Maria Urbana Pinto Brandão Rondon

In this study, we showed that females and males develop a similar hypoxia-induced impairment in endurance performance, perceived and performance fatigability during a 4-km cycling time trial. These novel findings indicate that females and males regulate their power output similarly during a 4-km cycling time trial under moderate hypoxia, likely to avoid prematurely exacerbating metabolic disturbances and thereby reaching comparable levels of performance fatigability by the end of the task.

High-density lipoprotein (HDL) is associated with decreased incidence of cardiovascular events, and its functionality also influences prognosis. Exercise is an important tool to improve prognosis in the post-infarction (MI) population, but the role of exercise on HDL functionality is poorly understood. Sixty-two patients with acute MI were randomized in a supervised exercise program for 12–14 weeks (exercise group—EG) or a control group (CG). The main objective of the study was to analyze the role of exercise on esterified cholesterol (EC) and unesterified cholesterol (UC) transfer to HDL. For the total population, the baseline mean rate of EC transfer to HDL was 2.53 ± 0.83 and at the end of follow-up, it was 2.74 ± 0.64 (p = 0.03). The figures for UC were, respectively, 4.08 ± 1.2 and 4.4 ± 1.06 (p = 0.02). The difference (follow-up minus baseline) for EC was 0.15 ± 0.84 for the control group and 0.27 ± 0.69 for the exercise group (p = 0.53); for UC, the figures were 0.28 ± 1.14 and 0.35 ± 0.96 (p = 0.80), respectively, for the control and exercise groups. In post-MI patients, 12–14 weeks of supervised exercise did not improve HDL functionality.

Partial coherence analysis has been instrumental in demonstrating, for the first time, that cerebral blood velocity (CBv) is continuously influenced, not only by fluctuations in mean arterial pressure but also muscle sympathetic nervous activity (MSNA), leading to similar dynamic responses at rest and during different sympathoexcitatory maneuvers in healthy subjects. Modeling the temporal relationship between MSNA and CBv opens new opportunities for advancing knowledge regarding the role of the sympathetic nervous system in the regulation of cerebral circulation in health and disease.

The blood pressure‐lowering effect of aerobic training is preceded by improving cardiovascular autonomic control. We previously demonstrated that aerobic training conducted in the evening (ET) induces a greater decrease in blood pressure than morning training (MT). To study whether the greater blood pressure decrease after ET occurs through better cardiovascular autonomic regulation, this study aimed to compare MT versus ET on muscle sympathetic nerve activity (MSNA) and baroreflex sensitivity (BRS) in treated patients with hypertension. Elderly patients treated for hypertension were randomly allocated into MT (n = 12, 07.00–10.00 h) or ET (n = 11, 17.00–20.00 h) groups. Both groups trained for 10 weeks, 3 times/week, cycling for 45 min at moderate intensity. Beat‐to‐beat blood pressure (finger photoplethysmography), heart rate (electrocardiography) and MSNA (microneurography) were assessed at the initial and final phases of the study at baseline and during sequential bolus infusions of sodium nitroprusside and phenylephrine (modified‐Oxford technique) to evaluate cardiac and sympathetic BRS. Mean blood pressure decreased significantly after ET but not after MT (−9 ± 11 vs. −1 ± 8 mmHg, P = 0.042). MSNA decreased significantly only after ET with no change after MT (−12 ± 5 vs. −3 ± 7 bursts/100 heart beats, P = 0.013). Sympathetic BRS improved after ET but not after MT (−0.8 ± 0.7 vs. 0.0 ± 0.8 bursts/100 heart beats/mmHg, P = 0.052). Cardiac BRS improved similarly in both groups (ET: +1.7 ± 1.8 vs. MT: +1.4 ± 1.9 ms/mmHg, P_phase ≤ 0.001). In elderly patients treated for hypertension, only ET decreased mean blood pressure and MSNA and improved sympathetic BRS. These findings revealed that the sympathetic nervous system has a key role in ET's superiority to MT in blood pressure‐lowering effect. image Key points: Reducing muscle nerve sympathetic activity and increasing sympathetic baroreflex sensitivity plays a key role in promoting the greater blood pressure reduction observed with evening training. These findings indicated that simply changing the timing of exercise training may offer additional benefits beyond antihypertensive medications, such as protection against sympathetic overdrive and loss of baroreflex sensitivity, independent markers of mortality. Our new findings also suggest new avenues of investigation, such as the possibility that evening aerobic training may be beneficial in other clinical conditions with sympathetic overdrive, such as congestive heart failure and hypertrophic cardiomyopathy.

