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3.
Expert Opin Drug Saf ; 18(5): 393-402, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-31074301

RESUMO

INTRODUCTION: Heart failure with reduced ejection fraction (HFrEF) is associated with a worse outcome. Heart rate (HR) is related to outcome in HFrEF. Ivabradine selectively inhibits If (funny) channels in a concentration-dependent manner reducing HR. AREAS COVERED: The effects of ivabradine in HF were reviewed. The SHIFT trial results indicated that ivabradine improves chronic HFrEF outcomes, whereas published data suggest that amiodarone, digoxin, or verapamil may not be safe or the safety is controversial in HFrEF patients. In the CONSTATHE-DHF study, ivabradine reduced HR and improved left ventricular (LV) ejection fraction, LV diastolic functions, and right ventricle function in acute decompensated HF (ADHF). In chagasic patients, ivabradine reduced HR and a trend toward reduction in all-cause death was observed with ivabradine (p = 0.07). In children with HFrEF, ivabradine increased NYHA functional class. The most common side effects with ivabradine are bradycardia, atrial fibrillation, and phosphenes. Ivabradine was approved for HFrEF treatment by the EMA and FDA and seems to be cost-effective in HFrEF treatment. Ivabradine is indicated for HFrEF by the ESC HF Guidelines (IIa) and by the 2016 ACC/AHA/HFSA Guidelines (IIa-B-R). EXPERT OPINION: Published evidences demonstrate that ivabradine improves the outcome of chronic HFrEF and it seems to have a promising role in ADHF.


Assuntos
Fármacos Cardiovasculares/administração & dosagem , Insuficiência Cardíaca/tratamento farmacológico , Ivabradina/administração & dosagem , Animais , Fármacos Cardiovasculares/efeitos adversos , Fármacos Cardiovasculares/farmacologia , Relação Dose-Resposta a Droga , Insuficiência Cardíaca/fisiopatologia , Frequência Cardíaca/efeitos dos fármacos , Humanos , Ivabradina/efeitos adversos , Ivabradina/farmacologia , Guias de Prática Clínica como Assunto , Volume Sistólico/efeitos dos fármacos , Função Ventricular Esquerda/efeitos dos fármacos
5.
Int J Cardiovasc Imaging ; 35(5): 845-854, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30623354

RESUMO

Cardiac involvement in systemic light chain (AL) amyloidosis carries a poor prognosis mainly through involvement of the left ventricular (LV) myocardium. Despite its limitations, two-dimensional transthoracic echocardiography (2D-TTE) remains the main tool used for the assessment of LV systolic function in AL patients. We hypothesize that 3D-TTE coupled with speckle tracking imaging allows earlier detection of LV systolic dysfunction than 2D-TTE in AL amyloidosis. We prospectively studied 71 subjects including 58 patients with confirmed AL amyloidosis (mean age 66 ± 10 years, 60% male) and 21 healthy control (mean age 64 ± 7 years, 48% male) from 2011 to 2014 at the University Hospital of Limoges. The AL patients were divided into three groups according to Mayo Clinic (MC) staging and all subjects underwent 2D-TTE and 3D-TTE at the same setting. Using 2D-TTE, there was no significant difference in LV ejection fraction (EF) between the groups [LVEF = 63 ± 7% (control), 59 ± 6% (MC stage I), 60 ± 8% (MC stage II) and 57 ± 14% (MC stage III) (p = 0.24)]. In contrast, 3D-TTE demonstrated significantly worse LV systolic function in stage II and III patients using 3D-LVEF [MC II and III 45 ± 8% and 39 ± 12% vs. control 53 ± 8% (p < 0.0001)], global longitudinal strain (GLS) [MC II and III - 11 ± 4% and - 8 ± 3% vs. control - 15 ± 3% (p < 0.0001)] and global radial strain (GRS) [MC II and III 14 ± 9% and 10 ± 8% vs. control 25 ± 10% (p < 0.0001)]. Furthermore, MC III patients had significantly worse global circumferential strain and area tracking [- 17 ± 6% and - 25 ± 8% vs. - 24 ± 7% and - 36 ± 7% for control (p < 0.0001)]. Additionally, MC I had significantly better 3D GLS, GRS and global strain (- 15 ± 3%, 25 ± 10% and 28 ± 12%) than MC II (- 11 ± 4%, 14 ± 9% and 16 ± 10%) and MC III patients (- 8 ± 3%, 10 ± 8% and 12 ± 8%), respectively. Despite an apparently preserved LVEF by 2D-TTE, AL patients in MC stage II and III demonstrate evidence of LV systolic dysfunction by 3D imaging using LVEF and strain analysis. Worse LV involvement by AL amyloidosis was associated with more impaired 3D-TTE LV systolic parameters.


