Role of corticotropin-releasing factor neurotransmission in the lateral hypothalamus on baroreflex impairment evoked by chronic variable stress in rats.

Despite the importance of physiological responses to stress in a short-term, chronically these adjustments may be harmful and lead to diseases, including cardiovascular diseases. The lateral hypothalamus (LH) has been reported to be involved in expression of physiological and behavioral responses to stress, but the local neurochemical mechanisms involved are not completely described. The corticotropin-releasing factor (CRF) neurotransmission is a prominent brain neurochemical system implicated in the physiological and behavioral changes induced by aversive threats. Furthermore, chronic exposure to aversive situations affects the CRF neurotransmission in brain regions involved in stress responses. Therefore, in this study, we evaluated the influence of CRF neurotransmission in the LH on changes in cardiovascular function and baroreflex activity induced by chronic variable stress (CVS). We identified that CVS enhanced baseline arterial pressure and impaired baroreflex function, which were followed by increased expression of CRF2, but not CRF1, receptor expression within the LH. Local microinjection of either CRF1 or CRF2 receptor antagonist within the LH inhibited the baroreflex impairment caused by CVS, but without affecting the mild hypertension. Taken together, the findings documented in this study suggest that LH CRF neurotransmission participates in the baroreflex impairment related to chronic stress exposure.

Cardiac deceleration capacity is associated with severity of inflammation in COVID-19.

PURPOSE: In this pilot study, we investigated the cardiac autonomic activity of coronavirus disease 2019 (COVID-19)-infected hospitalized patients. COVID-19 is characterized by cough, fever, and dyspnea, which in some severe cases can lead to hypoxia, respiratory failure, and shock. Since breathing disorders and pulmonary diseases are tightly linked to autonomic dysfunction, we analyzed the cardiac autonomic activity by measuring the deceleration capacity (DC) in COVID-19 patients. METHODS: In 14 adults (4 men and 10 women) with a median age of 63.5 years and positive for SARS-CoV-2 by polymerase chain reaction (PCR) with severe symptoms requiring hospital treatment, a high-resolution digital 30 min electrocardiogram (ECG) in Frank leads configuration was performed in a resting supine position within the first 48 h after hospital admission. DC was assessed using validated software and associated with several markers of inflammation and clinical course. RESULTS: The study revealed a significant association between reduced DC (≤ 2.5 ms) and older age (74 years) in COVID-19 patients, compared to those with a higher DC > 2.5 ms (56.5 years). However, the duration of hospitalization was similar for both groups. There was a nonsignificant trend towards a higher maximum viral load in patients with reduced DC. Further, patients with a DC ≤ 2.5 ms showed higher levels of inflammatory markers such as C-reactive protein (CRP) and procalcitonin (PCT), as well as leukocytosis, compared to patients with a DC > 2.5 ms. Also, the COVID-19-severity marker ferritin was significantly elevated in patients with lower DC. Other markers associated with COVID-19, such as lactate dehydrogenase (LDH) and creatine kinase (CK), exhibited comparable levels in both groups. CONCLUSIONS: Reduced DC (≤ 2.5 ms) was significantly associated with older age, increased inflammatory markers, and elevated ferritin in patients with COVID-19. These findings suggest that DC might serve as a valuable indicator for predicting the risk of severe inflammation in COVID-19 and possibly complications associated with this disease, such as heart failure. Further studies are needed to confirm these observations and clarify the clinical significance of DC in COVID-19 and other infectious diseases.

Diurnal variation of cardiac autonomic activity in adolescent non-suicidal self-injury.

Heart rate (HR) and vagally mediated heart rate variability (HRV) are two distinct biomarkers of cardiac autonomic activity. Decreased cardiac vagal activity (or decreased HRV) in particular has been linked with impairments in the functional flexibility of the central autonomic network (CAN), resulting in impaired stress and emotion regulatory capacities. Decreased HRV is widely used as trait marker of psychopathology. Repetitive engagement in non-suicidal self-injury (NSSI) in adolescence correlates with both deficits in stress and emotion regulation, as well as decreased HRV. Existing research has, however, focused on short-term recordings of HR and HRV under resting and phasic conditions. In this study, we examined whether diurnal variation of cardiac autonomic activity, indexed by cosinor parameters of HR and HRV derived from 48 h of ambulatory ECG recording under natural conditions over a weekend, are altered in female adolescents with NSSI disorder compared to controls (HC; N = 30 per study group). Several important confounds, including physical activity, were controlled for. Female adolescents with NSSI show higher rhythm-adjusted 24 h mean levels and greater respective amplitude of HR, as well as lower rhythm-adjusted 24 h mean levels and smaller respective amplitude of HRV. Peak levels in both HR and HRV in the NSSI group were reached approximately 1 h later compared to HC. Severity of exposure to early life maltreatment might be linked with altered amplitudes of 24 h HR and HRV. Diurnal rhythms of cardiac autonomic activity might hold promise as objective indicators of disordered stress and emotion regulation in developmental psychopathology, and as such should be investigated in future studies with rigorous assessment and control of potential confounds.

