LIGIA DE MORAES ANTUNES CORREA
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- Effects of the exercise training on skeletal muscle oxygen consumption in heart failure patients with reduced ejection fraction(2021) GUIMARAES, Guilherme Veiga; RIBEIRO, Fernando; CASTRO, Rafael Ertner; ROQUE, Jean Marcelo; MACHADO, Alexander Douglas Teixeira; ANTUNES-CORREA, Ligia M.; FERREIRA, Silvia Ayub; BOCCHI, Edimar AlcidesAims: Skeletal muscle dysfunction is a systemic consequence of heart failure (HF) that correlates with functional capacity. However, the impairment within the skeletal muscle is not well established. We investigated the effect of exercise training on peripheral muscular performance and oxygenation in HF patients. Methods and results: HF patients with ejection fraction <= 40% were randomized 2:1 to exercise training or control for 12 weeks. Muscle tissue oxygen was measured noninvasively by near-infrared spectroscopy (NIPS) during rest and a symptom-limited cardiopulmonary exercise test (CPET) before and after intervention. Measurements included skeletal muscle oxygenated hemoglobin concentration, deoxygenated hemoglobin concentration, total hemoglobin concentration, VO2 peak, VE/VCO2 slope, and heart rate. Muscle sympathetic nerve activity by microneurography, and muscle blood flow by plethysmography were also assessed at rest pre and post 12 weeks. Twenty-four participants (47.5 +/- 7.4 years, 58% men, 75% no ischemic) were allocated to exercise training (ET, n = 16) or control (CG, n = 8). At baseline, no differences between groups were found. Exercise improved VO2 peak, slope VE/VCO2, and heart rate. After the intervention, significant improvements at rest were seen in the ET group in muscle sympathetic nerve activity and muscle blood flow. Concomitantly, a significant decreased in Oxy-Hb (from 29.4 +/- 20.4 to 15.7 +/- 9.0 mu mol, p = 0.01), Deoxi-Hb (from 16.3 +/- 8.2 to 12.2 +/- 6.0 mu mol, p = 0.003) and HbT (from 45.7 +/- 27.6 to 27.7 +/- 13.4 mu mol, p = 0.008) was detected at peak exercise after training. No changes were observed in the control group. Conclusion: Exercise training improves skeletal muscle function and functional capacity in HF patients with reduced ejection fraction. This improvement was associated with increased oxygenation of the peripheral muscles, increased muscle blood flow, and decreased sympathetic nerve activity.
- Exercise training prevents the deterioration in the arterial baroreflex control of sympathetic nerve activity in chronic heart failure patients(2015) GROEHS, Raphaela V.; TOSCHI-DIAS, Edgar; ANTUNES-CORREA, Ligia M.; TREVIZAN, Patricia F.; RONDON, Maria Urbana P. B.; OLIVEIRA, Patricia; ALVES, Maria J. N. N.; ALMEIDA, Dirceu R.; MIDDLEKAUFF, Holly R.; NEGRAO, Carlos E.Arterial baroreflex control of muscle sympathetic nerve activity (ABRMSNA) is impaired in chronic systolic heart failure (CHF). The purpose of the study was to test the hypothesis that exercise training would improve the gain and reduce the time delay of ABRMSNA in CHF patients. Twenty-six CHF patients, New York Heart Association Functional Class II-III, EF <= 40%, peak (V) over dot O-2 <= 20 ml.kg(-1).min(-1) were divided into two groups: untrained (UT, n = 13, 57 +/- 3 years) and exercise trained (ET, n = 13, 49 +/- 3 years). Muscle sympathetic nerve activity (MSNA) was directly recorded by microneurography technique. Arterial pressure was measured on a beat-to-beat basis. Time series of MSNA and systolic arterial pressure were analyzed by autoregressive spectral analysis. The gain and time delay of ABRMSNA was obtained by bivariate autoregressive analysis. Exercise training was performed on a cycle ergometer at moderate intensity, three 60-min sessions per week for 16 wk. Baseline MSNA, gain and time delay of ABRMSNA, and low frequency of MSNA (LFMSNA) to high-frequency ratio (HFMSNA) (LFMSNA/HFMSNA) were similar between groups. ET significantly decreased MSNA. MSNA was unchanged in the UT patients. The gain and time delay of ABRMSNA were unchanged in the ET patients. In contrast, the gain of ABRMSNA was significantly reduced [3.5 +/- 0.7 vs. 1.8 +/- 0.2, arbitrary units (au)/mmHg, P = 0.04] and the time delay of ABRMSNA was significantly increased (4.6 +/- 0.8 vs. 7.9 +/- 1.0 s, P = 0.05) in the UT patients. LFMSNA-to-HFMSNA ratio tended to be lower in the ET patients (P < 0.08). Exercise training prevents the deterioration of ABRMSNA in CHF patients.
