ESBL-Producing Enterobacterales at the Human-Domestic Animal-Wildlife Interface: A One Health Approach to Antimicrobial Resistance in Piauí, Northeastern Brazil.

The use, misuse, and overuse of antimicrobials is one of the main public health threats of the 21st century. We investigated the risk factor of the presence of extended-spectrum, cephalosporin-resistant Enterobacterales in feces of non-domestic and domestic birds and other domestic animals in Piauí State, northeast Brazil. We collected a total of 387 cloacal and rectal swab samples of free-living birds, domestic birds, and domestic mammals in five municipalities: Amarante, Água Branca, Lagoa Alegre, Parnaíba, and Teresina. A total of 59/387 (15.2%) of these samples harbored extended spectrum beta-lactamase (ESBL)-producing Enterobacterales. Using the MALDI-TOF technique, we identified fifty-seven samples as Escherichia coli and two samples as Klebsiella pneumoniae. Teresina and Parnaíba had the highest prevalence of animals with resistant bacteria (32.1% and 27.1%, respectively) and highest exposure risk factor (OR of 16.06 and 8.58, respectively, and p < 0.001 for all). Multidrug-resistant, ESBL-producing Enterobacterales were observed in 72.8% of the samples (43/59). For the free-living birds, the positive samples belonged to a great kiskadee (Pitangus sulphuratus) and a semipalmated sandpiper (Calidris pusilla) in migratory and resident species, respectively. For domestic animals, the swine samples showed the highest prevalence of antimicrobial resistance. The lack of access to veterinary care and information regarding antimicrobial therapy, along with the easy access to antimicrobials without medical prescription, favors the inadequate use of antimicrobials in Piauí.

A comparison of wavelet-based action potential detection from the NeuroAmp and the Iowa Bioengineering Nerve Traffic Analysis system.

Microneurographic recordings of muscle sympathetic nerve activity (MSNA) reflect postganglionic sympathetic axonal activity directed toward the skeletal muscle vasculature. Recordings are typically evaluated for spontaneous bursts of MSNA; however, the filtering and integration of raw neurograms to obtain multiunit bursts conceals the underlying c-fiber discharge behavior. The continuous wavelet transform with matched mother wavelet has permitted the assessment of action potential discharge patterns, but this approach uses a mother wavelet optimized for an amplifier that is no longer commercially available (University of Iowa Bioengineering Nerve Traffic Analysis System; Iowa NTA). The aim of this project was to determine the morphology and action potential detection performance of mother wavelets created from the commercially available NeuroAmp (ADinstruments), from distinct laboratories, compared with a mother wavelet generated from the Iowa NTA. Four optimized mother wavelets were generated in a two-phase iterative process from independent datasets, collected by separate laboratories (one Iowa NTA, three NeuroAmp). Action potential extraction performance of each mother wavelet was compared for each of the NeuroAmp-based datasets. The total number of detected action potentials was not significantly different across wavelets. However, the predictive value of action potential detection was reduced when the Iowa NTA wavelet was used to detect action potentials in NeuroAmp data, but not different across NeuroAmp wavelets. To standardize approaches, we recommend a NeuroAmp-optimized mother wavelet be used for the evaluation of sympathetic action potential discharge behavior when microneurographic data are collected with this system.NEW & NOTEWORTHY The morphology of custom mother wavelets produced across laboratories using the NeuroAmp was highly similar, but distinct from the University of Iowa Bioengineering Nerve Traffic Analysis System. Although the number of action potentials detected was similar between collection systems and mother wavelets, the predictive value differed. Our data suggest action potential analysis using the continuous wavelet transform requires a mother wavelet optimized for the collection system.

Intra- and interday reliability of sympathetic transduction to blood pressure in young, healthy adults.

