Abnormal neurovascular control during central and peripheral chemoreceptors stimulation in heart failure patients with preserved ejection fraction.

PURPOSE: Central and peripheral chemoreceptors are hypersensitized in patients with heart failure with reduced ejection fraction. Whether this autonomic alteration occurs in patients with heart failure with preserved ejection fraction (HFpEF) remains little known. We test the hypothesis that the central and peripheral chemoreflex control of muscle sympathetic nerve activity (MSNA) is altered in HFpEF. METHODS: Patients aged 55-80 years with symptoms of heart failure, body mass index ≤ 35 kg/m2, left ventricular ejection fraction > 50%, left atrial volume index > 34 mL/m2, left ventricular early diastolic filling velocity and early diastolic tissue velocity of mitral annulus ratio (E/e' index) ≥ 13, and BNP levels > 35 pg/mL were included in the study (HFpEF, n = 9). Patients without heart failure with preserved ejection fraction (non-HFpEF, n = 9), aged-paired, were also included in the study. Peripheral chemoreceptors stimulation (10% O2 and 90% N2, with CO2 titrated) and central chemoreceptors stimulation (7% CO2 and 93% O2) were conducted for 3 min. MSNA was evaluated by microneurography technique, and forearm blood flow (FBF) by venous occlusion plethysmography. RESULTS: During hypoxia, MSNA responses were greater (p < 0.001) and FBF responses were lower in patients with HFpEF (p = 0.006). Likewise, MSNA responses during hypercapnia were higher (p < 0.001) and forearm vascular conductance (FVC) levels were lower (p = 0.030) in patients with HFpEF. CONCLUSIONS: Peripheral and central chemoreflex controls of MSNA are hypersensitized in patients with HFpEF, which seems to contribute to the increase in MSNA in these patients. In addition, peripheral and central chemoreceptors stimulation in patients with HFpEF causes muscle vasoconstriction.

Adjuvant Treatment with 5-Fluorouracil and Oxaliplatin Does Not Influence Cardiac Function, Neurovascular Control, and Physical Capacity in Patients with Colon Cancer.

BACKGROUND: Adjuvant chemotherapy with 5-fluorouracil (5-FU) and oxaliplatin increases recurrence-free and overall survival in patients with colon adenocarcinoma. It is known that these drugs have been associated with cardio- and neurotoxicity. We investigated the effects of 5-FU ± oxaliplatin on cardiac function, vascular responses, neurovascular control, and physical capacity in patients with colon cancer. METHODS: Twenty-nine patients with prior colectomy for stage II-III adenocarcinoma and clinical indication for adjuvant chemotherapy were allocated to receive 5-FU (n = 12) or 5-FU + oxaliplatin (n = 17), according to the oncologist's decision. All the analyses were performed just before and after the end of chemotherapy. Cardiac function was assessed by echocardiography and speckle tracking, and cardiac autonomic control was assessed by heart rate variability (HRV). Vascular endothelial function was assessed by flow-mediated dilation (FMD). Muscle sympathetic nerve activity (MSNA) was directly recorded by microneurography technique, and muscle blood flow by venous occlusion plethysmography. Physical capacity was evaluated by cardiopulmonary exercise test. RESULTS: Chemotherapy (pooled data) did not significantly change left ventricular ejection fraction (58 ± 1 vs. 55 ± 2%, p = .14), longitudinal strain (-18 ± 1 vs. -18 ± 1%, p = .66), and HRV. Likewise, chemotherapy did not significantly change FMD, muscle blood flow, and MSNA (33 ± 2 vs. 32 ± 1 bursts/min, p = .31). Physical capacity was not significantly changed in both groups. Similar findings were observed when the patients were subdivided in 5-FU and 5-FU + oxaliplatin treatment groups. 5-FU and 5-FU + oxaliplatin did not significantly change cardiac function, HRV, vascular responses, MSNA, and physical capacity. CONCLUSION: This study provides evidence that adjuvant treatment with 5-FU ± oxaliplatin is well tolerated and does not promote changes compatible with long-term cardiotoxicity. IMPLICATIONS FOR PRACTICE: Adjuvant chemotherapy with 5-fluorouracil (5-FU) and oxaliplatin increases recurrence-free and overall survival in patients with colon adenocarcinoma; however, these drugs have been associated with cardio- and neurotoxicity. This study investigated the effects of these drugs on cardiac function, vascular responses, neurovascular control, and physical capacity in patients with colon cancer. It was found that 5-FU and oxaliplatin did not significantly change cardiac function, cardiac autonomic control, vascular endothelial function, muscle sympathetic nerve activity, and physical capacity. This study provides evidence that adjuvant treatment with 5-FU ± oxaliplatin is well tolerated and does not promote changes compatible with long-term cardiotoxicity.

