CARLOS EDUARDO NEGRAO
Projetos de Pesquisa
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EFB, EEFE - Docente
Instituto do Coração, Hospital das Clínicas, Faculdade de Medicina
Instituto do Coração, Hospital das Clínicas, Faculdade de Medicina
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conferenceObject Influence of the concentration and molecular composition on the LDL and HDL functional characteristics in patients with the metabolic syndrome(2012) CASELLA-FILHO, Antonio; TROMBETTA, Ivani C.; CASELLA, Lia B.; DENARDI, Celise; DOURADO, Paulo; SEGRE, Alexandre; ROEVER-BORGES, Leonardo; NEGRAO, Carlos Eduardo; MARANHAO, Raul; CHAGAS, Antonio CarlosIntroduction: Long-term exercise associated with diet changes lipoproteins plasma levels. Objectives: We sought to analize the effects of short-term exercise training without any specific diet (T) on the concentration,composition and functional characteristics of LDL and HDL in patients with metabolic syndrome (MS). Methods: Forty sedentary persons were studied,30 with MS and 10 controls.Twenty of those with MS were subjected to a 3 times/week controlled training load (45 min/day) for 3 months on a bicycle ergometer.LDL and HDL subfractions were obtained by plasma ultracentrifugation 1 and their compositions were analyzed. LDL from control subjects was incubated with HDL2a,HDL3b from the MS patients (before and after T) and the in vitro resistance to oxidation was verified. An artificial lipoprotein emulsion (LDE) labeled with 14C-phospholipid, 3 H-triglycerides, 14 C-cholesterol and 3 H-cholesteryl ester was incubated with plasma from the participants. After precipitation of VLDL, LDL and LDE the HDL-containing supernatant was counted for radioactivity to verify the HDL ability to accept lipids. 2 Results: T decreased triglycerides (TG) but did not change apoB,apoA-I,LDL-C and HDL-C plasma levels. LDL resistance to oxidation increased (+91%) after T,associated with a decrease in the LDL content of apoB (-16%) and TG (-14%) and in the concentration of the small and dense LDL particles. Oxidizability of control LDL decreased when mixed with HDL2a or 3b from patients with MS, before vs. after T (-23% for HDL2a and -18% for HDL3b),associated with an increase in PON1 activity in the MS group (58.3±36.2 before vs.70.7±38.4ng/ml/min after T, p<0.05) and with a significant decrease in the content of total cholesterol (TC) and TG in HDL3b and HDL3c but with an increase in cholesterol ester (CE) in HDL3b. T did not significantly modify concentrations of TC and TG in HDL2a, 2b and 3a. Phospholipids and total protein content did not change in all HDL subfractions.T significantly increased free cholesterol and CE transfer from LDE to HDL in MS group to levels similar to those observed in controls. Conclusion: In patients with the MS, T influences the LDL and HDL functionality by earlier changes in molecular composition rather than their concentration, emphasizing the early benefits of exercise and highlighting the importance of evaluating the functional aspects of the lipoproteins besides their plasma levels- Android to gynoid fat ratio and its association with functional capacity in male patients with heart failure(2020) SANTOS, Marcelo Rodrigues Dos; FONSECA, Guilherme Wesley Peixoto da; SHERVENINAS, Leticia Pironato; SOUZA, Francis Ribeiro de; BATTAGLIA FILHO, Antonio Carlos; NOVAES, Caio Eduardo; PEREIRA, Rosa Maria Rodrigues; NEGRAO, Carlos Eduardo; BARRETTO, Antonio Carlos Pereira; ALVES, Maria-Janieire de Nazare NunesAims We studied the association between android (A) to gynoid (G) fat ratio and functional capacity (peak VO2) in male patients with heart failure with reduced ejection fraction (HFrEF). Methods and results We enrolled 118 male patients with HFrEF with left ventricular ejection fraction (LVEF) <40%. Body composition (by using dual x-ray absorptiometry) and peak VO2 (by cardiopulmonary exercise testing) were measured. Sarcopenic obesity was defined according to the Foundation for the National Institutes of Health criteria (FNIH). Blood sample for metabolic and hormonal parameters were measured. Fifteen patients (12.7%) showed sarcopenic obesity (body mass index > 25 kg/m(2) with FNIH index < 0.789). The median A/G ratio was 0.55. A/G ratio > 0.55 was detected in 60 patients. Relative peak VO2 was lower in patients with A/G ratio > 0.55 than in patients with A/G ratio <0.55 (18.7 +/- 5.3 vs. 22.5 +/- 6.1 mL/kg/min, P < 0.001). Logistic regression analysis showed A/G ratio >0.55 to be independently associated with reduced peak VO2 adjusted for age, body mass index, LVEF, presence of sarcopenia, anabolic hormones, and haemoglobin (odds ratio 3.895, 95% confidence interval 1.030-14.730, P = 0.045). Conclusions Body fat distribution, particularly android and gynoid fat composition, together with other cofactors, might have an important adverse role on functional capacity in male patients with HFrEF. Future studies are needed to address possible mechanisms involved in this relationship.
