Computational modeling for the quantitative assessment of cardiac autonomic response to orthostatic stress.

The Autonomic Nervous System (ANS) plays a critical role in regulating cardiac functions. Early detection of ANS dysfunctions is crucial for preventing or slowing the progression of cardiovascular diseases. Current methods for analyzing ANS activity, such as heart rate variability analysis and muscle sympathetic nerve activity recording, face challenges such as poor temporal resolution, invasiveness, and insufficient sensitivity to individual physiological variations, which limit personalized health assessments. This study aims to introduce the open-loop Mathematical Model of Autonomic Regulation of the Cardiac System under Supine-to-stand Maneuver (MMARCS) to overcome the limitations of existing ANS analysis methods. The MMARCS model is designed to offer a balance between physiological fidelity and simplicity, focusing on the ANS cardiac control subsystems' input-output curve. The MMARCS model simplifies the complex internal dynamics of ANS cardiac control by emphasizing input-output relationships and utilizing sensitivity analysis and parameter subset selection to increase model specificity and eliminate redundant parameters. This approach aims to enhance the model's capacity for personalized health assessments. The application of the MMARCS model revealed significant differences in ANS regulation between healthy (14 females and 19 males) and diabetic subjects (8 females and 6 males). Parameters indicated heightened sympathetic activity and diminished parasympathetic response in diabetic subjects compared to healthy subjects (p<0.05), and also suggested a more sensitive and potentially more reactive sympathetic response among diabetic subjects (p<0.05). The MMARCS model represents an innovative computational approach for quantifying ANS functionality, offering potential benefits for clinical measurements of cardiovascular, disease progression monitoring, and home health monitoring via wearable technology. Its balance between physiological accuracy and model simplicity makes it a promising tool for personalized health assessments.

Impact of optimized transcutaneous auricular vagus nerve stimulation on cardiac autonomic profile in healthy subjects and heart failure patients.

Objective.To determine the optimal frequency and site of stimulation for transcutaneous vagus nerve stimulation (tVNS) to induce acute changes in the autonomic profile (heart rate (HR), heart rate variability (HRV)) in healthy subjects (HS) and patients with heart failure (HF).Approach.We designed three single-blind, randomized, cross-over studies: (1) to compare the acute effect of left tVNS at 25 Hz and 10 Hz (n= 29, age 60 ± 7 years), (2) to compare the acute effect of left and right tVNS at the best frequency identified in study 1 (n= 28 age 61 ± 7 years), and (3) to compare the acute effect of the identified optimal stimulation protocol with sham stimulation in HS and HF patients (n= 30, age 59 ± 5 years, andn= 32, age 63 ± 7 years, respectively).Main results.In study 1, left tragus stimulation at 25 Hz was more effective than stimulation at 10 Hz in decreasing HR (-1.0 ± 1.2 bpm,p< 0.001 and -0.5 ± 1.6 bpm, respectively) and inducing vagal effects (significant increase in RMSSD, and HF power). In study 2, the HR reduction was greater with left than right tragus stimulation (-0.9 ± 1.5 bpm,p< 0.01 and -0.3 ± 1.4 bpm, respectively). In study 3 in HS, left tVNS at 25 Hz significantly reduced HR, whereas sham stimulation did not (-1.1 ± 1.2 bpm,p< 0.01 and -0.2 ± 2.9 bpm, respectively). In HF patients, both active and sham stimulation produced negligible effects.Significance.Left tVNS at 25 Hz is effective in acute modulation of cardiovascular autonomic control (HR, HRV) in HS but not in HF patients (NCT05789147).

Diagnostic yield of head-up tilt table test in hypertrophic cardiomyopathy and unexplained syncope: the knot does not seem to be unraveling.