Microneurographic recordings of muscle sympathetic nerve activity (MSNA) and the succeeding changes in beat-to-beat blood pressure (i.e., sympathetic transduction) provide important insights into the neural control of the circulation in humans. Despite its widespread use, the reliability of this technique remains unknown. Herein, we assessed the intra- and interday test-retest reliability of signal-averaging sympathetic transduction to blood pressure. Data were analyzed from 15 (9 M/6 F) young, healthy participants who completed two baseline recordings of fibular nerve MSNA separated by 60 min (intraday). The interday reliability was obtained in a subset of participants (n = 13, 9 M/4 F) who completed a follow-up MSNA study. Signal-averaging sympathetic transduction was quantified as peak change in diastolic (DBP) and mean arterial pressure (MAP) following a burst of MSNA. Analyses were also computed considering different MSNA burst sizes (quartiles of normalized MSNA) and burst patterns (singlets, couplets, triplets, and quadruplets+), as well as nonburst responses. Intraclass-correlation coefficients (ICCs) were used as the main reliability measure. Peak changes in MAP [intraday: ICC = 0.76 (0.30-0.92), P = 0.006; interday: ICC = 0.91 (0.63-0.97), P < 0.001] demonstrated very good to excellent reliability. Sympathetic transduction of MSNA burst size displayed moderate to very good reliability, though the reliability of MSNA burst pattern was poor to very good. Nonburst responses revealed poor intraday [ICC = 0.37 (-1.05 to 0.80), P = 0.21], but very good interday [ICC = 0.76 (0.18-0.93), P = 0.01] reliability. Intraday reliability measures were consistently lower than interday reliability. Similar results were obtained using DBP. Collectively, these findings provide evidence that the burst-triggering signal-averaging technique is a reliable measure of sympathetic transduction to blood pressure in young, healthy adults.NEW & NOTEWORTHY We found that signal-averaging sympathetic transduction to blood pressure displayed very good to excellent intra- and interday test-retest reliability in healthy, young adults. Reliability analyses according to muscle sympathetic burst size, burst pattern, and nonburst response were less consistent. Results were similar when using diastolic or mean arterial pressure in the transduction calculation. These findings suggest that the signal-averaging technique can be used with confidence to investigate sympathetic transduction to blood pressure in humans across time.

Altered locomotor muscle metaboreflex control of ventilation in patients with COPD.

We investigated the locomotor muscle metaboreflex control of ventilation, circulation, and dyspnea in patients with chronic obstructive pulmonary disease (COPD). Ten patients [forced expiratory volume in 1 second (FEV1; means ± SD) = 43 ± 17% predicted] and nine age- and sex-matched controls underwent 1) cycling exercise followed by postexercise circulatory occlusion (PECO) to activate the metaboreflex or free circulatory flow to inactivate it, 2) cold pressor test to interpret whether any altered reflex response was specific to the metaboreflex arc, and 3) muscle biopsy to explore the metaboreflex arc afferent side. We measured airflow, dyspnea, heart rate, arterial pressure, muscle blood flow, and vascular conductance during reflexes activation. In addition, we measured fiber types, glutathione redox balance, and metaboreceptor-related mRNAs in the vastus lateralis. Metaboreflex activation increased ventilation versus free flow in patients (∼15%, P < 0.020) but not in controls (P > 0.450). In contrast, metaboreflex activation did not change dyspnea in patients (P = 1.000) but increased it in controls (∼100%, P < 0.001). Other metaboreflex-induced responses were similar between groups. Cold receptor activation increased ventilation similarly in both groups (P = 0.46). Patients had greater type II skeletal myocyte percentage (14%, P = 0.010), lower glutathione ratio (-34%, P = 0.015), and lower nerve growth factor (NGF) mRNA expression (-60%, P = 0.031) than controls. Therefore, COPD altered the locomotor muscle metaboreflex control of ventilation. It increased type II myocyte percentage and elicited redox imbalance, potentially producing more muscle metaboreceptor stimuli. Moreover, it decreased NGF expression, suggesting a downregulation of metabolically sensitive muscle afferents.NEW & NOTEWORTHY This study's integrative physiology approach provides evidence for a specific alteration in locomotor muscle metaboreflex control of ventilation in patients with COPD. Furthermore, molecular analyses of a skeletal muscle biopsy suggest that the amount of muscle metaboreceptor stimuli derived from type II skeletal myocytes and redox imbalance overcame a downregulation of metabolically sensitive muscle afferents.

Undergraduate students' perception of cardiorespiratory physiology during exercise: teleological vs. mechanistic thinking.