- 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.
- Cardiac resynchronization therapy restores muscular metaboreflex control(2019) SPAGGIARI, Caio V.; KUNIYOSHI, Ricardo R.; ANTUNES-CORREA, Ligia M.; GROEHS, Raphaela V.; SIQUEIRA, Sergio F. de; MARTINELLI FILHO, MartinoIntroduction The muscular metaboreflex, whose activation regulates blood flow during isometric and aerobic exercise, is blunted in patients with heart failure (HF), and cardiac resynchronization therapy (CRT) may restore this regulatory reflex. Objective To evaluate metaboreflex responses after CRT. Methods Thirteen HF patients and 12 age-matched healthy control subjects underwent the following evaluations (pre- and post-CRT implantation in the patient group): (a) heart rate, blood pressure, and forearm blood flow measurements; (b) muscle sympathetic nerve activity (MSNA) evaluation; and (c) peak oxygen consumption (VO2peak). Examinations were performed at rest, during moderate isometric exercise (IE), and during forearm ischemia (metaboreflex activation). The primary outcome was the increment in MSNA during limb ischemia compared to the rest moment (Delta MSNA rest to metaboreflex activation). Results After CRT, rest MSNA decreased in the HF participants: 50.4 +/- 9.2 bursts/min pre-CRT vs 34.0 +/- 14.4 bursts/min post-CRT, P = .001, accompanied by an improvement in systolic blood pressure and in rate-pressure product. MSNA during limb ischemia decreased: 56.6 +/- 11.5 bursts/min pre-CRT vs 43.6 +/- 12.7 bursts/min post-CRT, P = .001, and the Delta MSNA rest to metaboreflex activation increased: 0% (interquartile range [IQR)], -7 to 9) vs 13% (IQR, 5-30), P = .03. An augmentation of mean blood pressure during limb ischemia post-CRT was noticed: 94 mmHg (IQR, 81-104) vs 110 mmHg (IQR, 100-117), P = .04. CRT improved VO2peak, and this improvement was correlated with diminution in Delta MSNA pre- to post-CRT at rest moment (r(s) = -0.74, P = .006). Conclusion CRT provides metaboreflex sensitization and MSNA enhancement. The restoration of sympathetic responsiveness correlates with the improvement in functional capacity.