BACKGROUND: Conflicting results have been published considering the diagnostic performance of head-up tilt test (HUTT) in patients with hypertrophic cardiomyopathy (HCM). We aimed to conduct a meta-analysis to evaluate the diagnostic value of HUTT in the evaluation of unexplained syncope in patients with HCM. METHODS: We performed a structured systematic database search using the following keywords: hypertrophic cardiomyopathy, syncope, unexplained syncope, head-up tilt test, tilt table test, tilt testing, orthostatic stress, autonomic function, autonomic response. Studies in which the HUTT was used to define autonomic dysfunction in patients with syncope at baseline or without syncope were included in the final analysis. RESULTS: A total of 252 HCM patients from 6 studies (159 patients without a history of syncope and 93 with a history of syncope, respectively) were evaluated. HUTT was positive in 50 (19.84%) of 252 patients (in 21 of 93 patients (22.58%) with a history of syncope and in 29 of 159 patients (18.24%) without a history of syncope, respectively). The pooled total sensitivity and specificity of the HUTT for detecting syncope were 22.1% (14.8-35.1%) and 83.6% (73.2-91.6%), respectively. The summary receiver operator curve showed that HUTT had an only modest discriminative ability for syncope with an area under the curve value of 0.565 (0.246-0.794). CONCLUSION: Although HUTT has significant limitations in diagnosis of unexplained syncope in patients with HCM, it may still be used to determine hypotensive susceptibility. Other autonomic tests can be used in diagnostic workflow in this population.

Effects of Exercise Training on Heart Rate Variability in Healthy Adults: A Systematic Review and Meta-analysis of Randomized Controlled Trials.

This meta-analysis was conducted to investigate the effects of exercise training on heart rate variability (HRV) parameters associated with the autonomic nervous system (ANS) activity. Randomized controlled trials (RCTs) involving healthy adults (aged ≥ 18 years) were included. We searched PubMed, Scopus, Web of Science, and EBSCO databases to identify relevant studies. A random-effects meta-analysis was performed using the standardized mean difference (SMD) and 95% confidence interval (CI). Sixteen RCTs with a total of 623 participants were selected for the final analysis. The analysis showed that exercise training improved the standard deviation of normal-to-normal intervals (SDNN) (SMD: 0.58 (0.16, 1.00); p = 0.007), the root mean square of successive differences in heart period series (RMSSD) (SMD: 0.84 (0.36, 1.31); p = 0.0005), and the absolute power of high-frequency band (HF) (SMD: 0.89 (0.27, 1.51); p = 0.005) parameters compared to the control group. Analysis of the moderator variables showed that the effect of exercise on HRV indices may be influenced by sex, age, and type of exercise used, specifically in HF band, absolute power of low-frequency band (LF), and LF/HF ratio parameters. Despite the limited number of existing RCTs related to the subject, the results suggest that exercise training enhances HRV parameters associated with vagal-related activity (RMSSD and HF) and both sympathetic and parasympathetic activities (SDNN). This study overcomes the lack of meta-analyses on the effects of exercise training on autonomic modulation among healthy adults and may bridge the gap in understanding the potential physiological underpinnings of the acknowledged positive health benefits of exercise.

The association of diabetic peripheral neuropathy with cardiac autonomic neuropathy in individuals with diabetes mellitus: A systematic review.

This systematic review aimed to explore the relationship between diabetic peripheral neuropathy (DPN) and cardiac autonomic neuropathy (CAN) in individuals with type 1 and 2 diabetes mellitus (DM). METHODS: The systematic review follow the protocol registered in Prospero (CRD42020182899). Two authors independently searched the PubMed, Scopus, Embase, Cochrane, and Web of Science databases. Discrepancies were resolved by a third author. The review included observational studies investigating the relationship between CAN and DPN in individuals with DM. RESULTS: Initially, out of 1165 studies, only 16 were selected, with 42.8 % involving volunteers with one type of diabetes, 14.3 % with both types of diabetes and 14.3 % not specify the type. The total number of volunteers was 2582, mostly with type 2 DM. It was analyzed that there is a relationship between CAN and DPN. It was observed that more severe levels of DPN are associated with worse outcomes in autonomic tests. Some studies suggested that the techniques for evaluating DPN might serve as risk factors for CAN. CONCLUSION: The review presents a possible relationship between DPN and CAN, such as in their severity.

Diverse stimuli induce piloerection and yield varied autonomic responses in humans.