- Mechanisms of Blunted Muscle Vasodilation During Peripheral Chemoreceptor Stimulation in Heart Failure Patients(2012) ALVES, M. J. N. N.; SANTOS, Marcelo Rodrigues dos; NOBRE, Thais Simoes; MARTINEZ, Dg; BARRETTO, Antonio Carlos Pereira; BRUM, Patricia Chakur; RONDON, Maria Urbana P. B.; MIDDLEKAUFF, Holly R.; NEGRAO, Carlos EduardoWe described recently that systemic hypoxia provokes vasoconstriction in heart failure (HF) patients. We hypothesized that either the exaggerated muscle sympathetic nerve activity and/or endothelial dysfunction mediate the blunted vasodilatation during hypoxia in HF patients. Twenty-seven HF patients and 23 age-matched controls were studied. Muscle sympathetic nerve activity was assessed by microneurography and forearm blood flow (FBF) by venous occlusion plethysmography. Peripheral chemoreflex control was evaluated through the inhaling of a hypoxic gas mixture (10% O-2 and 90% N-2). Basal muscle sympathetic nerve activity was greater and basal FBF was lower in HF patients versus controls. During hypoxia, muscle sympathetic nerve activity responses were greater in HF patients, and forearm vasodilatation in HF was blunted versus controls. Phentolamine increased FBF responses in both groups, but the increase was lower in HF patients. Phentolamine and N-G-monomethyl-L-arginine infusion did not change FBF responses in HF but markedly blunted the vasodilatation in controls. FBF responses to hypoxia in the presence of vitamin C were unchanged and remained lower in HF patients versus controls. In conclusion, muscle vasoconstriction in response to hypoxia in HF patients is attributed to exaggerated reflex sympathetic nerve activation and blunted endothelial function (NO activity). We were unable to identify a role for oxidative stress in these studies. (Hypertension. 2012; 60: 669-676.) . Online Data Supplement
- Brazilian Cardio-oncology Guideline-2020(2020) HAJJAR, Ludhmila Abrahao; COSTA, Isabela Bispo Santos da Silva da; LOPES, Marcelo Antonio Cartaxo Queiroga; HOFF, Paulo Marcelo Gehm; DIZ, Maria Del Pilar Estevez; FONSECA, Silvia Moulin Ribeiro; BITTAR, Cristina Salvadori; REHDER, Marilia Harumi Higuchi dos Santos; RIZK, Stephanie Itala; ALMEIDA, Dirceu Rodrigues; FERNANDES, Gustavo S. Santos; BECK-DA-SILVA, Luis; CAMPOS, Carlos Augusto Homem de Magalhaes; MONTERA, Marcelo Westerlund; ALVES, Silvia Marinho Martins; FUKUSHIMA, Julia Tizue; SANTOS, Maria Veronica Camara dos; NEGRAO, Carlos Eduardo; SILVA, Thiago Liguori Feliciano da; FERREIRA, Silvia Moreira Ayub; MALACHIAS, Marcus Vinicius Bolivar; MOREIRA, Maria da Consolacao Vieira; VALENTE NETO, Manuel Maria Ramos; FONSECA, Veronica Cristina Quiroga; SOEIRO, Maria da Carolina Feres de Almeida; ALVES, Juliana Barbosa Sobral; SILVA, Carolina Maria Pinto Domingues Carvalho; SBANO, Joao; PAVANELLO, Ricardo; PINTO, Ibraim Masciarelli F.; SIMAO, Antonio Felipe; DRACOULAKIS, Marianna Deway Andrade; HOFF, Ana Oliveira; ASSUNCAO, Bruna Morhy Borges Leal; NOVIS, Yana; TESTA, Laura; ALENCAR FILHO, Aristoteles Comte de; CRUZ, Cecilia Beatriz Bittencourt Viana; PEREIRA, Juliana; GARCIA, Diego Ribeiro; NOMURA, Cesar Higa; ROCHITTE, Carlos Eduardo; MACEDO, Ariane Vieira Scarlatelli; MARCATTI, Patricia Tavares Felipe; MATHIAS JUNIOR, Wilson; WIERMANN, Evanius Garcia; VAL, Renata do; FREITAS, Helano; COUTINHO, Anelisa; MATHIAS, Clarissa Maria de Cerqueira; VIEIRA, Fernando Meton de Alencar Camara; SASSE, Andre Deeke; ROCHA, Vanderson; RAMIRES, Jose Antonio Franchini; KALIL FILHO, Roberto
