Neuromuscular electrical stimulation changes glucose, but not its variability in type 2 diabetes: a randomized clinical trial.

Neuromuscular electrical stimulation (NMES) can be an alternative to conventional exercising. This randomized clinical trial evaluated the effect of NMES in type 2 diabetes patients. Twenty-eight individuals with type 2 diabetes were assigned to NMES (n=14) or NMES-placebo (n=14) applied to knee extensor muscles for 60 minutes. Glucose variability, microvascular function and endothelial function were evaluated through continuous glucose monitoring system, near infrared spectroscopy and flow-mediated dilatation, respectively. Glucose levels (mg/dl) decreased 2h (184 ± 11 vs 223 ±15), 3h (179 ± 12 vs 219 ±14) and 4h (177 ± 12 vs 212 ±12) after NMES, in comparison to NMES-placebo. No differences in glucose variability were found: coefficient of variation (%) at 0-6h (11.4±1.3 vs 11.4±1.2), 6-12h (9.8±1.0 vs 11.6±1.6), 12-18h (15.5±2.0 vs 11.4±2.1), 18-24h (12.8±2.3 vs 10.0±1.6); standard deviation (mg/dl) at 0-6h (21.6±2 vs 24.6±3.5), 6-12h (19.5±1.8 vs 20.3±2.8), 12-18h (29.9±3.5 vs 21.3±2.8),18-24h (22.8±4.1 vs 16.6±2.0) and mean amplitude of glycemic excursions (mg/dl) 54.9±25.0 vs 70.3±35.7. Endothelial and microvascular functions did not change. In conclusion, one acute NMES session was strong enough to trigger glucose reduction in individuals with type 2 DM, but it failed to induce any significant change in glucose variability, endothelial and microvascular functions.

The prefrontal cortex conscious and unconscious response to social/emotional facial expressions involve sex, hemispheric laterality, and selective activation of the central cardiac modulation.

The human prefrontal cortex (PFC) processes complex sensory information for the elaboration of social behaviors. The non-invasive neuroimaging technique near-infrared spectroscopy (NIRS) identifies hemodynamic changes and concentration of oxygenated (HbO2) and deoxygenated (HHb) hemoglobin in the cerebral cortex. We studied the responses detected by NIRS in the right and left PFC activation of 28 participants (n = 14 adult young females and males) while processing social/emotional facial expressions, i.e., in conscious perception of different expressions (neutral, happy, sad, angry, disgust, and fearful) and in unconscious/masked perception of negative expressions (fearful and disgust overlapped by neutral). The power spectral analysis from concomitant ECG signals revealed the sympathetic and parasympathetic modulation of cardiac responses. We found higher HbO2 values in the right PFC of females than in males during, and in the left PFC after, following the conscious perception of the happy face. In males, the left PFC increased and the right PFC decreased HbO2 while viewing the happy expression. In both sexes, HHb values were higher during the masked presentation of disgust than fearful expression, and after the masked presentation of fearful expression than during it. Higher sympathetic and lower parasympathetic activity (LF/ HF components) occurred in females when consciously and unconsciously processing negative emotions (p < 0.05 in all cases). These results demonstrate that the human PFC displays a selective activation depending on sex, hemispheric laterality, attention, time for responding to conscious and unconscious emotionally loaded stimuli with simulataneous centrally modulated cardiovascular responses.

Acute inspiratory muscle exercise effect on glucose levels, glucose variability and autonomic control in patients with type 2 diabetes: A crossover randomized trial.

Inspiratory muscle exercise (IME) can be an alternative to conventional exercise. We aimed to evaluate the effect of IME on glucose, glucose variability, and autonomic cardiovascular control in type 2 diabetes. Fourteen diabetic subjects were randomly assigned to IME with 2% maximal inspiratory pressure (PImax) or 60% PImax wearing a continuous glucose monitoring system for three days. Glucose variability [glucose variance (VAR), glucose coefficient of variation (CV%), glucose standard deviation (SD), and mean amplitude of glycemic excursions (MAGE)] were evaluated. Glucose reduction was observed in 5 min (60% of PImax 33.2% and 2% of PImax 32.0%), 60 min (60% of PImax 29.6% and 2% of PImax 31.4%) and 120 min (60% of PImax 21.4% and 2% of PImax 24.0%) after IME (vs.1 h before the exercise), with no difference between loads. This reduction in glucose levels was observed in all moments of the IME protocol. Glucose variability was reduced after 12 h and 18 h of the IME (ΔCV: P < 0.001, ΔSD: P < 0.001 and ΔVAR: P < 0.001) for both loads. No difference was found in MAGE (P = 0.594) after IME. Mean arterial pressure and heart rate rose during the exercise session with 60% of PImax. Although sufficiently strong to induce cardiovascular changes, an inspiratory muscle exercise session with 60% of PImax in subjects with type 2 diabetes has failed to induce any significant improvement in glucose, glucose variability and autonomic control, compared to the 2% Plmax exercise session.