This research provides an in-depth exploration into the triggers and corresponding autonomic responses of piloerection, a phenomenon prevalent across various species. In non-human species, piloerection occurs in reaction to a variety of environmental changes, including social interactions and temperature shifts. However, its understanding in humans has been confined to emotional contexts. This is problematic because it reflects solely upon subjective experience rather than an objective response to the environment. Further, given our shared evolutionary paths, piloerection should function similarly in humans and other animals. I observed 1,198 piloerection episodes from eight participants while simultaneously recording multiple autonomic and body temperature indices, finding that piloerection in humans can be elicited by thermal, tactile, and audio-visual stimuli with equal effectiveness. The data also revealed variations in cardiac reactivity measures: audio-visual piloerection was associated with greater sympathetic arousal, while tactile piloerection was linked to greater parasympathetic arousal. Despite prevailing notions of piloerection as a vestigial response in humans, it does respond to decreases in skin temperature and is associated with a rise in skin temperature during episodes. This research underscores that piloerection in humans is not purely vestigial, nor is it solely an affective response to emotional stimuli. Rather, it is best understood as a reflexive response to environmental changes, suggesting a shared functional similarity with other species.

Adult attachment assessed via the ASA and AAI: Empirical convergence and links with autonomic physiological responding during attachment assessments.

This study examined the empirical convergence of Attachment Script Assessment (ASA) deactivation, hyperactivation, and anomalous scripts with conceptually corresponding attachment patterns assessed via the Adult Attachment Interview (AAI), and the significance of ASA dimensions for autonomic physiological reactivity during adult attachment assessments. Young adults' (50% male; Mage = 19 years; 80% White/European American) ASA deactivation, hyperactivation, and anomalous content were significantly associated with AAI dismissing (r = .26-.38), preoccupied (r = .31-.35), and unresolved (r = .37) states of mind, respectively. ASA hyperactivation and anomalous content were associated with heightened RSA reactivity to the AAI and ASA, aligning with expectations that these attachment patterns capture the tendency to heighten expressions of negative, traumatic experiences. ASA deactivation was associated with smaller increases in electrodermal activity to the ASA-indicative of less sympathetic arousal-converging with the tendency of individuals higher in deactivation to avoid discussing attachment themes in the ASA.

Research Progress of Vagal Nerve Regulation Mechanism in Acupuncture Treatment of Atrial Fibrillation.

Atrial fibrillation (AF) is the most common arrhythmia in clinical practice. It has a high prevalence and poor prognosis. The application of antiarrhythmic drugs and even surgery cannot completely treat the disease, and there are many sequelae. AF can be classified into the category of "palpitation" in Chinese medicine according to its symptoms. Acupuncture has a significant effect on AF. The authors find that an important mechanism of acupuncture in AF treatment is to regulate the cardiac vagus nerve. Therefore, this article intends to review the distribution and function of vagus nerve in the heart, the application and the regulatroy effect for the treatment of AF.

Autonomic Dysfunction in Amyotrophic Lateral Sclerosis - A Case-Control Study.

INTRODUCTION: This study aimed to explore autonomic nervous system involvement in amyotrophic lateral sclerosis (ALS) patients by evaluating sympathetic skin response (SSR). MATERIALS AND METHODS: The study included 35 sporadic (ALS) patients (cases), and 35 healthy age and sex-matched participants (controls) aged <60 years. SSR was recorded in the electrophysiology lab of the Neurology Department of Bangabandhu Sheikh Mujib Medical University (BSMMU), Dhaka, Bangladesh. Patients with diseases associated with peripheral or autonomic neuropathy were excluded. Prolonged latency (delayed SSR) or an absent response was considered abnormal SSR. RESULTS: SSR was found to be abnormal in 17 (48.6 %) ALS cases, with an absent response in the upper limbs of six cases (17.1%). Abnormal SSR was more prevalent in the lower limbs, with 33 (94.3%) and 20 (57.1%) cases having a delayed or absent response, respectively. In comparison, SSR was normal in all control participants (P-value <0.05). Abnormal SSR was significantly more common in the lower limbs of ALS cases with bulbar palsy than those without bulbar palsy (P-value=0.04). There was no association of SSR with disease severity and duration. CONCLUSION: ALS is significantly associated with abnormal SSR, indicating autonomic nervous system involvement. There could also be an association between bulbar palsy and abnormal SSR among ALS patients. Further studies should be carried out to determine the association of abnormal SSR with disease severity, duration, and type.