Time-domain heart rate dynamics in the prognosis of progressive atherosclerosis.

BACKGROUND AND AIM: The regular uptake of a high-fat diet (HFD) with changing lifestyle causes atherosclerosis leading to cardiovascular diseases and autonomic dysfunction. Therefore, the current study aimed to investigate the correlation of autonomic activity to lipid and atherosclerosis markers. Further, the study proposes a support vector machine (SVM) based model in the prediction of atherosclerosis severity. METHODS AND RESULTS: The Lead-II electrocardiogram and blood markers were measured from both the control and the experiment subjects each week for nine consecutive weeks. The time-domain heart rate variability (HRV) parameters were derived, and the significance level was tested using a one-way Analysis of Variance. The correlation analysis was performed to determine the relation between autonomic parameters and lipid and atherosclerosis markers. The statistically significant time-domain values were used as features of the SVM. The observed results demonstrated the reduced time domain HRV parameters with the increase in lipid and atherosclerosis index markers with the progressive atherosclerosis severity. The correlation analysis revealed a negative association between time-domain HRV parameters with lipid and atherosclerosis parameters. The percentage accuracy increases from 86.58% to 98.71% with the increase in atherosclerosis severity with regular consumption of HFD. CONCLUSIONS: Atherosclerosis causes autonomic dysfunction with reduced HRV. The negative correlation between autonomic parameters and lipid profile and atherosclerosis indexes marker revealed the potential role of vagal activity in the prognosis of atherosclerosis progression. The support vector machine presented a respectable accuracy in the prediction of atherosclerosis severity from the control group.

Effect of Heart Rate Variability Biofeedback on Cardiac Autonomic Activation and Diabetes Self-Care in Patients with Type II Diabetes Mellitus.

In type 2 diabetes mellitus (T2DM), decreased autonomic activation and heightened negative emotions may worsen glycemic control. This study investigated the effects of heart rate variability biofeedback (HRVB) on autonomic activation, negative emotions, diabetes self-care, and glycemic control in patients with T2DM. A total of 61 participants with T2DM were assigned to either the HRVB group (n = 30; 62.67 ± 7.28 years; 14 females) or the control group (n = 31; 63.39 ± 6.96 years; 14 females). Both groups received the treatment as usual, and the HRVB group received 60 min of HRVB sessions weekly for 6 weeks. Participants completed psychological questionnaires, a resting electrocardiogram (ECG), and breathing rate assessments at pre- and post-tests. Heart rate variability (HRV) indices were derived from ECG data, and glycated hemoglobin (HbA1c) levels were collected from the electronic medical records. The analysis revealed significant Group × Time interaction effects on HRV indices, breathing rate, depression symptoms, and diabetes self-care behavior. The HRVB group demonstrated higher HRV indices, lower breathing rate, and improved diabetes self-care behavior compared to the control group. Moreover, the HRVB group showed enhanced HRV indices and diabetes self-care behavior, as well as reduced breathing rate and depression in the post-test compared to the pre-test. However, there was no significant interaction effect on HbA1c levels. Six sessions of HRVB proved effective as a complementary therapy for T2DM, enhancing HRV indices, alleviating depressive symptoms, and promoting better diabetes self-care behaviors.

Anti-Inflammatory Effects of Two-Week Sacral Nerve Stimulation Therapy in Patients With Ulcerative Colitis.

