CARLOS EDUARDO NEGRAO
Projetos de Pesquisa
Unidades Organizacionais
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
- Exercise Training Preserves Myocardial Strain and Improves Exercise Tolerance in Doxorubicin-Induced Cardiotoxicity(2021) GOMES-SANTOS, Igor L.; JORDAO, Camila P.; PASSOS, Clevia S.; BRUM, Patricia C.; OLIVEIRA, Edilamar M.; CHAMMAS, Roger; CAMARGO, Anamaria A.; NEGRAO, Carlos E.Doxorubicin causes cardiotoxicity and exercise intolerance. Pre-conditioning exercise training seems to prevent doxorubicin-induced cardiac damage. However, the effectiveness of the cardioprotective effects of exercise training concomitantly with doxorubicin treatment remains largely unknown. To determine whether low-to-moderate intensity aerobic exercise training during doxorubicin treatment would prevent cardiotoxicity and exercise intolerance, we performed exercise training concomitantly with chronic doxorubicin treatment in mice. Ventricular structure and function were accessed by echocardiography, exercise tolerance by maximal exercise test, and cardiac biology by histological and molecular techniques. Doxorubicin-induced cardiotoxicity, evidenced by impaired ventricular function, cardiac atrophy, and fibrosis. Exercise training did not preserve left ventricular ejection fraction or reduced fibrosis. However, exercise training preserved myocardial circumferential strain alleviated cardiac atrophy and restored cardiomyocyte cross-sectional area. On the other hand, exercise training exacerbated doxorubicin-induced body wasting without affecting survival. Finally, exercise training blunted doxorubicin-induced exercise intolerance. Exercise training performed during doxorubicin-based chemotherapy can be a valuable approach to attenuate cardiotoxicity.
conferenceObject Discriminating sarcopenia in male patients with heart failure: the influence of body mass index(2018) SANTOS, M. R. Dos; FONSECA, G. W. P.; SOUZA, F. R.; CASTRO, V. M.; TAKAYAMA, L.; PEREIRA, R. M. R.; NEGRAO, C. E.; ALVES, M. J. N. N.- Exercise training preserves vagal preganglionic neurones and restores parasympathetic tonus in heart failure(2016) ICHIGE, Marcelo H. A.; SANTOS, Carla R.; JORDAO, Camila P.; CERONI, Alexandre; NEGRAO, Carlos E.; MICHELINI, Lisete C.Exercise training is an efficient tool to attenuate sympathoexcitation, a hallmark of heart failure (HF). Although sympathetic modulation in HF is widely studied, information regarding parasympathetic control is lacking. We examined the combined effects of sympathetic and vagal tonus to the heart in sedentary (Sed) and exercise trained (ET) HF rats and the contribution of respective premotor and preganglionic neurones. Wistar rats submitted to coronary artery ligation or sham surgery were assigned to training or sedentary protocols for 6weeks. After haemodynamic, autonomic tonus (atropine and atenolol i.v.) and ventricular function determinations, brains were collected for immunoreactivity assays (choline acetyltransferase, ChATir; dopamine -hydroxylase, DBHir) and neuronal counting in the dorsal motor nucleus of vagus (DMV), nucleus ambiguus (NA) and rostroventrolateral medulla (RVLM). HF-Sed vs. SHAM-Sed exhibited decreased exercise capacity, reduced ejection fraction, increased left ventricle end diastolic pressure, smaller positive and negative dP/dt, decreased intrinsic heart rate (IHR), lower parasympathetic and higher sympathetic tonus, reduced preganglionic vagal neurones and ChATir in the DMV/NA, and increased RVLM DBHir. Training increased treadmill performance, normalized autonomic tonus and IHR, restored the number of DMV and NA neurones and corrected ChATir without affecting ventricular function. There were strong positive correlations between parasympathetic tonus and ChATir in NA and DMV. RVLM DBHir was also normalized by training, but there was no change in neurone number and no correlation with sympathetic tonus. Training-induced preservation of preganglionic vagal neurones is crucial to normalize parasympathetic activity and restore autonomic balance to the heart even in the persistence of cardiac dysfunction.
- Dynamic Cerebral Autoregulation Changes during Sub-Maximal Handgrip Maneuver(2013) NOGUEIRA, Ricardo C.; BOR-SENG-SHU, Edson; SANTOS, Marcelo R.; NEGRAO, Carlos E.; TEIXEIRA, Manoel J.; PANERAI, Ronney B.Purpose: We investigated the effect of handgrip (HG) maneuver on time-varying estimates of dynamic cerebral autoregulation (CA) using the autoregressive moving average technique. Methods: Twelve healthy subjects were recruited to perform HG maneuver during 3 minutes with 30% of maximum contraction force. Cerebral blood flow velocity, end-tidal CO2 pressure (PETCO2), and noninvasive arterial blood pressure (ABP) were continuously recorded during baseline, HG and recovery. Critical closing pressure (CrCP), resistance area-product (RAP), and time-varying autoregulation index (ARI) were obtained. Results: PETCO2 did not show significant changes during HG maneuver. Whilst ABP increased continuously during the maneuver, to 27% above its baseline value, CBFV raised to a plateau approximately 15% above baseline. This was sustained by a parallel increase in RAP, suggestive of myogenic vasoconstriction, and a reduction in CrCP that could be associated with metabolic vasodilation. The time-varying ARI index dropped at the beginning and end of the maneuver (p<0.005), which could be related to corresponding alert reactions or to different time constants of the myogenic, metabolic and/or neurogenic mechanisms. Conclusion: Changes in dynamic CA during HG suggest a complex interplay of regulatory mechanisms during static exercise that should be considered when assessing the determinants of cerebral blood flow and metabolism.
conferenceObject Effects of Aerobic and Inspiratory Training on Skeletal Muscle Microrna-1 and Downstream-Associated Pathways in Patients With Systolic Heart Failure(2019) ANTUNES-CORREA, Ligia M.; TREVIZAN, Patricia; BACURAU, Aline V.; FERREIRA-SANTOS, Larissa; GOMES, Joao L.; URIAS, Ursula; OLIVEIRA, Patricia; ALVES, Maria-Janieire N.; ALMEIDA, Dirceu R.; BRUM, Patricia C.; OLIVEIRA, Edilamar M.; HAJJAR, Ludhmila; KALIL FILHO, Roberto; NEGRAO, Carlos E.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