Vagal Modulation Research Articles

Cardiovascular autonomic nervous function in children conceived by assisted reproductive technology with frozen or fresh embryo transfer.

As a result of epigenetic changes, children conceived by assisted reproduction may be at risk of premature cardiovascular aging with notably increased blood pressures. Their cardiovascular autonomic nervous function is unknown. Therefore, this study investigated the cardiovascular autonomic nervous function in 8-12-yr-old children (51% girls) conceived naturally (n = 33) or by assisted reproduction with frozen (n = 34) or fresh (n = 38) embryo transfer by evaluating heart rate variability, during rest; from provocation maneuvers; and from baroreflex function. Heart rate and blood pressure response to provocation maneuvers and baroreflex function were comparable between children conceived naturally or by assisted reproduction. The mean RR-interval and high-frequency component of heart rate variability were lower in children conceived by assisted reproduction than in children conceived naturally. Children conceived by fresh embryo transfer had ∼17% lower heart rate-corrected standard deviation of normal-to-normal R-R intervals; ∼22% lower heart rate-corrected square root of the mean of the squared difference between successive R-R intervals; and ∼37% higher low-frequency/high-frequency ratio than naturally conceived children. Children conceived by assisted reproduction still had lower heart rate variability and vagal modulation than naturally conceived children after adjustment for confounders. Thus, these results raise the possibility of sympathetic predominance in children conceived by assisted reproduction. Therefore, it is important to reproduce these results in larger and older cohorts as sympathetic predominance relates with cardiovascular and metabolic diseases.NEW & NOTEWORTHY We observed that children conceived by assisted reproductive technology (both frozen and fresh embryo transfer) had lowered heart rate variability during rest as compared with children conceived naturally. During physiological stress maneuvers, however, the cardiovascular autonomic nervous regulation was comparable between children conceived by assisted reproductive technologies and naturally. Our findings highlight the potential that lowered heart rate variability during rest in children conceived by assisted reproductive technologies may precede premature hypertension.

Acute Cardiorespiratory Coupling Impairment in Worsening Sleep Apnea-Related Intermittent Hypoxemia.

Hypoxic load is one of the main characteristics of obstructive sleep apnea (OSA) contributing to sympathetic overdrive and weakened cardiorespiratory coupling (CRC). Whether this association changes with increasing hypoxic load has remained obscure. Therefore, we aimed to study our hypothesis that increasing hypoxic load acutely decreases the CRC. We retrospectively analyzed the electrocardiography and nasal pressure signals in 5-min segment pairs (n = 36 926) recorded during clinical polysomnographies of 603 patients with suspected OSA. The segment pairs were pooled into five groups based on the hypoxic load severity described with the the total integrated area under the blood oxygen saturation curve during desaturations. In these severity groups, we determined the frequency-domain heart rate variability (HRV) parameters, the HRV and respiratory high-frequency (HF, 0.15-0.4 Hz) peaks, and the difference between those peaks. We also computed the spectral HF coherence between HRV and respiration in the HF band. The ratio of low-frequency (LF, 0.04-0.15 Hz) to HF power increased from 1.047 to 1.805 (p < 0.001); the difference between the HRV and respiratory HF peaks increased from 0.001 Hz to 0.039 Hz (p < 0.001); and the spectral coherence between HRV and respiration in the HF band decreased from 0.813 to 0.689 (p < 0.001) as the hypoxic load increased. The vagal modulation decreases and CRC weakens significantly with increasing hypoxic load. Thus, the hypoxic load could be utilized more thoroughly in contemporary OSA diagnostics to better assess the severity of OSA-related cardiac stress.

Ultra-short heart rate variability over 15 seconds is associated with increased long-term risk of cardiovascular disease

