Autonomic Control Of Heart Rate Research Articles

Autonomic cardiovascular control is unaffected in children referred for assessment of excessive daytime sleepiness.

There is conflicting evidence for impaired autonomic control of heart rate (HR) in adults with narcolepsy and idiopathic hypersomnolence (IH). Despite these chronic hypersomnia conditions primarily being diagnosed around the age of puberty, there are limited studies in children. The present study investigated cardiovascular control using heart rate variability (HRV) and the extent of nocturnal HR dipping during sleep in children and adolescents with narcolepsy and IH. Children having an overnight polysomnographic study followed by a multiple sleep latency test (MSLT) for investigation of excessive daytime sleepiness (EDS) between May 2010 to December 2023 were included: 28 children diagnosed with narcolepsy, 11 with IH, and 26 subjectively sleepy children who did not meet the diagnostic criteria for either narcolepsy or IH. Each clinically referred child was matched for age and sex with a control. Time domain and frequency domain HRV were calculated from ECG recorded at 512 Hz. There were no differences in either time domain or spectral analysis of HRV between clinical groups or between clinical groups and their control group. The expected sleep state differences in HRV were observed in all groups. There was also no difference in HR nocturnal dipping between groups. Despite evidence for abnormal autonomic function in adults with narcolepsy and IH, our study did not identify any abnormalities in HR, HR control, or nocturnal dipping of HR in children referred for assessment of EDS. This suggests that autonomic dysfunction may be a feature of these conditions that develops in later life.

Development of autonomic heart rate modulations during childhood and adolescence

Autonomic control of heart rate is well known in adult subjects, but limited data are available on the development of the heart rate control during childhood and adolescence. Continuous 12-lead electrocardiograms were recorded in 1045 healthy children and adolescents (550 females) aged 4 to 19 years during postural manoeuvres involving repeated 10-min supine, unsupported sitting, and unsupported standing positions. In each position, heart rate was measured, and heart rate variability indices were evaluated (SDNN, RMSSD, and high (HF) and low (LF) frequency components were obtained). Quasi-normalized HF frequency components were defined as qnHF = HF/(HF + LF). These measurements were, among others, related to age using linear regressions. In supine position, heart rate decreases per year of age were significant in both sexes but lower in females than in males. In standing position, these decreases per year of age were substantially lowered. RMSSD and qnHF indices were independent of age in supine position but significantly decreased with age in sitting and standing positions. Correspondingly, LF/HF proportions showed steep increases with age in sitting and standing positions but not in the supine position. The study suggests that baseline supine parasympathetic influence shows little developmental changes during childhood and adolescence but that in young children, sympathetic branch is less responsive to vagal influence. While vagal influences modulate cardiac periods in young and older children equally, they are less able to suppress the sympathetic influence in younger children.

Effect of series of periodic limb movements in sleep on blood pressure, heart rate and high frequency heart rate variability.

The phenomenon known as periodic limb movements in sleep (PLMS) has been linked to a change in autonomic nervous system (ANS) activity and its effect on circulatory regulation. Autonomic dysfunction or dysregulation in patients with PLMS has been described in some domains; however, any relationship between heart rate variability (HRV) and PLMS has not been clearly established. HRV analysis is a recognised, non-invasive research method that describes the influence of the ANS on heart rate (HR). The aim of our study was to further investigate the dysregulation of autonomic HR control in patients with PLMS. We undertook a retrospective analysis of the polysomnographic (PSG), demographic and medical data of five patients with a total number of 1,348 PLMS. We analysed HR, HRV HF, systolic blood pressure (SBP), and diastolic blood pressure (DBP) for 10 heartbeats before the series of PLMS and 10 consecutive heartbeats as beat-to-beat measurements. The presented method of using successive, short, 10 RR interval segments refers to the time-frequency measurement, which is very clear and useful for presenting changes in the calculated parameters over time and thereby illustrating their dynamics. This method allowed us to assess dynamic changes in HRV HF during successive PLMS series. Statistical analysis was performed using IBM SPSS Statistics (v. 28.0.0.0). The Kruskal-Wallis test was performed to find statistically significant changes from baseline. No statistically significant changes in HR, SBP, or DBP were found in our group, although an increase in the value of the HRV HF was noted, suggesting an increase in intracardiac parasympathetic activity during the subsequent series of PLMS. Our study indicates an increase in parasympathetic activity during the appearance of successive PLMS, which, with the simultaneous lack of changes in HR, may suggest an increase in sympathetic activity, and therefore the appearance of so-called 'autonomic co-activation' resulting in the possibility of life-threatening cardiac events. Our findings add to the literature information regarding HRV in PLMS, and highlight the need for further studies to elucidate the effects of these conditions on the ANS, and on cardiovascular health.