BACKGROUND AND AIMS: Sacral nerve stimulation (SNS) showed anti-inflammatory properties in animal models of inflammatory bowel disease. We aimed to evaluate the effectiveness and safety of SNS in patients with ulcerative colitis (UC). MATERIALS AND METHODS: Twenty-six patients with mild and moderate disease were randomized into two groups: SNS (delivered at S3 and S4 sacral foramina) and sham-SNS (delivered 8-10 mm away from sacral foramina), with the therapy applied once daily for one hour, for two weeks. We evaluated the Mayo score and several exploratory biomarkers, including C-reactive protein in the plasma, pro-inflammatory cytokines and norepinephrine in the serum, assessment of autonomic activity, and diversity and abundance of fecal microbiota species. RESULTS: After two weeks, 73% of the subjects in the SNS group achieved clinical response, compared with 27% in the sham-SNS group. Levels of C-reactive protein, pro-inflammatory cytokines in the serum, and autonomic activity were significantly improved toward a healthy profile in the SNS group but not in the sham-SNS group. Absolute abundance of fecal microbiota species and one of the metabolic pathways were changed in the SNS group but not in the sham-SNS group. Significant correlations were observed between pro-inflammatory cytokines and norepinephrine in the serum on the one side and fecal microbiota phyla on the other side. CONCLUSIONS: Patients with mild and moderate UC were responsive to a two-week SNS therapy. After performing further studies to evaluate its efficacy and safety, temporary SNS delivered through acupuncture needles may become a useful screening tool for identifying SNS therapy responders before considering long-term implantation of the implantable pulse generator and SNS leads for performing long-term SNS therapy.

The brain-derived neurotrophic factor Val66met polymorphism is associated with better attention and working memory performance and resilience to mild chronic stress.

The val66met polymorphism of the brain-derived neurotrophic factor (BDNF) gene has been identified as a potential moderator for the relationship between chronic stress and executive functioning. However, whether the presence of the met allele increases cognitive vulnerability or resilience to stress has yet to be determined. Given the established effects of autonomic activity and psychological arousal on executive functioning, in the present study, 56 healthy university students completed self-report measures of chronic stress, positive arousal (vigour) and negative arousal (anxiety) and measured heart-rate variability to quantify autonomic activity. Participants then completed a cognitive test battery that measured attention, decision-making, visual learning and working memory. Regression analyses demonstrated that Val/met participants performed better on attention and working memory tasks than Val/val participants, but no differences were seen in decision-making and visual learning. Further, Val/met participants were protected from stress-related differences in attention seen in Val/val participants. Val66met was not associated with physiological or psychological arousal. This study demonstrates that val66met plays an important but selective role in cognitive performance.

Identifying phenotypic and physiological subgroups of preschoolers with autism spectrum disorder.

BACKGROUND: To understand the emergence of symptoms in autism spectrum disorder (ASD), we need to identify the mechanisms that underpin the development of core social skills. Mounting evidence indicates that young children with later ASD attend less to other people, which could compromise learning opportunities with cascading effects. Passive looking behaviour does not tell us about engagement with visual information, but measures of physiological arousal can provide information on the depth of engagement. In the current study, we use heart rate (HR) and heart rate variability (HRV) to measure engagement with social dynamic stimuli in ASD. METHODS: Sixty-seven preschoolers with ASD and 65 typical developing preschoolers between 2 and 4 years of age participated in a study where HR was measured during viewing of social and non-social videos. Using latent profile analyses, more homogeneous subgroups of children were created based on phenotype and physiology. RESULTS: Preschool-aged children with ASD, regardless of their non-verbal, verbal and social competencies, do not differ in overall HR or HRV compared to TD children. However, the ASD group showed a larger increase in HR (more disengagement) than the TD group to later-presented social stimuli. Phenotypic and physiological profiles showed this was primarily the case for children with below average verbal and non-verbal skills, but not necessarily those with more ASD symptoms. CONCLUSION: Children with ASD, especially a subgroup showing moderate cognitive delays, show an increase in HR to social stimuli over time; this may reflect difficulties re-engaging with social information when attention is waning.

Autonomic activity, posttraumatic and nontraumatic nightmares, and PTSD after trauma exposure.

BACKGROUND: Nightmares are a hallmark symptom of posttraumatic stress disorder (PTSD). This strong association may reflect a shared pathophysiology in the form of altered autonomic activity and increased reactivity. Using an acoustic startle paradigm, we investigated the interrelationships of psychophysiological measures during wakefulness and PTSD diagnosis, posttraumatic nightmares, and nontraumatic nightmares. METHODS: A community sample of 122 trauma survivors were presented with a series of brief loud tones, while heart rate (HRR), skin conductance (SCR), and orbicularis oculi electromyogram (EMGR) responses were measured. Prior to the tone presentations, resting heart rate variability (HRV) was assessed. Nightmares were measured using nightmare logs. Three dichotomous groupings of participants were compared: (1) current PTSD diagnosis (n = 59), no PTSD diagnosis (n = 63), (2) those with (n = 26) or without (n = 96) frequent posttraumatic nightmares, and (3) those with (n = 22) or without (n = 100) frequent nontraumatic nightmares. RESULTS: PTSD diagnosis was associated with posttraumatic but not with nontraumatic nightmares. Both PTSD and posttraumatic nightmares were associated with a larger mean HRR to loud tones, whereas nontraumatic nightmare frequency was associated with a larger SCR. EMGR and resting HRV were not associated with PTSD diagnosis or nightmares. CONCLUSIONS: Our findings suggest a shared pathophysiology between PTSD and posttraumatic nightmares in the form of increased HR reactivity to startling tones, which might reflect reduced parasympathetic tone. This shared pathophysiology could explain why PTSD is more strongly related to posttraumatic than nontraumatic nightmares, which could have important clinical implications.

