 %), respectively. Time to 50 % Ca2+ decay was prolonged in T2DMOb, suggesting a possible impairment in Ca2+recapture and/or removal. CONCLUSION: Type 2 diabetes mellitus in obesity promotes prolongation of cardiomyocyte contractile function with protein carbonylation damage and impaired Ca2+ handling.

Atrial contractile function and fibrosis in patients with paroxysmal atrial fibrillation in sinus rhythm / Función contráctil auricular y fibrosis en pacientes con fibrilación auricular paroxística en ritmo sinusal

Abstract Objectives: The aim of the study was to investigate atrial contractile function in patients with paroxysmal atrial fibrillation (AF) in sinus rhythm using transthoracic echocardiography (EchoCG). Methods and results: Thirty-five patients with paroxysmal AF and arterial hypertension (mean age 62 ± 10 years, 43% male) in sinus rhythm were enrolled in the study. The control group was composed of comparable patients with arterial hypertension without heart rhythm disturbances. EchoCG was performed during sinus rhythm according to an extended protocol, which included the ejection fraction (EF) of the left atrium (LA) and tissue Doppler measurements. Myocardial fibrosis was assessed quantitatively by videodensitometry in intraventricular and intraatrial (IAS) septa using an original image post-processing algorithm. We found a significant decrease in the left atrial contraction function during sinus rhythm in patients with AF when compared to controls. LA EF (34 ± 14 vs. 54 ± 17, p = 0.03) and A' velocity (0.17 ± 0.04 vs. 0.22 ± 0.04, p = 0.008) decreased while A/A' ratio (2.7 ± 0.2 vs. 1.9 ± 0.1, p = 0.006) increased. Peak A velocity was not affected. Videodensitometric analysis revealed a 2.3-fold increase in IAS fibrosis fraction in AF patients compared with controls (p = 0.01). Conclusion: Patients with AF in sinus rhythm have markedly depressed atrial contractile function. Videodensitometry of IAS has the potential to be used as inexpensive method of atrial fibrosis assessment in patients with AF.

Resumen Objetivo: El objetivo del estudio fue investigar la función contráctil auricular en pacientes con fibrilación auricular paroxística (FA) en ritmo sinusal mediante una ecocardiografía transtorácica (EchoCG). Material y métodos: Treinta y cinco pacientes con FA paroxística e hipertensión arterial (edad media de 62 ± 10 años, el 43% varones) se inscribieron en el estudio en ritmo sinusal. El grupo de control estaba compuesto por pacientes comparables con hipertensión arterial sin alteraciones del ritmo cardíaco. Se realizó una ecocardiografía durante el ritmo sinusal, según el protocolo extendido, incluidas la fracción de eyección (FE) de la aurícula izquierda (AI) y las mediciones Doppler tisulares. La fibrosis miocárdica se evaluó cuantitativamente mediante una videodensitometría de los septos interventricular e interauricular (IAS) utilizando un algoritmo de posprocesamiento de imágenes originales. Resultados: Encontramos una disminución significativa en la función de contracción de la aurícula izquierda durante el ritmo sinusal en pacientes con FA en comparación con el grupo de control. Cabe destacar que la FE de la AI (34 ± 14 vs. 54 ± 17, p = 0.03) y la velocidad A' disminuyeron (0.17 ± 0.04 vs. 0.22 ± 0.04, p = 0,008) mientras que la relación A/A' aumentó (2,7 ± 0,2 vs. 1.9 ± 0.1, p = 0,006). La velocidad pico A no se vio afectada. El análisis videodensitométrico reveló que la fracción de fibrosis IAS en pacientes con FA fue 2.3 veces mayor que en el grupo de control (p = 0.01). Conclusiones: Incluso en ritmo sinusal, los pacientes con FA tienen una función contráctil auricular marcadamente deprimida. La videodensitometría de IAS tiene el potencial de utilizarse como método económico de diagnóstico de la fibrosis auricular en pacientes con FA.

Resistance training promotes reduction in Visceral Adiposity without improvements in Cardiomyocyte Contractility and Calcium handling in Obese Rats.