- The influence of aetiology on the benefits of exercise training in patients with heart failure(2017) ANTUNES-CORREA, Ligia M.; UENO-PARDI, Linda M.; TREVIZAN, Patricia F.; SANTOS, Marcelo R.; SILVA, Carlos Henrique P. da; FRANCO, Fabio G. M.; ALVES, Maria Janieire N. N.; RONDON, Maria Urbana P. B.; NEGRAO, Carlos E.Background: Exercise training improves neurovascular control and functional capacity in heart failure (HF) patients. However, the influence of the aetiology on these benefits is unknown. We compared the effects of exercise training on neurovascular control and functional capacity in idiopathic, ischaemic and hypertensive HF patients. Design: Subjects consisted of 45 exercise-trained HF patients from our database (2000-2015), aged 40-70 years old, functional class II/ III and ejection fraction <= 40%, and they were divided into three groups: idiopathic (n = 11), ischaemic (n = 18) and hypertensive (n = 16). Methods: Functional capacity was determined by cardiopulmonary exercise testing. Muscle sympathetic nerve activity (MSNA) was recorded by microneurography. Forearm blood flow (FBF) was measured by venous occlusion plethysmography. Results: Four months of exercise training significantly reduced MSNA and significantly increased FBF in all groups. However, the relative reduction in MSNA was greater in hypertensive patients compared with that in idiopathic patients (frequency: -34% vs. -15%, p -0.01; incidence: -31% vs. -12%, p -0.02). No differences were found between hypertensive patients and ischaemic patients. The relative increase in FBF was greater in hypertensive patients than in ischaemic and idiopathic patients (42% vs. 15% and 17%, respectively, p = 0.02). The relative increase in forearm vascular conductance was greater in hypertensive patients compared with those in ischaemic and idiopathic patients (57% vs. 13% and 26%, respectively, p = 0.001). Exercise training significantly and similarly increased peak oxygen consumption in all groups. Conclusion: The exercise-induced improvement in neurovascular control is more pronounced in hypertensive HF patients than in idiopathic and ischaemic HF patients. The increase in functional capacity is independent of aetiology.
- High levels of C-reactive protein are associated with reduced vagal modulation and low physical activity in young adults(2012) SOARES-MIRANDA, L.; NEGRAO, C. E.; ANTUNES-CORREA, L. M.; NOBRE, T. S.; SILVA, P.; SANTOS, R.; VALE, S.; MOTA, J.The purpose of this study was to examine the relationship between cardiac autonomic control derived from heart rate variability (HRV), high-sensitivity C-reactive protein (hs-CRP) and physical activity (PA) levels measured using accelerometers. A total of 80 healthy university students volunteered to participate in this study (20.56 +/- 0.82 years, 1.36 +/- 1.5 mg/L of hs-CRP). The participants were divided into groups based on tertiles of hs-CRP. Analysis of covariance adjusted to PA was used to assess group differences in HRV. Associations between hs-CRP, HRV indices and PA were analyzed using Pearson's correlation. The participants at the highest tertile of hs-CRP (tertile 3) had lower cardiac vagal modulation (SDNN, tertile 1=78.05 +/- 5.9,tertile 2=82.43 +/- 5.9,tertile 3=56.03 +/- 6.1; SD1, tertile 1=61.27 +/- 5.3, tertile 2=62.93 +/- 5.4, tertile 3=40.03 +/- 5.5). In addition, vagal indices were inversely correlated with hs-CRP but positively correlated with PA (SDNN r=-0.320, SD1 r=-0.377; SDNN r=0.304, SD1 r=0.299; P<0.05). Furthermore, the most physically active subjects had lower levels of hs-CRP and the highest levels of vagal modulation.
- Effects of aerobic and inspiratory training on skeletal muscle microRNA-1 and downstream-associated pathways in patients with heart failure(2020) ANTUNES-CORREA, Ligia M.; TREVIZAN, Patricia F.; BACURAU, Aline V. N.; FERREIRA-SANTOS, Larissa; GOMES, Joao L. P.; URIAS, Ursula; OLIVEIRA, Patricia A.; ALVES, Maria Janieire N. N.; ALMEIDA, Dirceu R. de; BRUM, Patricia C.; OLIVEIRA, Edilamar M.; HAJJAR, Ludhmila; KALIL FILHO, Roberto; NEGRAO, Carlos EduardoBackground The exercise intolerance in chronic heart failure with reduced ejection fraction (HFrEF) is mostly attributed to alterations in skeletal muscle. However, the mechanisms underlying the skeletal myopathy in patients with HFrEF are not completely understood. We hypothesized