Parasympathetic Modulation Of Heart Rate Research Articles

Glucose metabolism and autonomic function in healthy individuals and patients with type 2 diabetes mellitus at rest and during exercise.

Autonomic dysfunction is a common complication of type 2 diabetes mellitus (T2DM). However, the character of dysfunction varies in different reports. Differences in measurement methodology and complications might have influenced the inconsistent results. We sought to evaluate comprehensively the relationship between abnormal glucose metabolism and autonomic function at rest and the response to exercise in healthy individuals and T2DM patients. We hypothesized that both sympathetic and parasympathetic indices would decrease with the progression of abnormal glucose metabolism in individuals with few complications related to high sympathetic tone. Twenty healthy individuals and 11 T2DM patients without clinically evident cardiovascular disease other than controlled hypertension were examined. Resting muscle sympathetic nerve activity (MSNA), heart rate variability, spontaneous cardiovagal baroreflex sensitivity (CBRS), sympathetic baroreflex sensitivity and the MSNA response to handgrip exercise were measured. Resting MSNA was lower in patients with T2DM than in healthy control subjects (P=0.011). Resting MSNA was negatively correlated with haemoglobin A1c in all subjects (R=-0.45, P=0.024). The parasympathetic components of heart rate variability and CBRS were negatively correlated with glycaemic/insulin indices in all subjects and even in the control group only (all, P<0.05). In all subjects, the MSNA response to exercise was positively correlated with fasting blood glucose (R=0.69, P<0.001). Resting sympathetic activity and parasympathetic modulation of heart rate were decreased in relationship to abnormal glucose metabolism. Meanwhile, the sympathetic responses to handgrip were preserved in diabetics. The responses were correlated with glucose/insulin parameters throughout diabetic and control subjects. These results suggest the importance of a comprehensive assessment of autonomic function in T2DM.

Relationship Between Esophageal Motility Disorders and Autonomic Nervous System in Diabetic Patients: Pilot North African Study.

Little attention has been given to esophageal disorders in diabetes mellitus. Pathophysiology of esophageal motility disorders (EMD) in patients with diabetes mellitus is multifactorial. The aims of the present study were: (a) to evaluate the prevalence of EMD in patients with Type 2 diabetes mellitus and (b) to determine the relationship between EMD and autonomic neuropathy as assessed by heart rate variability (HRV). All the patients completed a questionnaire about diabetes characteristics and gastrointestinal symptoms. Conventional esophageal manometry was performed in all patients. HRV was measured in three different situations (Lying Position 1, standing position, and Lying Position 2). The temporal and frequency domain parameters were considered for analysis. The prevalence of EMD in our patients was 60.5% (n = 23). Low score physical activity was significantly more frequent in patients with EMD (p = .03). There was an increase in sympathetic activity represented by the low frequency (LF) parameter (p = .027) in the presence of EMD. Whereas parasympathetic modulation of heart rate represented by the high frequency (HF) parameter (p = .027) was declined in patients with EMD compared to those without. The LF/HF ratio was significantly higher (p = .002) in patients with EMD. EMD were prevalent in diabetes mellitus and were associated to autonomic nervous system dysfunction predominantly at the parasympathetic component.

Experimental uninephrectomy associates with less parasympathetic modulation of heart rate and facilitates sodium-dependent arterial hypertension.

Blood pressure is known to be increased in kidney donors following living-donor kidney transplantation. However, the physiological underpinnings of the blood-pressure increase following uninephrectomy remain unclear. We hypothesized that changes in sympathetic tone or in parasympathetic modulation of sinus node function are involved in the blood-pressure increase following experimental kidney-mass reduction. C57BL6N mice (6 to 11 per group) subjected to sham surgery (controls) or uninephrectomy with or without a one-week course of sodium chloride-enriched, taurine-deficient diet were studied. Uninephrectomized mice treated with a subcutaneous infusion of angiotensin-II over a period of one week were positive controls. A transfemoral aortic catheter with telemetry unit was implanted, readings of heart-rate and blood-pressure were recorded. Powerspectral analysis of heart rate and systolic blood pressure was performed to gain surrogate parameters of sympathetictone and parasympathetic modulation of sinus node function. Baroreflex sensitivity of heart rate was determined from awake, unrestrained mice using spontaneous baroreflex gain technique. Systolic arterial blood pressure, heart rate and baroreflex sensitivity were not different in uninephrectomized mice when compared to controls. Parasympathetic modulation of sinus node function was less in uninephrectomized mice in comparison to controls. Uninephrectomized mice of the high-angiotensin-II model or of the high-salt and taurine-deficiency model had an increased systolic arterial blood pressure. Uninephrectomy associated with less parasympathetic modulation of sinus node function. The combination of uninephrectomy, taurine-deficiency and high-salt intake led to arterial hypertension.