Chemotherapy acutely impairs neurovascular and hemodynamic responses in women with breast cancer.

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.

Diet associated with exercise improves baroreflex control of sympathetic nerve activity in metabolic syndrome and sleep apnea patients.

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 (ABRMSNA, 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, ABRMSNA 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 ABRMSNA 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.

Baroreflex gain and vasomotor sympathetic modulation in resistant hypertension.

PURPOSE: The aim of this study was to determine the gain and latency of arterial baroreflex control of heart rate in patients with resistant hypertension compared to patients with essential hypertension and normotensive subjects. METHODS: Eighteen patients with resistant hypertension (56 ± 10 years, mean of four antihypertensive drugs), 17 patients with essential hypertension (56 ± 11 years, mean of two antihypertensive drugs), and 17 untreated normotensive controls (50 ± 15 years) were evaluated by spectral analysis of the spontaneous fluctuations of arterial pressure (beat-to-beat) and heart rate (ECG). This analysis estimated vasomotor and cardiac autonomic modulations, respectively. The transfer function analysis quantified the gain and latency of the response of output signal (RR interval) per unit of spontaneous change of input signal (systolic arterial pressure). RESULTS: The gain was similarly lower in patients with resistant hypertension and patients with essential hypertension in relation to normotensive subjects (4.67 ± 2.96 vs. 6.60 ± 3.30 vs. 12.56 ± 8.81 ms/mmHg; P < 0.01, respectively). However, the latency of arterial baroreflex control of heart rate was significantly higher only in patients with resistant hypertension when compared to patients with essential hypertension and normotensive subjects (-4.01 ± 3.19 vs. -2.91 ± 2.10 vs. -1.82 ± 1.09 s; P = 0.04, respectively). In addition, the index of vasomotor sympathetic modulation was significantly increased only in patients with resistant hypertension when compared to patients with essential hypertension and normotensive subjects (4.04 ± 2.86 vs. 2.65 ± 1.88 vs. 2.06 ± 1.70 mmHg2; P < 0.01, respectively). CONCLUSIONS: Patients with resistant hypertension have reduced gain and increased latency of arterial baroreflex control of heart rate. These patients also have increased vasomotor sympathetic modulation.

Exercise training prevents the deterioration in the arterial baroreflex control of sympathetic nerve activity in chronic heart failure patients.

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 V̇o2 ≤ 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.

Time delay of baroreflex control and oscillatory pattern of sympathetic activity in patients with metabolic syndrome and obstructive sleep apnea.

The incidence and strength of muscle sympathetic nerve activity (MSNA) depend on the magnitude (gain) and latency (time delay) of the arterial baroreflex control (ABR). However, the impact of metabolic syndrome (MetS) and obstructive sleep apnea (OSA) on oscillatory pattern of MSNA and time delay of the ABR of sympathetic activity is unknown. We tested the hypothesis that MetS and OSA would impair the oscillatory pattern of MSNA and the time delay of the ABR of sympathetic activity. Forty-three patients with MetS were allocated into two groups according to the presence of OSA (MetS + OSA, n = 21; and MetS - OSA, n = 22). Twelve aged-paired healthy controls (C) were also studied. OSA (apnea-hypopnea index > 15 events/h) was diagnosed by polysomnography. We recorded MSNA (microneurography), blood pressure (beat-to-beat basis), and heart rate (EKG). Oscillatory pattern of MSNA was evaluated by autoregressive spectral analysis and the ABR of MSNA (ABRMSNA, sensitivity and time delay) by bivariate autoregressive analysis. Patients with MetS + OSA had decreased oscillatory pattern of MSNA compared with MetS - OSA (P < 0.01) and C (P < 0.001). The sensitivity of the ABRMSNA was lower and the time delay was greater in MetS + OSA compared with MetS - OSA (P < 0.001 and P < 0.01, respectively) and C (P < 0.001 and P < 0.001, respectively). Patients with MetS - OSA showed decreased oscillatory pattern of MSNA compared with C (P < 0.01). The sensitivity of the ABRMSNA was lower in MetS - OSA than in C group (P < 0.001). In conclusion, MetS decreases the oscillatory pattern of MSNA and the magnitude of the ABRMSNA. OSA exacerbates these autonomic dysfunctions and further increases the time delay of the baroreflex response of MSNA.

