P095 Heart Rate Variability during Sleep in Paroxysmal Atrial Fibrillation patients with and without Obstructive Sleep Apnoea

Introduction Physiological studies have demonstrated the importance of the autonomic nervous system in mediating acute apnoea-induced atrial fibrillation (AF). We aimed to compare Heart Rate Variability (HRV) markers of autonomic function in paroxysmal atrial fibrillation (PAF) patients with and without obstructive sleep apnoea (OSA). A secondary aim was the analysis of ectopic beats in these groups. Methods Nocturnal ECG traces from 89 PAF patients who underwent in-laboratory polysomnography were included. After identifying ectopic beats in the ECGs, periods of arrhythmia as well as sleep apnoea events were excluded. HRV time and frequency domains were reported by sleep stage (REM vs Non-REM) for patients with and without OSA. Results Frequency domain analysis of HRV during non-REM sleep in PAF patients with OSA showed increased cardiac parasympathetic modulation (HF-nu: 39.13 ± 15.74 vs 47.98 ± 14.60, p = 0.008*) and reduced cardiac sympathetic modulation (LF/HF ratio: 2.05 ± 2.02 vs 1.17 ± 0.98, p = 0.007*). Results remained significant after adjusting for age, sex and BMI (adjusted p values 0.024 and 0.018 respectively). PAF patients with severe OSA (AHI ≥ 30/hr) had more AF beats and Ventricular Ectopic Beats than those without severe OSA (22.7 ± 42.8% vs 3.7 ± 17.9%, p = 0.006*, 1.7 ± 3.8 vs 0.3 ± 0.9%, p = 0.004* respectively). Conclusions This is the first study of HRV in AF patients with and without OSA. It suggests a chronic increase in parasympathetic nervous modulation and relative reduction in sympathetic modulation in PAF patients with OSA.

O004 Obstructive sleep apnoea severity is associated with parasympathetic withdrawal in coronary artery disease

Introduction Patients with Coronary Artery Disease (CAD) are exposed to myocardial ischemia and hypoxia, resulting in altered autonomic function. Obstructive sleep apnoea (OSA) is highly prevalent in CAD and is associated with increased sympathetic activity which could further exacerbate cardiovascular risk. We aimed to determine whether OSA severity is associated with altered autonomic function in CAD patients. Methods Patients presenting to the coronary care unit with CAD underwent level 2 portable polysomnography to assess the presence and severity of OSA. Autonomic function was calculated from continuous blood pressure and 3-lead ECG 5 minute recordings while awake. Mean spontaneous baroreceptor sensitivity (sBRS msec/mmHg); vagally mediated heart rate variability (HRV) markers (pNN50%, RMSSD, HF-HRV); and, sympathetically mediated vascular autonomic function (LF-BPV) were measured. Autonomic function was assessed in relation to OSA severity (Apnoea Hypopnea Index, AHI; oxygen desaturation index, ODI). Results OSA was present in 49/51 (96%) participants with CAD (age 54±9 years; BMI 28.9±5.4 kg/m2; male 41(77%)). No association was found between sBRS and AHI. There was a modest inverse correlation between AHI and vagally mediated HRV (RMSSD, r= -0.28 p=0.04; HF, r= -0.31 p=0.03). AHI positively correlated with LF-SBP (r=0.29, p=0.04) suggesting upregulation of sympathetic modulation. Linear regression analyses, adjusted for age, sex, and BMI, showed AHI was a determinant of parasympathetically modulated HRV measures (pNN50% -0.25(0.12), p=0.05). Conclusions In patients with CAD, increased AHI was associated with parasympathetic withdrawal suggesting that OSA could increase poor cardiovascular prognosis in this population.