Abstract Background Heart rate variability (HRV) is an established cardiac autonomic marker with prognostic value, whose application at scale is limited by the fact it requires relatively long ECG recordings (≥ 5-min). Ultra-short HRV (usHRV) is derived from much shorter recordings and can be measured at scale using standard and wearable ECGs, but its association with cardiovascular events is undetermined. Purpose (1) To validate usHRV measured using 15-second ECGs and (2) To investigate association with multiple outcomes in individuals without cardiovascular disease. Methods Data from the National Survey for Health and Development (N=1,337) was used to assess the agreement between usHRV and standard HRV (which requires ≥5-minute ECGs). Participants from the first visit of the UK Biobank study (2009-2013), without cardiovascular disease and with an ECG (N=51,628, 64% male, median age 58) were recruited to assess association of usHRV with outcomes. Exposures included usHRV time-domain indices RMSSD and SDSD, which measure fast heart rate variations related to cardiac vagal modulation, and usHRV spectral index PHF, which is related to respiratory sinus arrhythmia. Outcomes included incident atrial fibrillation (AF), major adverse cardiovascular events (MACE), stroke and mortality. Results HRV indices RMSSD and SDSD measured in 15-second ECGs showed excellent agreement (median correlation coefficient ≥0.84 and narrow limits of agreement in Bland-Altman analyses, Fig. 1) with indices measured from 6-minute ECGs, while PHF showed good agreement (median correlation coefficient 0.70 and small positive bias). In the UK Biobank, after a median follow-up of 11.5 (11.4-11.7) years, incidence of AF, MACE, stroke, and mortality was 3.8%, 3.9%, 1.7% and 4.3%, respectively. An inverse linear association was found between usHRV and AF and stroke, with hazard ratios between 1.07 and 1.13 for a standard deviation decrease in RMSSD, SDSD and PHF, p&amp;lt;0.05. Non-linear cox regressions (Fig. 2) showed that the association of RMSSD (and SDSD) with MACE and mortality was U-shaped with individuals in the bottom quintiles of usHRV indices showing increased risk with respect to those in the third quintile (hazard ratios between 1.16 and 1.29, p&amp;lt;0.05). Conclusions Cardiac autonomic dysfunction measured with usHRV from 15-second ECGs is associated with increased risk of AF, MACE, stroke, and mortality in individuals without cardiovascular disease. usHRV can be measured from both standard clinical ECGs and novel wearable devices and may have a role to monitor autonomic function at scale and improve understanding and prevention of cardiovascular disease.Fig1: 6-min vs 15-sec HRVFig2: usHRV association with outcomes

Influence of Fluid Ingestion on Heart Rate, Cardiac Autonomic Modulation and Blood Pressure in Response to Physical Exercise: A Systematic Review with Meta-Analysis and Meta-Regression.

A systematic review was undertaken to investigate the involvement of hydration in heart rate (HR), HR variability (HRV) and diastolic (DBP) and systolic (SBP) blood pressure in response to exercise. Data synthesis: The EMBASE, MEDLINE, Cochrane Library, CINAHL, LILACS and Web of Science databases were searched. In total, 977 studies were recognized, but only 36 were included after final screening (33 studies in meta-analysis). This study includes randomized controlled trials (RCTs) and non-RCTs with subjects > 18 years old. The hydration group consumed water or isotonic drinks, while the control group did not ingest liquids. For the hydration protocol (before, during and after exercise), the HR values during the exercise were lower compared to the controls (-6.20 bpm, 95%CI: -8.69; -3.71). In the subgroup analysis, "water ingested before and during exercise" showed lower increases in HR during exercise (-6.20, 95%CI: 11.70 to -0.71), as did "water was ingested only during exercise" (-6.12, 95%CI: -9.35 to -2.89). Water intake during exercise only revealed a trend of avoiding greater increases in HR during exercise (-4,60, 95%CI: -9.41 to 0.22), although these values were not significantly different (p = 0.06) from those of the control. "Isotonic intake during exercise" showed lower HRs than the control (-7.23 bpm, 95% CI: -11.68 to -2.79). The HRV values following the exercise were higher in the hydration protocol (SMD = 0.48, 95%CI: 0.30 to 0.67). The values of the SBP were higher than those of the controls (2.25 mmHg, 95%CI: 0.08 to 4.42). Conclusions: Hydration-attenuated exercise-induced increases in HR during exercise, improved autonomic recovery via the acceleration of cardiac vagal modulation in response to exercise and caused a modest increase in SBP values, but did not exert effects on DBP following exercise.

Effect Of 12 Weeks Yoga Training And 12 Weeks Detraining on Heart Rate Variability on Subjects with Hypertension

