Impact of neonatal hyperoxia on adult cardiac autonomic function in rats: Role of angiotensin II type 1 receptor activation.

Individuals born preterm present altered cardiac autonomic function, a risk factor to heart diseases. Neonatal renin-angiotensin-system activation contributes to adult cardiomyopathy in rats exposed to neonatal hyperoxia, a well-established model of preterm birth-related conditions. Central angiotensin II receptor activation is a key modulator of the autonomic drive to the heart. Whether neonatal hyperoxia leads to alteration of the cardiac autonomic function through activation of the angiotensin II receptor type 1 (AT1) is unknown and was examined in the present study. Sprague-Dawley pups were exposed to hyperoxia or room air from postnatal days 3-10. AT1 antagonist losartan or water was given orally postnatal days 8-10. Blood pressure, autonomic function, left ventricular sympathetic innervation, ß-adrenergic-receptors expression, and AT1 expression in the solitary-tract-nucleus were examined in adult rats. Neonatal hyperoxia led to loss of day-night blood pressure variation, decreased heart rate variability, increased sympathovagal balance, increased AT1 expression in the solitary-tract, decreased left ventricle sympathetic innervation, and increased ß1-adrenergic-receptor protein expression. Losartan prevented the autonomic changes and AT1 expression in the solitary-tract but did not impact the loss of circadian blood pressure variation nor the changes in sympathetic innervation and in ß1-adrenergic-receptor expression. In conclusion, neonatal hyperoxia leads to both central autonomic and cardiac sympathetic changes, partly programmed by neonatal activation of the renin-angiotensin system.

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.

Automatic Classification of Emotions Based on Cardiac Signals: A Systematic Literature Review.

Emotions play a pivotal role in human cognition, exerting influence across diverse domains of individuals' lives. The widespread adoption of artificial intelligence and machine learning has spurred interest in systems capable of automatically recognizing and classifying emotions and affective states. However, the accurate identification of human emotions remains a formidable challenge, as they are influenced by various factors and accompanied by physiological changes. Numerous solutions have emerged to enable emotion recognition, leveraging the characterization of biological signals, including the utilization of cardiac signals acquired from low-cost and wearable sensors. The objective of this work was to comprehensively investigate the current trends in the field by conducting a Systematic Literature Review (SLR) that focuses specifically on the detection, recognition, and classification of emotions based on cardiac signals, to gain insights into the prevailing techniques employed for signal acquisition, the extracted features, the elicitation process, and the classification methods employed in these studies. A SLR was conducted using four research databases, and articles were assessed concerning the proposed research questions. Twenty seven articles met the selection criteria and were assessed for the feasibility of using cardiac signals, acquired from low-cost and wearable devices, for emotion recognition. Several emotional elicitation methods were found in the literature, including the algorithms applied for automatic classification, as well as the key challenges associated with emotion recognition relying solely on cardiac signals. This study extends the current body of knowledge and enables future research by providing insights into suitable techniques for designing automatic emotion recognition applications. It emphasizes the importance of utilizing low-cost, wearable, and unobtrusive devices to acquire cardiac signals for accurate and accessible emotion recognition.

Advances in Non-Invasive Neuromodulation: Designing Closed-Loop Devices for Respiratory-Controlled Transcutaneous Vagus Nerve Stimulation.

Studies suggest non-invasive transcutaneous auricular vagus nerve stimulation (taVNS) as a potential therapeutic option for various pathological conditions, such as epilepsy and depression. Exhalation-controlled taVNS, which synchronizes stimulation with internal body rhythms, holds promise for enhanced neuromodulation, but there is no closed-loop system in the literature capable of performing such integration in real time. In this context, the objective was to develop real-time signal processing techniques and an integrated closed-loop device with sensors to acquire physiological data. After a conditioning stage, the signal is processed and delivers synchronized electrical stimulation during the patient's expiratory phase. Additional modules were designed for processing, software-controlled selectors, remote and autonomous operation, improved analysis, and graphical visualization. The signal processing method effectively extracted respiratory cycles and successfully attenuated signal noise. Heart rate variability was assessed in real time, using linear statistical evaluation. The prototype feedback stimulator device was physically constructed. Respiratory peak detection achieved an accuracy of 90%, and the real-time processing resulted in a small delay of up to 150 ms in the detection of the expiratory phase. Thus, preliminary results show promising accuracy, indicating the need for additional tests to optimize real-time processing and the application of the prototype in clinical studies.