The effect of total sleep deprivation on autonomic nervous system and cortisol responses to acute stressors in healthy individuals: A systematic review.

OBJECTIVE: To synthesise the literature examining the autonomic nervous system (ANS) and cortisol responses to an acute stressor following total sleep deprivation (TSD) in healthy adult subjects. METHODS: We conducted a systematic review (CRD42022293857) following the latest PRISMA statement. We searched Medline (via Ovid), Embase (via Ovid), PsycINFO (via Ovid), CINAHL complete and Scopus databases, without year restriction, using search terms related to "sleep deprivation", "stress", "autonomic nervous system" and "cortisol". Two independent team members used pre-defined inclusion/exclusion criteria to assess eligibility and extract data. We used RoB 2 to assess the risk of bias in randomised controlled trials, and ROBINS-I for non-randomised studies. RESULTS: Sixteen studies, with 581 participants (mean age = 29 ± 12 years), were eligible for inclusion in the descriptive syntheses. Half of the studies (n = 8) were conducted in the United States of America. The most commonly used study designs were randomised crossover studies (n = 7) and randomised controlled trials (n = 5). Most studies used a single night of TSD (n = 13) which was followed by a psychological (n = 6), physical (n = 5) or psychological and physical (n = 5) acute stressor event. Heart rate (n = 8), cortisol (n = 7) and blood pressure (n =6) were the most reported outcomes, while only a single study used forearm vascular conductance and forearm blood flow. Ten studies found that TSD changed, at least, one marker of ANS or cortisol response. TSD compared with a sleep control condition increased cortisol level (n=1), systolic blood pressure (n=3), diastolic blood pressure (n=2), mean arterial pressure (n=1), and electrodermal activity (n=1) after acute stress. Also, compared with a sleep control, TSD blunted cortisol (n=2), heart rate (n=1) and systolic blood pressure (n=2) responses after acute stress. However, TSD did not change ANS or cortisol responses to acute stressors in 73 % of the total reported outcomes. Furthermore, 10 RCT studies (62.5 %) were assigned as "some concerns" and two RCT studies (12.5 %) were attributed "high" risk of bias. Additionally, one non-randomised trial was classified as "moderate" and three non-randomised trials as "serious" risk of bias. CONCLUSION: The markers of ANS and cortisol responses to acute stress after TSD in healthy individuals reveal a scarcity of consistent evidence. The included studies present enough evidence that TSD induces either blunted or exaggerated ANS or cortisol responses to laboratory stresses supporting the "bidirectional multi-system reactivity hypothesis.". It appears that a comprehensive understanding of this phenomenon still lacks robust evidence, and further research is needed to clarify these relationships.

Pilot epinephrine dose-finding study to counter epidural-related blood pressure reduction.

OBJECTIVE: An unwanted side effect associated with epidural analgesia is the reduction in blood pressure (BP) due to the sympathetic blockade. This study evaluated the hemodynamic effects of adding different epinephrine concentrations to epidurally injected local anesthetic solution to counteract sympathectomy. We hypothesized that epinephrine could mitigate the decrease in BP possibly caused by the local anesthetic, specifically decreasing the incidence of hypotension. METHODS: Sixty-six patients were enrolled in a randomized, controlled, quadruple-blinded prospective study into three groups: epidural ropivacaine 0.2% without epinephrine (control) or with 2 µg/mL or 5 µg/mL epinephrine. Our primary outcome was the assessment of differences in hypotension between groups, defined as a >20% decrease in hypotension from baseline to the end of the intraoperative period. RESULTS: Forty-seven patients completed the study, and 19 were withdrawn. Fifteen patients were in the control group, while 16 patients received 0.2% ropivacaine +2 µg/mL epinephrine, and 16 received 0.2% ropivacaine +5 µg/mL epinephrine. The overall rate of hypotension was 21.3% (10/47). There were no statistically significant differences in hypotension rates between the control group (33%) and groups receiving either +2 µg/mL (13%, p=0.165) or +5 µg/mL (19%, p=0.353) of epinephrine. In secondary analyses, respiratory rate showed greater decreases in control groups across the perioperative period compared with treatment groups (p=0.016) CONCLUSION: Adding epinephrine to the epidural local anesthetic did not significantly decrease the rate of hypotension. However, epinephrine mitigated decreases in respiratory rate across the perioperative period. Future studies will focus on increasing group size and higher epinephrine concentrations (10 µg/mL). TRIAL REGISTRATION NUMBER: NCT02722746.