Background: Healthy lifestyle modifications can prevent hypertension, an early predictor of cardiovascular disease. Yoga is an effective way to manage stress-induced disorders, such as hypertension. Objective: This study investigated the effects of yoga training on hypertensive individuals receiving routine treatment over a 12-week period, comparing and analyzing heart rate variability (HRV) parameters at and after the 12-week yoga training period (the 12th week) with hypertensives receiving routine treatment (the non-yoga group). Materials and methods: A total of 132 hypertensive subjects between the ages of 25 and 45 were randomly assigned to control or experimental groups (N=66), and 66 of these subjects were exposed to yoga therapy (N=66). Before, after, and during the study period, HRV parameters were obtained. Results: RM ANOVA was used to compare time domain and frequency domain parameters of HRV of the control group at pre, post, and detrain, and it was found that no significant difference existed between the groups. Test group mean values show a significant increase in time domain parameters compared with pre-training values after training. Test group post-training and detrain values significantly increased when compared to control group post-training and detrain values. Test group detrain values decreased significantly from post-training to test group detrain values. Conclusion: Yoga therapy increases the HRV values in essential hypertension at rest. An increase in vagal modulation, a reduction in sympathetic activity, and an increase in baroreflex sensitivity may be responsible for the harmonization of autonomic cardiovascular rhythms. The results of detraining from yoga did not result in an increase in HRV. As a result, the present study shows that regular yoga practice reduces hypertension, and deep rest keeps the body healthy.

Effect Of 12 Weeks Yoga Training And 12 Weeks Detraining on Blood Pressure Subjects with Hypertension

Background: Hypertension, an early predictor of cardiovascular disease can be prevented by healthy lifestyle modification. Stress-induced disorders such as hypertension can be effectively managed with the holistic science of yoga. Objective: In hypertensive individuals who are receiving routine treatment, we investigated the effects of yoga training for 12 weeks and compare as well as analyze these parameters at the end of yoga training (12th week) and after 12 weeks of follow-up with hypertensive on regular treatment (non-yoga group). Materials and methods: The study involved randomly assigned 124 hypertensive subjects to either experimental or control groups where N=65, and the yoga groups where n=61 between age of 25 to 45 years were included. In both the yoga group and the control group, heart rates (HR), Systolic Blood Pressures (SBP), Diastolic Blood Pressures (DBP), Pulse Pressures (PP), Mean Arterial Pressures (MAPs), and mean arterial pressure products were recorded before, after, and during the study period. Results: The means of RPP, HR, PP, SBP, MAP and DBP of pre-post, and follow-up values of the control group were compared by RM ANOVA and also there was no significant difference were found that exists among the groups. The mean values in the test group of post-training and follow-up show a significant decrease when compared with pre-training values. There are a significant decrease in test group follow-up values and post-training compared with follow-up values of control group and post-training respectively. In test group follow-up values the significant increase is found when compared with the test group post-training. Conclusion: Yoga reduced HR, SBP, DBP, PP, MAP, and RPP in essential hypertension under resting conditions. Reduced Sympathetic Activity, Enhanced Vagal Modulation and the increased sensitivity of baroreflex might be responsible for the harmonization of autonomic cardiovascular rhythms. Detraining from yoga, on the other hand, did not result in an increase in blood pressure. In conclusion, the present study shows that regular practice in yoga is helpful in reducing the hypertension, and that deep rest keeps the body healthy.

Quantitative assessment of transient autonomic modulation after single-shot pulmonary vein isolation with pulsed-field ablation.

Pulmonary vein isolation (PVI) with thermal energy is characterized by concomitant ablation of the surrounding ganglionated plexi (GP). Pulsed-field ablation (PFA) selectively targets the myocardium and seems associated with only negligible effects on the autonomic nervous system (ANS). However, little is known about the dynamic effects of PFA on the GP immediately after PVI. This study sought to investigate the degree and acute vagal modulation induced by the FarapulseTM PFA system during PVI compared with single-shot thermal ablation. A total of 76 patients underwent first-time PVI with either FarapulseTM PFA (PFA group, n = 40) or cryoballoon ablation (thermal ablation group, n = 36) for paroxysmal atrial fibrillation (AF). The effect on the ANS in the two groups was assessed before and after PVI with extracardiac vagal stimulation (ECVS). To capture any transient effects of PFA on the ANS, in a subgroup of PFA patients ECVS was repeated at three predefined timepoints: (1) before PVI (T0); (2) immediately after PVI (T1); and (3) 10 min after the last energy application (T2). Despite similar baseline values, the vagal response induced by ECVS after PVI almost disappeared in the thermal ablation group but persisted in the PFA group (thermal group: 840 [706-1090] ms, p < .001 compared to baseline; PFA group: 11 466 [8720-12 293] ms, p = .70 compared to baseline). Intraprocedural vagal reactions (defined as RR increase >50%, transitory asystole, or atrioventricular block) occurred more frequently with PFA than thermal ablation (70% vs. 28%, p = .001). Moreover, heart rate 24 h post-PVI increased more with thermal ablation than with PFA (16.5 ± 9.0 vs. 2.6 ± 6.1 beats/min, p < .001). In the subgroup of PFA patients undergoing repeated ANS modulation assessment (n = 11), ECVS demonstrated that PFA determined a significant acute suppression of the vagal response immediately after PVI (p < .001 compared to baseline), which recovered almost completely within 10 min. PVI with the FarapulseTM PFA system is associated with only transitory and short-lasting vagal effects on the ANS which recover almost completely within a few minutes after ablation. The impact of this phenomenon on AF outcome needs to be further investigated.

