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
22 resultados
Resultados de Busca
Agora exibindo 1 - 10 de 22
- 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
- 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.
- 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
- Neurovascular Control and Cardiac Structure in Amateur Runners with Hypertension(2016) PERLINGEIRO, Patricia De Sa; AZEVEDO, Luciene Ferreira; GOMES-SANTOS, Igor Lucas; BORTOLOTTO, Luiz Aparecido; RONDON, Maria Urbana Pinto Brandao; NEGRAO, Carlos Eduardo; MATOS, Luciana Diniz Nagem Janot dePurpose The neurovascular mechanisms underlying hypertension are minimized by exercise training. However, it is not known whether previously trained individuals with hypertension would have deleterious repercussion of this disease. Our aim was to investigate the neurovascular control and the cardiac structure of athletes with hypertension. Methods Muscle sympathetic nerve activity (MSNA) (microneurography), baroreflex sensitivity (intravenous infusion of phenylephrine and nitroprusside), arterial stiffness (pulse wave velocity and echotracking), and cardiac structure (echocardiography) were evaluated in 17 runners with hypertension (42 1 yr) and 20 normotensive (43 1 yr) amateur runners. Results Runners with hypertension had higher MSNA (+24% burst frequency, P = 0.02; +24%, burst incidence, P < 0.01), left ventricular mass (+22%, P < 0.01), septum wall thickness (+9%, P = 0.04), posterior wall thickness (+11%, P = 0.04), and left atrium (+11%, P < 0.001) compared with normotensive runners. Baroreflex control of heart rate was lower in runners with hypertension during increase (P = 0.05) but not during decrease (P = 0.11) of systolic blood pressure when compared with normotensive runners. There was no difference between groups in baroreflex control of MSNA during increase (P = 0.38) and decrease (P = 0.36) of diastolic blood pressure. Pulse wave velocity (P = 0.71) and carotid variables: intima media thickness (P = 0.18), diameter (P = 0.09), and distension (P = 0.79) were similar between groups. Conclusions Sympathetic overactivity seems to be involved in the underlying mechanisms of hypertension in amateur runners. Alterations in cardiac structure and decreased baroreflex control of heart rate suggest limited protection from exercise training. However, baroreflex control of MSNA and elastic properties of artery are preserved in this population.
- Exercise Training Increases Metaboreflex Control in Patients with Obstructive Sleep Apnea(2019) GUERRA, Renan S.; GOYA, Thiago T.; SILVA, Rosyvaldo F.; LIMA, Marta F.; BARBOSA, Eline R. F.; ALVES, Maria Janieire De N. N.; RODRIGUES, Amanda G.; LORENZI-FILHO, Geraldo; NEGRAO, Carlos Eduardo; UENO-PARDI, Linda M.Introduction/Purpose We demonstrated that patients with obstructive sleep apnea (OSA) have reduced muscle metaboreflex control of muscle sympathetic nerve activity (MSNA). In addition, exercise training increased muscle metaboreflex control in heart failure patients. Objective We tested the hypothesis that exercise training would increase muscle metaboreflex control of MSNA in patients with OSA. Methods Forty-one patients with OSA were randomized into the following two groups: 1) nontrained (OSANT, n = 21) and 2) trained (OSAT, n = 20). Muscle sympathetic nerve activity was assessed by microneurography technique, muscle blood flow (FBF) by venous occlusion plethysmography, heart rate by electrocardiography, and blood pressure with an automated oscillometric device. All physiological variables were simultaneously assessed at rest, during isometric handgrip exercise at 30% of the maximal voluntary contraction, and during posthandgrip muscle ischemia (PHMI). Muscle metaboreflex sensitivity was calculated as the difference in MSNA between PHMI and the rest period. Patients in the OSAT group underwent 72 sessions of moderate exercise training, whereas patients in the OSANT group were clinical follow-up for 6 months. Results The OSANT and OSAT groups were similar in anthropometric, neurovascular, hemodynamic and sleep parameters. Exercise training reduced the baseline MSNA (34 2 bursts per minute vs 25 +/- 2 bursts per minute; P < 0.05) and increased the baseline FBF (2.1 +/- 0.2 mLmin(-1) per 100 g vs 2.4 +/- 0.2 mLmin(-1) per 100 g; P < 0.05). Exercise training significantly reduced MSNA levels and increased FBF responses during isometric exercise. Exercise training significantly increased MSNA responses during PHMI (6.5 +/- 1 vs -1.7 +/- 1 bursts per minute, P < 0.01). No significant changes in FBF or hemodynamic parameters in OSANT patients were found. Conclusions Exercise training increases muscle metaboreflex sensitivity in patients with OSA. This autonomic change associated with increased muscle blood flow may contribute to the increase in exercise performance in this set of patients.