Assuntos
Cardiomiopatias/diagnóstico por imagem , Ecocardiografia Tridimensional , Amiloidose de Cadeia Leve de Imunoglobulina/diagnóstico por imagem , Volume Sistólico , Disfunção Ventricular Esquerda/diagnóstico por imagem , Função Ventricular Esquerda , Idoso , Cardiomiopatias/imunologia , Cardiomiopatias/fisiopatologia , Estudos de Casos e Controles , Bases de Dados Factuais , Diagnóstico Precoce , Feminino , Humanos , Amiloidose de Cadeia Leve de Imunoglobulina/imunologia , Amiloidose de Cadeia Leve de Imunoglobulina/fisiopatologia , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Estudos Prospectivos , Reprodutibilidade dos Testes , Índice de Gravidade de Doença , Sístole , Disfunção Ventricular Esquerda/imunologia , Disfunção Ventricular Esquerda/fisiopatologia
7.
PLoS One ; 13(9): e0202731, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30192778

RESUMO

The study aimed at evaluating the effects of combined aerobic and resistance exercise training on cardiac morphometry and function, oxidative stress and inflammatory parameters in diabetic ovariectomized rats. For this, female Wistar rats (10 weeks-old) were divided into 4 groups (n = 8): euglycemic (E), diabetic (streptozotocin, 50 mg/kg, iv) (D), diabetic ovariectomized (DO) and trained diabetic ovariectomized (TDO). The combined exercise training was performed on a treadmill and in a ladder adapted to rats (8 weeks, at 40-60% of maximal capacity). The left ventricle (LV) morphometry and function were evaluated by echocardiography. Oxidative stress and inflammatory markers were measured on ventricles tissue. The sedentary diabetic animals (D and DO) showed impaired systolic and diastolic functions, as well as increased cardiac overload, evaluated by myocardial performance index (MPI- D: 0.32 ± 0.05; DO: 0.39 ± 0.13 vs. E: 0.25 ± 0.07), in relation to E group. Systolic and MPI dysfunctions were exacerbated in DO when compared to D group. The DO group presented higher protein oxidation and TNF-α/IL-10 ratio than D groups. Glutathione redox ratio (GSH/GSSG) and IL-10 were decreased in both D and DO groups when compared to E group. Exercise training improved exercise capacity, systolic and diastolic functions and MPI (0.18±0.11). The TDO group showed reduced protein oxidation and TNF-α/IL-10 ratio and increased GSH/GSSG and IL-10 in relation to the DO group. These results showed that combined exercise training was able to attenuate the cardiac dysfunctions, probably by reducing inflammation and oxidative stress in an experimental model of diabetes and menopause.


Assuntos
Diabetes Mellitus/fisiopatologia , Coração/fisiopatologia , Menopausa , Treinamento de Resistência , Animais , Diabetes Mellitus/metabolismo , Diabetes Mellitus/terapia , Feminino , Estresse Oxidativo , Ratos , Ratos Wistar
8.
PLoS Negl Trop Dis ; 12(2): e0006207, 2018 02.
Artigo em Inglês | MEDLINE | ID: mdl-29432453

RESUMO

AIMS: Explore the association between clinical findings and prognosis in patients with acute decompensated heart failure (ADHF) and analyze the influence of etiology on clinical presentation and prognosis. METHODS AND RESULTS: Prospective cohort of 500 patients admitted with ADHF from Aug/2013-Feb/2016; patients were predominantly male (61.8%), median age was 58 (IQ25-75% 47-66 years); etiology was dilated cardiomyopathy in 141 (28.2%), ischemic heart disease in 137 (27.4%), and Chagas heart disease in 113 (22.6%). Patients who died (154 [30.8%]) or underwent heart transplantation (53[10.6%]) were younger (56 years [IQ25-75% 45-64 vs 60 years, IQ25-75% 49-67], P = 0.032), more frequently admitted for cardiogenic shock (20.3% vs 6.8%, P<0.001), had longer duration of symptoms (14 days [IQ25-75% 4-32.8 vs 7.5 days, IQ25-75% 2-31], P = 0.004), had signs of congestion (90.8% vs 76.5%, P<0.001) and inadequate perfusion more frequently (45.9% vs 28%, P<0.001), and had lower blood pressure (90 [IQ25-75% 80-100 vs 100, IQ25-75% 90-120], P<0.001). In a logistic regression model analysis, systolic blood pressure (P<0.001, OR 0.97 [95%CI 0.96-0.98] per mmHg) and jugular distention (P = 0.004, OR 1.923 [95%CI 1.232-3.001]) were significant. Chagas patients were more frequently admitted for cardiogenic shock (15%) and syncope/arrhythmia (20.4%). Pulmonary congestion was rare among Chagas patients and blood pressure was lower. The rate of in-hospital death or heart transplant was higher among patients with Chagas (50.5%). CONCLUSIONS: A physical exam may identify patients at higher risk in a contemporaneous population. Our findings support specific therapies targeted at Chagas patients in the setting of ADHF.