Sex differences in cardiac transcriptomic response to neonatal sleep apnea.

Pediatric obstructive sleep apnea poses a significant health risk, with potential long-term consequences on cardiovascular health. This study explores the dichotomous nature of neonatal cardiac response to chronic intermittent hypoxia (CIH) between males and females, aiming to fill a critical knowledge gap in the understanding of sex-specific cardiovascular consequences of sleep apnea in early life. Neonates were exposed to CIH until p28 and underwent comprehensive in vivo physiological assessments, including whole-body plethysmography, treadmill stress-tests, and echocardiography. Results indicated that male CIH rats weighed 13.7% less than age-matched control males (p = 0.0365), while females exhibited a mild yet significant increased respiratory drive during sleep (93.94 ± 0.84 vs. 95.31 ± 0.81;p = 0.02). Transcriptomic analysis of left ventricular tissue revealed a substantial sex-based difference in the cardiac response to CIH, with males demonstrating a more pronounced alteration in gene expression compared to females (5986 vs. 3174 genes). The dysregulated miRNAs in males target metabolic genes, potentially predisposing the heart to altered metabolism and substrate utilization. Furthermore, CIH in males was associated with thinner left ventricular walls and dysregulation of genes involved in the cardiac action potential, possibly predisposing males to CIH-related arrhythmia. These findings emphasize the importance of considering sex-specific responses in understanding the cardiovascular implications of pediatric sleep apnea.

High plasticity of temperament as a marker of flexible autonomic regulation of the cardiovascular system in urgent adaptive response to cold in young people.

The properties of temperament are due to differences in the excitability of brain systems that integrate the behavior of an individual, his emotions and autonomic functions and play an important role in the adaptation of the body to the environment. The mechanisms of mutual influences of individual characteristics of temperament properties and regulation of the cardiovascular system have not been fully elucidated. The aim of this study to assess the relationship between expression of temperament traits and the autonomic regulation of the cardiovascular system in the baseline condition and in response to exposure to cold. The study involved 25 healthy male volunteers aged between 18 and 21 years. Temperament traits were measured using the Structure of Temperament Questionnaire. During the study, heart rate variability (HRV) parameters (5 min), systolic and diastolic blood pressure (SBP and DBP) were recorded at room temperature. In the period from 5 to 10 min of exposure in an UShZ-25N cold chamber (-20°C), HRV were assessed. Immediately after the subjects came out from the cold chamber, blood pressure was measured. Then, 5 min after they left the cold chamber, SBP, DBP, HRV were recorded. The results showed that in young people with different expressions of temperamental properties, no differences were found in the regulation of heart rhythm by the autonomic nervous system in the baseline condition. The high object-related plasticity, i.e. the ease of switching from one type of activity to another, linked with autonomic flexibility and blood pressure control, which restrains a significant increase in blood pressure when exposed to short-term cold, and contributes to the preservation of health.

Functional-Molecular Mechanisms of Sympathetic-Parasympathetic Dysfunction in PVC-Induced Cardiomyopathy Revealed by Dual Stressor PVC-Exercise Challenge.