- Effects of exercise training on neurovascular control and skeletal myopathy in systolic heart failure(2015) NEGRAO, Carlos E.; MIDDLEKAUFF, Holly R.; GOMES-SANTOS, Igor L.; ANTUNES-CORREA, Ligia M.Neurohormonal excitation and dyspnea are the hallmarks of heart failure (HF) and have long been associated with poor prognosis in HF patients. Sympathetic nerve activity (SNA) and ventilatory equivalent of carbon dioxide (VE/VO2) are elevated in moderate HF patients and increased even further in severe HF patients. The increase in SNA in HF patients is present regardless of age, sex, and etiology of systolic dysfunction. Neurohormonal activation is the major mediator of the peripheral vasoconstriction characteristic of HF patients. In addition, reduction in peripheral blood flow increases muscle inflammation, oxidative stress, and protein degradation, which is the essence of the skeletal myopathy and exercise intolerance in HF. Here we discuss the beneficial effects of exercise training on resting SNA in patients with systolic HF and its central and peripheral mechanisms of control. Furthermore, we discuss the exercise-mediated improvement in peripheral vasoconstriction in patients with HF. We will also focus on the effects of exercise training on ventilatory responses. Finally, we review the effects of exercise training on features of the skeletal myopathy in HF. In summary, exercise training plays an important role in HF, working synergistically with pharmacological therapies to ameliorate these abnormalities in clinical practice.
- Muscle electrical stimulation improves neurovascular control and exercise tolerance in hospitalised advanced heart failure patients(2016) GROEHS, Raphaela V.; ANTUNES-CORREA, Ligia M.; NOBRE, Thais S.; ALVES, Maria-Janieire N. N.; RONDON, Maria Urbana P. B.; BARRETO, Antonio Carlos Pereira; NEGRAO, Carlos E.Background We investigated the effects of muscle functional electrical stimulation on muscle sympathetic nerve activity and muscle blood flow, and, in addition, exercise tolerance in hospitalised patients for stabilisation of heart failure. Methods Thirty patients hospitalised for treatment of decompensated heart failure, class IV New York Heart Association and ejection fraction30% were consecutively randomly assigned into two groups: functional electrical stimulation (n=15; 542 years) and control (n=15; 492 years). Muscle sympathetic nerve activity was directly recorded via microneurography and blood flow by venous occlusion plethysmography. Heart rate and blood pressure were evaluated on a beat-to-beat basis (Finometer), exercise tolerance by 6-minute walk test, quadriceps muscle strength by a dynamometer and quality of life by Minnesota questionnaire. Functional electrical stimulation consisted of stimulating the lower limbs at 10Hz frequency, 150ms pulse width and 70 mA intensity for 60minutes/day for 8-10 consecutive days. The control group underwent electrical stimulation at an intensity of<20 mA. Results Baseline characteristics were similar between groups, except age that was higher and C-reactive protein and forearm blood flow that were smaller in the functional electrical stimulation group. Functional electrical stimulation significantly decreased muscle sympathetic nerve activity and increased muscle blood flow and muscle strength. No changes were found in the control group. Walking distance and quality of life increased in both groups. However, these changes were greater in the functional electrical stimulation group. Conclusion Functional electrical stimulation improves muscle sympathetic nerve activity and vasoconstriction and increases exercise tolerance, muscle strength and quality of life in hospitalised heart failure patients. These findings suggest that functional electrical stimulation may be useful to hospitalised patients with decompensated chronic heart failure.