Assuntos
Cardiomiopatia Chagásica/patologia , Insuficiência Cardíaca/patologia , Função Ventricular , Idoso , Cardiomiopatia Chagásica/mortalidade , Feminino , Hospitalização , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Prospectivos , Análise de Sobrevida
9.
Can J Physiol Pharmacol ; 96(6): 541-549, 2018 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-29120671

RESUMO

Myocardial remodeling includes inappropriate collagen deposition in the interstitium. Erythropoietin (EPO) may have cardioprotective effects. We aimed to assess the role of EPO on myocardial remodeling during the chronic phase. We studied 60 Wistar rats divided into the following groups: control (CT), control + EPO (CT + EPO), myocardial infarction + EPO (MI + EPO), and myocardial infarction (MI). The interstitial collagen volume fraction (ICVF) was quantified and echocardiography was performed. We quantified asymmetric dimethylarginine and glutathione by ELISA, and used real-time PCR to assess apoptosis and inflammation. Western blotting was used to evaluate inflammatory proteins and tissue inhibitors of metalloproteinases (TIMPs), and TUNEL staining was used to detect apoptosis. For matrix metalloproteinases (MMPs), we performed zymography. Parametric and nonparametric analyses were performed according to normality testing. ICVF was greater in MI groups (p < 0.001) and was attenuated by EPO (p = 0.05). The MMP-2 did not show any difference between groups. The TIMP-1 and TIMP-2 did not have difference between groups. The MI groups had worse fraction shortening (p < 0.001), without EPO protection (p = 0.666). The MI groups had increased left ventricle diastolic dimension (p < 0.001) without EPO attenuation (p = 0.79). EPO did not act on oxidative stress. Apoptosis and inflammation were not modulated by EPO. We concluded that EPO attenuated interstitial collagen accumulation, but did not protect from heart dilation or dysfunction.


Assuntos
Colágeno/metabolismo , Eritropoetina/farmacologia , Coração/efeitos dos fármacos , Infarto do Miocárdio/metabolismo , Miocárdio/metabolismo , Animais , Apoptose/efeitos dos fármacos , Arginina/análogos & derivados , Arginina/metabolismo , Diástole/efeitos dos fármacos , Glutationa/metabolismo , Coração/fisiopatologia , Hematócrito , Hemoglobinas/metabolismo , Masculino , Infarto do Miocárdio/patologia , Miocárdio/patologia , Estresse Oxidativo/efeitos dos fármacos , Ratos
10.
Open Heart ; 5(2): e000923, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30687507

RESUMO

Objectives: The prognostic significance of transient use of inotropes has been sufficiently studied in recent heart failure (HF) populations. We hypothesised that risk stratification in these patients could contribute to patient selection for advanced therapies. Methods: We analysed a prospective cohort of adult patients admitted with decompensated HF and ejection fraction (left ventricular ejection fraction (LVEF)) less than 50%. We explored the outcomes of patients requiring inotropic therapy during hospital admission and after discharge. Results: The study included 737 patients, (64.0% male), with a median age of 58 years (IQR 48-66 years). Main aetiologies were dilated cardiomyopathy in 273 (37.0%) patients, ischaemic heart disease in 195 (26.5%) patients and Chagas disease in 163 (22.1%) patients. Median LVEF was 26 % (IQR 22%-35%). Inotropes were used in 518 (70.3%) patients. In 431 (83.2%) patients, a single inotrope was administered. Inotropic therapy was associated with higher risk of in-hospital death/urgent heart transplant (OR=10.628, 95% CI 5.055 to 22.344, p<0.001). At 180-day follow-up, of the 431 patients discharged home, 39 (9.0%) died, 21 (4.9%) underwent transplantation and 183 (42.4%) were readmitted. Inotropes were not associated with outcome (death, transplant and rehospitalisation) after discharge. Conclusions: Inotropic drugs are still widely used in patients with advanced decompensated HF and are associated with a worse in-hospital prognosis. In contrast with previous results, intermittent use of inotropes during hospitalisation did not determine a worse prognosis at 180-day follow-up. These data may add to prognostic evaluation in patients with advanced HF in centres where mechanical circulatory support is not broadly available.

11.
Am J Physiol Heart Circ Physiol ; 313(4): H795-H809, 2017 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-28710069