that (i) aerobic exercise training (AET) and inspiratory muscle training (IMT) would change skeletal muscle microRNA-1 expression and downstream-associated pathways in patients with HFrEF and (ii) AET and IMT would increase leg blood flow (LBF), functional capacity, and quality of life in these patients. Methods Patients age 35 to 70 years, left ventricular ejection fraction (LVEF) <= 40%, New York Heart Association functional classes II-III, were randomized into control, IMT, and AET groups. Skeletal muscle changes were examined by vastus lateralis biopsy. LBF was measured by venous occlusion plethysmography, functional capacity by cardiopulmonary exercise test, and quality of life by Minnesota Living with Heart Failure Questionnaire. All patients were evaluated at baseline and after 4 months. Results Thirty-three patients finished the study protocol: control (n = 10; LVEF = 25 +/- 1%; six males), IMT (n = 11; LVEF = 31 +/- 2%; three males), and AET (n = 12; LVEF = 26 +/- 2%; seven males). AET, but not IMT, increased the expression of microRNA-1 (P = 0.02; percent changes = 53 +/- 17%), decreased the expression of PTEN (P = 0.003; percent changes = -15 +/- 0.03%), and tended to increase the p-AKT(ser473)/AKT ratio (P = 0.06). In addition, AET decreased HDAC4 expression (P = 0.03; percent changes = -40 +/- 19%) and upregulated follistatin (P = 0.01; percent changes = 174 +/- 58%), MEF2C (P = 0.05; percent changes = 34 +/- 15%), and MyoD expression (P = 0.05; percent changes = 47 +/- 18%). AET also increased muscle cross-sectional area (P = 0.01). AET and IMT increased LBF, functional capacity, and quality of life. Further analyses showed a significant correlation between percent changes in microRNA-1 and percent changes in follistatin mRNA (P = 0.001, rho = 0.58) and between percent changes in follistatin mRNA and percent changes in peak VO2 (P = 0.004, rho = 0.51). Conclusions AET upregulates microRNA-1 levels and decreases the protein expression of PTEN, which reduces the inhibitory action on the PI3K-AKT pathway that regulates the skeletal muscle tropism. The increased levels of microRNA-1 also decreased HDAC4 and increased MEF2c, MyoD, and follistatin expression, improving skeletal muscle regeneration. These changes associated with the increase in muscle cross-sectional area and LBF contribute to the attenuation in skeletal myopathy, and the improvement in functional capacity and quality of life in patients with HFrEF. IMT caused no changes in microRNA-1 and in the downstream-associated pathway. The increased functional capacity provoked by IMT seems to be associated with amelioration in the respiratory function instead of changes in skeletal muscle. (Identifier: NCT01747395)
- Post-Exercise Neurovascular Control in Chronic Heart Failure Patients(2016) NOBRE, T. S.; GROEHS, R. V.; AZEVEDO, L. F.; ANTUNES-CORREA, L. M.; MARTINEZ, D. G.; ALVES, M. J. N. N.; NEGRAO, C. E.It remains unknown whether or not a reduction in muscle sympathetic nerve activity in heart failure patients is associated over time with the effects of long- or short-term repeated exercise. 10 chronic heart failure patients, age 49 +/- 3 years old, functional class I-III NYHA, ejection fraction <40% were randomly submitted to either an acute bout of moderate continuous exercise OR high-intensity interval exercise. Muscle sympathetic nerve activity (microneurography) and forearm blood flow (venous occlusion plethysmography) were evaluated pre- and post-exercise sessions. The moderate exercise consisted of cycle exercise at an intensity corresponding to anaerobic threshold. The interval exercise consisted of a 2-min cycle exercise at intensity corresponding to anaerobic threshold, followed by a 1-min exercise set at respiratory compensation point. Exercise capacity was evaluated by cardiopulmonary exercise test. The caloric expenditure in both sessions was 100kcal. Baseline muscle sympathetic nerve activity and forearm blood flow levels were not different between sessions. Moderate or high-intensity exercise caused no significant changes in muscle sympathetic nerve activity and forearm blood flow. These findings suggest that the reduction in muscle sympathetic nerve activity and the increase in forearm blood flow provoked by exercise training in chronic heart failure patients are due to cumulative effects over time.