Symptoms of anxiety and mood disturbance alter cardiac and peripheral autonomic control in patients with metabolic syndrome.

Previous investigations show that metabolic syndrome (MetSyn) causes sympathetic hyperactivation. Symptoms of anxiety and mood disturbance (AMd) provoke sympatho-vagal imbalance. We hypothesized that AMd would alter even further the autonomic function in patients with MetSyn. Twenty-six never-treated patients with MetSyn (ATP-III) were allocated to two groups, according to the levels of anxiety and mood disturbance: (1) with AMd (MetSyn + AMd, n = 15), and (2) without AMd (MetSyn, n = 11). Ten healthy control subjects were also studied (C, n = 10). AMd was determined using quantitative questionnaires. Muscle sympathetic nerve activity (MSNA, microneurography), blood pressure (oscillometric beat-to-beat basis), and heart rate (ECG) were measured during a baseline 10-min period. Spectral analysis of RR interval and systolic arterial pressure were analyzed, and the power of low (LF) and high (HF) frequency bands were determined. Sympatho-vagal balance was obtained by LF/HF ratio. Spontaneous baroreflex sensitivity (BRS) was evaluated by calculation of α-index. MSNA was greater in patients with MetSyn + AMd compared with MetSyn and C. Patients with MetSyn + AMd showed higher LF and lower HF power compared with MetSyn and C. In addition, LF/HF balance was higher in MetSyn + AMd than in MetSyn and C groups. BRS was decreased in MetSyn + AMd compared with MetSyn and C groups. Anxiety and mood disturbance alter autonomic function in patients with MetSyn. This autonomic dysfunction may contribute to the increased cardiovascular risk observed in patients with mood alterations.

Daily rhythm of dynamic cerebral autoregulation in patients after stroke.

Dynamic cerebral autoregulation (dCA) in healthy young adults displays a daily variation. Whether the rhythm exists in patients with stroke is unknown. We studied 28 stroke patients (age: 26-83 years, 7 females) within 48 hours after thrombolysis. dCA was assessed 54 times in these patients during supine rest (twice in 26 and once in 2 patients): 9 assessments between 0-9AM, 12 between 9AM-2PM, 20 between 2-7PM, and 13 between 7PM-12AM. To estimate dCA, phase shifts between spontaneous oscillations of cerebral blood flow velocity (CBFV) in the middle cerebral artery and arterial blood pressure (BP) were obtained in four frequency bands: <0.05 Hz, 0.05-0.1 Hz, 0.1-0.2 Hz, and >0.2 Hz. CBFV-BP phase shifts at <0.05 Hz were significantly larger between 2-7PM, suggesting better dCA, than those at other times (p < 0.0001), and the daily rhythm was consistent for stroke and non-stroke sides. No significant rhythms were observed at higher frequencies (all p > 0.2). All results were independent of age, sex, stroke type and severity, and other cardiovascular conditions. dCA after stroke showed a daily rhythm, leading to a better regulation of CBFV at <0.05 Hz during the afternoon. The finding may have implications for daily activity management of stroke patients.

High-dose Chemotherapy Impairs Cardiac Autonomic Control of Hospitalized Cancer Patients Undergoing Autologous Hematopoietic Stem Cell Transplantation.