BACKGROUND: Physiology is widely recognized as a difficult course, which can potentially increase students' withdrawal and failures rates. Several factors are likely contributing to the difficulties in learning physiology, including inherent features of the discipline as well as aspects related to instructions and/or students' perception. With regards to the later, it is currently unknown how students of exercise physiology think and explain physiology in terms of its cause or consequence (i.e., teleological or mechanistic thinking). Therefore, the aims of the present study were to determine 1) whether undergraduate students' perception of cardiorespiratory physiology during exercise follows a predominant teleological or mechanistic thinking, and 2) whether prior enrollment in physiology courses can influence the predominance of teleological vs. mechanistic thinking. METHODS: The test instrument was an online questionnaire about exercise physiology consisting of nine incomplete sentences about exercise physiology where students had to choose between a teleological or a mechanistic complement. The questionnaire was administered to undergraduate students in the following areas: 1) Movement Sciences (n = 152), 2) Health-related (n = 81) and, 3) Health-unrelated programs (n = 64). Students in Movement Sciences and Health-related programs were also analyzed separately in the following categories: 1) students who previously undertook physiology courses, and 2) students who did not take physiology courses. RESULTS: Overall, all groups presented a percentage of teleological thinking above 58%, which is considerably high. Teleological thinking was significantly higher in health-unrelated programs than health-related and movement sciences programs (76 ± 16% vs. 58 ± 26% vs. 61 ± 25%; P < 0.01). Further, students with prior enrollment in physiology classes presented a significantly lower percentage of teleological thinking than students without physiology classes (59 ± 25% vs. 72 ± 22%, respectively; P < 0.01), but the overall teleological reasoning remained predominant. CONCLUSIONS: These results confirm the hypothesis that undergraduate students tend to present teleological as opposed to mechanistic thinking in exercise physiology. Furthermore, although undergraduate students with prior enrollment in physiology classes presented significantly lower teleological thinking, it remained highly predominant suggesting that teleological thinking is partially independent of the degree of familiarity with this discipline.

Enhanced Respiratory Frequency Response to Lower Limb Mechanoreceptors Activation in Patients with Chronic Obstructive Pulmonary Disease.

PURPOSE: To investigate the mechanoreflex control of respiration and circulation in patients with chronic obstructive pulmonary disease (COPD). METHODS: Twenty-eight patients with moderate-to-severe COPD (mean ± SD: 67.0 ± 7.9 yr, 10 women) and 14 age- and sex-matched controls (67.9 ± 2.6 yr, 7 women) participated in the study. Their dominant knee was passively moved to stimulate mechanoreceptors, whereas vastus lateralis surface electrical activity checked active contractions. A differential pressure flowmeter, an electrocardiogram, and a servo-controlled finger photoplethysmograph acquired cardiorespiratory data. To gain insight into the mechanoreflex arc, we further analyzed reduced/oxidized glutathione ratio and mechanoreceptor-related gene expression in a vastus lateralis biopsy of additional nine patients (63.9 ± 8.1 yr, 33% women) and eight controls (62.9 ± 9.1 yr, 38% women). RESULTS: Patients with COPD had a greater peak respiratory frequency response (COPD: Δ = 3.2 ± 2.3 vs Controls: 1.8 ± 1.2 cycles per minute, P = 0.036) and a smaller peak tidal volume response to passive knee movement than controls. Ventilation, heart rate, stroke volume, and cardiac output peak responses, and total peripheral resistance nadir response, were unaltered by COPD. In addition, patients had a diminished glutathione ratio (COPD: 13.3 ± 3.8 vs controls: 20.0 ± 5.5 a.u., P = 0.015) and an augmented brain-derived neurotrophic factor expression (COPD: 2.0 ± 0.7 vs controls: 1.1 ± 0.4 a.u., P = 0.002) than controls. Prostaglandin E receptor 4, cyclooxygenase 2, and Piezo1 expression were similar between groups. CONCLUSIONS: Respiratory frequency response to mechanoreceptors activation is increased in patients with COPD. This abnormality is possibly linked to glutathione redox imbalance and augmented brain-derived neurotrophic factor expression within locomotor muscles, which could increase mechanically sensitive afferents' stimulation and sensitivity.

Bibliometric indicators in Physical Education research: Brazil in comparison / Indicadores bibliométricos na pesquisa em Educação Física: o Brasil em comparação / Indicadores bibliométricos en la investigación en Educación Física: Brasil en comparación

ABSTRACT Scopus and Web of Science were used to evaluate papers on Physical Education worldwide and in Brazil. Most documents are published in the USA and England, Brazil being the 6th largest. Brazilians tend to publish in Brazil. Countries with a higher % of documents in Q1 journals have higher % of top 10% cited documents. Most countries increase their Top 10% score when publishing in open access, while Brazil decreases. Differentiation between country clusters is due to % documents in Q1 journals, international collaboration, Open Access, citations/paper and documents in Top 10%. Brazil researches similar topics to those worldwide. Publishing in Q1 journals, and more industry and international collaboration can increase the impact of publications by Brazilian authors.

