Cardiac Autonomic Adjustments During Baroreflex Test in Obese and Non-Obese Preadolescents

Abstract Background: Recent studies have shown changes in cardiac autonomic control of obese preadolescents. Objective: To assess the heart rate responses and cardiac autonomic modulation of obese preadolescents during constant expiratory effort. Methods: This study assessed 10 obese and 10 non-obese preadolescents aged 9 to 12 years. The body mass index of the obese group was between the 95th and 97th percentiles of the CDC National Center for Health Statistics growth charts, while that of the non-obese group, between the 5th and 85th percentiles. Initially, they underwent anthropometric and clinical assessment, and their maximum expiratory pressures were obtained. Then, the preadolescents underwent a constant expiratory effort of 70% of their maximum expiratory pressure for 20 seconds, with heart rate measurement 5 minutes before, during and 5 minutes after it. Heart rate variability (HRV) and heart rate values were analyzed by use of a software. Results: The HRV did not differ when compared before and after the constant expiratory effort intra- and intergroup. The heart rate values differed (p < 0.05) during the effort, being the total variation in non-obese preadolescents of 18.5 ± 1.5 bpm, and in obese, of 12.2 ± 1.3 bpm. Conclusion: The cardiac autonomic modulation did not differ between the groups when comparing before and after the constant expiratory effort. However, the obese group showed lower cardiovascular response to baroreceptor stimuli during the effort, suggesting lower autonomic baroreflex sensitivity.

Aerobic Training after Myocardial Infarction: Remodeling Evaluated by Cardiac Magnetic Resonance

Abstract Background: Numerous studies show the benefits of exercise training after myocardial infarction (MI). Nevertheless, the effects on function and remodeling are still controversial. Objectives: To evaluate, in patients after (MI), the effects of aerobic exercise of moderate intensity on ventricular remodeling by cardiac magnetic resonance imaging (CMR). Methods: 26 male patients, 52.9 ± 7.9 years, after a first MI, were assigned to groups: trained group (TG), 18; and control group (CG), 8. The TG performed supervised aerobic exercise on treadmill twice a week, and unsupervised sessions on 2 additional days per week, for at least 3 months. Laboratory tests, anthropometric measurements, resting heart rate (HR), exercise test, and CMR were conducted at baseline and follow-up. Results: The TG showed a 10.8% reduction in fasting blood glucose (p = 0.01), and a 7.3-bpm reduction in resting HR in both sitting and supine positions (p < 0.0001). There was an increase in oxygen uptake only in the TG (35.4 ± 8.1 to 49.1 ± 9.6 mL/kg/min, p < 0.0001). There was a statistically significant decrease in the TG left ventricular mass (LVmass) (128.7 ± 38.9 to 117.2 ± 27.2 g, p = 0.0032). There were no statistically significant changes in the values of left ventricular end-diastolic volume (LVEDV) and ejection fraction in the groups. The LVmass/EDV ratio demonstrated a statistically significant positive remodeling in the TG (p = 0.015). Conclusions: Aerobic exercise of moderate intensity improved physical capacity and other cardiovascular variables. A positive remodeling was identified in the TG, where a left ventricular diastolic dimension increase was associated with LVmass reduction.

Spectrum of cardiac lesions associated with Isolated Cleft Mitral Valve and their impact on therapeutic choices