Purpose To investigate the effect of inspiratory muscle training (IMT) in addition to conventional physical rehabilitation on muscle strength, functional capacity, mobility, hemodynamics, fatigue, and quality of life in hospitalized patients undergoing hematopoietic stem cell transplantation (HSCT). Methods We conducted a randomized controlled trial in 57 inpatients with hematological diseases undergoing HSCT. Conventional inpatient physical rehabilitation was delivered to the IMT (n = 27) and control (CON; n = 30) groups according to usual care, and the first group additionally performed IMT. The IMT was prescribed according to clinical and laboratory parameters at 40% of maximal inspiratory pressure (MIP), 5 days/week throughout the hospitalization, in sessions of 10–20 min. The primary outcome was MIP and the secondary outcomes were maximal expiratory pressure (MEP), peripheral muscle strength (handgrip and sit-to-stand tests), functional capacity (6-min step test), mobility (timed up and go test), blood pressure, quality of life (EORTC-QLQ-C30), and fatigue (FACT-F) at admission and hospital discharge. Results The population was predominately autologous HSCT. The IMT group significantly increased the MIP (P < 0.01) and decreased both fatigue (P = 0.01) and blood pressure (P < 0.01) compared with control. No differences were found between admission and hospital discharge in peripheral and expiratory muscle strength, functional capacity, mobility, and quality of life in both groups (P > 0.05). Conclusions Our results support the effectiveness of IMT as part of rehabilitation for HSCT inpatients, improving inspiratory muscle strength, and reducing fatigue and blood pressure. Trial registration NCT03373526 (clinicaltrials.gov).

Sympathetic hyperactivation and baroreflex dysfunction are hallmarks of heart failure with reduced ejection fraction (HFrEF). However, it is unknown whether the progressive loss of phasic activity of sympathetic nerve bursts is associated with baroreflex dysfunction in HFrEF patients. Therefore, we investigated the association between the oscillatory pattern of muscle sympathetic nerve activity (LF_MSNA/HF_MSNA) and the gain and coupling of the sympathetic baroreflex function in HFrEF patients. In a sample of 139 HFrEF patients, two groups were selected according to the level of LF_MSNA/HF_MSNA index: (1) Lower LF_MSNA/HF_MSNA (lower terciles, n = 46, aged 53 ± 1 y) and (2) Higher LF_MSNA/HF_MSNA (upper terciles, n = 47, aged 52 ± 2 y). Heart rate (ECG), arterial pressure (oscillometric method), and muscle sympathetic nerve activity (microneurography) were recorded for 10 min in patients while resting. Spectral analysis of muscle sympathetic nerve activity was conducted to assess the LF_MSNA/HF_MSNA, and cross-spectral analysis between diastolic arterial pressure, and muscle sympathetic nerve activity was conducted to assess the sympathetic baroreflex function. HFrEF patients with lower LF_MSNA/HF_MSNA had reduced left ventricular ejection fraction (26 ± 1 vs. 29 ± 1%, P = 0.03), gain (0.15 ± 0.03 vs. 0.30 ± 0.04 a.u./mmHg, P < 0.001) and coupling of sympathetic baroreflex function (0.26 ± 0.03 vs. 0.56 ± 0.04%, P < 0.001) and increased muscle sympathetic nerve activity (48 ± 2 vs. 41 ± 2 bursts/min, P < 0.01) and heart rate (71 ± 2 vs. 61 ± 2 bpm, P < 0.001) compared with HFrEF patients with higher LF_MSNA/HF_MSNA. Further analysis showed an association between the LF_MSNA/HF_MSNA with coupling of sympathetic baroreflex function (R = 0.56, P < 0.001) and left ventricular ejection fraction (R = 0.23, P = 0.02). In conclusion, there is a direct association between LF_MSNA/HF_MSNA and sympathetic baroreflex function and muscle sympathetic nerve activity in HFrEF patients. This finding has clinical implications, because left ventricular ejection fraction is less in the HFrEF patients with lower LF_MSNA/HF_MSNA.