Maintenance of plasma glucose variability after an acute session of aerobic exercise despite changes in insulin and glucagon-like peptide-1 levels in type 2 diabetes

ABSTRACT Objective: The present study aimed to evaluate glucose variability and hormonal responses during and after an aerobic exercise session performed after breakfast in type 2 diabetes patients treated with metformin. Materials and methods: In this quasi-experimental study individuals underwent clinical and laboratory evaluations and maximal exercise test. After two weeks an aerobic exercise session (30 minutes at 60%-70% of the peak heart rate) was performed. At rest, during and after the exercise session, glucose variability (mean amplitude glucose excursions, glucose coefficient of variation, and glucose standard deviation) and levels of plasma glucose, insulin, glucagon, and glucagon-like-peptide-1 were evaluated. Results: Thirteen patients were enrolled in the study. Plasma glucose increased at 15 minutes during the exercise session (244.6 ± 61.9 mg/dL), and decreased at 60 min after exercise (195.6 ± 50.0 mg/dL). Glucose variability did not show any difference before and after exercise. Insulin levels at 15 min [27.1 µU/mL (14.2-42.1)] and 30 min [26.3 µU/mL (14.6-37.4)] during the exercise were higher than those at fasting [11.2 µU/mL (6.7-14.9)] but decreased 60 minutes after exercise (90 minutes) [16.6 µU/mL (8.7-31.7)]. Glucagon levels did not show any difference. GLP-1 levels increased at 30 min [7.9 pmol/L (7.1-9.2)] during exercise and decreased 60 min after exercise (90 minutes) [7.7 pmol/L (6.8-8.5)]. Conclusion: Subjects with type 2 diabetes presented expected changes in insulin, glucagon and GLP-1 levels after breakfast and a single aerobic exercise session, not accompanied by glycemic variability changes.

Maintenance of plasma glucose variability after an acute session of aerobic exercise despite changes in insulin and glucagon-like peptide-1 levels in type 2 diabetes.

Objective: The present study aimed to evaluate glucose variability and hormonal responses during and after an aerobic exercise session performed after breakfast in type 2 diabetes patients treated with metformin. Methods: In this quasi-experimental study individuals underwent clinical and laboratory evaluations and maximal exercise test. After two weeks an aerobic exercise session (30 minutes at 60%-70% of the peak heart rate) was performed. At rest, during and after the exercise session, glucose variability (mean amplitude glucose excursions, glucose coefficient of variation, and glucose standard deviation) and levels of plasma glucose, insulin, glucagon, and glucagon-like-peptide-1 were evaluated. Results: Thirteen patients were enrolled in the study. Plasma glucose increased at 15 minutes during the exercise session (244.6 ± 61.9 mg/dL), and decreased at 60 min after exercise (195.6 ± 50.0 mg/dL). Glucose variability did not show any difference before and after exercise. Insulin levels at 15 min [27.1 µU/mL (14.2-42.1)] and 30 min [26.3 µU/mL (14.6-37.4)] during the exercise were higher than those at fasting [11.2 µU/mL (6.7-14.9)] but decreased 60 minutes after exercise (90 minutes) [16.6 µU/mL (8.7-31.7)]. Glucagon levels did not show any difference. GLP-1 levels increased at 30 min [7.9 pmol/L (7.1-9.2)] during exercise and decreased 60 min after exercise (90 minutes) [7.7 pmol/L (6.8-8.5)]. Conclusion: Subjects with type 2 diabetes presented expected changes in insulin, glucagon and GLP-1 levels after breakfast and a single aerobic exercise session, not accompanied by glycemic variability changes.