RESUMO Scopus e Web of Science foram usados ​​para avaliar artigos sobre Educação Física no mundo e no Brasil. A maioria dos documentos é publicada nos EUA e na Inglaterra, sendo o Brasil o 6º maior. Brasileiros tendem a publicar no Brasil. Os países com maior % de documentos em periódicos do 1º quartil têm maior % dos citados. A maioria dos países aumenta seu impacto publicando em acesso aberto, enquanto o Brasil diminui. A diferença entre países deve-se à % de documentos em periódicos do 1º quartil, colaboração internacional, acesso aberto, citações/artigos e documentos no Top 10%. O Brasil pesquisa temas semelhantes aos do mundo. A publicação em periódicos do 1º quartil, mais colaboração industrial e internacional podem aumentar o impacto das publicações de autores brasileiros.

RESUMEN Scopus y Web of Science se utilizaron para evaluar artículos sobre Educación Física en el mundo y Brasil. La mayoría de los documentos se publican en EEUU e Inglaterra, siendo Brasil el sexto más grande. Los brasileños tienden a publicar en Brasil. Los países con un % más alto de documentos en revistas Q1 tienen un % más alto citados en el 10% superior, y publican en acceso abierto, mientras que Brasil disminuye. La diferenciación entre países se debe a % de documentos en revistas Q1, colaboración internacional, acceso abierto, citas/artículo y documentos en el 10% superior. Brasil investiga temas similares a los del mundo. La publicación en revistas Q1, una mayor colaboración internacional y de la industria pueden aumentar el impacto de las publicaciones de autores brasileños.

The exercise pressor reflex: An update.

The exercise pressor reflex is a feedback mechanism engaged upon stimulation of mechano- and metabosensitive skeletal muscle afferents. Activation of these afferents elicits a reflex increase in heart rate, blood pressure, and ventilation in an intensity-dependent manner. Consequently, the exercise pressor reflex has been postulated to be one of the principal mediators of the cardiorespiratory responses to exercise. In this updated review, we will discuss classical and recent advancements in our understating of the exercise pressor reflex function in both human and animal models. Particular attention will be paid to the afferent mechanisms and pathways involved during its activation, its effects on different target organs, its potential role in the abnormal cardiovascular response to exercise in diseased states, and the impact of age and biological sex on these responses. Finally, we will highlight some unanswered questions in the literature that may inspire future investigations in the field.

Immediate post-exercise blood pressure and arterial stiffness in hypertensive and normotensive older females.

Although it has been suggested that increased arterial stiffness is linked to exaggerated blood pressure (BP) from brief moderate exercise, it is not clear whether this occurs in older adults with and without hypertension. This study investigates whether the immediate post-exercise systolic BP following brief moderate exercise is associated with arterial stiffness in older females with different BP status. This cross-sectional study included 191 older females aged 60-80 years without known cardiovascular disease (CVD). Arterial stiffness was determined by aortic pulse wave velocity (aPWV). Systolic BP was measured before and immediately following a 3-min moderate walking test (stage 1 Bruce protocol). Specific quartile-based thresholds were used to define an exaggerated immediate post-exercise systolic BP for hypertensive and normotensive older females (quartile 4 as an exaggerated response). Traditional CVD risk factors were assessed (covariates). Older females from the highest quartile of immediate post-exercise absolute systolic BP showed higher aPWV compared to their peers from the lowest quartile (ß = .22 m/s, p = .018). The quartile-based threshold to define the exaggerated post-exercise systolic BP was higher in hypertensive than in normotensive older females (174 vs. 172 mmHg). In summary, exaggerated immediate post-exercise systolic BP following a brief moderate exercise is associated with higher arterial stiffness in older females with different BP status.

Sex differences in the sympathetic neurocirculatory responses to chemoreflex activation.