The 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/m²) and CY (600 mg/m²) 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.

Obstructive sleep apnea (OSA) is a risk factor frequently present in patients with metabolic syndrome (MetS). Additionally, moderate and severe OSA are highly prevalent in patients with cardiac disease, as they increase the riskfor cardiovascular events by 80%. The gold standard diagnostic method for OSA is overnight polysomnography (PSG), which remains unaffordable for the overall population. The aim of the present study was to evaluate whether the Berlin Questionnaire (BQ) is anuseful tool for assessing the risk of OSA in patients with MetS. 97 patients, previously untreated and recently diagnosed with MetS (National Cholesterol Education Program, Adult Treatment Panel III, ATP-III) underwent a PSG. OSA was characterized by the apnea-hypopnea index (AHI). BQ was administered before PSG and we evaluated sensitivity, specificity, positive and negative predictive values, and accuracy. Of the 97 patients with MetS, 81 patients had OSA, with 47 (48.5%) presenting moderate and severe OSA. For all MetS with OSA (AHI≥5 events/hour), the BQ showed good sensitivity (0.65, 95% CI 0.54 to 0.76) and fair specificity (0.38, 95% CI 0.15–0.65) with a positive predictive value of 0.84, a negative predictive value of 0.18 and an 84% accuracy. Similarly, for moderate-to-severe OSA (AHI≥15 events/hour) we found good sensitivity (0.73, 95% CI 0.58–0.85) and fair specificity (0.40, 95% CI 0.27–0.55). Interestingly, for severe OSA (AHI≥30 events/hour), there was a very good sensitivity (0.91, 95% CI 0.72–0.99) and moderate specificity (0.42, 95% CI 0.31–0.54). The BQ is a valid tool for screening the risk of OSA in MetS patients in general, and it is particularly useful in predicting severe OSA.

Keywords: autonomic modulation; exercise test; hypertensive patients; prognostic index

Purpose We tested the hypothesis that (i) diet associated with exercise would improve arterial baroreflex (ABR) control in metabolic syndrome (MetS) patients with and without obstructive sleep apnea (OSA) and (ii) the effects of this intervention would be more pronounced in patients with OSA. Methods Forty-six MetS patients without (noOSA) and with OSA (apnea-hypopnea index, AHI > 15 events/h) were allocated to no treatment (control, C) or hypocaloric diet (− 500 kcal/day) associated with exercise (40 min, bicycle exercise, 3 times/week) for 4 months (treatment, T), resulting in four groups: noOSA-C (n = 10), OSA-C (n = 12), noOSA-T (n = 13), and OSA-T (n = 11). Muscle sympathetic nerve activity (MSNA), beat-to-beat BP, and spontaneous arterial baroreflex function of MSNA (ABR_MSNA, gain and time delay) were assessed at study entry and end. Results No significant changes occurred in C groups. In contrast, treatment in both patients with and without OSA led to a significant decrease in weight (P < 0.05) and the number of MetS factors (P = 0.03). AHI declined only in the OSA-T group (31 ± 5 to 17 ± 4 events/h, P < 0.05). Systolic BP decreased in both treatment groups, and diastolic BP decreased significantly only in the noOSA-T group. Treatment decreased MSNA in both groups. Compared with baseline, ABR_MSNA gain increased in both OSA-T (13 ± 1 vs. 24 ± 2 a.u./mmHg, P = 0.01) and noOSA-T (27 ± 3 vs. 37 ± 3 a.u./mmHg, P = 0.03) groups. The time delay of ABR_MSNA was reduced only in the OSA-T group (4.1 ± 0.2 s vs. 2.8 ± 0.3 s, P = 0.04). Conclusions Diet associated with exercise improves baroreflex control of sympathetic nerve activity and MetS components in patients with MetS regardless of OSA.