Increased Maximal Expiratory Pressure, Abdominal and Thoracic Respiratory Expansibility in Healthy Yoga Practitioners Compared to Healthy Sedentary Individuals

Abstract Background Increasing thoracic expansion is effective at reducing blood pressure in hypertensive subjects. Yoga prescribes many respiratory techniques with a growing number of practitioners. However, very little is known whether sedentary or yoga practitioners show measurable differences in their respiratory patterns. Objective This study aims to demonstrate differences between healthy sedentary individuals and healthy yoga practitioners regarding maximal respiratory pressures and thoracic and abdominal respiratory expansibility. Methods Maximal inspiratory and expiratory pressures (MIP and MEP, respectively) were evaluated by manovacuometry, while respiratory expansion was assessed by the cirtometry of abdominal (CA), thoracic xiphoidal (CTX), and thoracic axillary (CTA) circumferences at rest (end expiratory moment) and at full inspiration in healthy sedentary individuals (SED) and yoga practitioners (YOGA). A delta derived from rest and full inspiration measures (ΔCA, ΔCTX, and ΔCTA, respectively), followed by a percentage of each item (ΔCA/CA, ΔCTX/CTX, and ΔCTA/CTA) was then calculated. Groups were compared by means of an unpaired Student's t-test, with a significance level p < 0.05. Results All respiratory expansion measures were significantly higher in in the YOGA group. A significantly higher MEP (cmH2O) was also detected in yoga practitioners: SED 89.3 ± 19.3 and YOGA 114.7 ± 24.8 ( p = 0.007), along with decreased heart rate at rest (bpm): SED 84±6 and YOGA 74±15 ( p = 0.001). Conclusions Yoga practitioners have shown greater thoracic and abdominal expansion and increased MEP, when compared to healthy sedentary individuals, as well as significantly lower heart rates at rest and body mass index (BMI). However, whether or not these findings are related to respiratory patterns is uncertain.

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.

Effect of exercise on glucose variability in healthy subjects: randomized crossover trial.

The aim of this study was to evaluate the acute effect of aerobic (AER) and eccentric (ECC) exercise on glucose variability, correlating it with circulating markers of inflammation and oxidative stress in healthy subjects. Sixteen healthy subjects (32 ± 12 years old) wore a continuous glucose monitoring system for three days. Participants randomly performed single AER and ECC exercise sessions. Glucose variability was evaluated by glucose variance (VAR), glucose coefficient of variation (CV%) and glucose standard deviation (SD). Blood samples were collected to evaluate inflammatory and oxidative stress markers. When compared with the pre-exercise period of 0-6 h, all the indices of glucose variability presented comparable reductions 12-18 h after both exercises (∆AER: VAR= 151.5, ∆CV% = 0.55 and ∆SD = 3.1 and ECC: ∆VAR = 221.2 , ∆CV% = 3.7 and ∆SD = 6.5). Increased interleukin-6 (IL-6) levels after AER (68.5%) and ECC (30.8%) (P<0.001) were observed, with no differences between sessions (P = 0.459). Uric acid levels were increased after exercise sessions (3% in AER and 4% in ECC, P = 0.001). In conclusion, both AER and ECC exercise sessions reduced glucose variability in healthy individuals. Inflammatory cytokines, such as IL-6, and stress oxidative markers might play a role in underlying mechanisms modulating the glucose variability responses to exercise (clinicalTrials.gov NCT02262208).

Optimization of Vagal Stimulation Protocol Based on Spontaneous Breathing Rate.

Controlled breathing maneuver is being widely applied for cardiovascular autonomic control evaluation and cardiac vagal activation through reduction of breathing rate (BR). However, this maneuver presented contradictory results depending on the protocol and the chosen BR. These variations may be related to the individual intrinsic profile baseline sympathetic tonus, as described before by others. In this study, we evaluated the effect of controlled breathing maneuver on cardiovascular autonomic control in 26 healthy subjects allocated into two protocols: (1) controlled breathing in three different rates (10, 15, and 20 breaths/min) and (2) controlled breathing in rates normalized by the individual spontaneous breathing rate (SBR) at 100, 80, 70, and 50%. Our results showed autonomic responses favorable to vagal modulation with the lower BR maneuvers. Nevertheless, while this activation was variable using the standard protocol, all participants of the normalized protocol demonstrated an increase of vagal modulation at 80% BR (HFnu 80 = 67.5% vs. 48.2%, p < 0.0001). These results suggest that controlled breathing protocols to induce vagal activation should consider the SBR, being limited to values moderately lower than the baseline.