Doxorubicin Dose-Dependent Impact on Physiological Balance-A Holistic Approach in a Rat Model.

Doxorubicin (DOX) is commonly used in several chemotherapies to treat various cancers, but it is known to cause cardiotoxicity and cardiac symptoms. Autonomic dysfunction is thought to contribute to the cardiotoxic effects of DOX, but the specific dose required to disrupt homeostatic processes is still unclear and is influenced by numerous factors. This study aimed to investigate how the DOX dosage affects autonomic function and physiological parameters, to elucidate the neurocardiac mechanisms underlying the observed cardiovascular side effects. Wistar rats were treated with DOX for four weeks and divided into three dosing groups: DOX8 (2 mg/kg/week), DOX16 (4 mg/kg/week), and DOX20 (5 mg/kg/week). A control group received NaCl 0.9% saline (1 mL/kg/week). In an acute experiment, we recorded blood pressure (BP), electrocardiogram, heart rate (HR), and respiratory rate (RF). Baroreflex gain and chemoreflex sensitivity were calculated, and cardiac tissue was analyzed with picrosirius histochemistry to measure collagen content. Our results showed that the LF/HF ratio, indicative of autonomic activity, was altered along with hypotension and bradycardia at a cumulative DOX dose threshold of 16 mg/kg. We observed a positive correlation between DOX dose and BP, HR, urinary norepinephrine, LF/HF ratio, and fibrotic heart area. Lower LF/HF ratios were associated with high DOX doses, reflecting drug-induced impairment of autonomic control of HR. This study provides valuable insights into the dose-dependent effects of DOX on physiological parameters and the development of cardiovascular dysfunction. These findings are critical, which is important for optimizing the management and therapeutic strategies for patients undergoing DOX-based chemotherapy.

Electromagnetic Fields - Do They Pose a Cardiovascular Risk?

Mobile wireless communication technologies have now become an everyday part of our lives, 24 hours a day, 7 days a week. Monitoring the autonomous system under exposition to electromagnetic fields may play an important role in broading of our still limited knowledge on their effect on human body. Thus, we studied the interaction of the high frequency electromagnetic field (HF EMF) with living body and its effect on the autonomic control of heart rate using Heart Rate Variability (HRV) linear and nonlinear analyses in healthy volunteers. A group of young healthy probands (n=30, age mean: 24.2 ± 3.5 years) without any symptoms of disease was exposed to EMF with f=2400 MHz (Wi Fi), and f=2600 MHz (4G) for 5 minutes applied on the chest area. The short-term heart rate variability (HRV) metrics were used as an indicator of complex cardiac autonomic control. The evaluated HRV parameters: RR interval (ms), high frequency spectral power (HF-HRV in [ln(ms2)]) as an index of cardiovagal control, and a symbolic dynamic index of 0V %, indicating cardiac sympathetic activity. The cardiac-linked parasympathetic index HF-HRV was significantly reduced (p =0.036) and sympathetically mediated HRV index 0V % was significantly higher (p=0.002) during EMF exposure at 2400 MHz (Wi-Fi), compared to simulated 4G frequency 2600 MHz. No significant differences were found in the RR intervals. Our results revealed a shift in cardiac autonomic regulation towards sympathetic overactivity and parasympathetic underactivity indexed by HRV parameters during EMF exposure in young healthy persons. It seems that HF EMF exposure results in abnormal complex cardiac autonomic regulatory integrity which may be associated with higher risk of later cardiovascular complications already in healthy probands.