- Chemotherapy acutely impairs neurovascular and hemodynamic responses in women with breast cancer(2019) SALES, Allan Robson Kluser; NEGRAO, Marcelo Vailati; TESTA, Laura; FERREIRA-SANTOS, Larissa; GROEHS, Raphaela Villar Ramalho; CARVALHO, Bruna; TOSCHI-DIAS, Edgar; ROCHA, Natalia Galito; LAURINDO, Francisco Rafael Martins; DEBBAS, Victor; RONDON, Maria Urbana P. B.; MANO, Max Sena; HAJJAR, Ludhmila Abrahao; HOFF, Paulo Marcelo Gehm; KALIL FILHO, Roberto; NEGRAO, Carlos EduardoThe purpose of the present study was to test the hypothesis that doxorubicin (DX) and cyclophosphamide (CY) adjuvant chemotherapy (CHT) acutely impairs neurovascular and hemodynamic responses in women with breast cancer. Sixteen women (age: 47.0 +/- 2.0 yr; body mass index: 24.2 +/- 1.5 kg/m) with stage II-III breast cancer and indication for adjuvant CHT underwent two experimental sessions, saline (SL) and CHT. In the CHT session, DX (60 mg/m (2)) and CY (600 mg/m(2)) were administered over 45 min. In the SL session, a matching SL volume was infused in 45 min. Muscle sympathetic nerve activity (MSNA) from peroneal nerve (microneurography), calf blood flow (CBF; plethysmography) and calf vascular conductance (CVC), heart rate (HR; electrocardiography), and beat-to-beat blood pressure (BP: finger plethysmography) were measured at rest before, during, and after each session. Venous blood samples (5 ml) were collected before and after both sessions for assessment of circulating endothelial microparticles (EMPs: flow cytometry). a surrogate marker for endothelial damage. MSNA and BP responses were increased (P < 0.001), whereas CBF and CVC responses were decreased (P < 0.001), during and after CHT session when compared with SL session. Interestingly, the vascular alterations were also observed at the molecular level through an increased EMP response to CHT (P = 0.03, CHT vs. SL session). No difference in HR response was observed (P > 0.05). Adjuvant CHT with DX and CY in patients treated for breast cancer increases sympathetic nerve activity and circulating EMP levels and, in addition, reduces muscle vascular conductance and elevates systemic BP. These responses may be early signs of CHT-induced cardiovascular alterations and may represent potential targets for preventive interventions. NEW & NOTEWORTHY It is known that chemotherapy regimens increase the risk of cardiovascular events in patients treated for cancer. Here, we identified that a single cycle of adjuvant chemotherapy with doxorubicin and cyclophosphamide in women treated for breast cancer dramatically increases sympathetic nerve activity and circulating endothelial microparticle levels, reduces the muscle vascular conductance, and elevates systemic blood pressure.