ß-blockers interfere with cell homing receptors and regulatory proteins in a model of spontaneously hypertensive rats.

AIM: To examine the interference of ß-blockers with the chemokine stromal cell-derived factor-1 (SDF-1) found in cell homing receptors, C-X-C chemokine receptor type 4 (CXCR-4) and CXCR-7, and regulatory proteins of homing pathways, we administered atenolol, carvedilol, metoprolol, and propranolol for 30 days using an orogastric tube to hypertensive rats. METHOD: We collected blood samples before and after treatment and quantified the levels of SDF-1 with enzyme-linked immunosorbent assay (ELISA). On day 30 of treatment, the spontaneously hypertensive rats (SHR) were euthanized, and heart, liver, lung, and kidney tissues were biopsied. Proteins were isolated for determining the expression of CXCR-4, CXCR-7, GRK-2 (G protein-coupled receptors kinase 2), ß-arrestins (ß1-AR and ß2-AR), and nuclear factor kappa B (NFκB). RESULTS: We found that the study drugs modulated these proteins, and metoprolol and propranolol strongly affected the expression of ß1-AR (P = .0102) and ß2-AR (P = .0034). CONCLUSION: ß-blockers modulated tissue expression of the proteins and their interactions following 30 days of treatment. It evidences that this class of drugs can interfere with proteins of cell homing pathways.

Correlation between Very Short and Short-Term Blood Pressure Variability in Diabetic-Hypertensive and Healthy Subjects.

BACKGROUND: Blood pressure (BP) variability can be evaluated by 24-hour ambulatory BP monitoring (24h-ABPM), but its concordance with results from finger BP measurement (FBPM) has not been established yet. OBJECTIVE: The aim of this study was to compare parameters of short-term (24h-ABPM) with very short-term BP variability (FBPM) in healthy (C) and diabetic-hypertensive (DH) subjects. METHODS: Cross-sectional study with 51 DH subjects and 12 C subjects who underwent 24h-ABPM [extracting time-rate, standard deviation (SD), coefficient of variation (CV)] and short-term beat-to-beat recording at rest and after standing-up maneuvers [FBPM, extracting BP and heart rate (HR) variability parameters in the frequency domain, autoregressive spectral analysis]. Spearman correlation coefficient was used to correlate BP and HR variability parameters obtained from both FBPM and 24h-ABPM (divided into daytime, nighttime, and total). Statistical significance was set at p < 0.05. RESULTS: There was a circadian variation of BP levels in C and DH groups; systolic BP and time-rate were higher in DH subjects in all periods evaluated. In C subjects, high positive correlations were shown between time-rate index (24h-ABPM) and LF component of short-term variability (FBPM, total, R = 0.591, p = 0.043); standard deviation (24h-ABPM) with LF component BPV (FBPM, total, R = 0.608, p = 0.036), coefficient of variation (24h-ABPM) with total BPV (FBPM, daytime, -0.585, p = 0.046) and alpha index (FBPM, daytime, -0.592, p = 0.043), time rate (24h-ABPM) and delta LF/HF (FBPM, total, R = 0.636, p = 0.026; daytime R = 0,857, p < 0.001). Records obtained from DH showed weak positive correlations. CONCLUSIONS: Indices obtained from 24h-ABPM (total, daytime) reflect BP and HR variability evaluated by FBPM in healthy individuals. This does not apply for DH subjects.

Correlation between Very Short and Short-Term Blood Pressure Variability in Diabetic-Hypertensive and Healthy Subjects / Correlação entre a Variabilidade da Pressão Arterial de Muito Curto Prazo e Curto Prazo em Indivíduos Diabéticos-Hipertensos e Saudáveis

Abstract Background: Blood pressure (BP) variability can be evaluated by 24-hour ambulatory BP monitoring (24h-ABPM), but its concordance with results from finger BP measurement (FBPM) has not been established yet. Objective: The aim of this study was to compare parameters of short-term (24h-ABPM) with very short-term BP variability (FBPM) in healthy (C) and diabetic-hypertensive (DH) subjects. Methods: Cross-sectional study with 51 DH subjects and 12 C subjects who underwent 24h-ABPM [extracting time-rate, standard deviation (SD), coefficient of variation (CV)] and short-term beat-to-beat recording at rest and after standing-up maneuvers [FBPM, extracting BP and heart rate (HR) variability parameters in the frequency domain, autoregressive spectral analysis]. Spearman correlation coefficient was used to correlate BP and HR variability parameters obtained from both FBPM and 24h-ABPM (divided into daytime, nighttime, and total). Statistical significance was set at p < 0.05. Results: There was a circadian variation of BP levels in C and DH groups; systolic BP and time-rate were higher in DH subjects in all periods evaluated. In C subjects, high positive correlations were shown between time-rate index (24h-ABPM) and LF component of short-term variability (FBPM, total, R = 0.591, p = 0.043); standard deviation (24h-ABPM) with LF component BPV (FBPM, total, R = 0.608, p = 0.036), coefficient of variation (24h-ABPM) with total BPV (FBPM, daytime, -0.585, p = 0.046) and alpha index (FBPM, daytime, -0.592, p = 0.043), time rate (24h-ABPM) and delta LF/HF (FBPM, total, R = 0.636, p = 0.026; daytime R = 0,857, p < 0.001). Records obtained from DH showed weak positive correlations. Conclusions: Indices obtained from 24h-ABPM (total, daytime) reflect BP and HR variability evaluated by FBPM in healthy individuals. This does not apply for DH subjects.