Impact of Obstructive Sleep Apnea on Cardiac Autonomic Control during the Respiratory Sinus Arrhythmia Maneuver in Patients with Chronic Obstructive Pulmonary Disease

Background: Chronic obstructive pulmonary disease (COPD) leads to pulmonary and systemic involvement that could damage the cardiac autonomic modulation (CAM), increasing cardiovascular risks and mortality rates. The obstructive sleep apnea (OSA) syndrome is also associated to harmed CAM. However, it is not clear if the presence of OSA in COPD patients causes an additional loss on the autonomic nervous function. Objective: To compare the responses of CAM during the respiratory sinus arrhythmia maneuver (RSA-M) between patients with OSA and COPD overlapped and COPD on isolation. Materials and Methods: Twenty-four patients (COPD, n = 11; OSA-COPD, n = 13) underwent pulmonary, cardiac function, and home sleep tests for diagnosis and staging of the disease. Heart rate (HR) and R-R intervals were collected during spontaneous breathing (SB) (sitting [10 min]) and the slow and deep breaths to trigger RSA-M (sitting [4 min]). Results: Both groups showed impaired responses when SB and RSA-M were compared. Both COPD and OSA-COPD patients showed increased sympathetic modulation, observed through increased LF (low frequency), and LF/HF ratio (P < 0.05) and decreased HF (high frequency) (P < 0.05), an opposite pattern to that expected for RSA-M. In addition, OSA-COPD showed worse HR variability complexity response on RSA-M (interaction effect, P < 0.05) and reduced spectral peak when contrasted with COPD alone (P < 0.05). Conclusions: The results suggest the presence of both COPD and OSA lead to a negative impact on the autonomic control of HR and deep-breathing exercises. Future clinical trials that investigate the impact of breathing exercises on these autonomic indices should address the relevance of improving the autonomic balance in these patients.

Attenuated cardiac autonomic function in humans with high-affinity hemoglobin and compensatory polycythemia.

During hypoxic exposure, humans with high-affinity hemoglobin (and compensatory polycythemia) have blunted increases in heart rate compared with healthy humans with typical oxyhemoglobin dissociation curves. This response may be associated with altered autonomic control of heart rate. Our hypothesis-generating study aimed to investigate cardiac baroreflex sensitivity and heart rate variability among nine humans with high-affinity hemoglobin [6 females, O2 partial pressure at 50% [Formula: see text] (P50) = 16 ± 1 mmHg] compared with 12 humans with typical affinity hemoglobin (6 F, P50 = 26 ± 1 mmHg). Participants breathed normal room air for a 10-min baseline, followed by 20 min of isocapnic hypoxic exposure, designed to lower the arterial partial pressure O2 ([Formula: see text]) to ∼50 mmHg. Beat-by-beat heart rate and arterial blood pressure were recorded. Data were averaged in 5-min periods throughout the hypoxia exposure, beginning with the last 5 min of baseline in normoxia. Spontaneous cardiac baroreflex sensitivity and heart rate variability were determined using the sequence method and the time and frequency domain analyses, respectively. Cardiac baroreflex sensitivity was lower in humans with high-affinity hemoglobin than controls at baseline and during isocapnic hypoxic exposure (normoxia: 7 ± 4 vs. 16 ± 10 ms/mmHg, hypoxia minutes 15-20: 4 ± 3 vs. 14 ± 11 ms/mmHg; group effect: P = 0.02, high-affinity hemoglobin vs. control, respectively). Heart rate variability calculated in both the time (standard deviation of the N-N interval) and frequency (low frequency) domains was lower in humans with high-affinity hemoglobin than in controls (all P < 0.05). Our data suggest that humans with high-affinity hemoglobin may have attenuated cardiac autonomic function.