BACKGROUND: Autologous hematopoietic stem cell transplantation (HSCT) patients have intermediary and late cardiac autonomic dysfunction, which is an independent mortality predictor. However, it is unknown when this HSCT-related autonomic dysfunction begins during hospitalization for HSCT and whether cardiac autonomic control (CAC) is related to cardiotoxicity in these patients. PATIENTS AND METHODS: CAC was assessed in 36 autologous-HSCT inpatients (HSCT group) and 23 cancer-free outpatients (CON group) using heart rate variability analysis. The HSCT group was assessed at five time-points from admission to hospital discharge during hospitalization period. The CON group was assessed once. The severity of cardiotoxicity (CTCAE 5.0) and cardiac troponin I were recorded. RESULTS: The CAC was significantly reduced after high-dose chemotherapy (HDC) (reduction of MNN, SDNN, RMSSD, LFms2 and HFnu, and increase of LFnu and LF/HF; P<0.05). At the onset of neutropenia, pNN50 and HFms2 were also reduced (P<0.05) compared to the admission ones. Although both groups were similar regarding CAC at hospital admission, the HSCT patients showed impaired CAC at hospital discharge (P<0.05). The LF/HF was positively associated with cardiac troponin I and RMSSD was inversely associated with the severity of cardiotoxicity (P≤0.05). CONCLUSION: CAC worsened during hospitalization for autologous-HSCT, mainly after HDC. In addition, it seems associated to early signs of cardiotoxicity in these patients.

Cardiac autonomic control in Rett syndrome: Insights from heart rate variability analysis.

Rett syndrome (RTT) is a rare and severe neurological disorder mainly affecting females, usually linked to methyl-CpG-binding protein 2 (MECP2) gene mutations. Manifestations of RTT typically include loss of purposeful hand skills, gait and motor abnormalities, loss of spoken language, stereotypic hand movements, epilepsy, and autonomic dysfunction. Patients with RTT have a higher incidence of sudden death than the general population. Literature data indicate an uncoupling between measures of breathing and heart rate control that could offer insight into the mechanisms that lead to greater vulnerability to sudden death. Understanding the neural mechanisms of autonomic dysfunction and its correlation with sudden death is essential for patient care. Experimental evidence for increased sympathetic or reduced vagal modulation to the heart has spurred efforts to develop quantitative markers of cardiac autonomic profile. Heart rate variability (HRV) has emerged as a valuable non-invasive test to estimate the modulation of sympathetic and parasympathetic branches of the autonomic nervous system (ANS) to the heart. This review aims to provide an overview of the current knowledge on autonomic dysfunction and, in particular, to assess whether HRV parameters can help unravel patterns of cardiac autonomic dysregulation in patients with RTT. Literature data show reduced global HRV (total spectral power and R-R mean) and a shifted sympatho-vagal balance toward sympathetic predominance and vagal withdrawal in patients with RTT compared to controls. In addition, correlations between HRV and genotype and phenotype features or neurochemical changes were investigated. The data reported in this review suggest an important impairment in sympatho-vagal balance, supporting possible future research scenarios, targeting ANS.

Cognitive Processes and Legal Capacity in Patients With Bipolar Disorder: A Brief Research Report.

The current study verified the association between cognitive process such as attention, executive functioning, and legal capacity in patients with bipolar disorder (BD). The sample consisted of 72 participants, assorted to episodic patients (n = 21), euthymic patients (n = 22), and healthy controls (HCs) (n = 29). We used the following neuropsychological measures: subtests of the Wechsler Abbreviated Intelligence Scale (WASI): vocabulary and matrix reasoning; Continuous Performance Test (CPT); Five Digit Test (FDT); and Rey-Osterrieth Complex Figure (ROCF). Euthymic patients expressed slower processing speed (FDT) compared to HC. They tended to make more errors with slightly worse discrimination, suggesting more impulsiveness (CPT, p < 0.01). On the contrary, episodic patients showed worse discrimination, committed more omissions, were more inconsistent with regard to response speed (CPT-3, p < 0.01), showed more difficulties in organizing their actions (ROCF: copy, p = 0.03), and were more rigid (FDT: flexibility, p = 0.03). The results suggest that bipolar patients in episode express more cognitive impairments that can compromise the quality of legal capacity. These results highlight the need for more protective support for episodic BD patients regarding legal capacity.

Exercise training reduces sympathetic nerve activity and improves executive performance in individuals with obstructive sleep apnea.