Impact of treatment with glibenclamide or vildagliptin on glucose variability after aerobic exercise in type 2 diabetes: A randomized controlled trial.

AIMS: To evaluate the glucose variability, oxidative stress, metabolic and cardiovascular responses after an aerobic exercise session in diabetic patients on treatment with metformin plus vildagliptin or glibenclamide. METHODS: Parallel clinical trial including patients with type 2 diabetes treated with metformin plus vildagliptin or glibenclamide for 12 weeks. Glucose variability, oxidative stress, metabolic (plasma glucose, insulin and glucagon-like-peptide-1) and cardiovascular responses were evaluated at rest, during and after a 30 min aerobic exercise session (70% of the peak heart rate). RESULTS: Thirteen patients were included, seven in vildagliptin group (METV) and six in glibenclamide group (METG), baseline glycated hemoglobin (HbA1c) 8.8 ±â€¯0.3%. Treatment reduced HbA1c (1.2% and 1.5% for METV and METG, respectively). The aerobic exercise session did not change glucose variability in both groups. A decrease in glucose during exercise recovery was found, with area under the curve lower in the METG vs. METV (p = 0.04). After the intervention, systolic blood pressure (SBP) decreased in both groups. Patients treated with vildagliptin showed lower SBP variability compared to those treated with glibenclamide. CONCLUSIONS: Besides improvement in glucose control and reduction of SBP obtained by both treatments, lower blood pressure variability was observed in patients receiving vildagliptin. Glucose variability remained unaffected by both interventions and the 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.

Exercise training versus T3 and T4 hormones treatment: The differential benefits of thyroid hormones on the parasympathetic drive of infarcted rats.

AIMS: This study aimed to investigate whether beneficial effects of thyroid hormones are comparable to those provided by the aerobic exercise training, to verify its applicability as a therapeutic alternative to reverse the pathological cardiac remodeling post-infarction. MATERIALS AND METHODS: Male rats were divided into SHAM-operated (SHAM), myocardial infarction (MI), MI subjected to exercise training (MIE), and MI who received T3 and T4 treatment (MIH) (n = 8/group). MI, MIE and MIH groups underwent an infarction surgery while SHAM was SHAM-operated. One-week post-surgery, MIE and MIH groups started the exercise training protocol (moderate intensity on treadmill), or the T3 (1.2 µg/100 g/day) and T4 (4.8 µg/100 g/day) hormones treatment by gavage, respectively, meanwhile SHAM and MI had no intervention for 9 weeks. The groups were accompanied until 74 days after surgery, when all animals were anesthetized, left ventricle echocardiography and femoral catheterization were performed, followed by euthanasia and left ventricle collection for morphological, oxidative stress, and intracellular kinases expression analysis. KEY FINDINGS: Thyroid hormones treatment was more effective in cardiac dilation and infarction area reduction, while exercise training provided more protection against fibrosis. Thyroid hormones treatment increased the lipoperoxidation and decreased GSHPx activity as compared to MI group, increased the t-Akt2 expression as compared to SHAM group, and increased the vascular parasympathetic drive. SIGNIFICANCE: Thyroid hormones treatment provided differential benefits on the LV function and autonomic modulation as compared to the exercise training. Nevertheless, the redox unbalance induced by thyroid hormones highlights the importance of more studies targeting the ideal duration of this treatment.

Mesenchymal stem cells from sternum: the type of heart disease, ischemic or valvular, does not influence the cell culture establishment and growth kinetics.