O034 Autonomic control of heart rate stabilises with improvement of sleep disordered breathing in children with Down syndrome

Abstract Background Sleep disordered breathing (SDB) alters autonomic function, assessed using heart rate variability (HRV) in typically developing (TD) and children with Down syndrome (DS). SDB resolution in TD children normalises HRV, but the effects in children with DS are unknown. We compared HRV in children with DS with improved SDB (decrease in obstructive apnoea hypopnoea index (OAHI) to ≤ 50% of baseline OAHI) to those with unimproved SDB 2 y following baseline study. Methods 24 children (3-19 y at baseline) were included. Power spectral analysis of the ECG determined low frequency (LF, parasympathetic and sympathetic activity), high frequency (HF, parasympathetic activity) power and LF/HF (sympathovagal balance). Children were grouped into Improved (n=12; 7 treated between studies) and Unimproved (n=12; 2 treated between studies). Results OAHI decreased between studies in the Improved group (baseline, 29.5 (1.6,154.0) [mean (min,max)] events/h; follow-up, 8.4 (0,77.0); p&amp;lt;0.05), and worsened in the Unimproved group (baseline 6.1 (0,22.9); follow-up 14.4 (0.3, 54.6); p&amp;lt;0.05). LF power was lower at follow-up in the Unimproved group compared to baseline during Total Sleep (p&amp;lt;0.05), N3 (p&amp;lt;0.05) and REM (p&amp;lt;0.01). HF power was also lower at follow-up in the Unimproved group during REM (p&amp;lt;0.05). HRV remained unchanged between baseline and follow-up for the Improved group. Conclusion Autonomic control worsened as indicated by lower sympathetic and parasympathetic activity in children whose SDB was not improved. In contrast, in those children with improved SDB autonomic control remained the same, suggesting improvement in SDB severity prevents further worsening of autonomic control in children with DS.

Heart rate surge at respiratory event termination in preterm and term born children with sleep disordered breathing

BackgroundRepetitive surges in heart rate (HR) at respiratory event termination underpin the altered autonomic HR control associated with sleep disordered breathing (SDB). As children born preterm are at greater risk of adverse cardiovascular outcomes, we aimed to determine whether the HR response to obstructive respiratory events was elevated compared to term-born children. MethodsFifty children (3–12 years) born preterm, were matched for SDB severity, age and gender with term born children. Multilevel modelling determined the effect of preterm birth and arousal on HR changes between a 10s baseline to the latter half of respiratory events and 15s post event during NREM and REM. Results1203 events were analysed (NREM: term 380; preterm 383; REM: term 207; preterm 233). During NREM fewer events terminated in arousal in the preterm compared with term group (preterm 68%; term 84%; χ2 = 27.2, p < 0.001). There were no differences in REM. During NREM, HR was lower in the preterm group at all event phases, with and without associated arousals (P < 0.01 for all). % change in HR from baseline to post event was higher in the preterm compared with term group (preterm: median 23% IQR (12%,34%); term: 18% (10%,29%); p < 0.01) and late event to post event (preterm: 30% (21%, 32%); term 28% (20%,39%); p < 0.01) in events associated with arousals. ConclusionThe greater magnitude of surges in HR following respiratory events terminating with arousal in preterm born children, although small, occur repeatedly throughout the night and may contribute to adverse cardiovascular outcomes, although further studies are required.

Impact of cold mud pack on abdomen and eyes on the autonomic control of heart rate

Mud therapy is a system of naturopathic medicine where treatment is given using various forms of mud. Hence, the present study aims to evaluate the physiological effects of simultaneous application cold mud pack over the abdomen and eyes by determining the cardiovascular and autonomic parameters of the study participants. 30 healthy volunteers were recruited for the study. All volunteers were subjected to two sessions of treadmill run up to 10 minutes and subsequently to supine rest. Their first session was considered under control trial, during which they were given a dry abdomen and an eye pack after the treadmill run for 20 minutes. With a gap of 15 days in between, in the experimental trial, they were given a cold mud packs to the abdomen and eyes during the supine rest after the treadmill run. HRV Assessments were done during the intervention and their BP and pulse were recorded immediately after the intervention. All HRV parameters in the time domain and HF in frequency domain remain increased during the mud pack trial.