Resumo Fundamento: A variabilidade da pressão arterial (PA) pode ser avaliada por meio da monitorização ambulatorial da PA em 24 horas (MAPA-24h), mas sua concordância com os resultados da medição da PA digital (MPAD) ainda não foi estabelecida. Objetivo: O objetivo deste estudo foi comparar os parâmetros da variabilidade a curto prazo (MAPA-24h) com a variabilidade da PA a muito curto prazo (MPAD) em sujeitos saudáveis (C) e diabéticos-hipertensos (DH). Métodos: Estudo transversal com 51 sujeitos DH e 12 sujeitos C que se submeteram a MAPA-24h [extraindo time rate, desvio padrão (SD) e coeficiente de variação (CV)] e registro batimento-a-batimento em repouso e após manobra de manobra de ortostatismo ativo [MPAD, extraindo parâmetros de variabilidade da PA e da frequência cardíaca (FC) no domínio da frequência, análise espectral por modelagem autoregressiva]. O coeficiente de correlação de postos de Spearman foi utilizado para correlacionar os parâmetros de variabilidade de PA e FC obtidos tanto da MPAD quanto da MAPA-24h (dividida em dia, noite e total). A significância estatística foi estabelecida em p < 0.05. Resultados: Houve uma variação circadiana dos níveis de PA nos grupos C e DH; A PA sistólica e a taxa de tempo foram maiores em indivíduos DH em todos os períodos avaliados. Em indivíduos C, foram apresentadas altas correlações positivas entre o índice de taxa de tempo (MAPA-24h) e o componente de baixa frequência (LF, do inglês low frequency) da variabilidade de curto prazo (MPAD, total, R = 0,591, p = 0,043); desvio padrão (MAPA-24h) com o componente de LF VPA (MPAD, total, R = 0,608, p = 0,036), coeficiente de variação (24h-ABPM) com VPA total (MPAD, dia, -0,585, p = 0,046) e índice alfa (MPAD, dia, -0,592, p = 0,043), taxa de tempo (MAPA-24h) e delta LF/HF (MPAD, total, R = 0,636, p = 0,026; dia R = 0,857, p < 0,001). Os registros obtidos dos pacientes DH apresentaram correlações positivas fracas. Conclusões: Os índices obtidos a partir da MAPA-24h (total, durante o dia) refletem a variabilidade da PA e da FC avaliada pela MPAD em indivíduos saudáveis, o que não se aplica a indivíduos DH.

Contribution of Impaired Parasympathetic Activity to Right Ventricular Dysfunction and Pulmonary Vascular Remodeling in Pulmonary Arterial Hypertension.

BACKGROUND: The beneficial effects of parasympathetic stimulation have been reported in left heart failure, but whether it would be beneficial for pulmonary arterial hypertension (PAH) remains to be explored. Here, we investigated the relationship between parasympathetic activity and right ventricular (RV) function in patients with PAH, and the potential therapeutic effects of pyridostigmine (PYR), an oral drug stimulating the parasympathetic activity through acetylcholinesterase inhibition, in experimental pulmonary hypertension (PH). METHODS: Heart rate recovery after a maximal cardiopulmonary exercise test was used as a surrogate for parasympathetic activity. RV ejection fraction was assessed in 112 patients with PAH. Expression of nicotinic (α-7 nicotinic acetylcholine receptor) and muscarinic (muscarinic acetylcholine type 2 receptor) receptors, and acetylcholinesterase activity were evaluated in RV (n=11) and lungs (n=7) from patients with PAH undergoing heart/lung transplantation and compared with tissue obtained from controls. In addition, we investigated the effects of PYR (40 mg/kg per day) in experimental PH. PH was induced in male rats by SU5416 (25 mg/kg subcutaneously) injection followed by 4 weeks of hypoxia. In a subgroup, sympathetic/parasympathetic modulation was assessed by power spectral analysis. At week 6, PH status was confirmed by echocardiography, and rats were randomly assigned to vehicle or treatment (both n=12). At the end of the study, echocardiography was repeated, with additional RV pressure-volume measurements, along with lung, RV histological, and protein analyses. RESULTS: Patients with PAH with lower RV ejection fraction (<41%) had a significantly reduced heart rate recovery in comparison with patients with higher RV ejection fraction. In PAH RV samples, α-7 nicotinic acetylcholine receptor was increased and acetylcholinesterase activity was reduced versus controls. No difference in muscarinic acetylcholine type 2 receptor expression was observed. Chronic PYR treatment in PH rats normalized the cardiovascular autonomic function, demonstrated by an increase in parasympathetic activity and baroreflex sensitivity. PYR improved survival, increased RV contractility, and reduced RV stiffness, RV hypertrophy, RV fibrosis, RV inflammation, and RV α-7 nicotinic acetylcholine receptor and muscarinic acetylcholine type 2 receptor expression, as well. Furthermore, PYR reduced pulmonary vascular resistance, RV afterload, and pulmonary vascular remodeling, which was associated with reduced local and systemic inflammation. CONCLUSIONS: RV dysfunction is associated with reduced systemic parasympathetic activity in patients with PAH, with an inadequate adaptive response of the cholinergic system in the RV. Enhancing parasympathetic activity by PYR improved survival, RV function, and pulmonary vascular remodeling in experimental PH.