Neuro-Cardiovascular Responses to Sympathetic Stimulation in Fighter Pilots.

INTRODUCTION: The chronic effects of regular exposure to high acceleration levels (G-force) on the neuro-cardiovascular system are unclear. We compared the mean arterial pressure (MAP) and cardiac autonomic modulation between nonpilots (NP) vs. military fighter (FP) and transport (TP) pilots. Additionally, we correlated the cardiac autonomic indices with the cardiorespiratory fitness and flight experience of FP.METHODS: A total of 21 FP, 8 TP, and 20 NP performed a tilt test (TT), during which beat-to-beat blood pressure and heart rate were recorded.RESULTS: No difference was detected between groups for changes in MAP and heart rate variability indices during the TT. However, the analysis of areas under the curves showed a greater increase in MAP in FP vs. TP and NP. Conversely, there was a greater decrease in indices reflecting vagal modulation in TP vs. FP and NP (rMSSD, pNN50, and SDNN), and a greater increase in heart rate and sympathovagal balance in TP vs. other groups (LF/HF). The maximal oxygen uptake was strongly correlated with the vagal reserve in FP (r = -0.74). Moreover, the total flying hours of FP were positively correlated with resting HFnu (r = 0.47) and inversely correlated with resting LFnu (r = -0.55) and LF/HF (r = -0.46).CONCLUSION: FP had a higher pressor response to TT than TP and NP. Vagal withdrawal and sympathovagal increase induced by TT in FP were similar vs. NP and attenuated vs. TP. Greater cardiorespiratory fitness and accumulated flying hours in FP seemed to favor lower sympathetic and greater vagal modulation at rest.dos Santos Rangel MV, de Sá GB, Farinatti P, Borges JP. Neuro-cardiovascular responses to sympathetic stimulation in fighter pilots. Aerosp Med Hum Perform. 2023; 94(10):761-769.

Vagally-mediated HRV as a marker of trait rumination in healthy individuals? A large cross-sectional analysis.

The tendency to ruminate (i.e., repetitive, self-referential, negative thoughts) is a maladaptive form of emotional regulation and represents a transdiagnostic vulnerability factor for stress-related psychopathology. Vagally-mediated heart rate variability (vmHRV) provides a non-invasive, surrogate measure of vagal modulation of the heart, and higher HRV is considered an indicator of susceptibility, or ability to respond to stress. Past research has suggested a link between trait rumination and vmHRV; however, inconsistent results exist in healthy individuals. In this study, we investigated the association between the tendency to ruminate, brooding, and reflection (using the Ruminative Response Scale) with vmHRV measured at baseline in a healthy population using a large cross-sectional dataset (N = 1189, 88% female; mean age = 21.55, ranging from 17 to 48 years old), which was obtained by combining samples of healthy individuals from different studies from our laboratory. The results showed no cross-sectional correlation between vmHRV and trait rumination (confirmed by Bayesian analysis), even after controlling for important confounders such as gender, age, and depressive symptoms. Also, a non-linear relationship was rejected. In summary, based on our results in a large sample of healthy individuals, vmHRV is not a marker of trait rumination (as measured by the Ruminative Response Scale).

Linear and non‑linear indices of vagal nerve in relation to sex and inflammation in patients with Covid‑19.