Spectral analysis of signals of autonomic regulation of blood circulation in patients with COVID-19 and arterial hypertension

The work aims to carry out a comparative analysis of the spectral indices of the photoplethysmogram signals and RR-intervals of healthy volunteers, patients with COVID-19, as well as patients with COVID-19 and chronic arterial hypertension of 1-2 degrees. The study included 45 records of pairs of electrocardiogram and photoplethysmogram signals. Each sample included 15 pairs of 20-minute experimental signals. The study revealed an increase in the integrated power of the low-frequency (LF) band over the integrated power of the high-frequency (HF) band in the photoplethysmogram signals in patients with COVID-19, burdened with hypertension. In the signals of the RR-intervals, the largest values of the ratio of the LF to HF indices are associated with patients without cardiovascular diseases. In turn, this may be an indicator of the different effects of viral infection and arterial hypertension on the loops of autonomic control of heart rate and vascular tone.

Effect of Intensity on Changes in Cardiac Autonomic Control of Heart Rate and Arterial Stiffness After Equated Continuous Running Training Programs.

Background: It is well known that exercise training has positive effects on both cardiac autonomic function and arterial stiffness (AS). However, it is not clear that which exercise training variables, intensity or volume, or both, play a crucial role in this regard. This study investigates the chronic effects of high-volume moderate-intensity training (HVMIT) and low-volume high-intensity training (LVHIT) on heart rate variability (HRV) and AS in sedentary adult men.Materials and Methods: Notably, 45 males (age: 42 ± 5.7 years) were randomly assigned to a control (n = 15), HVMIT (n = 15), or LVHIT (n = 15). The HVMIT group ran three times per week on a treadmill at 50–60% of VO2max for 45–60 min, while the LVHIT trained at 70–85% of VO2max for 25–40 min. Both training protocols were equated by caloric expenditure. HRV, pulse wave velocity (PWV), hemodynamic variables, and body composition were measured before and after 12 weeks.Results: Both protocols (i.e., HVMIT and LVHIT) significantly increased the SD of normal sinus beat intervals (SDNN) and high-frequency (HF) bands (p < 0.05) after 12 weeks. Whereas the low-frequency (LF)-HF ratio decreased significantly in both training protocols (p < 0.05); however, these changes were significantly greater in the LVHIT protocol (p < 0.05). Furthermore, the root mean square of successive RR interval differences (RMSSD) significantly increased only in the LVHIT (p < 0.05). Moreover, a significant decrease in LF and PWV was only observed following the LVHIT protocol (p < 0.05). Some measures of HRV and PWV were significantly correlated (r = 0.275–0.559; p < 0.05).Conclusion: These results show that the LVHIT protocol was more efficient for improving HRV variables and PWV than the HVMIT protocol after 12 weeks of continuous running training. Interestingly, changes in some HRV parameters were related to changes in PWV. Further studies should elaborate on the link between central and peripheral cardiovascular adaptations after continuous and intermittent training regimens differing in intensity.

Synchronization Of Autonomic Control Loops Of Blood Circulation In Patients With COVID-19

This study aims to investigate the strength of synchronization between the autonomic control loops of the cardiovascular system (CVS) in patients with COronaVIrus Disease 2019 (COVID-19). Methods — We calculated the total percent of phase synchronization index (S index) between the loops of autonomic control of heart rate and vascular tone in two sample groups: healthy individuals and COVID-19 patients. Results — The group-average value of the S index in COVID-19 patients is lower comparing to healthy individuals, the Mann-Whitney U-test confirmed that the differences are statistically significant. Conclusion — Obtained results suggest that the decreased value of the S index reflects the presence of a viral disease, and the S index is a promising basis for non-invasive screening diagnostics of viral diseases, particularly of COVID-19.

Does bariatric surgery improve cardiac autonomic modulation assessed by heart rate variability? A systematic review