RESUMO

Increase in oxidative/nitrosative stress is one of the mechanisms associated with the development of cardiotoxicity due to doxorubicin (Dox), a potent chemotherapy drug. Previously, we reported mitigation of Dox-induced oxidative/nitrosative stress and apoptosis by vitamin C (Vit C) in isolated cardiomyocytes. In the present in vivo study in rats, we investigated the effect of prophylactic treatment with Vit C on Dox-induced apoptosis, inflammation, oxidative/nitrosative stress, cardiac dysfunction, and Vit C transporter proteins. Dox (cumulative dose: 15 mg/kg) in rats reduced systolic and diastolic cardiac function and caused structural damage. These changes were associated with a myocardial increase in reactive oxygen species, reduction in antioxidant enzyme activities, increased expression of apoptotic proteins, and inflammation. Dox also caused an increase in the expression of proapoptotic proteins Bax, Bnip-3, Bak, and caspase-3. An increase in oxidative/nitrosative stress attributable to Dox was indicated by an increase in superoxide, protein carbonyl formation, lipid peroxidation, nitric oxide (NO), NO synthase (NOS) activity, protein nitrosylation, and inducible NOS protein expression. Dox increased the levels of cardiac proinflammatory cytokines TNF-α, IL-1ß, and IL-6, whereas the expression of Vit C transporter proteins (sodium-ascorbate cotransporter 2 and glucose transporter 4) was reduced. Prophylactic and concurrent treatment with Vit C prevented all these changes and improved survival in the Vit C + Dox group. Vit C also improved Dox-mediated systolic and diastolic dysfunctions and structural damage. These results suggest a cardioprotective role of Vit C in Dox-induced cardiomyopathy by reducing oxidative/nitrosative stress, inflammation, and apoptosis, as well as improving Vit C transporter proteins.NEW & NOTEWORTHY This in vivo study provides novel data that vitamin C improves cardiac structure and function in doxorubicin-induced cardiomyopathy by reducing oxidative/nitrosative stress, apoptosis, and inflammation along with upregulation of cardiac vitamin C transporter proteins. The latter may have a crucial role in improving antioxidant status in this cardiomyopathy.


Assuntos
Anti-Inflamatórios não Esteroides/farmacologia , Antibióticos Antineoplásicos , Antioxidantes/farmacologia , Ácido Ascórbico/farmacologia , Cardiomiopatias/induzido quimicamente , Cardiomiopatias/tratamento farmacológico , Cardiotônicos/farmacologia , Doxorrubicina , Estresse Oxidativo/efeitos dos fármacos , Estresse Fisiológico/efeitos dos fármacos , Animais , Citocinas/biossíntese , Eletrocardiografia/efeitos dos fármacos , Masculino , Óxido Nítrico Sintase/biossíntese , Óxido Nítrico Sintase/metabolismo , Consumo de Oxigênio/efeitos dos fármacos , Ratos , Ratos Wistar , Espécies Reativas de Nitrogênio , Análise de Sobrevida
12.
Eur Heart J Cardiovasc Imaging ; 18(8): 915-921, 2017 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-28379356

RESUMO

Aims: The pathophysiological mechanisms of left ventricular non-compaction cardiomyopathy (LVNC) remain controversial. This study performed combined 18F-fluoro-2-deoxyglucose dynamic positron emission tomography (FDG-PET) and 99mTc-sestamibi single-photon emission computed tomography (SPECT) studies to evaluate myocardial glucose metabolism and perfusion in patients with LVNC and their clinical implications. Methods and results: Thirty patients (41 ± 12 years, 53% male) with LVNC, diagnosed by cardiovascular magnetic resonance (CMR) criteria, and eight age-matched healthy controls (42 ± 12 years, 50% male) were prospectively recruited to undergo FDG-PET with measurement of the myocardial glucose uptake rate (MGU) and SPECT to investigate perfusion-metabolism patterns. Patients with LVNC had lower global MGU compared with that in controls (36.9 ± 8.8 vs. 44.6 ± 5.4 µmol/min/100 g, respectively, P = 0.02). Of 17 LV segments, MGU levels were significantly reduced in 8, and also a reduction was observed when compacted segments from LVNC were compared with the segments from control subjects (P < 0.001). Perfusion defects were also found in 15 (50%) patients (45 LV segments: 64.4% match, and 35.6% mismatch perfusion-metabolism pattern). Univariate and multivariate analyses showed that beta-blocker therapy was associated with increased MGU (beta coefficient = 10.1, P = 0.008). Moreover, a gradual increase occurred in MGU across the beta-blocker dose groups (P for trend = 0.01). Conclusion: The reduction of MGU documented by FDG-PET in LVNC supports the hypothesis that a cellular metabolic pathway may play a role in the pathophysiology of LVNC. The beneficial effect of beta-blocker mediating myocardial metabolism in the clinical course of LVNC requires further investigation.


Assuntos
Miocárdio Ventricular não Compactado Isolado/diagnóstico por imagem , Miocárdio Ventricular não Compactado Isolado/fisiopatologia , Tomografia por Emissão de Pósitrons/métodos , Tomografia Computadorizada de Emissão de Fóton Único/métodos , Disfunção Ventricular Esquerda/diagnóstico por imagem , Adulto , Análise de Variância , Estudos de Casos e Controles , Estudos de Coortes , Feminino , Fluordesoxiglucose F18 , Glucose/metabolismo , Humanos , Aumento da Imagem , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Estudos Prospectivos , Índice de Gravidade de Doença , Volume Sistólico/fisiologia , Disfunção Ventricular Esquerda/fisiopatologia
13.
J Nutr Biochem ; 40: 219-227, 2017 02.
Artigo em Inglês | MEDLINE | ID: mdl-27951474