Sex differences in Black Veterans with PTSD: women versus men have higher sympathetic activity, inflammation, and blunted cardiovagal baroreflex sensitivity.

PURPOSE: Post-traumatic stress disorder (PTSD) is associated with greater risk of incident hypertension and cardiovascular disease (CVD). Inflammation and autonomic derangements are suggested as contributing mechanisms. Women and Black adults have higher CVD risk associated with stress; however, whether there is a sex difference in autonomic and inflammatory mechanisms among Black individuals with PTSD is not known. We hypothesized that Black women with PTSD have higher inflammation, sympathetic nervous system (SNS) activity and impaired baroreflex sensitivity (BRS). METHODS: In 42 Black Veterans with PTSD (Women, N = 18 and Men, N = 24), we measured inflammatory biomarkers, continuous blood pressure (BP), heart rate (HR) and muscle sympathetic nerve activity (MSNA) at rest and during arterial BRS testing via the modified Oxford technique. RESULTS: Groups were matched for age and body mass index (BMI). Resting BP was similar between groups, but HR was higher (76 ± 12 vs. 68 ± 9 beats/min, p = 0.021) in women compared to men. Although women had lower PTSD symptoms severity (57 ± 17 vs. 68 ± 12 a.u.), resting MSNA (27 ± 13 vs. 16 ± 5 bursts/min, p = 0.003) was higher in women compared to men, respectively. Likewise, cardiovagal BRS was blunted (p = 0.002) in women (7.6 ± 4.3 ms/mmHg) compared to men (15.5 ± 8.4 ms/mmHg) while sympathetic BRS was not different between groups (p = 0.381). Black women also had higher (p = 0.020) plasma levels of interleukin-2 (IL-2). CONCLUSION: Black women with PTSD have higher resting HR and MSNA, greater impairment of cardiovagal BRS and possibly higher inflammation. These findings suggest a higher burden of autonomic and inflammatory derangements in Black women compared to Black men with PTSD.

Heart rate response to cortical arousals in patients with isolated obstructive sleep apnea and with comorbid insomnia (COMISA).

PURPOSE: Comorbid insomnia often occurs in patients with obstructive sleep apnea (OSA), referred to as COMISA. Cortical arousals manifest as a common feature in both OSA and insomnia, often accompanied by elevated heart rate (HR). Our objective was to evaluate the heart rate response to nocturnal cortical arousals in patients with COMISA and patients with OSA alone. METHODS: We analyzed data from patients with COMISA and from patients with OSA matched for apnea-hypopnea index. Sleep staging and analysis of respiratory events and cortical arousals were performed using the Philips Somnolyzer automatic scoring system. Beat-by-beat HR was analyzed from the onset of the cortical arousal to 30 heartbeats afterwards. HR responses were divided into peak and recovery phases. Cortical arousals were separately evaluated according to subtype (related to respiratory events and spontaneous) and duration (3-6 s, 6-10 s, 10-15 s). RESULTS: A total of 72 patients with COMISA and 72 patients with OSA were included in this study. There were no overall group differences in the number of cortical arousals with and without autonomic activation. No significant differences were found for spontaneous cortical arousals. The OSA group had more cortical arousals related to respiratory events (21.0 [14.8-30.0] vs 16.0 [9.0-27.0], p = 0.016). However, the COMISA group had longer cortical arousals (7.2 [6.4-7.8] vs 6.7 [6.2-7.7] s, p = 0.024) and the HR recovery phase was prolonged (52.5 [30.8-82.5] vs 40.0 [21.8-55.5] beats/min, p = 0.017). Both the peak and the recovery phase for longer cortical arousals with a duration of 10-15 s were significantly higher in patients with COMISA compared to patients with OSA (47.0 [27.0-97.5] vs 34.0 [21.0-71.0] beats/min, p = 0.032 and 87.0 [47.0-132.0] vs 71.0 [43.0-103.5] beats/min, p = 0.049, respectively). CONCLUSIONS: The HR recovery phase after cortical arousals related to respiratory events is prolonged in patients with COMISA compared to patients with OSA alone. This response could be indicative of the insomnia component in COMISA.