Relationship between mood state and cardiac autonomic modulation in jiu-jitsu fighters in the pre- and post-competitive period: A pilot study

Aim: To characterize the changes in body composition, mood state and cardiac autonomic modulation in Brazilian Jiu-Jitsu (BJJ) of athletes in the pre- and post-competitive periods. Methods: Eight male athletes were evaluated in 3 moments: 14 days and 1 day before the fight, and 2 days after the competition. Evaluations of body composition, mood state, and cardiac autonomic modulation were performed. The repeated measures Anova test, Pearson and Spearman correlation were used for data analysis (p < 0.05). Results: We observed reductions in anger (6.80 ± 1.69 vs. 4.20 ± 1.67 vs. 3.40 ± 1.07) and tension (6.60 ± 0.81 vs. 5.40 ± 0.75 vs. 2.60 ± 0.88) after competition. Vigor was reduced one day before the competition and remained the same two days after the competition (12.80 ± 1.60 vs. 10.00 ± 1.95 vs. 10.40 ± 1.03). In addition, there was an increase in sympathetic modulation (LF-PI: 2942 ± 655.3 vs. 5479 ± 2035 vs. 5334 ± 2418 abs). There was a positive correlation between the state of vigor and sympathetic modulation (r = 0.55), a negative correlation between the states of depression and sympathetic modulation (r = -0.68) and confusion and sympathetic modulation (r = -0.67). Conclusion: These findings raised concerns about the preparation of these athletes for competitions since changes in the state of vigor might reduce performance and increase cardiovascular risk.

Adrenergic Attenuation of Immune Activity is Associated with Anhedonia in Adolescents

While inflammation has been implicated in the manifestation of psychiatric symptoms, the role of immune attenuation via sympathetic modulation in psychopathology remains unclear. Here, this study aimed to assess β2-agonist clenbuterol (CBL) as a promising agent to model adrenergic-induced immune response following ex vivo immune activation with lipopolysaccharide (LPS). Relationships between CBL-modulated cytokine levels and symptom measures were then explored. Adolescents were evaluated with semi-structure interviews and self-reported depression, anxiety, and anhedonia levels. Fasting whole-blood samples were collected and stimulated with LPS in the presence and absence of CBL for 6 hours, with supernatants being subjected to Luminex multiplex assay for 41 cytokines. Cytokine levels between conditions were compared using Bonferroni-corrected nonparametric tests. Exploratory factor analysis reduced 41 cytokines into fewer factors in each experimental condition, and their relationships with psychiatric symptoms were examined with Spearman correlations controlling for age, sex, and BMI. Data from 130 participants (15.25 ± 2.16 years old, 59% female) were analyzed. 10 cytokines were significantly affected by CBL treatment compared to LPS alone. LPS+CBL factor 3 significantly correlated with both anticipatory (rho = -0.39, p = 7.4 × 10-5) and consummatory anhedonia (rho = -0.36, p = 3.3 × 10-4), and these correlations remained significant when controlling additionally for depression. There were no significant associations between immune factors with depression or anxiety severity. Findings support our hypothesis that clenbuterol attenuates inflammatory effects thought to underlie psychiatric conditions in youth. Using a data-driven analytic method, distinctive relationships between CBL-affected cytokines and dimensional anhedonia were reported, further elucidating the role of β2-agonism in adolescent affective symptomatology.

Cardiac autonomic associations on exercise and ambulatory capacity in individuals with lower-extremity artery disease