RESUMO

Cardiac remodeling in diabetes involves cardiac hypertrophy and fibrosis, and fibroblast growth factor 2 (FGF2) is an important mediator of this process. Resveratrol, a polyphenolic antioxidant, reportedly promotes the improvement of cardiac dysfunction in diabetic rats. However, little information exists linking the amelioration of the cardiac function promoted by resveratrol and the expression of FGF2 and its co-receptors, heparan sulfate proteoglycans (HSPGs: Glypican-1 and Syndecan-4), in cardiac muscle of Type 2 diabetic rats. Diabetes was induced experimentally by the injection of streptozotocin and nicotinamide, and the rats were treated with resveratrol for 6 weeks. According to our results, there is an up-regulation of the expression of genes and/or proteins of Glypican-1, Syndecan-4, FGF2, peroxisome proliferator-activated receptor gamma and AMP-activated protein kinase in diabetic rats. On the other hand, resveratrol treatment promoted the attenuation of left ventricular diastolic dysfunction and the down-regulation of the expression of all proteins under study. The trigger for the changes in gene expression and protein synthesis promoted by resveratrol was the presence of diabetes. The negative modulation conducted by resveratrol on FGF2 and HSPGs expression, which are involved in cardiac remodeling, underlies the amelioration of cardiac function.


Assuntos
Diabetes Mellitus Experimental/tratamento farmacológico , Fator 2 de Crescimento de Fibroblastos/metabolismo , Coração/fisiopatologia , Proteoglicanas de Heparan Sulfato/metabolismo , Estilbenos/farmacologia , Animais , Diabetes Mellitus Experimental/metabolismo , Diabetes Mellitus Experimental/fisiopatologia , Regulação para Baixo/efeitos dos fármacos , Regulação da Expressão Gênica/efeitos dos fármacos , Glipicanas/metabolismo , Coração/efeitos dos fármacos , Proteoglicanas de Heparan Sulfato/genética , Ratos Wistar , Resveratrol , Sindecana-4/metabolismo
14.
Clin. biomed. res ; 37(2): 73-80, 2017. graf, tab
Artigo em Inglês | LILACS | ID: biblio-847904

RESUMO

Introduction: The purpose of this study was to investigate the effects of isolated vitamin B6 (VB6 ) supplementation on experimental hyperhomocysteinemia (Hhe) induced by homocysteine thiolactone (HcyT). Methods: Fifteen male Wistar rats were divided into three groups according to their treatment. Animals received water and food ad libitum and an intragastric probe was used to administer water for 60 days (groups: CB6, HcyT, and HB6 ). On the 30th day of treatment, two groups were supplemented with VB6 in the drinking water (groups: CB6 and HB6 ). After 60 days of treatment, homocysteine (Hcy), cysteine, and hydrogen peroxide concentration, nuclear factor (erythroid-derived 2)-like 2 (NRF2) and glutathione S-transferase (GST) immunocontent, and superoxide dismutase (SOD), catalase (CAT), and GST activities were measured. Results: The HcyT group showed an increase in Hcy concentration (62%) in relation to the CB6 group. Additionally, GST immunocontent was enhanced (51%) in the HB6 group compared to the HcyT group. Also, SOD activity was lower (17%) in the HB6 group compared to the CB6 group, and CAT activity was higher in the HcyT group (53%) compared to the CB6 group. Ejection fraction (EF) was improved in the HB6 group compared to the HcyT group. E/A ratio was enhanced in the HB6 group compared to the CB6 group. Correlations were found between CAT activity with myocardial performance index (MPI) (r = 0.71; P = 0.06) and E/A ratio (r = 0.6; P = 0.01), and between EF and GST activity (r = 0.62; P = 0.02). Conclusions: These findings indicate that isolated VB6 supplementation may lead to the reduction of Hcy concentration and promotes additional benefits to oxidative stress and heart function parameters (AU)


Assuntos
Animais , Ratos , Coração/efeitos dos fármacos , Hiper-Homocisteinemia/tratamento farmacológico , Estresse Oxidativo/efeitos dos fármacos , Vitamina B 6/uso terapêutico , Doenças Cardiovasculares/etiologia , Modelos Animais , Ratos Wistar
15.
PLoS One ; 10(7): e0131447, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26147101