BACKGROUND: In an attempt to increase the therapeutic potential for myocardial regeneration, there is a quest for new cell sources and types for cell therapy protocols. The pathophysiology of heart diseases may affect cellular characteristics and therapeutic results. METHODS: To study the proliferative and differentiation potential of mesenchymal stem cells (MSC), isolated from bone marrow (BM) of sternum, we made a comparative analysis between samples of patients with ischemic (IHD) or non-ischemic valvular (VHD) heart diseases. We included patients with IHD (n = 42) or VHD (n = 20), with average age of 60 years and no differences in cardiovascular risk factors. BM samples were collected (16.4 ± 6 mL) and submitted to centrifugation with Ficoll-Paque, yielding 4.5 ± 1.5 × 107 cells/mL. RESULTS: Morphology, immunophenotype and differentiation ability had proven that the cultivated sternal BM cells had MSC features. The colony forming unit-fibroblast (CFU-F) frequency was similar between groups (p = 0.510), but VHD samples showed positive correlation to plated cells vs. CFU-F number (r = 0.499, p = 0.049). The MSC culture was established in 29% of collected samples, achieved passage 9, without significant difference in expansion kinetics between groups (p > 0.05). Dyslipidemia and the use of statins was associated with culture establishment for IHD patients (p = 0.049 and p = 0.006, respectively). CONCLUSIONS: Together, these results show that the sternum bone can be used as a source for MSC isolation, and that ischemic or valvular diseases do not influence the cellular yield, culture establishment or in vitro growth kinetics.

Improved cardiovascular autonomic modulation in transgenic rats expressing an Ang-(1-7)-producing fusion protein.

Angiotensin-(1-7) counterbalances angiotensin II cardiovascular effects. However, it has yet to be determined how cardiovascular autonomic modulation may be affected by chronic and acute elevation of Ang-(1-7). Hemodynamics and cardiovascular autonomic profile were evaluated in male Sprague-Dawley (SD) rats and transgenic rats (TGR) overexpressing Ang-(1-7) [TGR(A1-7)3292]. Blood pressure (BP) was directly measured while cardiovascular autonomic modulation was evaluated by spectral analysis. TGR received A-779 or vehicle and SD rats received Ang-(1-7) or vehicle and were monitored for 5 h after i.v. administration. In another set of experiments with TGR, A-779 was infused for 7 days using osmotic mini pumps. Although at baseline no differences were observed, acute administration of A-779 in TGR produced a marked long-lasting increase in BP accompanied by increased BP variability (BPV) and sympathetic modulation to the vessels. Likewise, chronic administration of A-779 with osmotic mini pumps in TGR increased heart rate, sympathovagal balance, BPV, and sympathetic modulation to the vessels. Administration of Ang-(1-7) to SD rats increased heart rate variability values in 88% accompanied by 8% of vagal modulation increase and 18% of mean BP reduction. These results show that both acute and chronic alteration in the Ang-(1-7)-Mas receptor axis may lead to important changes in the autonomic control of circulation, impacting either sympathetic and (or) parasympathetic systems.

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.

Efeitos Agudos da Estimulação Elétrica Funcional e do Treinamento Muscular Inspiratório em Pacientes com Insuficiência Cardíaca: Ensaio Clínico Randomizado Cruzado / Acute Effects of Functional Electrical Stimulation and Inspiratory Muscle Training in Patients With Heart Failure: A Randomized Crossover Clinical Trial

Fundamentos: A insuficiência cardíaca é uma doença multissistêmica que inclui disfunção autonômica. Objetivo: Avaliar os efeitos agudos da Estimulação Elétrica Funcional (EEF) e do Treinamento Muscular Inspiratório (TMI) sobre o controle autonômico, a função endotelial e os níveis de citocinas inflamatórias em pacientes portadores de IC. Métodos: Estudo randomizado cruzado que incluiu 12 pacientes submetidos a três intervenções randomizadas: EEF, TMI, e EEF + TMI, com intervalo de 1 semana entre as sessões. O TMI foi realizado durante 15 minutos, com 30% da pressão inspiratória máxima. A EEF foi realizada nos músculos vasto lateral e vasto medial, a uma frequência de 20Hz durante 30 minutos. O controle autonômico foi medido através de monitorização de pressão batimento por batimento (Finapres); a função endotelial, através da técnica de dilatação mediada por fluxo (DMF); e os níveis de citocinas inflamatórias foram medidos antes e depois de cada sessão. Resultados: O controle autonômico após EEF diminuiu em termos de BF/AF (p=0,01) e BFn.u (p=0,03), e aumentou em termos de RR médio (p=0,005). Observou-se um aumento do RR médio após o TMI (p=0,005) e após EEF+TMI (p=0,02). Não houve diferenças na DMF e na concentração de lactato sérico. Quanto às citocinas, a EEF promoveu uma redução nos níveis de TNF-α (pré versus pós 24 horas, p = 0,05). O TMI resultou em níveis aumentados de IL-10 (pré versus 24 horas pós, p=0,05) e em níveis diminuídos de TNF-α (1 hora pós versus 24 horas pós, p = 0,03). Não houve diferenças quando as duas intervenções foram associadas. Conclusão: EEF, TMI, e EEF + TMI alteraram o controle autonômico, mas não a função endotelial. A EEF e o TMI isoladamente alteraram os níveis de citocinas inflamatórias. Ensaios Clínicos: NCT01325597