Chronic Treatment with Ivabradine Does Not Affect Cardiovascular Autonomic Control in Rats.

A low resting heart rate (HR) would be of great benefit in cardiovascular diseases. Ivabradine-a novel selective inhibitor of hyperpolarization-activated cyclic nucleotide gated (HCN) channels- has emerged as a promising HR lowering drug. Its effects on the autonomic HR control are little known. This study assessed the effects of chronic treatment with ivabradine on the modulatory, reflex and tonic cardiovascular autonomic control and on the renal sympathetic nerve activity (RSNA). Male Wistar rats were divided in 2 groups, receiving intraperitoneal injections of vehicle (VEH) or ivabradine (IVA) during 7 or 8 consecutive days. Rats were submitted to vessels cannulation to perform arterial blood pressure (AP) and HR recordings in freely moving rats. Time series of resting pulse interval and systolic AP were used to measure cardiovascular variability parameters. We also assessed the baroreflex, chemoreflex and the Bezold-Jarish reflex sensitivities. To better evaluate the effects of ivabradine on the autonomic control of the heart, we performed sympathetic and vagal autonomic blockade. As expected, ivabradine-treated rats showed a lower resting (VEH: 362 ± 16 bpm vs. IVA: 260 ± 14 bpm, p = 0.0005) and intrinsic HR (VEH: 369 ± 9 bpm vs. IVA: 326 ± 11 bpm, p = 0.0146). However, the chronic treatment with ivabradine did not change normalized HR spectral parameters LF (nu) (VEH: 24.2 ± 4.6 vs. IVA: 29.8 ± 6.4; p > 0.05); HF (nu) (VEH: 75.1 ± 3.7 vs. IVA: 69.2 ± 5.8; p > 0.05), any cardiovascular reflexes, neither the tonic autonomic control of the HR (tonic sympathovagal index; VEH: 0.91± 0.02 vs. IVA: 0.88 ± 0.03, p = 0.3494). We performed the AP, HR and RSNA recordings in urethane-anesthetized rats. The chronic treatment with ivabradine reduced the resting HR (VEH: 364 ± 12 bpm vs. IVA: 207 ± 11 bpm, p < 0.0001), without affecting RSNA (VEH: 117 ± 16 vs. IVA: 120 ± 9 spikes/s, p = 0.9100) and mean arterial pressure (VEH: 70 ± 4 vs. IVA: 77 ± 6 mmHg, p = 0.3293). Our results suggest that, in health rats, the long-term treatment with ivabradine directly reduces the HR without changing the RSNA modulation and the reflex and tonic autonomic control of the heart.

Preserved cardiac autonomic dynamics during sleep in subjects with spinal cord injuries.

BACKGROUND: Spinal cord injuries (SCI) are associated with altered cardiovascular autonomic control (CAC). Sleep is characterized by modifications of autonomic control across sleep stages; however, no data are available in SCI subjects on CAC during sleep. We aim to assess cardiac autonomic modulation during sleep in subjects with SCI. PATIENTS AND METHODS: 27 participants with a neurological and radiological diagnosis of cervical (Cerv, n = 12, ie, tetraplegic) and thoracic SCI (Thor, n = 15, ie, paraplegic) and healthy subjects (Controls) were enrolled. Overnight polysomnographic (PSG) recordings were obtained in all participants. Electrocardiography and respiration were extracted from PSG, divided into sleep stages [wakefulness (W), non-REM sleep (NREM) and REM] for assessment of CAC, using symbolic analysis (SA) and corrected conditional entropy (CCE). SA identified indices of sympathetic and parasympathetic modulation and CCE evaluated the degree of complexity of the heart period time series. RESULTS: SA revealed a reduction of sympathetic and predominant parasympathetic control during NREM compared to W and REM in SCI patients, independent of the level of the lesion, similar to the Controls. In all three groups, complexity of autonomic regulation was higher in NREM compared to W and REM. CONCLUSIONS: In subjects with SCI, cardiac autonomic control changed across sleep stages, with a reduction of sympathetic and an increase of parasympathetic modulation during NREM compared to W and REM, and a parallel increase of complexity during NREM, which was similar to the Controls. Cardiac autonomic dynamics during sleep are maintained in SCI, independent of the level of the lesion.