Our study aimed to explore the influence of bariatric surgery (BS) on heart rate (HR) variability (HRV) through a systematic review. Manuscripts were selected based on electronic searches of the MEDLINE, EMBASE, and CINAHL databases from the inception of each database up to year 2020, and followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) protocol. Searching of these studies was systematized using the Population Intervention Comparison Outcome Study Design strategy. We selected randomized and nonrandomized controlled trials and cohorts from prospective studies that reported the influence of BS on HRV. We assessed the quality rating using the Black and Downs questionnaire. Following the screening and eligibility stages, 14 studies were included in the review. All studies agreed that BS promotes an increase in parasympathetic HR control and HRV and a decrease in HR. Yet the literature does not provide evidence that these outcomes are directly caused by the surgical procedure. There is limited evidence to support that patients with type 2 diabetes have greater improvement in HRV as an interim measure, to individuals without. The decrease in insulin resistance was correlated with the increase in HRV in some studies, but, other studies are unsupportive of this outcome. Improvements in 2 metabolic parameters (e.g., leptin, N-terminal pro B-type natriuretic peptide) were connected with superior increases in HRV. This review demonstrated that BS promotes an increase in HRV, indicating improved autonomic control of HR.

Assessment of Alamandine in Pulmonary Fibrosis and Respiratory Mechanics in Rodents.

Introduction Pulmonary fibrosis (PF) is characterized by an accelerated decline in pulmonary function and has limited treatment options. Alamandine (ALA) is a recently described protective peptide of the renin-angiotensin system (RAS) with essential tasks in several conditions. Our group previously demonstrated that ALA is reduced by 365% in the plasma of patients with idiopathic PF, and thus, it is plausible to believe that stimulation of this peptide could represent an important therapeutic target. In this sense, this study investigates the effects of ALA in an experimental model of PF. Materials and Methods Bleomycin (BLM) was administrated in Wistar rats, and these fibrotic animals were treated with ALA for 14 days. Body weight, histology, respiratory, and hemodynamic parameters were analyzed to study the effects of ALA. Results ALA treatment attenuated the development of fibrosis (P < 0.0001), reduced respiratory system elastance (P < 0.0001), and preserved weight gain (P < 0.0001) in fibrotic animals without affecting the autonomic control of blood pressure and heart rate. Conclusion The data from this study demonstrate the potential of ALA to alleviate pulmonary fibrosis and improve respiratory system mechanics in vivo. The promising results encourage more detailed investigations of the potential of ALA as a future and efficient antifibrotic.

Changes in Resting and Exercise Hemodynamics Early After Heart Transplantation: A Simulation Perspective.

Introduction: During heart transplantation (HTx), cardiac denervation is inevitable, thus typically resulting in chronic resting tachycardia and chronotropic incompetence with possible consequences in patient quality of life and clinical outcomes. To this date, knowledge of hemodynamic changes early after HTx is still incomplete. This study aims at providing a model-based description of the complex hemodynamic changes at rest and during exercise in HTx recipients (HTxRs).Materials and Methods: A numerical model of early HTxRs is developed that integrates intrinsic and autonomic heart rate (HR) control into a lumped-parameter cardiovascular system model. Intrinsic HR control is realized by a single-cell sinoatrial (SA) node model. Autonomic HR control is governed by aortic baroreflex and pulmonary stretch reflex and modulates SA node activity through neurotransmitter release. The model is tuned based on published clinical data of 15 studies. Simulations of rest and exercise are performed to study hemodynamic changes associated with HTxRs.Results: Simulations of HTxRs at rest predict a substantially increased HR [93.8 vs. 69.5 beats/min (bpm)] due to vagal denervation while maintaining normal cardiac output (CO) (5.2 vs. 5.6 L/min) through a reduction in stroke volume (SV) (55.4 vs. 82 mL). Simulations of exercise predict markedly reduced peak CO (13 vs. 19.8 L/min) primarily resulting from diminished peak HRs (133.9 vs. 169 bpm) and reduced ventricular contractility. Yet, the model results show that HTxRs can maintain normal CO for low- to medium-intensity exercise by increased SV augmentation through the Frank–Starling mechanism.Conclusion: Relevant hemodynamic changes occur after HTx. Simulations suggest that (1) increased resting HRs solely result from the absence of vagal tone; (2) chronotropic incompetence is the main limiting factor of exercise capacity whereby peripheral factors play a secondary role; and (3) despite the diminished exercise capacity, HTxRs can compensate chronotropic incompetence by a preload-mediated increase in SV augmentation and thus maintain normal CO in low- to medium-intensity exercise.

Mechanosensory Signaling in Astrocytes.