RESUMO

BACKGROUND: Chagas disease (CD) induces autonomic dysfunction and inflammatory activity, which may promote metabolic abnormalities. We studied metabolism and his correlation with Autonomic Nervous System (ANS) and inflammation in CD. METHODS AND RESULTS: Sixty subjects were divided into 4 groups: control group (CG), IF (indeterminate form) group; ECG group (ECG abnormalities and normal left ventricular systolic function), and LVD group (left ventricular sistolic dysfunction). Levels of adiponectin, leptin, insulin, interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF-alpha) were assayed in serum samples by ELISA. ANS was assessed by heart rate variability in frequency domain in 24-hour Holter and postural tilt test (rest and orthostatic position). High frequency (HFr) component values were used to estimate parasympathetic activity and low frequency (LFr) component, sympathetic activity. Analyzes were made of the correlations of each of the metabolic parameters (leptin and adiponectin) with the inflammatory cytokines (interleukin-6 and TNF- alpha) and with the ANS assessment measurements. No significant differences were observed in leptin and insulin levels. Adiponectin was higher in ECG and LVD groups: [CG = 4766.5 (5529.5), IF = 4003.5 (2482.5), ECG = 8376.5 (8388.5), LVD = 8798 (4188.0) ng/mL, p<0.001)]. IL-6 and TNF-alpha were higher in LVD group: [IL-6: CG = 1.85 (6.41); IF = 1.58 (1.91); ECG = 1.0 (1.57); LVD= 31.44 (72.19) pg/ml; p = 0.001. TNF-alpha: CG = 22.57 (88.2); IF = 19.31 (33.16); ECG = 12.45 (3.07); LVD = 75.15 (278.57) pg/ml; p = 0.04]. Adiponectin levels had a positive association with the HFr component (r = 0.539; p = 0.038) and an inverse association with the LFr component (r = - 0.539; p = 0.038) in ECG group. Leptin levels had a negative association with the HFr component (r= - 0.632; p = 0.011) and a positive association with the LFr component (r = 0.632; p = 0.011) in LVD group. CONCLUSIONS: We found increased adiponectin levels in Chagas' heart disease with systolic dysfunction and in patients with ECG abnormalities and normal systolic function at rest. Adipocytokines levels (adiponectin and leptin) were associated with ANS parameters in Chagas' heart disease.


Assuntos
Adipocinas/sangue , Sistema Nervoso Autônomo/fisiopatologia , Cardiomiopatia Chagásica/fisiopatologia , Inflamação/fisiopatologia , Disfunção Ventricular Esquerda/fisiopatologia , Adiponectina/sangue , Adulto , Cardiomiopatia Chagásica/sangue , Eletrocardiografia , Feminino , Coração/fisiopatologia , Frequência Cardíaca/fisiologia , Humanos , Inflamação/sangue , Insulina/sangue , Interleucina-6/sangue , Leptina/sangue , Masculino , Pessoa de Meia-Idade , Fator de Necrose Tumoral alfa/sangue , Disfunção Ventricular Esquerda/sangue
16.
BMC Cardiovasc Disord ; 15: 7, 2015 Jan 24.
Artigo em Inglês | MEDLINE | ID: mdl-25618133

RESUMO

BACKGROUND: Noncompaction cardiomyopathy (NCC) is a rare genetic cardiomyopathy characterized by a thin, compacted epicardial layer and an extensive noncompacted endocardial layer. The clinical manifestations of this disease include ventricular arrhythmia, heart failure, and systemic thromboembolism. CASE PRESENTATION: A 43-year-old male was anticoagulated by pulmonary thromboembolism for 1 year when he developed progressive dyspnea. Cardiovascular magnetic resonance imaging showed severe biventricular trabeculation with an ejection fraction of 15%, ratio of maximum noncompacted/compacted diastolic myocardial thickness of 3.2 and the presence of exuberant biventricular apical thrombus. CONCLUSION: Still under discussion is the issue of which patients and when they should be anticoagulated. It is generally recommended to those presenting ventricular systolic dysfunction, antecedent of systemic embolism, presence of cardiac thrombus and atrial fibrillation. In clinical practice the patients with NCC and ventricular dysfunction have been given oral anticoagulation, although there are no clinical trials showing the real safety and benefit of this treatment.


Assuntos
Arritmia Sinusal/etiologia , Cardiomiopatias/complicações , Cardiomiopatias/diagnóstico , Trombose Coronária/etiologia , Embolia Pulmonar/etiologia , Disfunção Ventricular/etiologia , Adulto , Arritmia Sinusal/diagnóstico por imagem , Angiografia Coronária , Ecocardiografia , Coração/diagnóstico por imagem , Humanos , Angiografia por Ressonância Magnética , Masculino , Miocárdio/patologia , Tomografia Computadorizada por Raios X
17.
PLoS One ; 9(5): e98012, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-24859374