An orally active angiotensin-(1-7) inclusion compound and exercise training produce similar cardiovascular effects in spontaneously hypertensive rats.

Low angiotensin-(1-7) (Ang-(1-7)) concentration is observed in some cardiovascular diseases and exercise training seems to restore its concentration in the heart. Recently, a novel formulation of an orally active Ang-(1-7) included in hydroxy-propyl-beta-cyclodextrin (HPB-CD) was developed and chronically administered in experimental models of cardiovascular diseases. The present study examined whether chronic administration of HPB-CD/Ang-(1-7) produces beneficial cardiovascular effects in spontaneously hypertensive rats (SHR), as well as to compare the results obtained with those produced by exercise training. Male SHR (15-week old) were divided in control (tap water) or treated with HPB-CD/Ang-(1-7) (corresponding to 30µgkg(-1)day(-1) of Ang-(1-7)) by gavage, concomitantly or not to exercise training (treadmill, 10 weeks). After chronic treatment, hemodynamic, morphometric and molecular analysis in the heart were performed. Chronic HPB-CD/Ang-(1-7) decreased arterial blood pressure (BP) and heart rate in SHR. The inclusion compound significantly improved left ventricular (LV) end-diastolic pressure, restored the maximum and minimum derivatives (dP/dT) and decreased cardiac hypertrophy index in SHR. Chronic treatment improved autonomic control by attenuating sympathetic modulation on heart and vessels and the SAP variability, as well as increasing parasympathetic modulation and HR variability. Overall results were similar to those obtained with exercise training. These results show that chronic treatment with the HPB-CD/Ang-(1-7) inclusion compound produced beneficial effects in SHR resembling the ones produced by exercise training. This observation reinforces the potential cardiovascular therapeutic effect of this novel peptide formulation.

Low-dose estrogen is as effective as high-dose treatment in rats with postmenopausal hypertension.

: This study was conducted to test the hypothesis that 17ß-estradiol therapy improves redox balance by decreasing reactive oxygen species production and increasing nitric oxide (NO) bioavailability, favoring Akt pathway activation and resulting in a better autonomic vascular control. Ovariectomized female Wistar rats were divided into 4 groups: (1) vehicle (VL) and animals treated with a pellet of 17ß-estradiol for 21 days; (2) low dose (LE; 0.05 mg); (3) medium dose (ME; 0.2 mg); and (4) high dose (HE; 0.5 mg). Arterial pressure and its sympathetic nervous system modulation were evaluated by spectral analysis. Nitric oxide synthase and NADPH oxidase (Nox) activities, H2O2 concentration, redox status (GSH/GSSG), protein expression of Trx-1 and p-Akt/Akt were evaluated in the aorta, whereas NO metabolites were measured in the serum. Estrogen-treated groups showed a significant decrease in arterial pressure and sympathetic vascular drive. Redox status was significantly improved and NADPH oxidase and H2O2 were decreased in all estrogen-treated groups. Estrogen also induced an enhancement in NO metabolites, nitric oxide synthase activity, and Akt phosphorylation. This study demonstrated that estrogen treatment to ovariectomized rats induced cardioprotection, which was evidenced by reduced blood pressure variability and vascular sympathetic drive. These effects were associated with an improved redox balance and Akt activation, resulting in an enhanced NO bioavailability.

Heart rate variability in normal and pathological sleep.

Sleep is a physiological process involving different biological systems, from molecular to organ level; its integrity is essential for maintaining health and homeostasis in human beings. Although in the past sleep has been considered a state of quiet, experimental and clinical evidences suggest a noteworthy activation of different biological systems during sleep. A key role is played by the autonomic nervous system (ANS), whose modulation regulates cardiovascular functions during sleep onset and different sleep stages. Therefore, an interest on the evaluation of autonomic cardiovascular control in health and disease is growing by means of linear and non-linear heart rate variability (HRV) analyses. The application of classical tools for ANS analysis, such as HRV during physiological sleep, showed that the rapid eye movement (REM) stage is characterized by a likely sympathetic predominance associated with a vagal withdrawal, while the opposite trend is observed during non-REM sleep. More recently, the use of non-linear tools, such as entropy-derived indices, have provided new insight on the cardiac autonomic regulation, revealing for instance changes in the cardiovascular complexity during REM sleep, supporting the hypothesis of a reduced capability of the cardiovascular system to deal with stress challenges. Interestingly, different HRV tools have been applied to characterize autonomic cardiac control in different pathological conditions, from neurological sleep disorders to sleep disordered breathing (SDB). In summary, linear and non-linear analysis of HRV are reliable approaches to assess changes of autonomic cardiac modulation during sleep both in health and diseases. The use of these tools could provide important information of clinical and prognostic relevance.

A theoretically based index of consciousness independent of sensory processing and behavior.