Abstract Background: Isolated cleft mitral valve (ICMV) may occur alone or in association with other congenital heart lesions. The aim of this study was to describe the profile of cardiac lesions associated with ICMV and their potential impact on therapeutic management. Methods: We conducted a descriptive study with data retrieved from the Congenital Heart Disease (CHD) single-center registry of our institution, including patients with ICMV registered between December 2008 and November 2014. Results: Among 2177 patients retrieved from the CHD registry, 22 (1%) had ICMV. Median age at diagnosis was 5 years (6 days to 36 years). Nine patients (40.9%) had Down syndrome. Seventeen patients (77.3%) had associated lesions, including 11 (64.7%) with accessory chordae in the left ventricular outflow tract (LVOT) with no obstruction, 15 (88.2%) had ventricular septal defect (VSD), three had secundum atrial septal defect, and four had patent ductus arteriosus. Thirteen patients (59.1%) required surgical repair. The decision to proceed with surgery was mainly based on the severity of the associated lesion in eight patients (61.5%) and on the severity of the mitral regurgitation in four patients (30.8%). In one patient, surgery was decided based on the severity of both the associated lesion and mitral regurgitation. Conclusion: Our study shows that ICMV is rare and strongly associated with Down syndrome. The most common associated cardiac abnormalities were VSD and accessory chordae in the LVOT. We conclude that cardiac lesions associated with ICMV are of major interest, since in this study patients with cardiac lesions were diagnosed earlier. The decision to operate on these patients must take into account the severity of both mitral regurgitation and associated cardiac lesions.

Pentoxifylline Attenuates Cardiac Remodeling Induced by Tobacco Smoke Exposure

Abstract Background: Tobacco smoke exposure is an important risk factor for cardiac remodeling. Under this condition, inflammation, oxidative stress, energy metabolism abnormalities, apoptosis, and hypertrophy are present. Pentoxifylline has anti‑inflammatory, anti-apoptotic, anti-thrombotic and anti-proliferative properties. Objective: The present study tested the hypothesis that pentoxifylline would attenuate cardiac remodeling induced by smoking. Methods: Wistar rats were distributed in four groups: Control (C), Pentoxifylline (PX), Tobacco Smoke (TS), and PX-TS. After two months, echocardiography, invasive blood pressure measurement, biochemical, and histological studies were performed. The groups were compared by two-way ANOVA with a significance level of 5%. Results: TS increased left atrium diameter and area, which was attenuated by PX. In the isolated heart study, TS lowered the positive derivate (+dp/dt), and this was attenuated by PX. The antioxidants enzyme superoxide dismutase and glutathione peroxidase were decreased in the TS group; PX recovered these activities. TS increased lactate dehydrogenase (LDH) and decreased 3-hydroxyacyl Coenzyme A dehydrogenases (OH-DHA) and citrate synthase (CS). PX attenuated LDH, 3-OH-DHA and CS alterations in TS-PX group. TS increased IL-10, ICAM-1, and caspase-3. PX did not influence these variables. Conclusion: TS induced cardiac remodeling, associated with increased inflammation, oxidative stress, apoptosis, and changed energy metabolism. PX attenuated cardiac remodeling by reducing oxidative stress and improving cardiac bioenergetics, but did not act upon cardiac cytokines and apoptosis.

Influence of Smoking Consumption and Nicotine Dependence Degree in Cardiac Autonomic Modulation

Abstract Background: Smoking consumption alters cardiac autonomic function. Objective: Assess the influence of the intensity of smoking and the nicotine dependence degree in cardiac autonomic modulation evaluated through index of heart rate variability (HRV). Methods: 83 smokers, of both genders, between 50 and 70 years of age and with normal lung function were divided according to the intensity of smoking consumption (moderate and severe) and the nicotine dependency degree (mild, moderate and severe). The indexes of HRV were analyzed in rest condition, in linear methods in the time domain (TD), the frequency domain (FD) and through the Poincaré plot. For the comparison of smoking consumption, unpaired t test or Mann-Whitney was employed. For the analysis between the nicotine dependency degrees, we used the One-way ANOVA test, followed by Tukey's post test or Kruskal-Wallis followed by Dunn's test. The significance level was p < 0,05. Results: Differences were only found when compared to the different intensities of smoking consumption in the indexes in the FD. LFun (62.89 ± 15.24 vs 75.45 ± 10.28), which corresponds to low frequency spectrum component in normalized units; HFun (37.11 ± 15.24 vs 24.55 ± 10.28), which corresponds to high frequency spectrum component in normalized units and in the LF/HF ratio (2.21 ± 1.47 vs 4.07 ± 2.94). However, in the evaluation of nicotine dependency, significant differences were not observed (p > 0.05). Conclusion: Only the intensity of smoking consumption had an influence over the cardiac autonomic modulation of the assessed tobacco smokers. Tobacco smokers with severe intensity of smoking consumption presented a lower autonomic modulation than those with moderate intensity.