conferenceObject EFFECT OF EXERCISE TRAINING ON PLATELET AGGREGATION AND ON P2Y12 INHIBITOR RESISTANCE AFTER MYOCARDIAL INFARCTION: A RANDOMIZED CLINICAL TRIAL(2020) DALCOQUIO, Talia; FURTADO, Remo Holanda de Mendonca; ARANTES, Flavia Bittar Britto Britto; SANTOS, Mayara Alves dos; ALVES, Leandro Silva; RONDON, Maria Urbana Pinto Brandao; FERREIRA-SANTOS, Larissa; ALVES, Maria Janieire de Nazare Nunes; FERRARI, Aline Gehlen; GENESTRETI, Paulo Rizzo; BARACIOLI, Luciano Moreira; FRANCI, Andre; SALSOSO, Rocio; NEGRAO, Carlos Eduardo; NICOLAU, Jose Carlos- PBMCs express a transcriptome signature predictor of oxygen uptake responsiveness to endurance exercise training in men(2015) DIAS, Rodrigo Goncalves; SILVA, Michelle Sabrina Moreira; DUARTE, Nubia Esteban; BOLANI, Wladimir; ALVES, Cleber Rene; LEMOS JUNIOR, Jose Ribeiro; SILVA, Jeferson Luis da; OLIVEIRA, Patricia Alves de; ALVES, Guilherme Barreto; OLIVEIRA, Edilamar Menezes de; ROCHA, Cristiane Souza; MARSIGLIA, Julia Daher Carneiro; NEGRAO, Carlos Eduardo; KRIEGER, Eduardo Moacyr; KRIEGER, Jose Eduardo; PEREIRA, Alexandre CostaPeripheral blood cells are an accessible environment in which to visualize exercise-induced alterations in global gene expression patterns. We aimed to identify a peripheral blood mononuclear cell (PBMC) signature represented by alterations in gene expression, in response to a standardized endurance exercise training protocol. In addition, we searched for molecular classifiers of the variability in oxygen uptake ((V) over dotO(2)). Healthy untrained policemen recruits (n = 13, 25 +/- 3 yr) were selected. Peak (V) over dotO(2) (measured by cardiopulmonary exercise testing) and total RNA from PBMCs were obtained before and after 18 wk of running endurance training (3 times/wk, 60 min). Total RNA was used for whole genome expression analysis using Affymetrix GeneChip Human Gene 1.0 ST. Data were normalized by the robust multiarray average algorithm. Principal component analysis was used to perform correlations between baseline gene expression and (V) over dotO(2peak). A set of 211 transcripts was differentially expressed (ANOVA, P < 0.05 and fold change > 1.3). Functional enrichment analysis revealed that transcripts were mainly related to immune function, cell cycle processes, development, and growth. Baseline expression of 98 and 53 transcripts was associated with the absolute and relative (V) over dotO(2)peak response, respectively, with a strong correlation (r > 0.75, P < 0.01), and this panel was able to classify the 13 individuals according to their potential to improve oxygen uptake. A subset of 10 transcripts represented these signatures to a similar extent. PBMCs reveal a transcriptional signature responsive to endurance training. Additionally, a baseline transcriptional signature was associated with changes in (V) over dotO(2peak). Results might illustrate the possibility of obtaining molecular classifiers of endurance capacity changes through a minimally invasive blood sampling procedure.