One challenging aspect of the clinical assessment of brain-injured, unresponsive patients is the lack of an objective measure of consciousness that is independent of the subject's ability to interact with the external environment. Theoretical considerations suggest that consciousness depends on the brain's ability to support complex activity patterns that are, at once, distributed among interacting cortical areas (integrated) and differentiated in space and time (information-rich). We introduce and test a theory-driven index of the level of consciousness called the perturbational complexity index (PCI). PCI is calculated by (i) perturbing the cortex with transcranial magnetic stimulation (TMS) to engage distributed interactions in the brain (integration) and (ii) compressing the spatiotemporal pattern of these electrocortical responses to measure their algorithmic complexity (information). We test PCI on a large data set of TMS-evoked potentials recorded in healthy subjects during wakefulness, dreaming, nonrapid eye movement sleep, and different levels of sedation induced by anesthetic agents (midazolam, xenon, and propofol), as well as in patients who had emerged from coma (vegetative state, minimally conscious state, and locked-in syndrome). PCI reliably discriminated the level of consciousness in single individuals during wakefulness, sleep, and anesthesia, as well as in patients who had emerged from coma and recovered a minimal level of consciousness. PCI can potentially be used for objective determination of the level of consciousness at the bedside.

Diminazene aceturate improves autonomic modulation in pulmonary hypertension.

We have previously demonstrated that diminazene aceturate (DIZE), a putative angiotensin 1-7 converting enzyme activator, protects rats from monocrotaline (MCT)-induced pulmonary hypertension (PH). The present study was conducted to determine if the beneficial effects of DIZE are associated with improvements in autonomic nervous system (ANS) modulation. PH was induced in male rats by a single subcutaneous injection of MCT (50 mg/kg). A subset of MCT rats were treated with DIZE (15 mg/kg/day) for a period of 21 days, after which the ANS modulation was evaluated by spectral and symbolic analysis of heart rate variability (HRV). MCT administration resulted in a significant (P<0.001) increase in the right ventricular systolic pressure (62 ± 14 mmHg) when compared with other experimental groups (Control: 26 ± 6; MCT + DIZE: 31 ± 7 mmHg), while DIZE treatment was able to decrease this pressure. Furthermore MCT-treated rats had significantly reduced total power of HRV than the controls. On the other hand, although not significant, a trend towards increased HRV was observed in the MCT + DIZE group (Control: 108 ± 47; MCT: 12 ± 8.86 and MCT + DIZE: 40 ± 14), suggesting an improvement of the cardiac autonomic modulation. This observation was further confirmed by the low-frequency/high-frequency index of spectral analysis (Control: 0.74 ± 0.62; MCT: 1.45 ± 0.78 and MCT + DIZE: 0.34 ± 0.49) which showed that DIZE treatment was able to recover the ANS imbalance observed in the MCT-induced pulmonary hypertensive rats. Collectively, our results demonstrate that MCT-induced PH is associated with a significant increase in sympathetic modulation and a decrease in HRV, which are markedly improved by DIZE treatment.

Aerobic and combined exercise sessions reduce glucose variability in type 2 diabetes: crossover randomized trial.

PURPOSE: To evaluate the effects of aerobic (AER) or aerobic plus resistance exercise (COMB) sessions on glucose levels and glucose variability in patients with type 2 diabetes. Additionally, we assessed conventional and non-conventional methods to analyze glucose variability derived from multiple measurements performed with continuous glucose monitoring system (CGMS). METHODS: Fourteen patients with type 2 diabetes (56±2 years) wore a CGMS during 3 days. Participants randomly performed AER and COMB sessions, both in the morning (24 h after CGMS placement), and at least 7 days apart. Glucose variability was evaluated by glucose standard deviation, glucose variance, mean amplitude of glycemic excursions (MAGE), and glucose coefficient of variation (conventional methods) as well as by spectral and symbolic analysis (non-conventional methods). RESULTS: Baseline fasting glycemia was 139±05 mg/dL and HbA1c 7.9±0.7%. Glucose levels decreased immediately after AER and COMB protocols by ∼16%, which was sustained for approximately 3 hours. Comparing the two exercise modalities, responses over a 24-h period after the sessions were similar for glucose levels, glucose variance and glucose coefficient of variation. In the symbolic analysis, increases in 0 V pattern (COMB, 67.0±7.1 vs. 76.0±6.3, P = 0.003) and decreases in 1 V pattern (COMB, 29.1±5.3 vs. 21.5±5.1, P = 0.004) were observed only after the COMB session. CONCLUSIONS: Both AER and COMB exercise modalities reduce glucose levels similarly for a short period of time. The use of non-conventional analysis indicates reduction of glucose variability after a single session of combined exercises. TRIAL REGISTRATION: Aerobic training, aerobic-resistance training and glucose profile (CGMS) in type 2 diabetes (CGMS exercise). ClinicalTrials.gov ID: NCT00887094.

Glutamate and GABA in the medial amygdala induce selective central sympathetic/parasympathetic cardiovascular responses.

