Energy Metabolism in Cardiac Remodeling and Heart Failure

Fatty acids are the main substrates used by mitochondria to provide myocardial energy under normal conditions. During heart remodeling, however, the fuel preference switches to glucose. In the earlier stages of cardiac remodeling, changes in energy metabolism are considered crucial to protect the heart from irreversible damage. Furthermore, low fatty acid oxidation and the stimulus for glycolytic pathway lead to lipotoxicity, acidosis, and low adenosine triphosphate production. While myocardial function is directly associated with energy metabolism, the metabolic pathways could be potential targets for therapy in heart failure. © 2013 by Lippincott Williams & Wilkins.

Insulin Suppresses Atrophy- and Autophagy-related Genes in Heart Tissue and Cardiomyocytes Through AKT/FOXO Signaling

Insulin is an important regulator of the ubiquitin-proteasome system (UPS) and of lysosomal proteolysis in cardiac muscle. However, the role of insulin in the regulation of the muscle atrophy-related Ub-ligases atrogin-1 and MuRF1 as well as in autophagy, a major adaptive response to nutritional stress, in the heart has not been characterized. We report here that acute insulin deficiency in the cardiac muscle of rats induced by streptozotocin increased the expression of atrogin-1 and MuRF1 as well as LC3 and Gabarapl1, 2 autophagy-related genes. These effects were associated with decreased phosphorylation levels of Akt and its downstream target Foxo3a; this phenomenon is a well-known effect that permits the maintenance of Foxo in the nucleus to activate protein degradation by proteasomal and autophagic processes. The administration of insulin increased Akt and Foxo3a phosphorylation and suppressed the diabetes-induced expression of Ub-ligases and autophagy-related genes. In cultured neonatal rat cardiomyocytes, nutritional stress induced by serum/glucose deprivation strongly increased the expression of Ub-ligases and autophagy-related genes; this effect was inhibited by insulin. Furthermore, the addition of insulin in vitro prevented the decrease in Akt/Foxo signaling induced by nutritional stress. These findings demonstrate that insulin suppresses atrophy- and autophagy-related genes in heart tissue and cardiomyocytes, most likely through the phosphorylation of Akt and the inactivation of Foxo3a. © Georg Thieme Verlag KG.

Identification of poisonous plants in the heart of public squares of ribeirão Preto SP

Toxic plants, many ornamentals, may be present in gardens, backyards, parks, vases, squares and vacant lots around the cities. Some of these plants are well known and exuberant, with strong color and decorative aspects, but when swallowed or handled, can cause severe intoxication specially in children. The main objective was to identify the poisonous plants found in public squares of Ribeirão Preto downtown, among five squares: XV de Novembro Square, Carlos Gomes Square, Bandeiras Square, Luís de Camões Square and Sete de Setembro Square. In this study, a literature review was performed in order to know the species that have been recorded as toxic plant. For the species in question, the common name and therapeutic indication were recorded. Over all evaluated squares toxic species were found. Sete de Setembro Square was the most frequent species in a total of seven toxical species. The most common species in the surveyed places were: Euphorbia pulcherrima, Buxus semprevirens and Dracaena fragrans, popularly known as Poinsettia, Boxwood and Cornstalk Dracaena, respectively. The importance of doing studies in urban squares is to improve care to ensure the afforestation process of the cities.