Resistance training (RT) improves the cardiomyocyte calcium (Ca2+) cycling during excitation-contraction coupling. However, the role of RT in cardiomyocyte contractile function associated with Ca2+ handling in obesity is unclear. Wistar rats were distributed into four groups: control, sedentary obese, control plus RT, and obesity plus RT. The 10-wk RT protocol was used (4-5 vertical ladder climbs, 60-second interval, 3× a week, 50-100% of maximum load). Metabolic, hormonal, cardiovascular and biochemical parameters were determined. Reduced leptin levels, epididymal, retroperitoneal and visceral fat pads, lower body fat, and adiposity index were observed in RT. Obesity promoted elevation of collagen, but RT did not promote modifications of LV collagen in ObRT. RT induced elevation in maximum rates of contraction and relaxation, and reduction of time to 50% relaxation. ObRT group did not present improvement in the cardiomyocyte contractile function in comparison to Ob group. Reduced cardiac PLB serine16 phosphorylation (pPLB Ser16) and pPLB Ser16/PLB ratio with no alterations in sarcoplasmic reticulum Ca2+ ATPase (SERCA2a) and phospholamban (PLB) expression were observed in Ob groups. Resistance training improved body composition reduced fat pads and plasma leptin levels but did not promote positive alterations in cardiomyocyte contractile function, Ca2+ handling and phospholamban phosphorylation.

Left atrial size and contractile function in healthy dogs and dogs with chronic mitral valve disease / Tamanho e função sistólica atrial esquerda em cães sadios e com doença valvar crônica de mitral

In humans, left atrial enlargement and reduced contractile functions are associated with adverse cardiovascular events and a poor prognosis in many dilatation of the left atrium occurs with the gradual evolution of chronic mitral valve disease and is well diseases. The left atrium is the most compromised cardiac chamber in dogs with chronic mitral valve disease (CMVD). Therefore, this study aimed to compare the main parameters of left atrial enlargement (left atrium/aorta ratio, left atrial diameter and volume indices) and contractile function (transmitral flow peak velocity A wave and time velocity integral, atrial fraction, and atrial ejection force) at different stages of valve disease, and correlate the left atrial diameter, volume, and contractile function indices with echocardiographic variables predictive of heart failure in dogs (transmitral flow peak velocity E wave, E wave/IVRT ratio, E wave/E´wave ratio, and E wave/A wave ratio). The results showed that progressive characterized by the left atrium/aorta ratio and left atrium volume index. The left atrial diameter and volume indices and left atrium/aorta ratio correlated positively with the transmitral flow peak velocity E wave and E wave/IVRT ratio, which are important indices of diastolic function. The left atrial contractile function indices increased as CMVD evolved. Except for the atrial fraction, the left atrial contractile function indices correlated with the left ventricular filling pressure indices.(AU)

O tamanho e a função atrial esquerda estão relacionados em humanos com eventos cardiovasculares adversos e prognóstico nas principais cardiopatias. Na doença valvar crônica de mitral (DVCM) em cães, o átrio esquerdo é a câmara cardíaca mais comprometida. Portanto, os objetivos deste estudo foram comparar os principais parâmetros de aumento atrial esquerdo (relação átrio esquerdo/aorta, índice do diâmetro atrial esquerdo e índice do volume atrial esquerdo) e função contrátil de átrio esquerdo (velocidade máxima e integral de velocidade da onda A do fluxo transvalvar mitral, fração atrial e força de ejeção atrial) nos diferentes estágios da doença valvar; correlacionar diâmetro e volume atrial esquerdo e os índices de função contrátil atrial esquerda com as variáveis ecocardiográficas preditivas de insuficiência cardíaca em cães (velocidade máxima da onda E do fluxo transvalvar mitral, relação E/TRIV, relação E/E'par e relação E/A). Os resultados mostraram que com a evolução progressiva da doença valvar crônica de mitral, ocorre dilatação progressiva do átrio esquerdo, bem caracterizada pela relação átrio esquerdo/aorta e pelo índice de volume atrial esquerdo. O índice do diâmetro atrial esquerdo, o índice de volume atrial esquerdo e a relação átrio esquerdo/aorta correlacionam-se, positivamente, com a velocidade da onda E e com a relação E/TRIV, que são importantes índices de função diastólica. Os índices de função contrátil do átrio esquerdo aumentam à medida que a DVCM evolui. Os índices de função contrátil do átrio esquerdo apresentam correlação positiva com os índices de pressão de enchimento ventricular esquerdo, exceção feita à fração atrial.(AU)