Perceived Social Support and Heart Rate Variability: An Integrative Review.

The purpose of this integrative review is to explore and synthesize literature about the relationship between perceived social support and cardiac vagal modulation, measured by heart rate variability (HRV), during phases of an acute stress response to assess this potential relationship underlying the stress-buffering effects of perceived social support. A systematic search of seven databases was conducted, including MEDLINE, CINAHL, PsychINFO, Embase, ProQuest, medRxiv, and clinicaltrials.gov. Eight studies met the inclusion criteria and were systematically synthesized. A quality appraisal was completed for each included study. Majority of studies focused on time and frequency domain measures of HRV thought to reflect parasympathetic modulation of heart rate and identified them as positively associated with perceived social support during rest, stress induction, and recovery from an acute stressor. Results highlight the importance for nurses and other health care professionals to assess patients' perceived social support, as increased perceived social support may contribute to an adaptive stress response.

ANSIEDADE, DEPRESSÃO E ANÁLISE NÃO LINEAR DA VARIABILIDADE DA FREQUÊNCIA CARDÍACA EM INGRESSANTES NO ENSINO SUPERIOR

The non-linear analysis of the heart rate variability (HRV) is a potential correlation tool between physiological and emotional states. The aim of this study was correlate changes in non-linear parameters of the HRV with anxiety and depression indices in higher education entrants from Federal University of Goiás (UFG). To record HRV, the Polar Frequency Metermodel Polar® RS800cx (Electro Oi, Finland) was used. To analyze the levels of depression, the Beck Depression Inventory-I (BDI) was used, and for analysis of anxiety, the Inventories of State and Trace (IDATE T and E). Altogether, 50 (19.4±2.48 years) volunteers participated in the study. The scores of the depression and anxiety inventories indicated that the public had low and moderate indices of both conditions, respectively. Statistically significant correlations were found between the SD2 parameter (from the Poincaré plot in the HRV analysis), entropy data (ApEn and SampEn) and fractal property (DFA: α1) and trait and state anxiety levels. Although ApEn e SampEn still do not have well-defined physiological correspondences, DFA: α1 has been associated with parasympathetic modulation of heart rate. Therefore, it is concluded that chronic negative emotional states, such as anxiety and humor disorders, can be accompanied by parasympathetic increase in HRV, so the organism would be able to not wear out against long-term stressors. New studies are necessary to understand the physiological and evolutional bases of depression and anxiety.

Folic Acid Supplementation Increases Cardiac Parasympathetic Modulation of Heart Rate in Habitually Endurance Trained and Untrained Middle‐Aged Men