RESUMO

BACKGROUND: Accumulated evidence shows that the ACE-AngII-AT1 axis of the renin-angiotensin system (RAS) is markedly activated in chronic heart failure (CHF). Recent studies provide information that Angiotensin (Ang)-(1-7), a metabolite of AngII, counteracts the effects of AngII. However, this balance between AngII and Ang-(1-7) is still little understood in CHF. We investigated the effects of exercise training on circulating and skeletal muscle RAS in the ischemic model of CHF. METHODS/MAIN RESULTS: Male Wistar rats underwent left coronary artery ligation or a Sham operation. They were divided into four groups: 1) Sedentary Sham (Sham-S), 2) exercise-trained Sham (Sham-Ex), sedentary CHF (CHF-S), and exercise-trained CHF (CHF-Ex). Angiotensin concentrations and ACE and ACE2 activity in the circulation and skeletal muscle (soleus and plantaris) were quantified. Skeletal muscle ACE and ACE2 protein expression, and AT1, AT2, and Mas receptor gene expression were also evaluated. CHF reduced ACE2 serum activity. Exercise training restored ACE2 and reduced ACE activity in CHF. Exercise training reduced plasma AngII concentration in both Sham and CHF rats and increased the Ang-(1-7)/AngII ratio in CHF rats. CHF and exercise training did not change skeletal muscle ACE and ACE2 activity and protein expression. CHF increased AngII levels in both soleus and plantaris muscle, and exercise training normalized them. Exercise training increased Ang-(1-7) in the plantaris muscle of CHF rats. The AT1 receptor was only increased in the soleus muscle of CHF rats, and exercise training normalized it. Exercise training increased the expression of the Mas receptor in the soleus muscle of both exercise-trained groups, and normalized it in plantaris muscle. CONCLUSIONS: Exercise training causes a shift in RAS towards the Ang-(1-7)-Mas axis in skeletal muscle, which can be influenced by skeletal muscle metabolic characteristics. The changes in RAS circulation do not necessarily reflect the changes occurring in the RAS of skeletal muscle.


Assuntos
Insuficiência Cardíaca/sangue , Insuficiência Cardíaca/metabolismo , Músculo Esquelético/metabolismo , Condicionamento Físico Animal , Sistema Renina-Angiotensina , Angiotensina II/sangue , Angiotensina II/metabolismo , Animais , Insuficiência Cardíaca/fisiopatologia , Testes de Função Cardíaca , Masculino , Peptidil Dipeptidase A/sangue , Peptidil Dipeptidase A/metabolismo , Ratos , Ratos Wistar
18.
J Nucl Cardiol ; 21(3): 570-7, 2014 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-24627344

RESUMO

PURPOSE: High intensity systematic physical training leads to myocardial morphophysiological adaptations. The goal of this study was to investigate if differences in training were correlated with differences in cardiac sympathetic activity. METHODS: 58 males (19-47 years), were divided into three groups: strength group (SG), (20 bodybuilders), endurance group (EG), (20 endurance athletes), and a control group (CG) comprising 18 healthy non-athletes. Cardiac sympathetic innervation was assessed by planar myocardial (123)I-metaiodobenzylguanidine scintigraphy using the early and late heart to mediastinal (H/M) ratio, and washout rate (WR). RESULTS: Left ventricular mass index was significantly higher both in SG (P < .001) and EG (P = .001) compared to CG without a statistical significant difference between SG and EG (P = .417). The relative wall thickness was significantly higher in SG compared to CG (P < .001). Both left ventricular ejection fraction and the peak filling rate showed no significant difference between the groups. Resting heart rate was significantly lower in EG compared to CG (P = .006) and SG (P = .002). The late H/M ratio in CG was significantly higher compared to the late H/M for SG (P = .003) and EG (P = .004). However, WR showed no difference between the groups. There was no significant correlation between the parameters of myocardial sympathetic innervation and parameters of left ventricular function. CONCLUSIONS: Strength training resulted in a significant increase in cardiac dimensions. Both strength and endurance training seem to cause a reduction in myocardial sympathetic drive. However, myocardial morphological and functional adaptations to training were not correlated with myocardial sympathetic activity.


Assuntos
3-Iodobenzilguanidina , Frequência Cardíaca/fisiologia , Ventrículos do Coração/diagnóstico por imagem , Treinamento de Resistência/métodos , Esportes/fisiologia , Sistema Nervoso Simpático/fisiologia , Função Ventricular Esquerda/fisiologia , Adulto , Pressão Sanguínea/fisiologia , Ventrículos do Coração/inervação , Humanos , Pessoa de Meia-Idade , Tomografia por Emissão de Pósitrons/métodos , Compostos Radiofarmacêuticos , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Volume Sistólico/fisiologia , Adulto Jovem
19.
J Card Fail ; 19(7): 454-60, 2013 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-23834921