The purpose of this study was to determine whether there are sex differences in the cardiorespiratory and sympathetic neurocirculatory responses to central, peripheral, and combined central and peripheral chemoreflex activation. Ten women (29 ± 6 years, 22.8 ± 2.4 kg/m2 : mean ± SD) and 10 men (30 ± 7 years, 24.8 ± 3.2 kg/m2 ) undertook randomized 5 min breathing trials of: room air (eucapnia), isocapnic hypoxia (10% oxygen (O2 ); peripheral chemoreflex activation), hypercapnic hyperoxia (7% carbon dioxide (CO2 ), 50% O2 ; central chemoreflex activation) and hypercapnic hypoxia (7% CO2 , 10% O2 ; central and peripheral chemoreflex activation). Control trials of isocapnic hyperoxia (peripheral chemoreflex inhibition) and hypocapnic hyperoxia (central and peripheral chemoreflex inhibition) were also included. Muscle sympathetic nerve activity (MSNA; microneurography), mean arterial pressure (MAP; finger photoplethysmography) and minute ventilation ( V̇$\dot{\rm{V}}$E ; pneumotachometer) were measured. Total MSNA (P = 1.000 and P = 0.616), MAP (P = 0.265) and V̇$\dot{\rm{V}}$E (P = 0.587 and P = 0.472) were not different in men and women during eucapnia and during isocapnic hypoxia. Women exhibited attenuated increases in V̇$\dot{\rm{V}}$E during hypercapnic hyperoxia (27.3 ± 6.3 vs. 39.5 ± 7.5 l/min, P < 0.0001) and hypercapnic hypoxia (40.9 ± 9.1 vs. 53.8 ± 13.3 l/min, P < 0.0001) compared with men. However, total MSNA responses were augmented in women (hypercapnic hyperoxia 378 ± 215 vs. 258 ± 107%, P = 0.017; hypercapnic hypoxia 607 ± 290 vs. 362 ± 268%, P < 0.0001). No sex differences in total MSNA, MAP or V̇$\dot{\rm{V}}$E were observed during isocapnic hyperoxia and hypocapnic hyperoxia. Our results indicate that young women have augmented sympathetic responses to central chemoreflex activation, which explains the augmented MSNA response to combined central and peripheral chemoreflex activation. KEY POINTS: Sex differences in the control of breathing have been well studied, but whether there are differences in the sympathetic neurocirculatory responses to chemoreflex activation between healthy women and men is incompletely understood. We observed that, compared with young men, young women displayed augmented increases in muscle sympathetic nerve activity during both hypercapnic hyperoxia (central chemoreflex activation) and hypercapnic hypoxia (central and peripheral chemoreflex activation) but had attenuated increases in minute ventilation. In contrast, no sex differences were found in either muscle sympathetic nerve activity or minute ventilation responses to isocapnic hypoxia (peripheral chemoreceptor stimulation). Young women have blunted ventilator, but augmented sympathetic responses, to central (hypercapnic hyperoxia) and combined central and peripheral chemoreflex activation (hypercapnic hypoxia), compared with young men. The possible causative association between the reduced ventilation and heightened sympathetic responses in young women awaits validation.

Acute and Short-Term Autonomic and Hemodynamic Responses to Transcranial Direct Current Stimulation in Patients With Resistant Hypertension.

Previously, we demonstrated that acute transcranial direct current stimulation (tDCS) reduced blood pressure (BP) and improved autonomic modulation in hypertensives. We hypothesized that acute and short-term tDCS intervention can promote similar benefits in resistant hypertensive patients (RHT). We assessed the impact of one (acute intervention) and ten (short-term intervention) tDCS or SHAM (20 min, each) sessions on BP, pulse interval (PI) and systolic blood pressure variabilities, humoral mechanisms associated with BP regulation, and cytokines levels. True RHT subjects (n = 13) were randomly submitted to one and ten SHAM and tDCS crossing sessions (1 week of "washout"). Hemodynamic (Finometer®, Beatscope), office BP, and autonomic variables (accessed through spectral analysis of the pulse-to-pulse BP signal, in the time and frequency domain - Fast Fourrier Transform) were measured at baseline and after the short-term intervention. 24 h-ambulatory BP monitoring was measured after acute and short-term protocols. Acute intervention: tDCS reduced BP, cardiac output, and increase high-frequency band of PI (vagal modulation to the heart). Short-term protocol: tDCS did not change BP and cardiac output parameters. In contrast, central systolic BP (-12%), augmentation index (-31%), and pulse wave velocity (34%) were decreased by the short-term tDCS when compared to SHAM. These positive results were accompanied by a reduction in the low-frequency band (-37%) and an increase of the high-frequency band of PI (+62%) compared to SHAM. These findings collectively indicate that short-term tDCS concomitantly improves resting cardiac autonomic control and pulse wave behavior and reduces central BP in RHT patients, https://ensaiosclinicos.gov.br/rg/RBR-8n7c9p.

Potentiation of GABAergic synaptic transmission by diazepam acutely increases resting beat-to-beat blood pressure variability in young adults.