Background: Heart Failure is a multisystem disorder, which includes autonomic dysfunction. Objective: To evaluate the acute effects of Functional Electrical Stimulation (FES) and Inspiratory Muscle Training (IMT) on autonomic control, endothelial function and inflammatory cytokine levels in patients with HF. Methods: Randomized crossover trial including 12 patients undergoing three randomized interventions: FES, IMT, and FES+IMT, with a 1-week interval between sessions. IMT was performed for 15 minutes with 30% of the maximal inspiratory pressure. FES was performed in the vastus lateralis and vastus medialis muscles, at 20Hz for 30 minutes. The autonomic control was measured using beat-to-beat blood pressure monitoring (Finapres); the endothelial function, using the flow-mediated dilation technique (FMD); and inflammatory cytokine levels were assessed before and after the sessions. Results: Autonomic control after FES decreased regarding LF/HF (p=0.01) and LFn.u (p=0.03), and increased regarding mean RR (p=0.005). Increased mean RR was observed after IMT (p=0.005) and after FES+IMT (p=0.02). No differences were found in FMD and blood lactate concentration. As regards the cytokines, FES led to a decrease in TNF-α levels (pre vs. 24 hours post, p = 0.05). IMT resulted in increased IL-10 levels (pre vs. 24 hours post, p=0.05) and decreased TNF-α levels (1 hour post vs. 24 hours post, p = 0.03). No difference was observed when the two interventions were associated. Conclusion: FES, IMT, and FES+IMT changed the autonomic control without changing the endothelial function. FES and IMT separately changed inflammatory cytokine levels. Clinical Trials: NCT01325597

Increased vascular sympathetic modulation in mice with Mas receptor deficiency.

INTRODUCTION: The angiotensin-converting enzyme 2 (ACE2)/angiotensin (Ang)-(1-7)/Mas axis could modulate the heart rate (HR) and blood pressure variabilities (BPV) which are important predictors of cardiovascular risk and provide information about the autonomic modulation of the cardiovascular system. Therefore we investigated the effect of Mas deficiency on autonomic modulation in wild type and Mas-knockout (KO) mice. METHODS: Blood pressure was recorded at high sample rate (4000 Hz). Stationary sequences of 200-250 beats were randomly chosen. Frequency domain analysis of HR and BPV was performed with an autoregressive algorithm on the pulse interval sequences and on respective systolic sequences. RESULTS: The KO group presented an increase of systolic arterial pressure (SAP; 127.26±11.20 vs 135.07±6.98 mmHg), BPV (3.54±1.54 vs 5.87±2.12 mmHg(2)), and low-frequency component of systolic BPV (0.12±0.11 vs 0.47±0.34 mmHg(2)). CONCLUSIONS: The deletion of Mas receptor is associated with an increase of SAP and with an increased BPV, indicating alterations in autonomic control. Increase of sympathetic vascular modulation in absence of Mas evidences the important role of Ang-(1-7)/Mas on cardiovascular regulation. Moreover, the absence of significant changes in HR and HRV can indicate an adaptation of autonomic cardiac balance. Our results suggest that the Ang-(1-7)/Mas axis seems more important in autonomic modulation of arterial pressure than HR.