Glutamate and γ-aminobutyric acid (GABA) participate in central cardiovascular control, and are found in the rat posterodorsal medial amygdala (MePD), an area of the forebrain that modulates emotional/social behaviors. Here we tested whether these neurotransmitters in the MePD could change the basal activity, chemoreflex, and baroreflex cardiovascular responses in awake rats. Power spectral analysis and symbolic analysis were used to evaluate these responses. Microinjections of saline, glutamate (2 µg), or GABA (61 ng or 100 µg; n = 5-7 rats per group) did not affect basal parameters or chemoreflex responses. However, baroreflex responses showed marked changes. Glutamate increased power spectral and symbolic sympathetic indexes related to both cardiac and vascular modulations (P < 0.05). In turn, the displacement of the baroreflex half-maximal heart rate (HR) response was associated with a GABA (61 ng) mediated decrease in the upper plateau (P < 0.05). Administration of GABA (61 ng, but not 100 µg) also increased HR variability (P < 0.05), in association with parasympathetic activation. These data add novel evidence that the MePD can promote selective responses in the central regulation of the cardiovascular system, i.e., glutamate in the MePD evoked activation of a central sympathetic reflex adjustment, whereas GABA activated a central parasympathetic one.

Yoga respiratory training improves respiratory function and cardiac sympathovagal balance in elderly subjects: a randomised controlled trial.

OBJECTIVES: Since ageing is associated with a decline in pulmonary function, heart rate variability and spontaneous baroreflex, and recent studies suggest that yoga respiratory exercises may improve respiratory and cardiovascular function, we hypothesised that yoga respiratory training may improve respiratory function and cardiac autonomic modulation in healthy elderly subjects. DESIGN: 76 healthy elderly subjects were enrolled in a randomised control trial in Brazil and 29 completed the study (age 68 ± 6 years, 34% males, body mass index 25 ± 3 kg/m²). Subjects were randomised into a 4-month training program (2 classes/week plus home exercises) of either stretching (control, n=14) or respiratory exercises (yoga, n=15). Yoga respiratory exercises (Bhastrika) consisted of rapid forced expirations followed by inspiration through the right nostril, inspiratory apnoea with generation of intrathoracic negative pressure, and expiration through the left nostril. Pulmonary function, maximum expiratory and inspiratory pressures (PE(max) and PI(max), respectively), heart rate variability and blood pressure variability for spontaneous baroreflex determination were determined at baseline and after 4 months. RESULTS: Subjects in both groups had similar demographic parameters. Physiological variables did not change after 4 months in the control group. However, in the yoga group, there were significant increases in PE(max) (34%, p<0.0001) and PI(max) (26%, p<0.0001) and a significant decrease in the low frequency component (a marker of cardiac sympathetic modulation) and low frequency/high frequency ratio (marker of sympathovagal balance) of heart rate variability (40%, p<0.001). Spontaneous baroreflex did not change, and quality of life only marginally increased in the yoga group. CONCLUSION: Respiratory yoga training may be beneficial for the elderly healthy population by improving respiratory function and sympathovagal balance. Trial Registration CinicalTrials.gov identifier: NCT00969345; trial registry name: Effects of respiratory yoga training (Bhastrika) on heart rate variability and baroreflex, and quality of life of healthy elderly subjects.

Functional electrical stimulation training on functional capacity and blood pressure variability in a centenarian woman: case study.

BACKGROUND: Functional electrical stimulation (FES) is a rehabilitation method that can revert alterations provoked by aging, such as reductions in functional capacity and modifications on blood pressure variability (BPV). OBJECTIVES: To evaluate the training effects of FES on functional capacity and BPV in a centenarian woman. METHODS: A 101-year-old woman without previous disease underwent FES training for 12 weeks, with three 40 min sessions/week. FES was applied at a frequency of 20 Hz with a 0.5 ms pulse, 5 s contraction time, 10 s relaxation time, the maximum tolerable intensity and with progressive overload. Functional capacity was assessed with a six-minute walk test (6MWT) and proximal lower limb strength was assessed with a sit-and-stand test (STST). BPV was measured by continuous recording of pulse pressure and calculated by spectral analysis. All variables were measured before and after FES training. RESULTS: After training there was a 70% increase in distance walked in the 6MWT, a 300% increase in the number of STST repetitions, an 8 mmHg reduction in systolic blood pressure (SBP) and a 4 mmHg reduction in diastolic blood pressure (DBP) and mean blood pressure (MBP). Reductions in SBP (11.8 mmHg²), DBP (2.3 mmHg²) and MBP (6.0 mmHg²) variability were also observed. CONCLUSIONS: Three months of FES training improved functional capacity and BPV in a centenarian woman.