Resting beat-to-beat blood pressure variability is a powerful predictor of cardiovascular events and end-organ damage. However, its underlying mechanisms remain unknown. Herein, we tested the hypothesis that a potentiation of GABAergic synaptic transmission by diazepam would acutely increase resting beat-to-beat blood pressure variability. In 40 (17 females) young, normotensive subjects, resting beat-to-beat blood pressure (finger photoplethysmography) was continuously measured for 5-10 min, 60 min after the oral administration of either diazepam (10 mg) or placebo. The experiments were conducted in a randomized, double-blinded, and placebo-controlled design. Stroke volume was estimated from the blood pressure waveform (ModelFlow) permitting the calculation of cardiac output and total peripheral resistance. Direct recordings of muscle sympathetic nerve activity (MSNA, microneurography) were obtained in a subset of subjects (n = 13), and spontaneous cardiac and sympathetic baroreflex sensitivity were calculated. Compared with placebo, diazepam significantly increased the standard deviation of systolic blood pressure (4.7 ± 1.4 vs. 5.7 ± 1.5 mmHg, P = 0.001), diastolic blood pressure (3.8 ± 1.2 vs. 4.5 ± 1.2 mmHg, P = 0.007), and mean blood pressure (3.8 ± 1.1 vs. 4.5 ± 1.1 mmHg, P = 0.002), as well as cardiac output (469 ± 149 vs. 626 ± 259 mL/min, P < 0.001) and total peripheral resistance (1.0 ± 0.3 vs. 1.4 ± 0.6 mmHg/L/min, P < 0.001). Similar results were found using different indices of variability. Furthermore, diazepam reduced MSNA (placebo: 22 ± 6 vs. diazepam: 18 ± 8 bursts/min, P = 0.025) without affecting the arterial baroreflex control of heart rate (placebo: 18.6 ± 6.7 vs. diazepam: 18.8 ± 7.0 ms/mmHg, P = 0.87) and MSNA (placebo: -3.6 ± 1.2 vs. diazepam: -3.4 ± 1.5 bursts/100 Hb/mmHg, P = 0.55). Importantly, these findings were not impacted by biological sex. We conclude that GABAA receptors modulate resting beat-to-beat blood pressure variability in young adults.

Blood pressure oscillations impact signal-averaged sympathetic transduction of blood pressure: implications for the association with resting sympathetic outflow.

Signal-averaged sympathetic transduction of blood pressure (BP) is inversely related to resting muscle sympathetic nerve activity (MSNA) burst frequency in healthy cohorts. Whether this represents a physiological compensatory adaptation or a methodological limitation, remains unclear. The current analysis aimed to determine the contribution of methodological limitations by evaluating the dependency of MSNA transduction at different levels of absolute BP. Thirty-six healthy participants (27 ± 7 yr, 9 females) underwent resting measures of beat-to-beat heart rate, BP, and muscle sympathetic nerve activity (MSNA). Tertiles of mean arterial pressure (MAP) were computed for each participant to identify cardiac cycles occurring below, around, and above the MAP operating pressure (OP). Changes in hemodynamic variables were computed across 15 cardiac cycles within each MAP tertile to quantify sympathetic transduction. MAP increased irrespective of sympathetic activity when initiated below the OP, but with MSNA bursts provoking larger rises (3.0 ± 0.9 vs. 2.1 ± 0.7 mmHg; P < 0.01). MAP decreased irrespective of sympathetic activity when initiated above the OP, but with MSNA bursts attenuating the drop (-1.3 ± 1.1 vs. -3.1 ± 1.2 mmHg; P < 0.01). In participants with low versus high resting MSNA (12 ± 4 vs. 32 ± 10 bursts/min), sympathetic transduction of MAP was not different when initiated by bursts below (3.2 ± 1.0 vs. 2.8 ± 0.9 mmHg; P = 0.26) and above the OP (-1.0 ± 1.3 vs. -1.6 ± 0.8 mmHg; P = 0.08); however, low resting MSNA was associated with a smaller proportion of MSNA bursts firing above the OP (15 ± 5 vs. 22 ± 5%; P < 0.01). The present analyses demonstrate that the signal-averaging technique for calculating sympathetic transduction of BP is influenced by the timing of an MSNA burst relative to cyclic oscillations in BP.NEW & NOTEWORTHY The current signal-averaging technique for calculating sympathetic transduction of blood pressure does not consider the arterial pressure at which each muscle sympathetic burst occurs. A burst firing when mean arterial pressure is above the operating pressure was associated with a decrease in blood pressure. Thus, individuals with higher muscle sympathetic nerve activity demonstrate a reduced sympathetic transduction owing to the weighted contribution of more sympathetic bursts at higher levels of arterial pressure.

GABAA receptor activation modulates the muscle sympathetic nerve activity responses at the onset of static exercise in humans.