Hyperinflammation is one of the most important pathophysiological risk factors for poor prognosis in patients with coronavirus disease-2019 (Covid-19). Low vagal neuro-immune modulation can lead into this kind of immune dysregulation. The association between vagal activity, sex and inflammatory markers were investigated in patients with Covid-19. A total of 19 patients with Covid-19 were included in the present study. Vagus nerve activity was indexed by heart rate variability (HRV) derived from electrocardiogram at hospital admission. Linear HRV parameters included the root mean square of successive RR interval differences (RMSSD) and high-frequency HRV (HF-HRV), while non-linear parameters included 2 UV%. Immune/inflammatory parameters included C-reactive protein (CRP), interleukin-6 (IL-6), neutrophil/lymphocyte ratio (NLR), systemic inflammatory index (SII), and procalcitonin (PCT). It has been revealed that both linear HRV indices HF-HRV and RMSSD, are significantly negatively correlated with CRP and IL-6, independent of age. The non-linear index of 2 UV% is significantly negatively correlated with NLR and SII, which reflect subtle changes in the response of immunocompetent cells. Patients that received high-flow nasal oxygen therapy had significantly higher IL-6 and CRP levels and lower levels of HF-HRV and RMSSD. These patients also had a significantly longer length of stay in hospital (LOS) than patients receiving low-flow oxygen therapy. Men had higher plasma PCT levels and longer LOS in hospital than women, and PCT statistically explained (mediated) the association between sex and LOS. The present study showed different correlations of linear and non-linear vagal indexes of HRV and inflammatory markers in patients with Covid-19. Significant sex differences in certain inflammatory markers were also observed, which may very well verify previous findings of poor prognosis in men with Covid-19. HRV reflects a continuous interaction between the sympathetic and parasympathetic autonomic nervous systems, which are affected by mental or physical stress, and certain disease states. The increased sympathetic and decreased parasympathetic vagal tone contribute to a higher risk of diseases associated with inflammation, cardiovascular disease, cancer, pulmonary diseases and other pathologies, including infectious diseases such as Covid-19. The present study showed that higher RMSSD (a marker of vagal activity) in Covid-19 patients is associated with lower levels of inflammatory biomarkers, a lower need for treatment and is negatively correlated with intensive care unit admission, leading to a shorter hospital stay. These findings support the idea that activation of vagus nerve may help certain Covid-19 patients by reducing the cytokine storm and excessive inflammation.

Soluble interleukin-1 receptor type 2 plasma levels in Parkinson's disease: relationship with cardiac autonomic profile before and after peripheral mechanical somatosensory stimulation.

Introduction: Systemic inflammation promotes neurodegeneration in Parkinson's disease (PD). Interleukin-1 receptor type 2 (sIL-1R2) plasma levels increase during inflammation. Data on sIL-1R2 in PD patients and its relationship with PD cardiac autonomic profile are limited, given the possible anti-inflammatory effect of vagal activation. Previously, automated mechanical peripheral somatosensory stimulation (AMPSS) enhanced cardiac vagal modulation. Objectives were to 1) evaluate sIL-1R2 plasma concentrations in PD patients and healthy controls and 2) investigate the correlations between sIL-1R2 and cardiac autonomic indices obtained by spectrum analysis of heart rate variability before and after AMPSS. Methods: sIL-1R2 plasma levels were assessed in 48 PD patients and 50 healthy controls. Electrocardiogram and beat-by-beat arterial pressure were recorded at baseline and after 5 AMPSS sessions in 16 PD patients. Results: PD patients had higher sIL-1R2 levels than controls. In the PD subgroup, an inverse correlation between sIL-1R2 and HFnu was found. There was a negative correlation between changes induced by AMPSS on HFnu and sIL-1R2. Discussion: Higher sIL-1R2 levels in PD patients reflect the inflammatory dysregulation associated with the disease. In PD patients, higher sIL-1R2 was associated with reduced cardiovagal tone. Increased cardiovagal modulation following AMPSS was associated with lower sIL-1R2 levels in Parkinson's disease patients, suggesting inflammatory state improvement.

The Effect of Heart Rate Variability Biofeedback on Basketball Performance Tests.

The purpose of this study is to investigate the effects of 10-week heart rate variability biofeedback training on basketball skills, free throws, and heart rate variability parameters. Twenty-four basketball players (experimental, n = 12 and control, n = 12) aged 18-24 years volunteered to participate in this study. The experimental group participated in a 10-week heart rate variability biofeedback and basketball training program, while the control group only participated in the 10-week basketball training session. Basketball free-throw performance, basketball skills, and heart rate variability tests were conducted on the experimental and control groups before and after the 10-week intervention. Consequently, we discovered that basketball free-throw performance, breathing frequency, and heart rate variability parameters, which reflect vagal modulation of parasympathetic activity, improved in participants who underwent the 10-week heart rate variability biofeedback and basketball training, and not in those who took basketball training only. Our findings propose that heart rate variability biofeedback, alongside basketball workouts, can contribute to better basketball free-throw performance potentially through improved autonomic nervous system functioning.

Age Differences in Upper Gastrointestinal Symptoms and Vagal Modulation in Women With Irritable Bowel Syndrome.