Funding Acknowledgements Type of funding sources: Foundation. Main funding source(s): This work was in part supported by Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP #2019/19596-7), and Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq #303399/2018-0). OnBehalf Exercise and Chronic Disease Research Laboratory - Bauru, Brazil; Research Group for Cardiovascular Rehabilitation - Leuven, Belgium. INTRODUCTION Lower-extremity artery disease (LEAD) characterized by progressive atherosclerotic build-up in leg arteries is becoming increasingly prevalent, affecting more than 200 million people worldwide. In line with other atherosclerotic disorders, LEAD is often associated with autonomic dysfunction as evidenced by a reduced heart rate variability (HRV). To date, little is known on the impact of cardiac autonomic function on exercise and ambulatory capacity. PURPOSE We aimed to investigate whether autonomic function is associated with ambulatory capacity and exercise capacity in patients with LEAD. METHODS Thirty-four patients (age≥17 years) diagnosed with LEAD (ankle brachial index: ABI ≤ 0.9 and/or 20% decrease after a maximal treadmill test) suffering from intermittent claudication (Rutherford I-III) were recruited in the PROSECO-IC trial. Patients were grouped based on beta-blocker medication (β-blocker and non β-blocker). Intervals between R waves (i-RR) obtained by heart rate (HR) signal were acquired beat-to-beat via a digital telemetry system (Polar®️ H10) during 15 min of supine rest and were used for 5-minute HRV analysis. Time domain indexes (mean i-RR, SNDD, pNN50%), and frequency domains (high frequency band (HF), low frequency (LF, very LF (VLF)) and the ratio (LF/HF). HRV was analyzed in absolute (abs), normalized (nu) and log units (log). Ambulatory capacity was assessed by means of a submaximal treadmill test, graded maximal treadmill test using Gardner protocol (GTM) and 6 minutes walking test (6MWT); exercise capacity was assessed by means of a graded maximal cardiopulmonary exercise test (HR, blood pressure (BP) and peak oxygen uptake (VO2peak)) at resting, 2 minutes, and peak of exercise. RESULTS Pearson test showed that sympathetic modulation indexes were moderate associated with pain free distance in GTM (LF/HF: r = 0.52, p = 0.04), and pain free time in 6MWT (LFlog: r=-0.62, p = 0.01; VLF: r=-0.52, p = 0.04), respectively, in patients without β-blocker. Similar HR associations with HRV (time and frequency domain) were observed during submaximal treadmill test and cardiopulmonary exercise test (p ≤ 0.05). Test-t demonstrated a significantly increased response intra-groups in HR and BP during both tests (p ≤ 0.05). Average BP were positive associated with the earlier stages of the cardiopulmonary test (resting to 2 min) with LFlog (r = 0.70, p= &lt;0.001) in β-blocker while non-β-blocker were associated from 2 min to peak with LFabs (r = 0.67, p= &lt;0.001) and LF/HF (r = 0.52, p = 0.03). CONCLUSION Sympathetic modulation was correlated with a longer pain free walking capacity in non-β-blockers. Yet, individuals treated by -β-blockers showed an earlier sympathetic modulation through exercise pressor response during the first stages of cardiopulmonary exercise compared to non-β-blockers with LEAD.

Activation of the cholinergic antiinflammatory reflex by occipitoatlantal decompression and transcutaneous auricular vagus nerve stimulation

Context The parasympathetic-mediated inflammatory reflex inhibits excessive proinflammatory cytokine production. Noninvasive techniques, including occipitoatlantal decompression (OA-D) and transcutaneous auricular vagus nerve stimulation (taVNS), have been demonstrated to increase parasympathetic tone. Objectives To test the hypothesis that OA-D and taVNS increase parasympathetic nervous system activity and inhibit proinflammatory cytokine mobilization and/or production. Methods Healthy adult participants were randomized to receive OA-D (5 min of OA-D followed by 10 min of rest; n=8), taVNS (15 min; n=9), or no intervention (15 min, time control; n=10) on three consecutive days. Before and after these interventions, saliva samples were collected for determination of the cytokines interleukin-1β (IL-1β), interleukin-6 (IL-6), interleukin-8 (IL-8), and tumor necrosis factor α (TNF-α). Arterial blood pressure and the electrocardiogram were recorded for a 30-min baseline, throughout the intervention, and during a 30-min recovery period to derive heart rate and blood pressure variability markers as indices of vagal and sympathetic control. Results OA-D and taVNS increased root mean square of successive RR interval differences (RMSSD) and high frequency heart rate variability, which are established markers for parasympathetic modulation of cardiac function. In all three groups, the experimental protocol was associated with a significant increase in salivary cytokine concentrations. However, the increase in IL-1β was significantly less in the taVNS group (+66 ± 13 pg/mL; p<0.05) than in the time control group (+142 ± 24 pg/mL). A similar trend was observed in the taVNS group for TNF-α (+1.7 ± 0.3 pg/mL vs. 4.1 ± 1.3 pg/mL; p<0.10). In the OA-D group baseline IL-6, IL-8, and TNF-α levels on the third study day were significantly lower than on the first study day (IL-6: 2.3 ± 0.4 vs. 3.2 ± 0.6 pg/mL, p<0.05; IL-8: 190 ± 61 vs. 483 ± 125 pg/mL, p <0.05; TNF-α: 1.2 ± 0.3 vs. 2.3 ± 0.4 pg/mL, p<0.05). OA-D decreased mean blood pressure from the first (100 ± 8 mmHg) to the second (92 ± 6 mmHg; p<0.05) and third (93 ± 8 mmHg; p<0.05) study days and reduced low frequency spectral power of systolic blood pressure variability (19 ± 3 mmHg2 after OA-D vs. 28 ± 5 mmHg2 before OA-D; p<0.05), a marker of sympathetic modulation of vascular tone. OA-D also increased baroreceptor-heart rate reflex sensitivity from the first (13.7 ± 3.0 ms/mmHg) to the second (18.4 ± 4.3 ms/mmHg; p<0.05) and third (16.9 ± 4.2 ms/mmHg; p<0.05) study days. Conclusions Both OA-D and taVNS elicited antiinflammatory responses that were associated with increases in heart rate variability-derived markers for parasympathetic function. These findings suggest that OA-D and taVNS activate the parasympathetic antiinflammatory reflex. Furthermore, an antihypertensive effect was observed with OA-D that may be mediated by reduced sympathetic modulation of vascular tone and/or increased baroreceptor reflex sensitivity.