Left atrial size and contractile function in healthy dogs and dogs with chronic mitral valve disease / Tamanho e função sistólica atrial esquerda em cães sadios e com doença valvar crônica de mitral

In humans, left atrial enlargement and reduced contractile functions are associated with adverse cardiovascular events and a poor prognosis in many dilatation of the left atrium occurs with the gradual evolution of chronic mitral valve disease and is well diseases. The left atrium is the most compromised cardiac chamber in dogs with chronic mitral valve disease (CMVD). Therefore, this study aimed to compare the main parameters of left atrial enlargement (left atrium/aorta ratio, left atrial diameter and volume indices) and contractile function (transmitral flow peak velocity A wave and time velocity integral, atrial fraction, and atrial ejection force) at different stages of valve disease, and correlate the left atrial diameter, volume, and contractile function indices with echocardiographic variables predictive of heart failure in dogs (transmitral flow peak velocity E wave, E wave/IVRT ratio, E wave/E´wave ratio, and E wave/A wave ratio). The results showed that progressive characterized by the left atrium/aorta ratio and left atrium volume index. The left atrial diameter and volume indices and left atrium/aorta ratio correlated positively with the transmitral flow peak velocity E wave and E wave/IVRT ratio, which are important indices of diastolic function. The left atrial contractile function indices increased as CMVD evolved. Except for the atrial fraction, the left atrial contractile function indices correlated with the left ventricular filling pressure indices.(AU)

O tamanho e a função atrial esquerda estão relacionados em humanos com eventos cardiovasculares adversos e prognóstico nas principais cardiopatias. Na doença valvar crônica de mitral (DVCM) em cães, o átrio esquerdo é a câmara cardíaca mais comprometida. Portanto, os objetivos deste estudo foram comparar os principais parâmetros de aumento atrial esquerdo (relação átrio esquerdo/aorta, índice do diâmetro atrial esquerdo e índice do volume atrial esquerdo) e função contrátil de átrio esquerdo (velocidade máxima e integral de velocidade da onda A do fluxo transvalvar mitral, fração atrial e força de ejeção atrial) nos diferentes estágios da doença valvar; correlacionar diâmetro e volume atrial esquerdo e os índices de função contrátil atrial esquerda com as variáveis ecocardiográficas preditivas de insuficiência cardíaca em cães (velocidade máxima da onda E do fluxo transvalvar mitral, relação E/TRIV, relação E/E'par e relação E/A). Os resultados mostraram que com a evolução progressiva da doença valvar crônica de mitral, ocorre dilatação progressiva do átrio esquerdo, bem caracterizada pela relação átrio esquerdo/aorta e pelo índice de volume atrial esquerdo. O índice do diâmetro atrial esquerdo, o índice de volume atrial esquerdo e a relação átrio esquerdo/aorta correlacionam-se, positivamente, com a velocidade da onda E e com a relação E/TRIV, que são importantes índices de função diastólica. Os índices de função contrátil do átrio esquerdo aumentam à medida que a DVCM evolui. Os índices de função contrátil do átrio esquerdo apresentam correlação positiva com os índices de pressão de enchimento ventricular esquerdo, exceção feita à fração atrial.(AU)

Embryonic stem cells improve skeletal muscle recovery after extreme atrophy in mice.

INTRODUCTION: We injected embryonic stem cells into mouse tibialis anterior muscles subjected to botulinum toxin injections as a model for reversible neurogenic atrophy. METHODS: Muscles were exposed to botulinum toxin for 4 weeks and allowed to recover for up to 6 weeks. At the onset of recovery, a single muscle injection of embryonic stem cells was administered. The myofiber cross-sectional area, single twitch force, peak tetanic force, time-to-peak force, and half-relaxation time were determined. RESULTS: Although the stem cell injection did not affect the myofiber cross-sectional area gain in recovering muscles, most functional parameters improved significantly compared with those of recovering muscles that did not receive the stem cell injection. CONCLUSIONS: Muscle function recovery was accelerated by embryonic stem cell delivery in this durable neurogenic atrophy model. We conclude that stem cells should be considered a potential therapeutic tool for recovery after extreme skeletal muscle atrophy.