Heart failure-induced skeletal myopathy in spontaneously hypertensive rats

Background: Although skeletal muscle atrophy and changes in myosin heavy chain (MyHC) isoforms have often been observed during heart failure, their pathophysiological mechanisms are not completely defined. In this study we tested the hypothesis that skeletal muscle phenotype changes are related to myogenic regulatory factors and myostatin/follistatin expression in spontaneously hypertensive rats (SHR) with heart failure. Methods: After developing tachypnea, SHR were subjected to transthoracic echocardiogram. Pathological evidence of heart failure was assessed during euthanasia. Age-matched Wistar-Kyoto (WKY) rats were used as controls. Soleus muscle morphometry was analyzed in histological sections, and MyHC isoforms evaluated by electrophoresis. Protein levels were assessed by Western blotting. Statistical analysis: Student's t test and Pearson correlation. Results: All SHR presented right ventricular hypertrophy and seven had pleuropericardial effusion. Echocardiographic evaluation showed dilation in the left chambers and left ventricular hypertrophy with systolic and diastolic dysfunction in SHR. Soleus weight and fiber cross sectional areas were lower (WKY 3615±412; SHR 2035±224 μm2; P < 0.001), and collagen fractional volume was higher in SHR. The relative amount of type I MyHC isoform was increased in SHR. Myogenin, myostatin, and follistatin expression was lower and MRF4 levels higher in SHR. Myogenin and follistatin expression positively correlated with fiber cross sectional areas and MRF4 levels positively correlated with I MyHC isoform. Conclusion: Reduced myogenin and follistatin expression seems to participate in muscle atrophy while increased MRF4 protein levels can modulate myosin heavy chain isoform shift in skeletal muscle of spontaneously hypertensive rats with heart failure. © 2012 Elsevier B.V.

Diastolic function is associated with quality of life and exercise capacity in stable heart failure patients with reduced ejection fraction

Exercise capacity and quality of life (QOL) are important outcome predictors in patients with systolic heart failure (HF), independent of left ventricular (LV) ejection fraction (LVEF). LV diastolic function has been shown to be a better predictor of aerobic exercise capacity in patients with systolic dysfunction and a New York Heart Association (NYHA) classification >II. We hypothesized that the currently used index of diastolic function E/e' is associated with exercise capacity and QOL, even in optimally treated HF patients with reduced LVEF. This prospective study included 44 consecutive patients aged 55±11 years (27 men and 17 women), with LVEF,0.50 and NYHA functional class I-III, receiving optimal pharmacological treatment and in a stable clinical condition, as shown by the absence of dyspnea exacerbation for at least 3 months. All patients had conventional transthoracic echocardiography and answered the Minnesota Living with HF Questionnaire, followed by the 6-min walk test (6MWT). In a multivariable model with 6MWT as the dependent variable, age and E/e' explained 27% of the walked distance in 6MWT (P=0.002; multivariate regression analysis). No association was found between walk distance and LVEF or mitral annulus systolic velocity. Only normalized left atrium volume, a sensitive index of diastolic function, was associated with decreased QOL. Despite the small number of patients included, this study offers evidence that diastolic function is associated with physical capacity and QOL and should be considered along with ejection fraction in patients with compensated systolic HF.

Poincaré plot indexes of heart rate variability: Relationships with other nonlinear variables

The Poincaré plot for heart rate variability analysis is a technique considered geometrical and non-linear, that can be used to assess the dynamics of heart rate variability by a representation of the values of each pair of R-R intervals into a simplified phase space that describes the system's evolution. The aim of the present study was to verify if there is some correlation between SD1, SD2 and SD1/SD2 ratio and heart rate variability nonlinear indexes either in disease or healthy conditions. 114 patients with arterial coronary disease and 65 healthy subjects underwent 30. minute heart rate registration, in supine position and the analyzed indexes were as follows: SD1, SD2, SD1/SD2, Sample Entropy, Lyapunov Exponent, Hurst Exponent, Correlation Dimension, Detrended Fluctuation Analysis, SDNN, RMSSD, LF, HF and LF/HF ratio. Correlation coefficients between SD1, SD2 and SD1/SD2 indexes and the other variables were tested by the Spearman rank correlation test and a regression analysis. We verified high correlation between SD1/SD2 index and HE and DFA (α1) in both groups, suggesting that this ratio can be used as a surrogate variable. © 2013 Elsevier B.V.

Protective actions of melatonin against heart damage during chronic Chagas disease

Chronic cardiomyopathy is the most important clinical form of Chagas disease, and it is characterised by myocarditis that is associated with fibrosis and organ dysfunction. Alternative treatment options are important tools to modulate host immune responses. The main goal of this work was to evaluate the anti-inflammatory actions of melatonin during the chronic phase of Chagas disease. TNF-α, IL-10 and nitrite concentrations were evaluated as predictive factors of immune modulation. Creatine phosphokinase-MB (CK-MB), cardiac inflammatory foci and heart weight were assessed to evaluate the efficacy of the melatonin treatment. Male Wistar rats were infected with 1 × 105 blood trypomastigotes of the Y strain of Trypanosoma cruzi and kept untreated for 60 days to mimic chronic infection. After this period, the rats were orally treated with melatonin 50 mg/kg/day, and the experiments were performed 90, 120, and 180 days post-infection. Melatonin treatment significantly increased the concentration of IL-10 and reduced the concentrations of NO and TNF-α produced by cardiomyocytes. Furthermore, it led to decreased heart weight, serum CK-MB levels and inflammatory foci when compared to the untreated and infected control groups. We conclude that melatonin therapy is effective at protecting animals against the harmful cardiac inflammatory response that is characteristic of chronic T. cruzi infection. © 2013 Elsevier B.V. All rights reserved.