Functional electrical stimulation training on functional capacity and blood pressure variability in a centenarian woman: case study / Treinamento com estimulação elétrica funcional sobre a capacidade funcional e a variabilidade da pressão arterial em uma idosa centenária: estudo de caso

BACKGROUND: Functional electrical stimulation (FES) is a rehabilitation method that can revert alterations provoked by aging, such as reductions in functional capacity and modifications on blood pressure variability (BPV). OBJECTIVES: To evaluate the training effects of FES on functional capacity and BPV in a centenarian woman. METHODS: A 101-year-old woman without previous disease underwent FES training for 12 weeks, with three 40 min sessions/week. FES was applied at a frequency of 20 Hz with a 0.5 ms pulse, 5 s contraction time, 10 s relaxation time, the maximum tolerable intensity and with progressive overload. Functional capacity was assessed with a six-minute walk test (6MWT) and proximal lower limb strength was assessed with a sit-and-stand test (STST). BPV was measured by continuous recording of pulse pressure and calculated by spectral analysis. All variables were measured before and after FES training. RESULTS: After training there was a 70 percent increase in distance walked in the 6MWT, a 300 percent increase in the number of STST repetitions, an 8 mmHg reduction in systolic blood pressure (SBP) and a 4 mmHg reduction in diastolic blood pressure (DBP) and mean blood pressure (MBP). Reductions in SBP (11.8 mmHg²), DBP (2.3 mmHg²) and MBP (6.0 mmHg²) variability were also observed. CONCLUSIONS: Three months of FES training improved functional capacity and BPV in a centenarian woman.

CONTEXTUALIZAÇÃO: A estimulação elétrica funcional (EEF) é uma forma de reabilitação que pode reverter alterações provocadas pelo envelhecimento, como diminuição da capacidade funcional e modificações na variabilidade da pressão arterial (VPA). OBJETIVOS: Avaliar os efeitos do treinamento com EEF sobre a capacidade funcional e a VPA em uma idosa centenária. MÉTODOS: Paciente do sexo feminino, 101 anos e sem patologia prévia. O treinamento com EEF foi realizado durante 12 semanas, sendo três sessões/semana e tempo máximo de aplicação de 40 min/sessão. A EEF foi aplicada com frequência de 20 Hz, largura de pulso de 0,5 ms, tempo de contração de 5 s, tempo de repouso de 10 s, intensidade máxima tolerável e aplicação de sobrecarga progressiva. A capacidade funcional foi avaliada por meio do teste de caminhada de 6 minutos (TC6) e do teste de sentar e levantar (TSL). A VPA foi mensurada pelo registro contínuo da pressão de pulso e calculada pela análise espectral. Todas as variáveis foram mensuradas pré e pós-treinamento. RESULTADOS: Após treinamento, houve um aumento de 70 por cento na distância percorrida no TC6 e aumento de 300 por cento no número de repetições no TSL. Observou-se redução de 8 mmHg na pressão arterial sistólica (PAS) e de 4 mmHg na pressão arterial diastólica (PAD) e na pressão arterial média (PAM), havendo ainda uma redução na variabilidade da PAS (11,8 mmHg²), da PAD (2,3 mmHg²) e da PAM (6,0 mmHg²). CONCLUSÕES: O treinamento com EEF durante três meses proporcionou aumento da capacidade funcional e melhora da VPA em uma idosa centenária.

Renal denervation in an animal model of diabetes and hypertension: impact on the autonomic nervous system and nephropathy.

BACKGROUND: The effects of renal denervation on cardiovascular reflexes and markers of nephropathy in diabetic-hypertensive rats have not yet been explored. AIM: To evaluate the effects of renal denervation on nephropathy development mechanisms (blood pressure, cardiovascular autonomic changes, renal GLUT2) in diabetic-hypertensive rats. Forty-one male spontaneously hypertensive rats (SHR) ~250 g were injected with STZ or not; 30 days later, surgical renal denervation (RD) or sham procedure was performed; 15 days later, glycemia and albuminuria (ELISA) were evaluated. Catheters were implanted into the femoral artery to evaluate arterial pressure (AP) and heart rate variability (spectral analysis) one day later in conscious animals. Animals were killed, kidneys removed, and cortical renal GLUT2 quantified (Western blotting). RESULTS: Higher glycemia (p < 0.05) and lower mean AP were observed in diabetics vs. nondiabetics (p < 0.05). Heart rate was higher in renal-denervated hypertensive and lower in diabetic-hypertensive rats (384.8 +/- 37, 431.3+/- 36, 316.2 +/- 5, 363.8 +/- 12 bpm in SHR, RD-SHR,STZ-SHR and RD-STZ-SHR, respectively). Heart rate variability was higher in renal-denervated diabetic hypertensive rats (69.84 ± 37.91, 55.75 ± 25.21, 73.40 ±53.30, 148.4 ± 93 in SHR, RD-SHR, STZ-SHR- and RDSTZ-SHR, respectively, p < 0.05), as well as the LF component of AP variability (5.17 ± 5.24, 1.62 ± 0.9, 2.12 ±0.9, 7.38 ± 6.5 in SHR, RD-SHR, STZ-SHR and RDSTZ-SHR, respectively, p < 0.05). GLUT2 renal content was higher in all groups vs. SHR [corrected]. CONCLUSIONS: Renal denervation in diabetic-hypertensive rats improved previously reduced heart rate variability. The GLUT2 equally overexpressed by diabetes and renal denervation may represent a maximal derangement effect of each condition.