Patients with irritable bowel syndrome (IBS) often report upper gastrointestinal (GI) (e.g., nausea and heartburn), somatic, and emotional symptoms. This study seeks to examine the relationships among younger and older women with IBS and indicators of autonomic nervous system (ANS) function and daily nausea and heartburn symptoms. Women were recruited through clinics and the community. Nocturnal heart rate variability (HRV) was obtained using ambulatory electrocardiogram Holter monitors. Individual symptom severity and frequency were collected using 28-day diaries. All variables were stratified by younger (<46years) and older (≥46years) age groups. Eighty-nine women with IBS were included in this descriptive correlation study (n = 57 younger; n = 32 older). Older women had reduced indices of vagal activity when compared to younger women. In older women, there was an inverse correlation between nausea and vagal measures (Ln RMSSD, r = -.41, p = .026; Ln pNN50, r = -.39, p = .034). Heartburn in older women was associated with sleepiness (r = .59, p < .001) and anger (r = .48, p = .006). Nausea was significantly correlated with anger in the younger group (r = .41, p = .001). There were no significant relationships between HRV indicators and nausea and heartburn in younger women. Age-related differences in ANS function that are associated with nausea may portend unique opportunities to better understand the vagal dysregulation in women with IBS.

Guiding Breathing at the Resonance Frequency with Haptic Sensors Potentiates Cardiac Coherence.

Cardiac coherence is a state achieved when one controls their breathing rate during the so-called resonance frequency breathing. This maneuver allows respiratory-driven vagal modulations of the heart rate to superimpose with sympathetic modulations occurring at 0.1 Hz, thereby maximizing autonomous power in heart-to-brain connections. These stimulations have been shown to improve vagal regulations, which results in obvious benefits for both mental and organic health. Here, we present a device that is able to deliver visual and haptic cues, as well as HRV biofeedback information to guide the user in maintaining a 0.1 Hz breathing frequency. We explored the effectiveness of cardiac coherence in three guidance conditions: visual, haptic and visuo-haptic breathing. Thirty-two healthy students (sixteen males) were divided into three groups that experienced five minutes of either visual, haptic and visuo-haptic guided breathing at 0.1 Hz. The effects of guidance on the (adequate) breathing pattern and heart rate variability (HRV) were analyzed. The interest of introducing haptic breathing to achieve cardiac coherence was shown in the haptic and visuo-haptic groups. Especially, the P0.1 index, which indicates how the autonomous power is 'concentrated' at 0.1 Hz in the PSD spectrum, demonstrated the superiority of combining haptic with visual sensory inputs in potentiating cardiac coherence (0.55 ± 0.20 for visuo-haptic vs. 0.28 ± 0.14 for visual only guidance; p < 0.05) haptic-induced effectiveness could be an asset for a more efficient and time-saving practice, allowing improved health and well-being even under tight time constraints.

Heart rate fragmentation in renovascular hypertensive rats

Although rapid oscillations of the heart rate (HR) are attributed to vagal modulation of the heart, a pattern of ultra-rapid HR variation has been named heart rate fragmentation (HRF). It is a recently proposed approach to evaluate sino-atrial instability characterized by the presence of numerous inflections points in a series of successive values of cardiac intervals. HRF is increased in aging and coronary diseases. Hypertension markedly alters HRV indices and might affect HRF as well. This study aimed to investigate the HRF in renovascular hypertension in rats. Wistar rats were anesthetized, and hypertension was surgically induced by partial constriction of the left renal artery with a silver clip with a 0.2 mm gap. In one kidney one clip (1K1C) hypertension model, the contralateral kidney was removed. In two kidneys one clip (2K1C) model, the contralateral kidney was kept intact. Sham-operated control rats underwent to same surgical procedures without receiving the clip around the renal artery. After 45 days (2K1C) or 60 days (1K1C), animals were instrumented with a catheter into the femoral artery, and on the following day, their arterial pressure (AP) was directly recorded without the effect of anesthesia. For HRF analysis, pulse interval (PI) series were generated and transformed into a sequence of symbols “-1,” “0,” or “1” when the difference between successive PI values (transitions) was negative, zero, or positive, respectively. Following, sequences of 4 consecutive symbols were classified according to the number of transitions. The total percentage of inflection points (PIP) and the percentage of sequences with zero (W0), one (W1), two (W2), or three (W3) inflection points were quantified. As expected, the arterial pressure increased in both groups of hypertension rats compared to control counterparts. All HRF indices were found similar in 1K1C hypertensive rats compared to their control counterparts. Nevertheless, in 2K1C hypertensive rats HRF was found to be lower than normotensive controls (PIP: 64±7 vs. 79±1% and W2: 30±1 vs. 39±1% in 2K1C and normotensive controls, respectively). In conclusion, high blood pressure itself does not affect HRF, although, depending on the model of hypertension used, HRF can be markedly impaired. The interpretation of these findings is challenging, and the high levels of angiotensin in the 2K1C model may affect cardiac pacemaker cells, making their action potentials more stable than unstable. However, the specific mechanisms by which this could happen still need to be studied. Funding Sources: FAPESP, CAPES and CNPq This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Habitual physical activity improves vagal cardiac modulation and carotid baroreflex function in elderly women.