- Arousals Are Frequent and Associated With Exacerbated Blood Pressure Response in Patients With Primary Hypertension(2013) GARCIA, Carlos E. V.; DRAGER, Luciano F.; KRIEGER, Eduardo M.; NEGRAO, Carlos E.; BORTOLOTTO, Luiz A.; LORENZI-FILHO, Geraldo; UENO, Linda M.BACKGROUND Spontaneous arousals are relatively common during sleep, and induce hemodynamic responses. We sought to investigate the frequency and magnitude of blood pressure (BP) increases triggered by spontaneous arousals in patients with primary hypertension. METHODS We conducted a study in which we divided 18 nonobese, sedentary adults without sleep-disordered breathing into two groups, consisting of: (i) hypertensive (HT, n = 8) patients; and (ii) normotensive (NT, n = 10) controls. The groups were matched for age and body mass index. All subjects underwent full polysomnography with simultaneous monitoring of heart rate (HR) and beat-by-beat BR Each subject's BP and HR were analyzed immediately before BP peaks triggered by spontaneous arousals during stage 2 of nonrapid eye movement sleep. RESULTS The total sleep time, sleep efficiency, and sleep structure in the two study groups were similar. In contrast, the number of arousals was significantly higher in the HT than in the NT group, at 25 +/- 5 vs. 12 +/- 3 events/h, respectively (P < 0.05). The HR of the HT and NT groups was similar before arousal (65 +/- 3 bpm vs. 67 +/- 3 bpm, respectively, P < 0.01) and increased significantly and similarly in the two groups upon arousal (to 79 +/- 6 bpm vs. 74 +/- 4 bpm, respectively, P < 0.01). Systolic and diastolic BPs were significantly higher throughout sleep in the HT than in the NT group. During spontaneous arousals, BP increased in both groups (P < 0.05). However, the magnitude of the increase in systolic BP was significantly greater in the HT than in the NT group (22 +/- 3 mm Hg vs. 15 +/- 3 mm Hg, P < 0.05). CONCLUSIONS Patients with hypertension who do not have sleep-disordered breathing have an increased cardiovascular burden during sleep, which may be due to the greater number of arousals and exacerbated systolic BP response that they experience during sleep. These novel findings may have cardiovascular implications in patients with hypertension.
- Neurovascular and hemodynamic responses to mental stress and exercise in severe COVID-19 survivors(2023) FARIA, Diego; MOLL-BERNARDES, Renata; TESTA, Laura; MONIZ, Camila M. V.; RODRIGUES, Erika C.; MOTA, Jose M.; SOUZA, Francis R.; ALVES, Maria Janieire N. N.; ONO, Bruna E.; IZAIAS, Joao E.; SALES, Artur O.; RODRIGUES, Thais S.; SALEMI, Vera M. C.; JORDAO, Camila P.; ANGELIS, Katia De; CRAIGHEAD, Daniel H.; ROSSMAN, Matthew J.; BORTOLOTTO, Luiz A.; CONSOLIM-COLOMBO, Fernanda M.; IRIGOYEN, Maria C. C.; SEALS, Douglas R.; NEGRAO, Carlos E.; SALES, Allan R. K.Previous studies show that COVID-19 survivors have elevated muscle sympathetic nerve activity (MSNA), endothelial dysfunction, and aortic stiffening. However, the neurovascular responses to mental stress and exercise are still unexplored. We hypothesized that COVID-19 survivors, compared with age-and body mass index (BMI)-matched control subjects, exhibit abnormal neurovascular responses to mental stress and physical exercise. Fifteen severe COVID-19 survivors (aged: 49 +/- 2 yr, BMI: 30 +/- 1 kg/m(2)) and 15 well-matched control subjects (aged: 46 +/- 3 yr, BMI: 29 +/- 1 kg/m(2)) were studied. MSNA (microneurography), forearm blood flow (FBF), and forearm vascular conductance (FVC, venous occlusion plethysmography), mean arterial pressure (MAP, Finometer), and heart rate (HR, ECG) were measured during a 3-min mental stress (Stroop Color-Word Test) and during a 3-min isometric handgrip exercise (30% of maximal voluntary contraction). During mental stress, MSNA (frequency and incidence) responses were higher in COVID-19 survivors than in controls (P < 0.001), and FBF and FVC responses were attenuated (P < 0.05). MAP was similar between the groups (P > 0.05). In contrast, the MSNA (frequency and incidence) and FBF and FVC responses to handgrip exercise were similar between the groups (P > 0.05). MAP was lower in COVID-19 survivors (P < 0.05). COVID-19 survivors exhibit an exaggerated MSNA and blunted vasodilatory response to mental challenge compared with healthy adults. However, the neurovascular response to handgrip exercise is preserved in COVID-19 survivors. Overall, the abnormal neurovascular control in response to mental stress suggests that COVID-19 survivors may have an increased risk to cardiovascular events during mental challenge.
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