Acute Effects of Fatigue on Cardiac Autonomic Nervous Activity.

The onset of fatigue disrupts the functioning of the autonomic nervous system (ANS), potentially elevating the risk of life-threatening incidents and impairing daily performance. Previous studies mainly focused on physical fatigue (PF) and mental fatigue (MF) effects on the ANS, with limited knowledge concerning the influence of physical-mental fatigue (PMF) on ANS functionality. This study aimed to assess the immediate impact of PMF on ANS function and to compare its effects with those of PF and MF on ANS function. Thirty-six physically active college students (17 females) without burnout performed 60-min cycling exercises, AX-Continuous Performance Task (AX-CPT), and cycling combined with AX-CPT to induce PF, MF, and PMF respectively. Subjective fatigue levels were measured using the Rating of Perceived Exertion scale and the Visual Analog Scale-Fatigue. Heart rate variability was measured before and after each protocol to assess cardiac autonomic function. The proposed tasks successfully induced PF, MF, and PMF, demonstrated by significant changes in subjective fatigue levels. Compared with baseline, PMF decreased the root mean square of successive differences (RMSSD) between normal heartbeats (P < 0.001, d = 0.50), the standard deviation of normal-to-normal RR intervals (SDNN) (P < 0.01, d = 0.33), and the normalized high-frequency (nHF) power (P < 0.001, d = 0.32) while increased the normalized low-frequency (nLF) power (P < 0.001, d = 0.35) and the nLF/nHF ratio (P < 0.001, d = 0.40). Compared with MF, PMF significantly decreased RMSSD (P < 0.001, η2 = 0.431), SDNN (P < 0.001, η2 = 0.327), nLF (P < 0.01, η2 = 0.201), and nHF (P < 0.001, η2 = 0.377) but not the nLF/nHF ratio. There were no significant differences in ΔHRV (i.e., ΔRMSSD, ΔSDNN, ΔnLF/nHF, ΔnLF, and ΔnHF), heart rate, and training impulse between PF- and PMF-inducing protocols. Cognitive performance (i.e., accuracy) in AX-CPT during the PMF-inducing protocol was significantly lower than that during the MF-inducing protocol (P < 0.001, η2 = 0.101). PF and PMF increased sympathetic activity and decreased parasympathetic activity, while MF enhanced parasympathetic activity.

An orderly sequence of autonomic and neural events at transient arousal changes.

Resting-state functional magnetic resonance imaging (rsfMRI) allows the study of functional brain connectivity based on spatially structured variations in neuronal activity. Proper evaluation of connectivity requires removal of non-neural contributions to the fMRI signal, in particular hemodynamic changes associated with autonomic variability. Regression analysis based on autonomic indicator signals has been used for this purpose, but may be inadequate if neuronal and autonomic activities covary. To investigate this potential co-variation, we performed rsfMRI experiments while concurrently acquiring electroencephalography (EEG) and autonomic indicator signals, including heart rate, respiratory depth, and peripheral vascular tone. We identified a recurrent and systematic spatiotemporal pattern of fMRI (named as fMRI cascade), which features brief signal reductions in salience and default-mode networks and the thalamus, followed by a biphasic global change with a sensory-motor dominance. This fMRI cascade, which was mostly observed during eyes-closed condition, was accompanied by large EEG and autonomic changes indicative of arousal modulations. Importantly, the removal of the fMRI cascade dynamics from rsfMRI diminished its correlations with various signals. These results suggest that the rsfMRI correlations with various physiological and neural signals are not independent but arise, at least partly, from the fMRI cascades and associated neural and physiological changes at arousal modulations.

Emotional Effects in Object Recognition by the Visually Impaired People in Grocery Shopping.