The impact of habitual physical activity on vagal-cardiac function and baroreflex sensitivity in elderly women is poorly characterized. This study compared vagal-cardiac modulation and carotid baroreflex (CBR) function in eight physically active (67.6 ± 1.9 years; peak O2 uptake 29.1 ± 2.5 mL/min/kg) versus eight sedentary (67.3 ± 1.8 years; peak O2 uptake 18.6 ± 0.9 mL/min/kg) elderly women. Heart rate (HR) variabilities and maximal changes of HR and mean arterial pressure (MAP) elicited by 5-s pressure pulses between +40 and -80 mmHg applied to the carotid sinus were measured at rest and during carotid baroreceptor unloading effected by -15 mmHg lower-body negative pressure (LBNP). HR variability was greater in active than sedentary women in both low (0.998 ± 0.286 versus 0.255 ± 0.063 bpm2; P = 0.036) and high (0.895 ± 0.301 versus 0.156 ± 0.045 bpm2; P = 0.044) frequency domains. CBR-HR gains (bpm/mmHg) were greater (fitness factor P < 0.001) in active versus sedentary women at rest (-0.146 ± 0.014 versus -0.088 ± 0.011) and during LBNP (-0.105 ± 0.014 versus -0.065 ± 0.008). CBR-MAP gains (mmHg/mmHg) tended to be greater (fitness factor P = 0.077) in active versus sedentary women at rest (-0.132 ± 0.013 versus -0.110 ± 0.011) and during LBNP (-0.129 ± 0.015 versus -0.113 ± 0.013). However, LBNP did not potentiate CBR-MAP gains in either sedentary or active women (LBNP factor P = 0.94), and it depressed CBR-HR gains in both groups (LBNP factor P = 0.003). CBR-HR gains in the sedentary women did not differ (sex factor P = 0.65) from gains reported in age-matched sedentary men, although CBR-MAP gains tended to be greater (sex factor P = 0.109) in the men. Thus, tonic vagal modulation indicated by HR variability and dynamic vagal responses assessed by CBR-HR gain were augmented in physically active women. Enhanced vagal-cardiac function may protect against senescence-associated cardiac electrical and hemodynamic instability in elderly women.

Differences in cardiac vagal modulation and cortisol response in adolescents with and without Autism Spectrum Disorder

BackgroundPrevious research pointed towards a need of enhanced understanding of cardiac vagal modulation during resting and stress conditions in individuals with Autism Spectrum Disorder (ASD). This cross-sectional study addressed the following hypotheses: lower values of cardiac vagal modulation will be found in adolescents with ASD in comparison to typically developing (TD) peers; different levels of cardiac vagal reactivity and recovery will be found in adolescents with ASD. In addition, exploratory analyses examined the possible association between cardiac vagal modulation and psychosocial functioning and baseline cortisol levels. MethodsAge and sex matched groups of adolescents (13–17 year) with ASD (n = 47) and TD peers (n = 47) were included. Heart rate, breathing frequency and cortisol levels were determined during baseline and a standardized stress-provoking assessment. Behavioral data concerning autism and behavioral characteristics were collected prior to the assessment. ResultsAdolescents with ASD displayed lower levels of cardiac vagal modulation during baseline and stress-provocation compared to their TD peers. However, levels of cardiac vagal reactivity and recovery were similar across groups. Exploratory analyses indicated weak to moderate associations between the level of cardiac vagal modulation and self- and parent-reported measures of autism characteristics and psychosocial functioning in adolescents with ASD. No significant associations were found between baseline cortisol levels and cardiac vagal modulation in both groups. ConclusionThese findings suggest a parasympathetic hypo-activity in adolescents with ASD and, although the level of reactivity and recovery was the same as TD peers, this hypo-activity might be related to several aspects of psychosocial functioning.

Sex differences in heart rate and heart rate variability in rats: Implications for translational research.