Exercise is a well-known sympathoexcitatory stimulus. However, muscle sympathetic nerve activity (MSNA) can decrease during the onset of muscle contraction. Yet, the underlying mechanisms and neurotransmitters involved in the sympathetic responses at the onset of exercise remain unknown. Herein, we tested the hypothesis that GABAA receptors may contribute to the MSNA responses at the onset of static handgrip in humans. Thirteen young, healthy individuals (4 females) performed 30 s of ischemic static handgrip at 30% of maximum volitional contraction before and following oral administration of either placebo or diazepam (10 mg), a benzodiazepine that enhances GABAA activity. MSNA (microneurography), beat-to-beat blood pressure (finger photopletysmography), heart rate (electrocardiogram), and stroke volume (ModelFlow) were continuously measured. Cardiac output (CO = stroke volume × heart rate) and total vascular conductance (TVC = CO/mean blood pressure) were subsequently calculated. At rest, MSNA was reduced while hemodynamic variables were unchanged after diazepam administration. Before diazepam, static handgrip elicited a significant decrease in MSNA burst frequency (Δ-7 ± 2 bursts/min, P < 0.01 vs. baseline) and MSNA burst incidence (Δ-16 ± 2 bursts/100 heart beats, P < 0.01 vs. baseline); however, these responses were attenuated following diazepam administration (Δ-1 ± 2 bursts/min and Δ-7 ± 2 bursts/100 heart beats, respectively; P < 0.01 vs. before diazepam). Diazepam did not affect the increases in heart rate, blood pressure, CO, and TVC at the exercise onset. Importantly, the placebo had no effect on any variable at rest or exercise onset. These findings suggest that GABAA receptor activation modulates the MSNA responses at the onset of static exercise in young, healthy humans.NEW & NOTEWORTHY In this study, we found that the reduction in muscle sympathetic nerve activity at the onset of static handgrip exercise was blunted following GABAA receptor activation with oral administration of diazepam in young, healthy individuals. The present findings provide novel insight into neural circuitry mechanisms controlling muscle sympathetic outflow during exercise in humans.

Are Vascular Parameters Associated with Walking Impairment in Patients with Claudication?

BACKGROUND: The mechanisms underlying functional impairments in symptomatic PAD patients are controversial and poorly understood. Endothelial dysfunction and arterial stiffness have been proposed as potential mechanisms related to functional impairment in symptomatic PAD patients, however, more studies are needed to confirm these associations. OBJECTIVE: To analyze the association between vascular function and walking impairment in patients with peripheral arterial disease (PAD) and symptoms of claudication. METHODS: This was a cross-sectional study that included 68 patients with symptomatic PAD. All patients underwent an objective (Six-minute walk test [6MWT], 4-meter walk test) and a subjective (Walking Impairment Questionnaire [WIQ]) measurement of walking impairment. Vascular parameters measured were pulse-wave velocity (PWV) and flow-mediated dilation (FMD). Multiple linear regression was performed to investigate the association among walking impairment variables with vascular function parameters. RESULTS: No significant associations between the claudication onset distance (PWV: b=.060, P = 0.842; FMD: b=-.192, P = 0.456), 6MWT (PWV: b=.007, P = 0..975; FMD: b=.090, P = 0.725), WIQ distance (PWV: b=.337, P = 0.117; FMD: b=-.025, P = 0.895) WIQ speed (PWV: b=.320, P = 0.181; FMD: b=-.028, P = 0.497), WIQ stairs (PWV: b=.256, P = 0.204; FMD: b=-.228, P = 0.230), 4-meter usual walk (PWV: b=-.421, P = 0.107; FMD: b=-.338, P = 0.112), 4-meter fast walk (PWV: b=-.496, P = 0.063; FMD: b=-.371, P = 0.086) and vascular function were found. CONCLUSIONS: In symptomatic PAD patients, vascular function is not associated to walking impairment, even when adjusting for comorbid conditions and diabetes.

Signal-averaged resting sympathetic transduction of blood pressure: is it time to account for prevailing muscle sympathetic burst frequency?

Calculating the blood pressure (BP) response to a burst of muscle sympathetic nerve activity (MSNA), termed sympathetic transduction, may be influenced by an individual's resting burst frequency. We examined the relationships between sympathetic transduction and MSNA in 107 healthy males and females and developed a normalized sympathetic transduction metric to incorporate resting MSNA. Burst-triggered signal averaging was used to calculate the peak diastolic BP response following each MSNA burst (sympathetic transduction of BP) and following incorporation of MSNA burst cluster patterns and amplitudes (sympathetic transduction slope). MSNA burst frequency was negatively correlated with sympathetic transduction of BP (r = -0.42; P < 0.01) and the sympathetic transduction slope (r = -0.66; P < 0.01), independent of sex. MSNA burst amplitude was unrelated to sympathetic transduction of BP in males (r = 0.04; P = 0.78), but positively correlated in females (r = 0.44; P < 0.01) and with the sympathetic transduction slope in all participants (r = 0.42; P < 0.01). To control for MSNA, the linear regression slope of the log-log relationship between sympathetic transduction and MSNA burst frequency was used as a correction exponent. In subanalysis of males (38 ± 10 vs. 14 ± 4 bursts/min) and females (28 ± 5 vs. 12 ± 4 bursts/min) with high versus low MSNA, sympathetic transduction of BP and sympathetic transduction slope were lower in participants with high MSNA (all P < 0.05). In contrast, normalized sympathetic transduction of BP and normalized sympathetic transduction slope were similar in males and females with high versus low MSNA (all P > 0.22). We propose that incorporating MSNA burst frequency into the calculation of sympathetic transduction will allow comparisons between participants with varying levels of resting MSNA.