- Effects of Aerobic Exercise Training on Cardiac Renin-Angiotensin System in an Obese Zucker Rat Strain(2012) BARRETTI, Diego Lopes Mendes; MAGALHAES, Flavio de Castro; FERNANDES, Tiago; CARMO, Everton Crivoi do; ROSA, Kaleizu Teodoro; IRIGOYEN, Maria Claudia; NEGRAO, Carlos Eduardo; OLIVEIRA, Edilamar MenezesObjective: Obesity and renin angiotensin system (RAS) hyperactivity are profoundly involved in cardiovascular diseases, however aerobic exercise training (EXT) can prevent obesity and cardiac RAS activation. The study hypothesis was to investigate whether obesity and its association with EXT alter the systemic and cardiac RAS components in an obese Zucker rat strain. Methods: The rats were divided into the following groups: Lean Zucker rats (LZR); lean Zucker rats plus EXT (LZR+EXT); obese Zucker rats (OZR) and obese Zucker rats plus EXT (OZR+EXT). EXT consisted of 10 weeks of 60-min swimming sessions, 5 days/week. At the end of the training protocol heart rate (HR), systolic blood pressure (SBP), cardiac hypertrophy (CH) and function, local and systemic components of RAS were evaluated. Also, systemic glucose, triglycerides, total cholesterol and its LDL and HDL fractions were measured. Results: The resting HR decreased (, 12%) for both LZR+EXT and OZR+EXT. However, only the LZR+EXT reached significance (p, 0.05), while a tendency was found for OZR versus OZR+EXT (p = 0.07). In addition, exercise reduced (57%) triglycerides and (61%) LDL in the OZR+EXT. The systemic angiotensin I-converting enzyme (ACE) activity did not differ regardless of obesity and EXT, however, the OZR and OZR+EXT showed (66%) and (42%), respectively, less angiotensin II (Ang II) plasma concentration when compared with LZR. Furthermore, the results showed that EXT in the OZR prevented increase in CH, cardiac ACE activity, Ang II and AT2 receptor caused by obesity. In addition, exercise augmented cardiac ACE2 in both training groups. Conclusion: Despite the unchanged ACE and lower systemic Ang II levels in obesity, the cardiac RAS was increased in OZR and EXT in obese Zucker rats reduced some of the cardiac RAS components and prevented obesity-related CH. These results show that EXT prevented the heart RAS hyperactivity and cardiac maladaptive morphological alterations in obese Zucker rats.
- Exercise-Induced Muscle Vasodilatation and Treadmill Exercise Test Responses in Individuals without Overt Heart Disease(2014) NUNES, Rafael Amorim Belo; GIAMPAOLI, Viviana; FREITAS, Humberto Felicio Goncalves de; PEREIRA, Alexandre da Costa; ARAUJO, Fernando; CORREIA, Gustavo Ferreira; RONDON, Maria Urbana Pinto Brandao; NEGRAO, Carlos Eduardo; MANSUR, Alfredo JoseBackground:The beneficial effects of exercise on cardiovascular health may be related to the improvement in several physiologic pathways, including peripheral vascular function. The aim of this study was to evaluate the relationship between cardiovascular responses during the treadmill exercise test and exercise-induced muscle vasodilatation in individuals without overt heart disease. Methods: The study included 796 asymptomatic subjects (431 females and 365 males) without overt heart disease. We evaluated the heart rate (chronotropic reserve and heart rate recovery), blood pressure (maximum systolic and diastolic blood pressure as well as systolic blood pressure recovery) and exercise capacity during symptom-limited treadmill exercise testing. Exercise-induced muscle vasodilatation was studied with venous occlusion plethysmography and estimated by forearm blood flow and vascular conductance responses during a 3-min handgrip maneuver. Results: Forearm blood flow increase during the handgrip exercise was positively associated with heart rate recovery during treadmill exercise testing (p < 0.001). Forearm vascular conductance increase during the handgrip exercise was inversely associated with exercise diastolic blood pressure during exercise treadmill testing (p = 0.038). No significant association was found between exercise capacity and exercise-induced muscle vasodilation. Conclusion: In a sample of individuals without overt heart disease, exercise-induced muscle vasodilatation was associated with heart rate and blood pressure responses during treadmill exercise testing, but was not associated with exercise capacity. These findings suggest that favorable hemodynamic and chronotropic responses are associated with better vasodilator capacity, but exercise capacity does not predict muscle vasodilatation. (C) 2013 S. Karger AG, Basel