OBJECTIVE: To investigate the effects of exercise training (ET) on muscle sympathetic nerve activity (MSNA) and executive performance during Stroop Color Word Test (SCWT) also referred to as mental stress test. METHODS: Forty-four individuals with obstructive sleep apnea (OSA) and no significant co-morbidities were randomized into 2 groups; 15 individuals completed the control period, and 18 individuals completed the ET. Mini-mental state of examination and intelligence quotient were also assessed. MSNA assessed by microneurography, heart rate by electrocardiography, blood pressure (automated oscillometric device) were measured at baseline and during 3 min of the SCWT. Peak oxygen uptake (VO2 peak) was evaluated using cardiopulmonary exercise testing. Executive performance was assessed by the total correct responses during 3 min of the SCWT. ET consisted of 3 weekly sessions of aerobic exercise, resistance exercises, and flexibility (72 sessions, achieved in 40±3.9 weeks). RESULTS: Baseline parameters were similar between groups. Heart rate, blood pressure, and MSNA responses during SCWT were similar between groups (p>0.05). The comparisons between groups showed that the changes in VO2 (4.7±0.8 vs -1.2±0.4) and apnea-hypopnea index (-7.4±3.1 vs 5.5±3.3) in the exercise-trained group were significantly greater than those observed in the control group respectively (p<0.05) after intervention. ET reduced MSNA responses (p<0.05) and significantly increased the number of correct answers (12.4%) during SCWT. The number of correct answers was unchanged in the control group (p>0.05). CONCLUSIONS: ET improves sympathetic response and executive performance during SCWT, suggesting a prominent positive impact of ET on prefrontal functioning in individuals with OSA. ClinicalTrials.gov: NCT002289625.

Exaggerated Exercise Blood Pressure as a Marker of Baroreflex Dysfunction in Normotensive Metabolic Syndrome Patients.

INTRODUCTION: Exaggerated blood pressure response to exercise (EEBP = SBP ≥ 190 mmHg for women and ≥210 mmHg for men) during cardiopulmonary exercise test (CPET) is a predictor of cardiovascular risk. Sympathetic hyperactivation and decreased baroreflex sensitivity (BRS) seem to be involved in the progression of metabolic syndrome (MetS) to cardiovascular disease. OBJECTIVE: To test the hypotheses: (1) MetS patients within normal clinical blood pressure (BP) may present EEBP response to maximal exercise and (2) increased muscle sympathetic nerve activity (MSNA) and reduced BRS are associated with this impairment. METHODS: We selected MetS (ATP III) patients with normal BP (MetS_NT, n = 27, 59.3% males, 46.1 ± 7.2 years) and a control group without MetS (C, n = 19, 48.4 ± 7.4 years). We evaluated BRS for increases (BRS+) and decreases (BRS-) in spontaneous BP and HR fluctuations, MSNA (microneurography), BP from ambulatory blood pressure monitoring (ABPM), and auscultatory BP during CPET. RESULTS: Normotensive MetS (MetS_NT) had higher body mass index and impairment in all MetS risk factors when compared to the C group. MetS_NT had higher peak systolic BP (SBP) (195 ± 17 vs. 177 ± 24 mmHg, P = 0.007) and diastolic BP (91 ± 11 vs. 79 ± 10 mmHg, P = 0.001) during CPET than C. Additionally, we found that MetS patients with normal BP had lower spontaneous BRS- (9.6 ± 3.3 vs. 12.2 ± 4.9 ms/mmHg, P = 0.044) and higher levels of MSNA (29 ± 6 vs. 18 ± 4 bursts/min, P < 0.001) compared to C. Interestingly, 10 out of 27 MetS_NT (37%) showed EEBP (MetS_NT+), whereas 2 out of 19 C (10.5%) presented (P = 0.044). The subgroup of MetS_NT with EEBP (MetS_NT+, n = 10) had similar MSNA (P = 0.437), but lower BRS+ (P = 0.039) and BRS- (P = 0.039) compared with the subgroup without EEBP (MetS_NT-, n = 17). Either office BP or BP from ABPM was similar between subgroups MetS_NT+ and MetS_NT-, regardless of EEBP response. In the MetS_NT+ subgroup, there was an association of peak SBP with BRS- (R = -0.70; P = 0.02), triglycerides with peak SBP during CPET (R = 0.66; P = 0.039), and of triglycerides with BRS- (R = 0.71; P = 0.022). CONCLUSION: Normotensive MetS patients already presented higher peak systolic and diastolic BP during maximal exercise, in addition to sympathetic hyperactivation and decreased baroreflex sensitivity. The EEBP in MetS_NT with apparent well-controlled BP may indicate a potential depressed neural baroreflex function, predisposing these patients to increased cardiovascular risk.