Carlos Chagas Discoveries as a Drop Back to Scientific Construction of Chronic Chagas Heart Disease

Abstract The scientific construction of chronic Chagas heart disease (CCHD) started in 1910 when Carlos Chagas highlighted the presence of cardiac arrhythmia during physical examination of patients with chronic Chagas disease, and described a case of heart failure associated with myocardial inflammation and nests of parasites at autopsy. He described sudden cardiac death associated with arrhythmias in 1911, and its association with complete AV block detected by Jacquet's polygraph as Chagas reported in 1912. Chagas showed the presence of myocardial fibrosis underlying the clinical picture of CCHD in 1916, he presented a full characterization of the clinical aspects of CCHD in 1922. In 1928, Chagas detected fibrosis of the conductive system, and pointed out the presence of marked cardiomegaly at the chest X-Ray associated with minimal symptomatology. The use of serological reaction to diagnose CCHD was put into clinical practice in 1936, after Chagas' death, which along with the 12-lead ECG, revealed the epidemiological importance of CCHD in 1945. In 1953, the long period between initial infection and appearance of CCHD was established, whereas the annual incidence of CCHD from patients with the indeterminate form of the disease was established in 1956. The use of heart catheterization in 1965, exercise stress testing in 1973, Holter monitoring in 1975, Electrophysiologic testing in 1973, echocardiography in 1975, endomyocardial biopsy in 1981, and Magnetic Resonance Imaging in 1995, added to the fundamental clinical aspects of CCHD as described by Carlos Chagas.

Fractal Dimension in Quantifying Experimental-Pulmonary-Hypertension-Induced Cardiac Dysfunction in Rats

Abstract Background: Right-sided heart failure has high morbidity and mortality, and may be caused by pulmonary arterial hypertension. Fractal dimension is a differentiated and innovative method used in histological evaluations that allows the characterization of irregular and complex structures and the quantification of structural tissue changes. Objective: To assess the use of fractal dimension in cardiomyocytes of rats with monocrotaline-induced pulmonary arterial hypertension, in addition to providing histological and functional analysis. Methods: Male Wistar rats were divided into 2 groups: control (C; n = 8) and monocrotaline-induced pulmonary arterial hypertension (M; n = 8). Five weeks after pulmonary arterial hypertension induction with monocrotaline, echocardiography was performed and the animals were euthanized. The heart was dissected, the ventricles weighed to assess anatomical parameters, and histological slides were prepared and stained with hematoxylin/eosin for fractal dimension analysis, performed using box-counting method. Data normality was tested (Shapiro-Wilk test), and the groups were compared with non-paired Student t test or Mann Whitney test (p < 0.05). Results: Higher fractal dimension values were observed in group M as compared to group C (1.39 ± 0.05 vs. 1.37 ± 0.04; p < 0.05). Echocardiography showed lower pulmonary artery flow velocity, pulmonary acceleration time and ejection time values in group M, suggesting function worsening in those animals. Conclusion: The changes observed confirm pulmonary-arterial-hypertension-induced cardiac dysfunction, and point to fractal dimension as an effective method to evaluate cardiac morphological changes induced by ventricular dysfunction.

Chronic murine myocarditis due to Trypanosoma cruzi: an ultrastructural study and immunochemical characterization of cardiac interstitial matrix