Human Adaptations to Multiday Saturation on NASA NEEMO

Human adaptation to extreme environments has been explored for over a century to understand human psychology, integrated physiology, comparative pathologies, and exploratory potential. It has been demonstrated that these environments can provide multiple external stimuli and stressors, which are sufficient to disrupt internal homeostasis and induce adaptation processes. Multiday hyperbaric and/or saturated (HBS) environments represent the most understudied of environmental extremes due to inherent experimental, analytical, technical, temporal, and safety limitations. National Aeronautic Space Agency (NASA) Extreme Environment Mission Operation (NEEMO) is a space-flight analog mission conducted within Florida International University’s Aquarius Undersea Research Laboratory (AURL), the only existing operational and habitable undersea saturated environment. To investigate human objective and subjective adaptations to multiday HBS, we evaluated aquanauts living at saturation for 9–10 days via NASA NEEMO 22 and 23, across psychologic, cardiac, respiratory, autonomic, thermic, hemodynamic, sleep, and body composition parameters. We found that aquanauts exposed to saturation over 9–10 days experienced intrapersonal physical and mental burden, sustained good mood and work satisfaction, decreased heart and respiratory rates, increased parasympathetic and reduced sympathetic modulation, lower cerebral blood flow velocity, intact cerebral autoregulation and maintenance of baroreflex functionality, as well as losses in systemic bodyweight and adipose tissue. Together, these findings illustrate novel insights into human adaptation across multiple body systems in response to multiday hyperbaric saturation.

Sex Influence on Cardiovascular Autonomic Modulation and on Cardiac and Renal Oxidative Stress: Effects of Aerobic Exercise Training

The aim of this study was to investigate the difference between sexes after 8 weeks of aerobic exercise training on cardiovascular autonomic modulation and oxidative stress. Wistar rats were distributed into (n = 8/group): sedentary male (SM), trained male (TM), sedentary female (SF) and trained female (TF). Arterial pressure (AP) signals were directly recorded. Cardiovascular autonomic modulation was evaluated by spectral analysis. Aerobic exercise training was performed on treadmill (5 days/wk; 8 wks). Oxidative stress was evaluated on cardiac and renal tissues. Both trained groups presented bradycardia. Exercise training increased heart rate variability (VAR-PI) and decreased cardiac sympathovagal balance in both sexes. Although, no differences observed in AP, the female groups showed a lower vascular sympathetic modulation than the male groups. There was a positive correlation between vascular sympathetic modulation and renal membrane lipid peroxidation (LPO) (r = 0.6, p < 0.01). LPO in cardiac tissue was reduced in the TM, SF and TF groups when compared to the SM group and it was correlated with cardiac sympathetic modulation (r = 0.6, p < 0.01). Only the TF group presented AP variability and renal LPO decreased and cardiac glutathione redox balance (GSH/GSSG) improved when compared to the other groups. Moreover, the trained females showed greater improvement on VAR-PI (~ 1.8 times), on cardiac and renal antioxidant capacity (TRAP: ~2,1 and ~ 1.5 times, respectively), and on cardiac GSSG (~ 2.8 times) than the trained males. In conclusion, female rats showed additional aerobic exercise training induced-cardiovascular autonomic modulation and target organs oxidative stress profile improvement than male rats.