- Effects of inspiratory muscle training combined with aerobic exercise training on neurovascular control in chronic heart failure patients(2021) TREVIZAN, Patricia F.; ANTUNES-CORREA, Ligia M.; LOBO, Denise M. L.; OLIVEIRA, Patricia A.; ALMEIDA, Dirceu R. de; ABDUCH, Maria Cristina D.; MATHIAS JUNIOR, Wilson; HAJJAR, Ludhmila Abrahao; KALIL FILHO, Roberto; NEGRAO, Carlos EduardoAims We tested the hypothesis that the effects of combined inspiratory muscle training and aerobic exercise training (IMT + AET) on muscle sympathetic nerve activity (MSNA) and forearm blood flow in patients with heart failure with reduced ejection fraction are more pronounced than the effects of AET alone. Methods and results Patients aged 30-70 years, New York Heart Association Functional Class II-III, and left ventricular ejection fraction <= 40% were randomly assigned to four groups: IMT (n = 11), AET (n = 12), IMT + AET (n = 9), and non-training (NT; n = 10). MSNA was recorded using microneurography. Forearm blood flow was measured by venous occlusion plethysmography and inspiratory muscle strength by maximal inspiratory pressure. IMT consisted of 30 min sessions, five times a week, for 4 months. Moderate AET consisted of 60 min sessions, three times a week for 4 months. AET (-10 +/- 2 bursts/min, P = 0.03) and IMT + AET (-13 +/- 4 bursts/min, P = 0.007) reduced MSNA. These responses in MSNA were not different between AET and IMT + AET groups. IMT (0.22 +/- 0.08 mL/min/100 mL, P = 0.03), AET (0.27 +/- 0.09 mL/min/100 mL, P = 0.01), and IMT + AET (0.35 +/- 0.12 mL/min/100 mL, P = 0.008) increased forearm blood flow. No differences were found between groups. AET (3 +/- 1 mL/kg/min, P = 0.006) and IMT + AET (4 +/- 1 mL/kg/min, P = 0.001) increased peak oxygen consumption. These responses were similar between these groups. IMT (20 +/- 3 cmH(2)O, P = 0.005) and IMT + AET (18 +/- 3 cmH(2)O, P = 0.01) increased maximal inspiratory pressure. No significant changes were observed in the NT group. Conclusions IMT + AET causes no additive effects on neurovascular control in patients with heart failure with reduced ejection fraction compared with AET alone. These findings may be, in part, because few patients had inspiratory muscle weakness.
- Exercise training improves neurovascular control and functional capacity in heart failure patients regardless of age(2012) ANTUNES-CORREA, Ligia M.; KANAMURA, Bianca Y.; MELO, Ruth C.; NOBRE, Thais S.; UENO, Linda M.; FRANCO, Fabio G. M.; ROVEDA, Fabiana; BRAGA, Ana Maria; RONDON, Maria U. P. B.; BRUM, Patricia C.; BARRETTO, Antonio C. P.; MIDDLEKAUFF, Holly R.; NEGRAO, Carlos E.Background: Exercise training is a non-pharmacological strategy for treatment of heart failure. Exercise training improves functional capacity and quality of life in patients. Moreover, exercise training reduces muscle sympathetic nerve activity (MSNA) and peripheral vasoconstriction. However, most of these studies have been conducted in middle-aged patients. Thus, the effects of exercise training in older patients are much less understood. The present study was undertaken to investigate whether exercise training improves functional capacity, muscular sympathetic activation and muscular blood flow in older heart failure patients, as it does in middle-aged heart failure patients. Design: Fifty-two consecutive outpatients with heart failure from the database of the Unit of Cardiovascular Rehabilitation and Physiology Exercise were divided by age (middle-aged, defined as 45-59 years, and older, defined as 60-75 years) and exercise status (trained and untrained). Methods: MSNA was recorded directly from the peroneal nerve using the microneurography technique. Forearm Blood Flow (FBF) was measured by venous occlusion plethysmography. Functional capacity was evaluated by cardiopulmonary exercise test. Results: Exercise training significantly and similarly increased FBF and peak VO2 in middle-aged and older heart failure patients. In addition, exercise training significantly and similarly reduced MSNA and forearm vascular resistance in these patients. No significant changes were found in untrained patients. Conclusion: Exercise training improves neurovascular control and functional capacity in heart failure patients regardless of age.