Oscillatory Pattern of Sympathetic Nerve Bursts Is Associated With Baroreflex Function in Heart Failure Patients With Reduced Ejection Fraction.

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 (LFMSNA/HFMSNA) 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 LFMSNA/HFMSNA index: (1) Lower LFMSNA/HFMSNA (lower terciles, n = 46, aged 53 ± 1 y) and (2) Higher LFMSNA/HFMSNA (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 LFMSNA/HFMSNA, 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 LFMSNA/HFMSNA 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 LFMSNA/HFMSNA. Further analysis showed an association between the LFMSNA/HFMSNA 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 LFMSNA/HFMSNA 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 LFMSNA/HFMSNA.

Consequences of comorbid sleep apnea in the metabolic syndrome--implications for cardiovascular risk.

STUDY OBJECTIVES: Metabolic syndrome (MetSyn) increases overall cardiovascular risk. MetSyn is also strongly associated with obstructive sleep apnea (OSA), and these 2 conditions share similar comorbidities. Whether OSA increases cardiovascular risk in patients with the MetSyn has not been investigated. We examined how the presence of OSA in patients with MetSyn affected hemodynamic and autonomic variables associated with poor cardiovascular outcome. DESIGN: Prospective clinical study. PARTICIPANTS: We studied 36 patients with MetSyn (ATP-III) divided into 2 groups matched for age and sex: (1) MetSyn+OSA (n = 18) and (2) MetSyn-OSA (n = 18). MEASUREMENTS: OSA was defined by an apnea-hypopnea index (AHI) > 15 events/hour by polysomnography. We recorded muscle sympathetic nerve activity (MSNA - microneurography), heart rate (HR), and blood pressure (BP - Finapres). Baroreflex sensitivity (BRS) was analyzed by spontaneous BP and HR fluctuations. RESULTS: MSNA (34 +/- 2 vs 28 +/- 1 bursts/min, P = 0.02) and mean BP (111 +/- 3 vs. 99 +/- 2 mm Hg, P = 0.003) were higher in patients with MetSyn+OSA versus patients with MetSyn-OSA. Patients with MetSyn+OSA had lower spontaneous BRS for increases (7.6 +/- 0.6 vs 12.2 +/- 1.2 msec/mm Hg, P = 0.003) and decreases (7.2 +/- 0.6 vs 11.9 +/- 1.6 msec/mm Hg, P = 0.01) in BP. MSNAwas correlated with AHI (r = 0.48; P = 0.009) and minimum nocturnal oxygen saturation (r = -0.38, P = 0.04). CONCLUSION: Patients with MetSyn and comorbid OSA have higher BP, higher sympathetic drive, and diminished BRS, compared with patients with MetSyn without OSA. These adverse cardiovascular and autonomic consequences of OSA may be associated with poorer outcomes in these patients. Moreover, increased BP and sympathetic drive in patients with MetSyn+OSA may be linked, in part, to impairment of baroreflex gain.

Depression and cardiovascular autonomic control: a matter of vagus and sex paradox.

Depression is a well-established stress-related risk factor for several diseases, mainly for those with cardiovascular outcomes. The mechanisms that link depression disorders with cardiovascular diseases (CVD) include dysfunctions of the autonomic nervous system. Heart rate variability analysis is a widely-used non-invasive method that can simultaneously quantify the activity of the two branches of cardiac autonomic neural control and provide insights about their pathophysiological alterations. Recent scientific literature suggests that sex influences the relationship between depressive symptoms and cardiac autonomic dysfunction. Moreover, a few studies highlight a possible sex paradox: depressed women, despite a greater vagal tone, experience a higher risk of adverse cardiovascular events than depressed men. Although there are striking sex differences in the incidence of depression, scanty data on this topic are available. Lastly, studies on the heart-brain axis bidirectionality and the role of sex are fundamental not only to clarify the biological bases of depression-CVD comorbidity, but also to develop alternative therapies, where vagus nerve appears to be a promising target of non-invasive neuromodulation techniques.

Memory training combined with 3D visuospatial stimulus improves cognitive performance in the elderly: pilot study.