BACKGROUND: The significance of autonomic dysfunction in premature ventricular contraction-induced cardiomyopathy (PVC-CM) remain unknown. OBJECTIVE: Utilizing a novel "dual stressor" provocative challenge combining exercise with premature ventricular contraction (PVCs), the authors characterized the functional and molecular mechanisms of cardiac autonomic (cardiac autonomic nervous system) remodeling in a PVC-CM animal model. METHODS: In 15 canines (8 experimental, 7 sham), we implanted pacemakers and neurotelemetry devices and subjected animals to 12 weeks of bigeminal PVCs to induce PVC-CM. Sympathetic nerve activity (SNA), vagal nerve activity (VNA), and heart rate were continuously recorded before, during, and after treadmill exercise challenge with and without PVCs, at baseline and after development of PVC-CM. Western blot and enzyme-linked immunosorbent assay were used to evaluate molecular markers of neural remodeling. RESULTS: Exercise triggered an increase in both SNA and VNA followed by late VNA withdrawal. With PVCs, the degree of exercise-induced SNA augmentation was magnified, whereas late VNA withdrawal became blunted. After PVC-CM development, SNA was increased at rest but failed to adequately augment during exercise, especially with PVCs, coupled with impaired VNA and heart rate recovery after exercise. In the remodeled cardiac autonomic nervous system, there was widespread sympathetic hyperinnervation and elevated transcardiac norepinephrine levels but unchanged parasympathetic innervation, indicating sympathetic overload. However, cardiac nerve growth factor was paradoxically downregulated, suggesting an antineurotrophic counteradaptive response to PVC-triggered sympathetic overload. CONCLUSIONS: Sympathetic overload, sympathetic dysfunction, and parasympathetic dysfunction in PVC-CM are unmasked by combined exercise and PVC challenge. Reduced cardiac neurotrophic factor might underlie the mechanisms of this dysfunction. Neuromodulation therapies to restore autonomic function could constitute a novel therapeutic approach for PVC-CM.

Heart rate variability as a predictor of intraoperative autonomic nervous system homeostasis.

The aim of the proof-of-concept study is to investigate the level of concordance between the heart rate variability (HRV), the EEG-based Narcotrend Index as a surrogate marker for the depth of hypnosis, and the minimal alveolar concentration (MAC) of the inhalation anesthetic sevoflurane across the entire course of a surgical procedure. This non-blinded cross-sectional study recorded intraoperative HRV, Narcotrend Index, and MAC in 31 male patients during radical prostatectomy using the Da-Vinci robotic-assisted surgical system at Mannheim University Medical Center. The degree of concordance was calculated using repeated measures correlation with the R package (rmcorr) and presented using the rmcorr coefficient (rrm). The Narcotrend Index correlates significantly across all measures with the time-dependent parameter of HRV, the standard deviation of the means of RR intervals (SDNN) (rrm = 0.2; p < 0.001), the frequency-dependent parameters low frequency (LF) (rrm = 0.09; p = 0.04) and the low frequency/high frequency ratio (LF/HF ratio) (rrm = 0.11; p = 0.002). MAC correlated significantly negatively with the time-dependent parameter of heart rate variability, SDNN (rrm = -0.28; p < 0.001), the frequency-dependent parameter LF (rrm = -0.06; p < 0.001) and the LF/HF ratio (rrm = -0.18; p < 0.001) and the Narcotrend Index (rrm = -0.49; p < 0.001) across all measures. HRV mirrors the trend of the Narcotrend Index used to monitor depth of hypnosis and the inhibitory influence of the anesthetic sevoflurane on the autonomic nervous system. Therefore, HRV can provide essential information about the homeostasis of the autonomic nervous system during general anesthesia. DRKS00024696, March 9th, 2021.

Celastrol exerts antiarrhythmic effects in chronic heart failure via NLRP3/Caspase-1/IL-1ß signaling pathway.

OBJECTIVES: Celastrol has widespread therapeutic applications in various pathological conditions, including chronic inflammation. Previous studies have demonstrated the potent cardioprotective effects of celastrol. Nevertheless, limited attention has been given to its potential in reducing ventricular arrhythmias (VAs) following myocardial infarction (MI). Hence, this study aimed to elucidate the potential mechanisms underlying the regulatory effects of celastrol on VAs and cardiac electrophysiological parameters in rats after MI. METHODS: Sprague-Dawley rats were divided at random: the sham, MI, and MI + celastrol groups. The left coronary artery was occluded in the MI and MI + Cel groups. Electrocardiogram, heart rate variability (HRV), ventricular electrophysiological parameters analysis, histology staining of ventricles, Enzyme-linked immunosorbent assay (ELISA), western blotting and Quantitative real-time polymerase chain reaction (qRT-PCR) were performed to elucidate the underlying mechanism of celastrol. Besides, H9c2 cells were subjected to hypoxic conditions to create an in vitro model of MI and then treated with celastrol for 24 hours. Nigericin was used to activate the NLRP3 inflammasome. RESULTS: Compared with that MI group, cardiac electrophysiology instability was significantly alleviated in the MI + celastrol group. Additionally, celastrol improved HRV, upregulated the levels of Cx43, Kv.4.2, Kv4.3 and Cav1.2, mitigated myocardial fibrosis, and inhibited the NLRP3 inflammasome pathway. In vitro conditions also supported the regulatory effects of celastrol on the NLRP3 inflammasome pathway. CONCLUSIONS: Celastrol could alleviate the adverse effects of VAs after MI partially by promoting autonomic nerve remodeling, ventricular electrical reconstruction and ion channel remodeling, and alleviating ventricular fibrosis and inflammatory responses partly by through inhibiting the NLRP3/Caspase-1/IL-1ß pathway.