To date, neuroscientific literature on consumption patterns of specific categories of consumers, such as people with disability, is still scarce. This study explored the implicit emotional consumer experience of visually impaired (VI) consumers in-store. A group of VI and a control group explored three different product shelves and manipulated target products during a real supermarket shopping experience. Autonomic (SCL, skin conductance level; SCR, skin conductance response; HR, heart rate; PVA, pulse volume amplitude; BVP, blood volume pulse), behavioural and self-report data were collected in relation to three phases of the in-store shopping experience: (i) identification of a product (recognition accuracy, ACC, and reaction times, RTs); (ii) style of product purchase (predominant sense used for shelf exploration, store spatial representation, and ability to orientate themselves); (iii) consumers experience itself, underlying their emotional experience. In the VI group, higher levels of disorientation, difficulty in finding products, and repeating the route independently were discovered. ACC and RTs also varied by product type. VI also showed significantly higher PVA values compared to the control. For some specific categories (pasta category), PVA correlates negatively with time to recognition and positively with simplicity in finding products in the entire sample. In conclusion, VI emotional and cognitive experience of grocery shopping as stressful and frustrating and has a greater cognitive investment, which is mirrored by the activation of a larger autonomic response compared to the control group. Nevertheless, VI ability to search and recognise a specific product is not so different from people without visual impairment.

Morning sympathetic activity after evening binge alcohol consumption.

Binge alcohol consumption elicits acute and robust increases of muscle sympathetic nerve activity (MSNA), yet the impact of evening binge drinking on morning-after MSNA is unknown. The present study examined the effects of evening binge alcohol consumption on polysomnographic sleep and morning-after MSNA. We hypothesized that evening binge drinking (i.e. 4-5 drink equivalent in <2 h) would reduce sleep quality and increase morning-after blood pressure (BP) and MSNA. Following a familiarization night within the sleep laboratory, 22 participants (12 men, 10 women; 25 ± 1 yr) were examined after simulated binge drinking or fluid control (randomized, crossover design). Morning MSNA was successfully recorded across both conditions in 16 participants (8 men, 8 women) during a 10-min baseline and three Valsalva's maneuvers (VM). Binge drinking reduced rapid eye movement (REM) sleep (15 ± 1 vs. 20 ± 1%, P = 0.003), increased stage II sleep (54 ± 1 vs. 51 ± 1%, P = 0.002), and increased total urine output (2.9 ± 0.2 vs. 2.1 ± 0.1 liters, P < 0.001) but did not alter morning-after urine specific gravity. Binge drinking increased morning-after heart rate [65 (54-72) vs. 58 (51-67) beats/min, P = 0.013] but not resting BP or MSNA. Binge drinking elicited greater sympathoexcitation during VM (38 ± 3 vs. 43 ± 3 bursts/min, P = 0.036). Binge drinking augmented heart rate (P = 0.002), systolic BP (P = 0.022), and diastolic BP (P = 0.037) reactivity to VM phase IV and blunted cardiovagal baroreflex sensitivity during VM phases II (P = 0.028) and IV (P = 0.043). In conclusion, evening binge alcohol consumption disrupted REM sleep and morning-after autonomic function. These findings provide new mechanistic insight into the potential role of binge drinking on cardiovascular risk.NEW & NOTEWORTHY Chronic binge alcohol consumption is associated with future cardiovascular disease (CVD) risk in both men and women. In addition, binge alcohol consumption is known to disrupt normal sleep quality during the early morning hours, coinciding with the morning sympathetic surge. In the present study, an evening of binge alcohol consumption increased baseline morning heart rate and cardiovascular reactivity during the Valsalva maneuver (VM) strain. Specifically, muscle sympathetic nerve activity and phase IV hemodynamic responses increased during VM the morning after binge alcohol consumption. The autonomic dysfunction and increased cardiovascular reactivity during VM suggests a contributing mechanism to CVD risk present in individuals who binge drink.

Changes in cortical, cardiac, and respiratory activities in relation to spontaneous rhythmic jaw movements in ketamine-anesthetized guinea pigs.

It has been reported that rhythmic jaw movements (RJMs) spontaneously occur in ketamine-anesthetized animals. The present study investigated the physiological processes that occur during the cortical, cardiac, and respiratory events which contribute to the genesis of RJMs in animals after supplemental ketamine injections. Fourteen guinea pigs were prepared to allow electroencephalographic, electrocardiographic, and electromyographic activities to be recorded from the digastric muscle, measurement of jaw movements, and nasal expiratory airflow under ketamine-xylazine anesthesia. Rhythmic jaw movements spontaneously occurred with rhythmic digastric muscle contractions, 23-29 minutes after injection of supplemental ketamine (12.5 and 25.0 mg kg-1 , intravenously). The cycle length of RJMs did not differ significantly between the two doses of ketamine (mean±SD: 12.5 mg kg-1 , 326.5 ± 60.0 ms; 25 mg kg-1 , 278.5 ± 45.1 ms). Following injection of ketamine, digastric muscle activity, heart and respiratory rates, and cortical beta power significantly decreased, while cortical delta and theta power significantly increased. These changes were significantly larger in animals given 25.0 mg kg-1 of ketamine than in those given 12.5 mg kg-1 . With the onset of RJMs, the levels of these variables returned to pre-injection levels, regardless of the dose of ketamine administered. These results suggest that, following supplemental ketamine injections, spontaneous RJMs occur during a specific period when the pharmacological effects of ketamine wear off, and that these RJMs are characterized by stereotypical changes in cardiac, respiratory, and cortical activities.