In an attempt to define the mouse-model for chronic Chagas' disease, a serological, histopathological and ultrastructural study as well as immunotyping of myocardium collagenic matrix were performed on Swiss mice, chronically infected with Trypanosoma cruzi strains: 21 SF and mambaí (Type II); PMN and Bolivia (Type III), spontaneously surviving after 154 to 468 days of infection. Haemagglutination and indirect immunofluorescence tests showed high titres of specific antibodies. The ultrastructural study disclosed the cellular constitution of the inflammatory infiltrate showing the predominance of monocytes, macrophages with intense phagocytic activity, fibroblasts, myofibroblasts and abundant collagen matrix suggesting the association of the inflammatory process with fibrogenesis in chronic chagasic cardiomyopathy. Artertolar and blood capillary alterations together with dissociation of cardiac cells from the capillary wall by edema and inflammation were related to ultrastructural lesions of myocardial cells. Rupture of parasitized cardiac myocells contribute to intensify the inflammatory process in focal areas. Collagen immunotyping showed the predominance of Types III and IV collagen. Collagen degradation and phagocytosis were present suggesting a reversibility of the fibrous process. The mouse model seems to be valuable in the study of the pathogenetic mechanisms in Chagas cardiomyopathy, providing that T. cruzi strains of low virulence and high pathogenecity are used.

Reversibility of cardiac fibrosis in mice chronically infected with Trypanosoma cruzi, under specific chemotherapy

This investigation was performed to verify the effect of specific chemotherapy (Benznidazole or MK-346) on the inflammatory and fibrotic cardiac alterations in mice chronically infected with the strains 21 SF (Type II) and Colombian (Type III) of Trypanosoma cruzi. To obtain chronically infected mice, two groups of 100 Swiss mice each, were infected with either the 21 SF or the Colombian strain (2x 10 [raised to the power of] 4 and 5x 10 [raised to the power of] 4 blood forms respectively). The rate of morality in the acute phase was of 80% for both groups. Twenty surviving mice chronically infected with the 21 SF strain and 20 with the Colombian strain were then divided in treated and untreated groups. Excluding those that died during the course of treatment, 14 mice chronically infected with the 21 SF strain and 15 with the Colombian strain were evaluated in the present study. Chemotherapy was performed with Benznidazole (N-benzil-2-nitro-1-imidazolacetamide) in the dose of 100mg/k.b.w/day, for 60 days, or with the MK-436(3(1-methyl-5 nitroimidazol-2-yl) in two daily doses of 250 mg/k.b.w, for 20 days. Parasitological cure tests were performed (xenodiagnosis, haemoculture, subinovulation of the blood into newborn mice), and serological indirect immunofluorescence test. The treated and untreated mice as well as intact controls were killed at different periods after treatment and the heart were submitted to histopathological study with hematoxilineosin and picrosirius staining; ultrastructural study; collagen immunotyping, fibronectin and laminin identification by immunofluorescence tests. Results: the untreated controls either infected with 21 SF or Colombian strain, showed inflammatory and fibrotic alterations that were mild to moderate with the 21 SF strain and intense with the Colombian strain. Redpicrosirius staining showed bundles of collagen in the interstitial space and around cardiac fibers. Increased deposits of mitritial components and collagen fibers, macrophages and fibroblasts appeared at the ultra structural examination. Deposits of fibronectin, laminin, pro-III and IV collagens were seen, most intense in those infected with the Colombian strain. Treated nice, parasitologically cured, presented clear-cut regression of the inflammatory lesions and of the interstitial matrix thickening. Mice infected with the Colombian strain and treated with MK-436, was parasitologically cured in 5/6 cases and showed mild inflammatory infiltration and fibrosis. The mice treated with Benznidazole (Colombian strain) did not cure and showed moderate fibrosis and inflammation. Treatment of the nice infected with the 21 SF with Benznidazole determined parasitological cure of all animals, that showed mild inflammation and fibrosis of the myocardium. The cured mice of all groups and treated but uncured showed collagen degradation at electronmicroscopy and decrease of immunofluorescence pattern of the matrix.

Cardiac glycosides isolated from the Indian-snuff, Maquira sclerophylla Ducke

The hydroalcoholic extract of the powdered bark of the Indian-snuff Maquira sclerophylla Ducke was purified by column chromatography in silica-gel and the major cardenolide isolated from preparative TLC was identified by 1H-NMR, 1 2 C-NMR and IR analyses. The spectra showed that the active substance has strophanthidin as aglicone.