Pulmonary Vascular Responses to Chronic Intermittent Hypoxia in a Guinea Pig Model of Obstructive Sleep Apnea.

Experimental evidence suggests that chronic intermittent hypoxia (CIH), a major hallmark of obstructive sleep apnea (OSA), boosts carotid body (CB) responsiveness, thereby causing increased sympathetic activity, arterial and pulmonary hypertension, and cardiovascular disease. An enhanced circulatory chemoreflex, oxidative stress, and NO signaling appear to play important roles in these responses to CIH in rodents. Since the guinea pig has a hypofunctional CB (i.e., it is a natural CB knockout), in this study we used it as a model to investigate the CB dependence of the effects of CIH on pulmonary vascular responses, including those mediated by NO, by comparing them with those previously described in the rat. We have analyzed pulmonary artery pressure (PAP), the hypoxic pulmonary vasoconstriction (HPV) response, endothelial function both in vivo and in vitro, and vascular remodeling (intima-media thickness, collagen fiber content, and vessel lumen area). We demonstrate that 30 days of the exposure of guinea pigs to CIH (FiO2, 5% for 40 s, 30 cycles/h) induces pulmonary artery remodeling but does not alter endothelial function or the contractile response to phenylephrine (PE) in these arteries. In contrast, CIH exposure increased the systemic arterial pressure and enhanced the contractile response to PE while decreasing endothelium-dependent vasorelaxation to carbachol in the aorta without causing its remodeling. We conclude that since all of these effects are independent of CB sensitization, there must be other oxygen sensors, beyond the CB, with the capacity to alter the autonomic control of the heart and vascular function and structure in CIH.

Sensor-Assisted Analysis of Autonomic and Cerebrovascular Dysregulation following Concussion in an Individual with a History of Ten Concussions: A Case Study.

INTRODUCTION: Concussion is known to cause transient autonomic and cerebrovascular dysregulation that generally recovers; however, few studies have focused on individuals with an extensive concussion history. METHOD: The case was a 26-year-old male with a history of 10 concussions, diagnosed for bipolar type II disorder, mild attention-deficit hyperactivity disorder, and a history of migraines/headaches. The case was medicated with Valproic Acid and Escitalopram. Sensor-based baseline data were collected within six months of his injury and on days 1-5, 10, and 14 post-injury. Symptom reporting, heart rate variability (HRV), neurovascular coupling (NVC), and dynamic cerebral autoregulation (dCA) assessments were completed using numerous biomedical devices (i.e., transcranial Doppler ultrasound, 3-lead electrocardiography, finger photoplethysmography). RESULTS: Total symptom and symptom severity scores were higher for the first-week post-injury, with physical and emotional symptoms being the most impacted. The NVC response showed lowered activation in the first three days post-injury, while autonomic (HRV) and autoregulation (dCA) were impaired across all testing visits occurring in the first 14 days following his concussion. CONCLUSIONS: Despite symptom resolution, the case demonstrated ongoing autonomic and autoregulatory dysfunction. Larger samples examining individuals with an extensive history of concussion are warranted to understand the chronic physiological changes that occur following cumulative concussions through biosensing devices.