RESUMO

BACKGROUND: The influence of exercise on cardiac metabolic response in patients with Chagas disease is incompletely understood. METHODS AND RESULTS: Changes in cardiac energetic metabolism were investigated in Chagas disease patients before and during isometric handgrip exercise with (31)P magnetic resonance spectroscopy (MRS). Twenty-eight patients (10 with systolic dysfunction: group I; 10 with normal systolic function and electrocardiogram (ECG) abnormalities: group II; and 8 asymptomatic without ECG abnormalities: group III) and 8 healthy control subjects (group C) were evaluated by electrocardiogram, echocardiogram, functional tests for coronary artery disease, and image-selected localized cardiac (31)P-MRS. The myocardial phosphocreatine to [ß-phosphate]adenosine triphosphate ratio (PCr/ß-ATP) was measured at rest and during isometric handgrip exercise. Exercise testing or 99mTc-sestamibi scintigraphy were negative for myocardial ischemia in all individuals. At rest, cardiac PCr/ß-ATP was decreased in all Chagas groups (1.23 ± 0.37) versus group C (1.88 ± 0.08; P < .001) and was lower in group I (0.89 ± 0.24) versus groups II (1.44 ± 0.23) and III (1.40 ± 0.37; P < .001). There was no stress-induced change in cardiac PCr/ß-ATP (1.88 ± 0.08 at rest vs 1.89 ± 0.08 during exercise; P = NS) in group C. Mean cardiac PCr/ß-ATP was 0.89 ± 0.24 and 0.56 ± 0.21 at rest and during exercise, respectively, in group I (37% decrease; P < .001). In group II, PCr/ß-ATP was 1.44 ± 0.23 at rest and 0.97 ± 0.37 during exercise (33% decrease; P < .001). In group III, PCr/ß-ATP was 1.40 ± 0.37 at rest and 0.60 ± 0.19 during exercise (57% decrease; P < .001). CONCLUSIONS: Myocardial high-energy phosphates are reduced at rest in Chagas heart disease patients, and the reduction is greater in patients with left ventricular dysfunction. Regardless of left ventricular function, Chagas patients exhibit an exercise-induced decline in cardiac high-energy phosphates consistent with myocardial ischemia, suggesting the possibility that this metabolic approach may offer a tool to probe new interventions in Chagas disease patients.


Assuntos
Cardiomiopatia Chagásica/metabolismo , Teste de Esforço/métodos , Exercício/fisiologia , Miocárdio/metabolismo , Fosfatos/metabolismo , Adulto , Cardiomiopatia Chagásica/diagnóstico , Metabolismo Energético/fisiologia , Feminino , Força da Mão/fisiologia , Humanos , Espectroscopia de Ressonância Magnética/métodos , Masculino , Pessoa de Meia-Idade
20.
PLoS One ; 8(5): e62452, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-23658728

RESUMO

The use of ß-blockers is mandatory for counteracting heart failure (HF)-induced chronic sympathetic hyperactivity, cardiac dysfunction and remodeling. Importantly, aerobic exercise training, an efficient nonpharmacological therapy to HF, also counteracts sympathetic hyperactivity in HF and improves exercise tolerance and cardiac contractility; the latter associated with changes in cardiac Ca(2+) handling. This study was undertaken to test whether combined ß-blocker and aerobic exercise training would integrate the beneficial effects of isolated therapies on cardiac structure, contractility and cardiomyocyte Ca(2+) handling in a genetic model of sympathetic hyperactivity-induced HF (α2A/α2C- adrenergic receptor knockout mice, KO). We used a cohort of 5-7 mo male wild-type (WT) and congenic mice (KO) with C57Bl6/J genetic background randomly assigned into 5 groups: control (WT), saline-treated KO (KOS), exercise trained KO (KOT), carvedilol-treated KO (KOC) and, combined carvedilol-treated and exercise-trained KO (KOCT). Isolated and combined therapies reduced mortality compared with KOS mice. Both KOT and KOCT groups had increased exercise tolerance, while groups receiving carvedilol had increased left ventricular fractional shortening and reduced cardiac collagen volume fraction compared with KOS group. Cellular data confirmed that cardiomyocytes from KOS mice displayed abnormal Ca(2+) handling. KOT group had increased intracellular peak of Ca(2+) transient and reduced diastolic Ca(2+) decay compared with KOS group, while KOC had increased Ca(2+) decay compared with KOS group. Notably, combined therapies re-established cardiomyocyte Ca(2+) transient paralleled by increased SERCA2 expression and SERCA2:PLN ratio toward WT levels. Aerobic exercise trained increased the phosphorylation of PLN at Ser(16) and Thr(17) residues in both KOT and KOCT groups, but carvedilol treatment reduced lipid peroxidation in KOC and KOCT groups compared with KOS group. The present findings provide evidence that the combination of carvedilol and aerobic exercise training therapies lead to a better integrative outcome than carvedilol or exercise training used in isolation.


Assuntos
Antagonistas Adrenérgicos beta/farmacologia , Carbazóis/farmacologia , Terapia por Exercício , Insuficiência Cardíaca/terapia , Contração Miocárdica , Propanolaminas/farmacologia , Antagonistas Adrenérgicos beta/uso terapêutico , Animais , Pressão Sanguínea , Sinalização do Cálcio , Carbazóis/uso terapêutico , Carvedilol , Células Cultivadas , Terapia Combinada , Avaliação Pré-Clínica de Medicamentos , Tolerância ao Exercício , Insuficiência Cardíaca/metabolismo , Insuficiência Cardíaca/fisiopatologia , Frequência Cardíaca , Peroxidação de Lipídeos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Miocárdio/metabolismo , Miocárdio/patologia , Miócitos Cardíacos/metabolismo , Estresse Oxidativo , Condicionamento Físico Animal , Propanolaminas/uso terapêutico , ATPases Transportadoras de Cálcio do Retículo Sarcoplasmático/metabolismo , Remodelação Ventricular
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