Studies suggest that the engagement of aged participants in cognitive stimulation programs can reduce expected cognitive decline associated with age. OBJECTIVE: To evaluate the effects of memory training (MT) associated with three-dimensional multiple object tracking (3D-MOT) NeuroTracker (NT) in the elderly. METHODS: Forty-four participants (>60 years of age) were recruited and randomly distributed into two groups: experimental (EG; n=22) and comparative (CG; n=22). Both groups performed 12 one-hour MT sessions, twice a week, consisting of specific computerized stimuli associated with teaching of mnemonic strategies; 10 minutes of NT was part only of the EG's sessions. In pre- and post-training periods, both groups were evaluated using a sociodemographic questionnaire, neuropsychological assessment, as well as a specific measure offered by NT. RESULTS: Both groups benefited from the MT and reported more positive feelings regarding their memory and quality of life. However, the EG obtained better results in tests consistent with the strategies trained and which involved attentional resources, reaction time, visual processing speed, episodic, semantic, subjective and working memory as well as aspects of social cognition. CONCLUSIONS: This study showed that the combination of MT and 3D-MOT contributed for a better cognitive performance in the EG. Thus, the results of the present study encourage further research and the development of combined cognitive interventions for the elderly population with and without cognitive deficits.

Estudos sugerem que o envolvimento de idosos em programas de estimulação cognitiva pode reduzir o declínio cognitivo esperado associado à idade. OBJETIVO: Avaliar os efeitos de um treinamento de memória (TM) associado a um estímulo visuoespacial tridimensional (3D-MOT) NeuroTracker (NT) em idosos. MÉTODO: Quarenta e quatro participantes (>60 anos) foram recrutados e distribuídos aleatoriamente em dois grupos: experimental (GE; n=22) e comparativo (GC; n=22). Ambos os grupos realizaram 12 sessões do TM de uma hora, duas vezes por semana, consistindo em estímulos computadorizados específicos associados ao ensino de estratégias mnemônicas; apenas nas sessões do GE foram utilizados 10 minutos com o NT. Nos períodos pré- e pós-treinamento, ambos os grupos foram avaliados por meio de questionário sociodemográfico, avaliação neuropsicológica e medidas cognitivas específicas do NT. RESULTADOS: Ambos os grupos se beneficiaram do TM e relataram sentimentos mais positivos em relação à memória e à qualidade de vida. No entanto, o GE obteve melhores resultados em testes consistentes com as estratégias treinadas e que envolviam recursos atencionais, tempo de reação, velocidade de processamento visual, memória episódica, semântica, subjetiva e de trabalho, além de aspectos da cognição social. CONCLUSÕES: Este estudo mostrou que a combinação do TM e 3D-MOT contribuiu para um melhor desempenho cognitivo no GE. Dessa forma, os resultados do presente estudo incentivam novas pesquisas e o desenvolvimento de intervenções cognitivas combinadas para a população idosa com e sem déficits cognitivos.

Cardiac and Peripheral Autonomic Responses to Orthostatic Stress During Transcutaneous Vagus Nerve Stimulation in Healthy Subjects.

Previous studies showed that transcutaneous vagus nerve stimulation (tVNS) modulates the autonomic nervous system (ANS) in resting condition. However, the autonomic regulation in response to an orthostatic challenge during tVNS in healthy subjects remains unknown. We tested the hypothesis that tVNS reduces heart rate (HR) and alters the responsivity of ANS to orthostatic stress in healthy subjects. In a randomized and cross-over trial, thirteen healthy subjects underwent two experimental sessions on different days: (1) tVNS and (2) control. Using a tVNS device, an auricular electrode was placed on the left cymba conchae of the external ear; an electric current with a pulse frequency of 25 Hz and amplitude between 1 and 6 mA was applied. For the assessment of ANS, the beat-to-beat HR and systolic arterial pressure (SAP) were analyzed using linear and nonlinear approaches during clinostatic and orthostatic conditions. In clinostatic conditions, tVNS reduced HR (p < 0.01), SAP variability (p < 0.01), and cardiac and peripheral sympathetic modulation (p < 0.01). The responsivity of the peripheral sympathetic modulation to orthostatic stress during tVNS was significantly higher when compared to the control session (p = 0.03). In conclusion, tVNS reduces the HR and affects cardiac and peripheral autonomic control and increases the responses of peripheral autonomic control to orthostatic stress in healthy subjects.