Impact of Concurrent Exercise Training on Cardiac Autonomic Modulation, Metabolic Profile, Body Composition, Cardiorespiratory Fitness, and Quality of Life in Type 2 Diabetes with Cardiac Autonomic Neuropathy: A Randomized Controlled Trial.

Background: Type 2 diabetes mellitus (T2DM) often leads to cardiac autonomic neuropathy (CAN), a severe complication affecting cardiovascular health. Exercise training is a proven intervention for improving metabolic control and cardiovascular health in T2DM, but the effects of concurrent exercise training (CET), combining aerobic and resistance exercises, on CAN are not fully understood. Objective: This randomized controlled trial investigates the impact of a structured CET program on cardiac autonomic modulation, metabolic profile, body composition, cardiorespiratory fitness (CRF), and quality of life (QoL) in individuals with T2DM and CAN. Methods: A total of 96 participants, aged 35-70 years, with T2DM and CAN, were randomized into CET (n = 48) and control (n = 48) groups. The CET group engaged in combined aerobic and resistance training three times per week for 13 weeks, while the control group received standard care. Primary outcomes included heart rate variability (HRV) and heart rate recovery (HRR). Secondary outcomes were metabolic profile, body composition, CRF, and QoL, which were assessed using standardized protocols and validated questionnaires. The trial was registered with the Clinical Trials Registry-India (CTRI/2021/09/036711). Results: Significant improvements were noted in the CET group compared to controls. HRV metrics (SDNN, RMSSD, pNN50, TP, LF power, HF power, and LF/HF ratio) and HRR metrics (HRR30s, HRR1, HRR2, and HRR3) all showed significant enhancements (p < 0.01). The CET group also exhibited substantial reductions in fasting blood glucose, postprandial blood glucose, HbA1c, waist circumference, hip circumference, and percentage body fat (p < 0.01). Improvements were observed in lipid profile markers and CRF (VO2max) (p < 0.01). QoL scores improved significantly in the CET group as per the ADDQoL-19 (p < 0.01). Conclusions: CET significantly enhances cardiac autonomic modulation, metabolic profile, body composition, CRF, and QoL in individuals with T2DM and CAN. These findings support the integration of CET into standard T2DM management to improve clinical outcomes and QoL. Further research is needed to explore the long-term benefits and broader applicability of CET in diverse diabetic populations.

Cardiac autonomic function in REM-related obstructive sleep apnoea: insights from nocturnal heart rate variability profiles.

PURPOSE: In light of the reported association between REM-related obstructive sleep apnoea (OSA) and heightened cardiovascular risk, this study aims to compare cardiac autonomic function in patients with REM-OSA and OSA independent of sleep stage. We hypothesized that REM-OSA patients would exhibit higher sympathetic cardiac modulation based on heart rate variability (HRV) profiles. METHODS: HRV was compared between the OSA group (AHI ≥ 5 events/h, n = 252) and the REM-OSA group (AHI ≥ 5 events/h, AHIREM:AHINREM ≥ 2, n = 137). Time- and frequency-domain measures of HRV were analysed during N2 and REM sleep. RESULTS: Clinical characteristics between the two test groups differed significantly, 45% of REM-OSA patients were female, with mild OSA (median, interquartile range (IQR)) AHI of 10 (7) events/h. Only 26% of the OSA cohort were female with moderate OSA (AHI = 17 (20) events/h, p < 0.001). Compared with the OSA group, the low frequency to high frequency ratio (LF:HF) and LF power were lower and HF power was higher in the REM-OSA group during N2 (LF:HF, p = 0.012; LF; p = 0.013; HF, p = 0.007) and in REM sleep (LF:HF, p = 0.002; LF, p = 0.004; HF, p < 0.001). Patient sex and OSA severity had a significant combined effect on average N to N interval, LF power, and LF:HF ratio during N2 and REM sleep (all p < 0.001). CONCLUSION: Contrary to our hypothesis, REM-OSA patients demonstrated consistently higher cardiac vagal modulation, reflecting better cardiac autonomic adaptation. These results were attributed to differences in OSA severity and sex in these two groups, both independently affecting HRV. This study emphasises the need for future research into the underlying pathophysiology of REM-OSA and the potential implications of sex and OSA severity on cardiovascular risk.