Detection of Trypanosoma cruzi DNA within murine cardiac tissue sections by in situ polymerase chain reaction

The use of in situ techniques to detect DNA and RNA sequences has proven to be an invaluable technique with paraffin-embedded tissue. Advances in non-radioactive detection systems have further made these procedures shorter and safer. We report the detection of Trypanosoma cruzi, the causative agent of Chagas disease, via indirect and direct in situ polymerace chain reaction within paraffin-embedded murine cardiac tissue sections. The presence of three T. cruzi specific DNA sequences were evaluated: a 122 base pair (bp) sequence localized within the minicircle network, a 188 bp satellite nuclear repetitive sequence and a 177 bp sequence that codes for a flagellar protein. In situ hybridization alone was sensitive enough to detect all three T. cruzi specific DNA sequences.

Trypanosoma cruzi high infectivity in vitro is related to cardiac lesions during long-term infection in Beagledogs

Trypanosoma cruzi is a hemoflagelate parasite associated with heart dysfunctions causing serious problems in Central and South America. Beagle dogs develop the symptoms of Chagas disease in humans, and could be an important experimental model for better understanding the immunopathogenic mechanisms involved in the chagasic infection. In the present study we investigated the relation among biological factors inherent to the parasite (trypomastigote polymorphism and in vitro infectivity) and immunoglobulin production, inflammation, and fibrosis in the heart of Beagle dogs infected with either T. cruzi Y or Berenice-78 strains. In vitro infectivity of Vero cells as well as the extension of cardiac lesions in infected Beagle was higher for Y strain when compared to Berenice-78 strain. These data suggested that in vitro infectivity assays may correlate with pathogenicity in vivo. In fact, animals infected with Y strain, which shows prevalence of slender forms and high infectivity in vitro, presented cardiomegaly, inflammation, and fibrosis in heart area. Concerning the immunoglobulin production, no statistically significant difference was observed for IgA, IgM or IgG levels among T. cruzi infected animals. However, IgA together IgM levels have shown to be a good marker for the acute phase of Chagas disease.

Benznidazole biotransformation in rat heart microsomal fraction without observable ultrastructural alterations: comparison to Nifurtimox-induced cardiac effects

Benznidazole (Bz) and Nifurtimox (Nfx) have been used to treat Chagas disease. As recent studies have de-monstrated cardiotoxic effects of Nfx, we attempted to determine whether Bz behaves similarly. Bz reached the heart tissue of male rats after intragastric administration. No cytosolic Bz nitroreductases were detected, although microsomal NADPH-dependent Bz nitroreductase activity was observed, and appeared to be mediated by P450 reductase. No ultrastructurally observable deleterious effects of Bz were detected, in contrast to the overt cardiac effects previously reported for Nfx. In conclusion, when these drugs are used in chagasic patients, Bz may pose a lesser risk to heart function than Nfx when any cardiopathy is present.

Immunological imbalance between IFN-³ and IL-10 levels in the sera of patients with the cardiac form of Chagas disease

The immune response is crucial for protection against disease; however, immunological imbalances can lead to heart and digestive tract lesions in chagasic patients. Several studies have evaluated the cellular and humoral immune responses in chagasic patients in an attempt to correlate immunological findings with clinical forms of Chagas disease. Moreover, immunoglobulins and cytokines are important for parasitic control and are involved in lesion genesis. Here, cytokine and IgG isotype production were studied, using total epimastigote antigen on sera of chagasic patients with indeterminate (IND, n = 27) and cardiac (CARD, n = 16) forms of the disease. Samples from normal, uninfected individuals (NI, n = 30) were use as controls. The results showed that sera from both IND and CARD patients contained higher levels of Trypanosoma cruzi-specific IgG1 (IgG1) antibodies than sera from NI. No difference in IgG2 production levels was observed between NI, IND and CARD patients, nor was a difference in IL-10 and IFN-³ production detected in the sera of IND, CARD and NI patients. However, IND patients displayed a positive correlation between IL-10 and IFN-³ levels in serum, while CARD patients showed no such correlation, indicating an uncontrolled inflammatory response in CARD patients. These findings support the hypothesis that a lack of efficient regulation between IFN-³ and IL-10 productions in CARD patients may lead to cardiac immunopathology.