Age Affects Exercise-Induced Improvements in Heart Rate Response to Exercise

The aim of the present study was to analyze the effects of age on cardiorespiratory fitness (CRF), muscle strength and heart rate (HR) response to exercise adaptation in women in response to a long-term twice-weekly combined aerobic and resistance exercise program. 85 sedentary women, divided into young (YG; n=22, 30.3±6.2 years), early middle-aged (EMG; n=28, 44.1±2.5 years), late middle-aged (LMG; n=20, 56.7±3.5 years) and older (OG; n=15, 71.4±6.9 years) groups, had their CRF, muscle strength (1-repetition maximum test) and HR response to exercise (graded exercise test) measured before and after 12 months of combined exercise training. Exercise training improved CRF and muscle strength in all age groups (P<0.05), and no significant differences were observed between groups. Exercise training also improved resting HR and recovery HR in YG and EMG (P<0.05), but not in LMG and OG. Maximal HR did not change in any group. Combined aerobic and resistance training at a frequency of 2 days/week improves CRF and muscle strength throughout the lifespan. However, exercise-induced improvements in the HR recovery response to exercise may be impaired in late middle-aged and older women. © Georg Thieme Verlag KG.

Pressão arterial e frequência cardíaca avaliadas pela MAPA em primigestas durante o parto e puerpério imediato

Pós-graduação em Ginecologia, Obstetrícia e Mastologia - FMB

The effects of auditory stimulation with music on heart rate variability in healthy women

OBJECTIVES: There are no data in the literature with regard to the acute effects of different styles of music on the geometric indices of heart rate variability. In this study, we evaluated the acute effects of relaxant baroque and excitatory heavy metal music on the geometric indices of heart rate variability in women. METHODS: We conducted this study in 21 healthy women ranging in age from 18 to 35 years. We excluded persons with previous experience with musical instruments and persons who had an affinity for the song styles. We evaluated two groups: Group 1 (n = 21), who were exposed to relaxant classical baroque musical and excitatory heavy metal auditory stimulation; and Group 2 (n = 19), who were exposed to both styles of music and white noise auditory stimulation. Using earphones, the volunteers were exposed to baroque or heavy metal music for five minutes. After the first music exposure to baroque or heavy metal music, they remained at rest for five minutes; subsequently, they were re-exposed to the opposite music (70-80 dB). A different group of women were exposed to the same music styles plus white noise auditory stimulation (90 dB). The sequence of the songs was randomized for each individual. We analyzed the following indices: triangular index, triangular interpolation of RR intervals and Poincaré plot (standard deviation of instantaneous beat-by-beat variability, standard deviation of the long-term RR interval, standard deviation of instantaneous beat-by-beat variability and standard deviation of the long-term RR interval ratio), low frequency, high frequency, low frequency/high frequency ratio, standard deviation of all the normal RR intervals, root-mean square of differences between the adjacent normal RR intervals and the percentage of adjacent RR intervals with a difference of duration greater than 50 ms. Heart rate variability was recorded at rest for 10 minutes. RESULTS: The triangular index and the standard deviation of the long-term RR interval indices were reduced during exposure to both music styles in the first group and tended to decrease in the second group whereas the white noise exposure decreased the high frequency index. We observed no changes regarding the triangular interpolation of RR intervals, standard deviation of instantaneous beat-by-beat variability and standard deviation of instantaneous beat-by-beat variability/standard deviation in the long-term RR interval ratio. CONCLUSION: We suggest that relaxant baroque and excitatory heavy metal music slightly decrease global heart rate variability because of the equivalent sound level.