- Diminished cholesterol efflux mediated by HDL and coronary artery disease in young male anabolic androgenic steroid users(2019) SOUZA, Francis Ribeiro de; SANTOS, Marcelo Rodrigues Dos; PORELLO, Rafael Armani; FONSECA, Guilherme Wesley Peixoto da; SAYEGH, Ana Luiza Carrari; LIMA, Thais Pinheiro; FERREIRA, Fabiana Dias; OLIVEIRA, Tiago Franco de; YONAMINE, Mauricio; TAKAYAMA, Liliam; PEREIRA, Rosa Maria Rodrigues; NEGRAO, Carlos Eduardo; PASSARELLI, Marisa; ROCHITTE, Carlos Eduardo; ALVES, Maria Janieire de Nazare NunesBackground and aims: Anabolic androgenic steroids (AAS) have been associated with coronary artery disease (CAD). AAS abuse leads to a remarkable decrease in high-density lipoprotein (HDL) plasma concentration, which could be a key factor in the atherosclerotic process. Moreover, not only the concentration of HDL, but also its functionality, plays a pivotal role in CAD. We tested the functionality of HDL by cholesterol efflux and antioxidant capacity. We also evaluated the prevalence of CAD in AAS users. Methods: Twenty strength-trained AAS users (AASU) age 29 +/- 5 yr, 20 age-matched strength-trained AAS nonusers (AASNU), and 10 sedentary controls (SC) were enrolled in this cross-sectional study. Functionality of HDL was evaluated by C-14-cholesterol efflux and the ability of HDL in inhibiting LDL oxidation. Coronary artery was evaluated with coronary computed tomography angiography. Results: Cholesterol efflux was lower in AASU compared with AASNU and SC (20 vs. 23 vs. 24%, respectively, p < 0.001). However, the lag time for LDL oxidation was higher in AASU compared with AASNU and SC (41 vs 13 vs 11 min, respectively, p < 0.001). We found at least 2 coronary arteries with plaques in 25% of AASU. None of the AASNU and SC had plaques. The time of AAS use was negatively associated with cholesterol efflux. Conclusions: This study indicates that AAS abuse impairs the cholesterol efflux mediated by HDL. Long-term AAS use seems to be correlated with lower cholesterol efflux and early subclinical CAD in this population.
- Sympatho-Vagal Imbalance is Associated with Sarcopenia in Male Patients with Heart Failure(2019) FONSECA, Guilherme Wesley Peixoto da; SANTOS, Marcelo Rodrigues dos; SOUZA, Francis Ribeiro de; COSTA, Marcel Jose A. da; HAEHLING, Stephan von; TAKAYAMA, Liliam; PEREIRA, Rosa Maria R.; NEGRAO, Carlos Eduardo; ANKER, Stefan D.; ALVES, Maria Janieire de Nazare NunesBackground: Resting sympathetic hyperactivity and impaired parasympathetic reactivation after exercise have been described in patients with heart failure (HF). However, the association of these autonomic changes in patients with HF and sarcopenia is unknown. Objective: The aim of this study was to evaluate the impact of autonomic modulation on sarcopenia in male patients with HF. Methods: We enrolled 116 male patients with HF and left ventricular ejection fraction < 40%. All patients underwent a maximal cardiopulmonary exercise testing. Maximal heart rate was recorded and delta heart rate recovery (Delta HRR) was assessed at 1st and 2nd minutes after exercise. Muscle sympathetic nerve activity (MSNA) was recorded by microneurography. Dual-energy X-ray absorptiometry was used to measure body composition and sarcopenia was defined by the sum of appendicular lean muscle mass (ALM) divided by height in meters squared and handgrip strength. Results: Sarcopenia was identified in 33 patients (28%). Patients with sarcopenia had higher MSNA than those without (47 [41-52] vs. 40 [34-48] bursts/min, p = 0.028). Sarcopenic patients showed lower Delta HRR at 1st (15 [10-21] vs. 22 [16-30] beats/min, p < 0.001) and 2nd min (25 [19-39] vs. 35 [24-48] beats/min, p = 0.017) than non-sarcopenic. There was a positive correlation between ALM and HRR at 1st (r = 0.26, p = 0.008) and 2nd min (r = 0.25, p = 0.012). We observed a negative correlation between ALM and MSNA (r = -0.29, p = 0.003). Conclusion: Sympatho-vagal imbalance seems to be associated with sarcopenia in male patients with HF. These results highlight the importance of a therapeutic approach in patients with muscle wasting and increased peripheral sympathetic outflow.