Symptom severity impacts sympathetic dysregulation and inflammation in post-traumatic stress disorder (PTSD).

Post-traumatic stress disorder (PTSD) is associated with a greater risk of incident hypertension and cardiovascular disease. Inflammation, impaired baroreflex sensitivity (BRS) decreased parasympathetic nervous system (PNS) and overactive sympathetic nervous system (SNS) activity are suggested as contributing mechanisms. Increasing severity of PTSD symptoms has been linked to greater cardiovascular risk; however, the impact of PTSD symptom severity on inflammation and autonomic control of blood pressure has not yet been explored. We hypothesized that increasing PTSD symptom severity is linked to higher inflammation, greater SNS activity, lower PNS reactivity and impaired BRS. Seventy Veterans participated in this study: 28 with severe PTSD ((Clinical Administered PTSD Scale (CAPS) > 60; S-PTSD), 16 with moderate PTSD (CAPS ≥ 45 ≤ 60; M-PTSD) and 26 Controls (CAPS < 45; NO-PTSD). We recorded continuous blood pressure (BP), heart rate (HR) via EKG, heart rate variability (HRV) markers reflecting PNS and muscle sympathetic nerve activity (MSNA) at rest, during arterial baroreflex sensitivity (BRS) testing via the modified Oxford technique, and during 3 min of mental stress via mental arithmetic. Blood samples were analyzed for 12 biomarkers of systemic and vascular inflammation. While BP was comparable between severity groups, HR tended to be higher (p = 0.055) in S-PTSD (76 ±â€¯2 beats/min) than in Controls (67 ±â€¯2 beats/min) but comparable to M-PTSD (70 ±â€¯3 beats/min). There were no differences in resting HRV and MSNA between groups; however, cardiovagal BRS was blunted (p = 0.021) in S-PTSD (10 ±â€¯1 ms/mmHg) compared to controls (16 ±â€¯3 ms/mmHg) but comparable to M-PTSD (12 ±â€¯2 ms/mmHg). Veterans in the S-PTSD group had a higher (p < 0.001) combined inflammatory score compared to both M-PTSD and NO-PTSD. Likewise, while mental stress induced similar SNS and cardiovascular responses between the groups, there was a greater reduction in HRV in S-PTSD compared to both M-PTSD and NO-PTSD. In summary, individuals with severe PTSD symptoms have higher inflammation, greater impairment of BRS, a trend towards higher resting HR and exaggerated PNS withdrawal at the onset of mental stress that may contribute to cardiovascular risk in severe PTSD.

Autonomic activity and its relationship with the endogenous cardiotonic steroid marinobufagenin: the African-PREDICT study.

Aim: Marinobufagenin (MBG), a cardiotonic steroid and a natriuretic hormone, is elevated in response to high salt diet consumption. In animal models salt intake stimulates adrenocortical MBG secretion via increased angiotensin II, sympathetic activity and aldosterone. No evidence in humans exists to suggest the involvement of the angiotensinergic-sympatho-excitatory pathway in MBG production. We investigated whether MBG is related to indices of autonomic activity in men and women. Methods: This cross-sectional study included 680 black and white, men and women from the African-PREDICT study (aged 20-30 years). Continuous 24 hr ECG recordings were used to obtain low and high frequency (LF, HF) heart rate variability (HRV). We measured 24 hr urinary MBG excretion and serum aldosterone. Results: We found a positive association of MBG excretion with estimated salt intake (P < 0.001) and aldosterone (P < 0.001) in women and men. In women only, a positive relationship was evident between MBG excretion and LF HRV in multivariate adjusted regression analyses (Adj. R 2 = 0.33; ß = 0.11; P = 0.030). In men, MBG excretion associated positively with HF HRV in similar regression analyses (R 2 = 0.36; ß = 0.12; P = 0.034). Sex-specific results were corroborated only in blacks, namely, a positive association of MBG excretion with LF HRV in black women (R 2 = 0.38; ß = 0.13; P = 0.036), and negative association with HF HRV in black men (R 2 = 0.40; ß = 0.18; P = 0.045). No relationships were evident in white women (P = 0.58) or men (P = 0.27). Conclusion: Our findings in this human cohort support suggested mechanisms whereby MBG is elevated as a result of increased salt intake, including autonomic activity, previously demonstrated in Dahl salt-sensitive hypertension.