Mechanosensitivity is a well-known feature of astrocytes, however, its underlying mechanisms and functional significance remain unclear. There is evidence that astrocytes are acutely sensitive to decreases in cerebral perfusion pressure and may function as intracranial baroreceptors, tuned to monitor brain blood flow. This study investigated the mechanosensory signaling in brainstem astrocytes, as these cells reside alongside the cardiovascular control circuits and mediate increases in blood pressure and heart rate induced by falls in brain perfusion. It was found that mechanical stimulation-evoked Ca2+ responses in astrocytes of the rat brainstem were blocked by (1) antagonists of connexin channels, connexin 43 (Cx43) blocking peptide Gap26, or Cx43 gene knock-down; (2) antagonists of TRPV4 channels; (3) antagonist of P2Y1 receptors for ATP; and (4) inhibitors of phospholipase C or IP3 receptors. Proximity ligation assay demonstrated interaction between TRPV4 and Cx43 channels in astrocytes. Dye loading experiments showed that mechanical stimulation increased open probability of carboxyfluorescein-permeable membrane channels. These data suggest that mechanosensory Ca2+ responses in astrocytes are mediated by interaction between TRPV4 and Cx43 channels, leading to Cx43-mediated release of ATP which propagates/amplifies Ca2+ signals via P2Y1 receptors and Ca2+ recruitment from the intracellular stores. In astrocyte-specific Cx43 knock-out mice the magnitude of heart rate responses to acute increases in intracranial pressure was not affected by Cx43 deficiency. However, these animals displayed lower heart rates at different levels of cerebral perfusion, supporting the hypothesis of connexin hemichannel-mediated release of signaling molecules by astrocytes having an excitatory action on the CNS sympathetic control circuits.SIGNIFICANCE STATEMENT There is evidence suggesting that astrocytes may function as intracranial baroreceptors that play an important role in the control of systemic and cerebral circulation. To function as intracranial baroreceptors, astrocytes must possess a specialized membrane mechanism that makes them exquisitely sensitive to mechanical stimuli. This study shows that opening of connexin 43 (Cx43) hemichannels leading to the release of ATP is the key central event underlying mechanosensory Ca2+ responses in astrocytes. This astroglial mechanism plays an important role in the autonomic control of heart rate. These data add to the growing body of evidence suggesting that astrocytes function as versatile surveyors of the CNS metabolic milieu, tuned to detect conditions of potential metabolic threat, such as hypoxia, hypercapnia, and reduced perfusion.

Abstract MP40: Hiv Impairs Endothelial Function And Elevates Blood Pressure Via Tnfa Dependent Mechanisms In Male And Female Mice.

HIV is a major health concern with over 37 million individuals worldwide living with HIV. The onset of combination antiretroviral therapy (cART) patients with HIV (PWH) live longer but exhibit accelerated development of cardiovascular disease. Clinical evidence indicates that 35% of PWH exhibit hypertension, however, the etiopathology is still ill-defined. We plan to take advantage of a transgenic mouse model (Tg26) that mimics patients with a repressed virus, to test the hypothesis that viral infection independent of cART induces endothelial dysfunction and hypertension via a TNF-α mediated mechanism. Vascular reactivity was analyzed via wire myography and blood pressure (BP) recorded via radio-telemetry. Results showed that viral infection impaired aorta endothelium-dependent relaxation as reflected by a decrease in acetylcholine-mediated relaxation in both Tg26 mice (P&lt;0.05) which was ameliorated with the NOX 1/4 inhibitor GKT 137831. Smooth muscle cell-dependent relaxation (SNP) and contractility to phenylephrine and KCl remained intact in Tg26 mice. Viral infection increased systolic, diastolic, and mean arterial pressure (MAP: male: WT=112.3±1.3 vs Tg26=121.9±4.0 mmHg/ female: WT=110.6±3.01/ Tg26=120.3±6.9 mmHg) and elevated heart rate (HR) in both sexes (p&lt;0.05). We used atropine, propranolol, and hexamethonium in WT and Tg26 mice to investigate the contribution of the autonomic nervous system to hypertension. HR responses to both atropine (Female: +5.07±2.8% vs. male +4.3±5.4% of baseline) and propranolol (Female: 19.9±6.1% vs. male 12.0±4.3%) revealed no significance or sex differences in WT mice and no effects of viral infection on autonomic control of heart rate in Tg26 mice. BP responses to hexamethonium revealed no effect of sex or viral infection, supporting a limited contribution of the autonomic nervous system to hypertension in Tg26 mice. However, we found that TNFα inhibition with etanercept reduced mean arterial pressure in Tg26 mice to the level of the WT mice (WT=112.3±1.3, Treated=110.1±0.185) and improved endothelial function. These data indicate that HIV infection contributes to cardiovascular disease via inducing endothelial dysfunction and hypertension via NOX and TNFα-dependent mechanisms respectively.