Effect of Sex on Vascular Adaptations to Isometric Handgrip Training in Elderly Patients with Peripheral Artery Disease: A Randomized Controlled Trial.

BACKGROUND: Isometric handgrip training (IHT) promotes vascular adaptations in different populations. AIMS: We assessed the sex differences in vascular adaptations of IHT in a sample of older adults with symptomatic peripheral artery disease (PAD). METHODS: Fifty-three older patients with symptomatic PAD (6 women and 13 men in IHT and 13 women and 21 men in the control group) participated in this study. The IHT group performed 3 sessions per week, for 8 weeks, consisting of 4 sets of isometric contractions for 2 min at 30% of maximum voluntary contraction and a 4-min interval between sets. The control group received a compression ball in order to minimize the placebo effects, representing sham training. Blood flow and brachial flow-mediated dilation were analyzed at before and after 8 weeks of intervention. We compared the responses (Δ = post-pre values) of each group (women control, women IHT, men control, and men IHT) with a Kruskal-Wallis test. RESULTS: There were no differences in all groups after 8 weeks of IHT in Δ brachial diameter (p = 0.850), Δ flow-mediated dilation (p = 0.241), Δ time to peak diameter (p = 0.528), and Δ FMD/AUC (p = 0.397). CONCLUSIONS: There are no effects of sex on vascular adaptation after 8 weeks of IHT in older adults with symptomatic PAD.

Autonomic Function in Patients With Parkinson's Disease: From Rest to Exercise.

Parkinson's disease (PD) is a common neurodegenerative disorder classically characterized by symptoms of motor impairment (e.g., tremor and rigidity), but also presenting with important non-motor impairments. There is evidence for the reduced activity of both the parasympathetic and sympathetic limbs of the autonomic nervous system at rest in PD. Moreover, inappropriate autonomic adjustments accompany exercise, which can lead to inadequate hemodynamic responses, the failure to match the metabolic demands of working skeletal muscle and exercise intolerance. The underlying mechanisms remain unclear, but relevant alterations in several discrete central regions (e.g., dorsal motor nucleus of the vagus nerve, intermediolateral cell column) have been identified. Herein, we critically evaluate the clinically significant and complex associations between the autonomic dysfunction, fatigue and exercise capacity in PD.

Baroreflex dysfunction in Parkinson's disease: integration of central and peripheral mechanisms.

The incidence of Parkinson's disease (PD) is increasing worldwide. Although the PD hallmark is the motor impairments, nonmotor dysfunctions are now becoming more recognized. Recently, studies have suggested that baroreflex dysfunction is one of the underlying mechanisms of cardiovascular dysregulation observed in patients with PD. However, the large body of literature on baroreflex function in PD is unclear. The baroreflex system plays a major role in the autonomic, and ultimately blood pressure and heart rate, adjustments that accompany acute cardiovascular stressors on a daily basis. Therefore, impaired baroreflex function (i.e., decreased sensitivity or gain) can lead to altered neural cardiovascular responses. Since PD affects parasympathetic and sympathetic branches of the autonomic nervous system and both are orchestrated by the baroreflex system, understanding of this crucial mechanism in PD is necessary. In the present review, we summarize the potential altered central and peripheral mechanisms affecting the feedback-controlled loops that comprise the reflex arc in patients with PD. Major factors including arterial stiffness, reduced number of C1 and activation of non-C1 neurons, presence of central α-synuclein aggregation, cardiac sympathetic denervation, attenuated muscle sympathetic nerve activity, and lower norepinephrine release could compromise baroreflex function in PD. Results from patients with PD and from animal models of PD provide the reader with a clearer picture of baroreflex function in this clinical condition. By doing so, our intent is to stimulate future studies to evaluate several unanswered questions in this research area.