Effectiveness of sleep surgery versus a mandibular advancement device for obstructive sleep apnea in terms of nocturnal cardiac autonomic activity.

PURPOSE: Sleep surgery and mandibular advancement devices (MAD) are treatments for obstructive sleep apnea (OSA), but their comparative efficacy remains unclear. We compared their efficacy using various parameters. METHODS: Subjects treated for OSA with sleep surgery or MAD (n = 30/group)-matched for sex, body mass index (BMI), and baseline apnea-hypopnea index (AHI)-were enrolled. The efficacy of these treatments according to polysomnographic parameters, sleep quality questionnaires, and heart rate variability (HRV) time- and frequency-domain parameters were compared between pre-treatment and 3-month post-treatment. RESULTS: Polysomnographic and sleep quality questionnaire parameters improved significantly in both groups. In time-domain HRV analysis, average normal-to-normal intervals increased significantly in the surgery (942.2 ± 140.8 to 994.6 ± 143.1, P = 0.008) and MAD (901.1 ± 131.7 to 953.7 ± 123.1, P = 0.002) groups. Low frequency (LF) decreased significantly in the surgery group (P = 0.012); high frequency (HF) remained unchanged in both groups. The LF/HF ratio decreased in both groups (2.9 ± 1.8 to 2.3 ± 1.7, P = 0.017, vs. 3.0 ± 1.8 to 2.4 ± 1.4, P = 0.025). Normalized high frequency increased significantly in both groups (31.0 ± 13.2 to 36.8 ± 13.7, P = 0.009, vs. 29.1 ± 10.7 to 33.7 ± 12.5, P = 0.024), in contrast to normalized low frequency. However, no HRV parameter changes differed significantly between the groups after adjusting for age, BMI, and AHI. CONCLUSION: Sleep surgery and MAD are equally effective treatments for OSA according to cardiac autonomic activity.

Sympathetic neural responsiveness to sleep deprivation in older adults: sex differences.

Our laboratory has previously reported that total sleep deprivation (TSD) modifies muscle sympathetic neural activity (MSNA) differently in young men and women. Because postmenopausal women are among the highest risk for hypertension, this study compares MSNA responses with TSD in older men and women. We hypothesized that TSD would alter MSNA in older adults, with greater sympathoexcitation in postmenopausal women. Twenty-seven participants (14 men and 13 women) between the ages of 55 and 75 yr were tested twice, once after 24-h TSD and once after normal sleep (randomized, crossover design). Our primary outcome measure of MSNA (microneurography) was successful across both conditions in 20 participants (10 men and 10 women). Secondary outcome measures included seated blood pressure, heart rate, and fasting plasma testosterone, estradiol, and progesterone. Age (60 ± 1 vs. 61 ± 2 yr) and BMI (27 ± 1 vs. 26 ± 1 kg/m2) were not different between groups. TSD increased systolic blood pressure in both men (124 ± 5 to 130 ± 4 mmHg) and women (107 ± 5 to 116 ± 4 mmHg), but the increases were not different between groups (condition, P = 0.014; condition × sex, P > 0.05). In contrast, TSD elicited divergent MSNA responses in older men and women. Specifically, MSNA burst frequency increased in postmenopausal women (28 ± 3 to 34 ± 3 burst/min), but not older men (38 ± 3 to 35 ± 3 bursts/min; condition × sex, P = 0.032). In conclusion, TSD elicited sympathoexcitation in postmenopausal women but not age-matched men. These findings provide new mechanistic insight into reported links between sleep deprivation and hypertension.NEW & NOTEWORTHY Epidemiological studies report that sleep deprivation is more strongly associated with hypertension in women than in men. In the present study, 24-h total sleep deprivation (TSD) increased blood pressure in postmenopausal women and age-matched men. In contrast, only women demonstrated increases in muscle sympathetic nerve activity after TSD. The sympathoexcitation observed in postmenopausal women suggests a potential contributing mechanism for epidemiological observations and advances our understanding of the complex relations between sleep, sex, and hypertension.