Concussion in Adolescents Impairs Heart Rate Response to Brief Handgrip Exercise

Test the hypotheses that (1) concussion in adolescents impairs autonomic neural control of heart rate (HR), and (2) HR reactivity improves with symptom resolution. Observational, case-control. Nineteen concussed adolescents (8 female adolescents; age 15 ± 2 years) and 16 healthy controls (6 female adolescents, age 15 ± 2 years). All participants performed an isometric handgrip (IHG) at 30% maximum voluntary contraction lasting 30 seconds. Heart rate (electrocardiogram) and hemodynamic responses (photoplethysmographic Finometer) were recorded from 30 seconds of baseline and the last 10 seconds of handgrip. The HR response (ΔHR) at the onset of moderate-intensity IHG using a mixed 1-way analysis of variance. A group × time interaction (P < 0.005) indicated that handgrip evoked a greater ΔHR among control participants (13 ± 10 beats/min) compared with concussed (6.4 ± 6.3 beats/min; group P = 0.63; time P < 0.001; d = 0.77). These preliminary results suggest that a concussion impairs the ability to elevate HR at the exercise onset and, given the nature of the task, this could be interpreted to reflect reduced ability to withdraw cardiovagal control. Therefore, the data support the hypothesis of neural cardiac dysregulation in adolescents diagnosed with concussion. The IHG test could aid concussion diagnosis and support return-to-play decisions.

Impact of respiratory physical therapy on heart rate autonomic control in children with leukemia.

Considering that heart rate (HR) autonomic control is impaired in cancer and subsequent respiratory effort may overload the heart, we aimed to evaluate the effect of a respiratory physical therapy session on HR autonomic regulation in children with leukemia so as to confirm its safety. We selected children with leukemia (n = 10) and healthy children (n = 11), which were submitted to a session of respiratory physical therapy. We used Spiron Kids (NCS, Brazil), Children's Voldyne (HUDSON RCI, USA), and Shaker (NCS, Brazil) as respiratory devices. The respiratory exercise protocols were founded on three standardized protocols. HR variability (HRV) was analyzed before, in the first minute and 5 to 10min after intervention. We recognized no change between rest and recovery from intervention in HRV (rMSSD-square root mean square of the differences between adjacent normal R-R intervals)-Control: p = 0.8111, Leukemia: p = 0.1197, among groups: p = 0.6574; SD1-standard deviation from instantaneous beat-to-beat variability-Control: p = 0.8111, Leukemia: p = 0.131, among groups: p = 0.6556; 0V-with no variation (3 equal symbols, for example (2,2,2)-Control: p = 0.3679, Leukemia: p = 0.3553, among groups: p = 0.7421); 2UV-with two variations to the contrary (the three symbols form a peak or a valley, for instance (3,5,3)-Control: p = 0.3679, Leukemia: p = 0.2359, among groups: p = 0.4007). HF-high frequency component, range 0.15 to 0.4Hz-decreased 0 to 1min after intervention in the leukemia group (p = 0.0303) and no change was observed in the control group between rest versus recovery from intervention (p = 0.9761). No significant change was reported in HF between groups (p = 0.8700). Two leukemia subjects treated with vincristine presented different HRV responses to the intervention group. A respiratory physical therapy session did not significantly change autonomic control of HR in children with leukemia. Yet, clinicians should be mindful of subjects undergoing treatment with vincristine.