The present study aimed to investigate sex differences in measures of cardiac chronotropy and heart rate variability (HRV) in 132 young adult wild-type Groningen rats (n = 45 females). Electrocardiographic signals were recorded for 48h in freely moving rats to quantify heart rate (HR) and inter-beat interval (IBI) as measures of cardiac chronotropy, and time- and frequency-domain HRV parameters as physiological readouts of cardiac vagal modulation. Females showed greater vagally-mediated HRV despite having higher HR and shorter IBI than males during undisturbed conditions. Such differences were evident i) at any given level of HRV, and ii) both during the 12-h light/inactive and 12-h dark/active phase of the daily cycle. These findings replicate the paradoxical cardiac chronotropic control reported by human meta-analytic findings, since one would expect greater vagally-mediated HRV to be associated with lower HR and longer IBI. Lastly, the association between some HRV measures and HR was stronger in female than male rats. Overall, the current study in young adult rats provides data illustrating a sex-dependent association between vagally-mediated HRV and indexes of cardiac chronotropy. The current results i) are in line with human findings, ii) suggest to always consider biological sex in the analysis and interpretation of HRV data in rats, and iii) warrant the use of rats for investigating the neuro-hormonal basis and temporal evolution of the impact of sex on the association between vagally-mediated HRV and cardiac chronotropy, which could inform the human condition.

Cardiac autonomic control in Rett syndrome: Insights from heart rate variability analysis.

Rett syndrome (RTT) is a rare and severe neurological disorder mainly affecting females, usually linked to methyl-CpG-binding protein 2 (MECP2) gene mutations. Manifestations of RTT typically include loss of purposeful hand skills, gait and motor abnormalities, loss of spoken language, stereotypic hand movements, epilepsy, and autonomic dysfunction. Patients with RTT have a higher incidence of sudden death than the general population. Literature data indicate an uncoupling between measures of breathing and heart rate control that could offer insight into the mechanisms that lead to greater vulnerability to sudden death. Understanding the neural mechanisms of autonomic dysfunction and its correlation with sudden death is essential for patient care. Experimental evidence for increased sympathetic or reduced vagal modulation to the heart has spurred efforts to develop quantitative markers of cardiac autonomic profile. Heart rate variability (HRV) has emerged as a valuable non-invasive test to estimate the modulation of sympathetic and parasympathetic branches of the autonomic nervous system (ANS) to the heart. This review aims to provide an overview of the current knowledge on autonomic dysfunction and, in particular, to assess whether HRV parameters can help unravel patterns of cardiac autonomic dysregulation in patients with RTT. Literature data show reduced global HRV (total spectral power and R-R mean) and a shifted sympatho-vagal balance toward sympathetic predominance and vagal withdrawal in patients with RTT compared to controls. In addition, correlations between HRV and genotype and phenotype features or neurochemical changes were investigated. The data reported in this review suggest an important impairment in sympatho-vagal balance, supporting possible future research scenarios, targeting ANS.

Short-term evolution of heart rate variability following occipito-mastoid suture normalization in healthy subjects

Background&#x0D; Occipito-mastoid structure normalization (OMSN) is an osteopathy manipulative treatment aiming at reducing tensions around the jugular foramen, where cranial nerves IX, X and XI come out of the skull. Tensions in this area may induce compressions of those nerves, which might imply symptoms related to those nerves dysfunctions (e.g., dysphagia, gastrointestinal issues, cardiac issues, upper body muscle pain, fatigue). Vagus nerve X is the main parasympathetic nerves of this area. Heart rate variability (HRV) is a surrogate for vagal modulation, and purpose of this study was to observe how HRV variables evolved before and after an OMSN.&#x0D; Methods&#x0D; Pre- and post- intervention HRV was analyzed in two randomly distributed groups of 15 participants. One received the OMSN and the other a SHAM technique. HRV was collected supine 5 min before and 5 min after a10-minute application of either OMSN or SHAM. HRV was analyzed on the last 4 minutes of the 5 minutes sample in time- and frequency-domain.&#x0D; Results&#x0D; HR significantly decreased in both groups (change in mean (CIM) -2.6 (4.3), and -2.3 (2.1) bpm, for NSOM and SHAM, respectively) but without difference between groups (p = 0.245). Vagally-related HRV variable root mean square of successive differences (RMSSD) increased in both groups, but in a significantly higher proportion in OMSN group (CIM 8.1 ±6.4 and 2.8 ±6.2 ms, p = 0.030 for NSOM and SHAM, respectively). No differences between groups were observed on frequency-domain analysis.&#x0D; Conclusion&#x0D; Compared to a SHAM technique, OMSN had a significant effect on HRV vagally-related metric RMSSD. This effect was measured in the very short term and thus, OMSN may be used to imply a short-term influence on parasympathetic ANS modulations. Further research are needed to investigate medium and long-term influences of this manipulation.