IntroductionAgeing is associated with decreased, and exercise training increased, parasympathetic modulation of heart rate (HR). Cardiac parasympathetic control has prognostic significance in cardiac disease, but the mechanisms remain unclear. Nitric oxide (NO) is thought to play an important role, both at the level of the sinoatrial node and through modulation of autonomic control of HR. Folic acid (FA) increases vascular NO levels. The modulatory effects of FA, ageing and exercise training on autonomic control of HR, are unknown. Thus, we tested the hypothesis that FA supplementation would increase cardiac parasympathetic modulation of HR in habitually trained and untrained middle‐aged men, with FA and exercise training eliciting greater increases than either exercise or FA alone.MethodsTwo groups of healthy, normotensive, age‐matched (55±3 years; overall mean±SEM), habitually endurance trained (n=14; VO2peak 49±1 ml/kg/min; MAtr;) and untrained (n=14; 37±1 ml/kg/min; MAun) men were studied. A comparator group of young (26±1 years) untrained (n=14; 50±1 ml/kg/min; YMun) men were also studied. Heart rate variability (HRV), an index of cardiac modulation of HR, was recorded during 7 minutes of supine rest using lead II of an ECG, both before and after 4 weeks of FA supplementation (5mg/day). Fast Fourier frequency domain measures were determined: high frequency (HF), low frequency (LF), and very LF (VLF). Due to skewness, HF, LF and VLF data were log transformed. LF:HF ratio and total (VLF+LF+HF) HRV were calculated. Circulating levels of folate, plasma nitrite, a stable metabolite of NO, were determined.ResultsAt baseline, HFlog, LFlog and Total HRV did not differ (p&gt;0.05) between MA groups, but were higher in YMun (p&lt;0.05). VLFlog, LF:HF, and folate levels did not differ (p&gt;0.05) between groups. Resting HR was lower (p&lt;0.05) in MAtr versus MAun, but did not differ (p&gt;0.05) between MAun and YMun. Nitrite levels were highest (p&lt;0.05) in MAtr.Post‐FAWithin‐groups, HFlog, LFlog, Total HRV and folate levels were increased (p&lt;0.05). LF:HF, VLFlog, HR and nitrite levels were unaltered (p&lt;0.05). Between‐groups, HFlog, LFlog, and Total HRV remained similar (0&gt;0.05) between MA groups, and higher (p&lt;0.05) in YMun. VLFlog, LF:HF, and folate levels did not differ (p&gt;0.05) between groups. Resting HR remained lower (p&lt;0.05) in MAtr versus MAun, and similar (p&gt;0.05) between MAun and YMun. Nitrite levels were higher (p&lt;0.05) in MAtr versus YMun.ConclusionWe report similar HF, LF and Total HRV, and lower resting HR, in trained versus untrained MA men. After four‐weeks of FA supplementation, HF, LF and Total HRV were increased, and HR unaltered, in both groups. These findings suggest cardiac parasympathetic control of HR does not differ between endurance trained and untrained MA men. In contrast, short‐term FA supplementation augments cardiac parasympathetic modulation in both groups. Further, exercise training and FA do not confer additive effects. Given the clinical significance of cardiac parasympathetic modulation of HR, FA may independently provide protective cardiac autonomic effects with healthy ageing in men.Support or Funding InformationThe research was supported by the National Institute for Health Research (NIHR) Leicester BRC.

High Levels of Peripheral Vasoconstriction Detected By Polysomnography Predict More Acute Severe Pain Episodes in Children with Sickle Cell Anemia

Sickle cell anemia (SCA) is genetic disease associated with chronic hemolysis and severe vaso-occlusive pain. Triggers for vaso-occlusive pain include both extreme temperatures (hot and cold), and stress. Our prior work demonstrates that anticipatory pain, experimental pain, experimental mental stress, and cold exposure cause significant global vasoconstriction in SCA and vasoconstriction responses differ among subjects.Anything that decreases microvascular flow will increase the likelihood that the red blood cells will not escape the microvasculature before deoxyhemoglobin S (HbS) polymerizes, leading to vaso-occlusion. However, this theoretical model has not been proven at a macro scale in patients. We showed that hypoxia induced in SCA subjects causes loss of parasympathetic modulation of heart rate but not decreased microvascular flow. Consistent with this, a prospective cohort study of SCA subjects showed no significant association between low mean nocturnal SpO2 and the incidence of VOC. However, surges in sympathetic activity accompany transient arousals and respiratory events during sleep, and lead to varying levels of peripheral vasoconstriction. In a prospective NIH funded cohort study of children with SCA, we tested the hypothesis that children with SCA and high levels when compared to low levels of intrinsic microvascular vasoreactivity (based on vasoconstriction events detected by polysomnography (PSG)) have a higher incidence rate of severe vaso-occlusive pain that requires hospitalization within 6 months of the PSG. We analyzed the time-series of R-R intervals (RRI) derived from the electrocardiogram and beat-to-beat amplitudes of finger photoplethysmography reflecting peripheral blood flow (PPGa) derived from the scored PSGs and clinical records of 212 children, who participated in the multi-center prospective SCA cohort study reported by Willen et al. (Am J Hematol 2018; 93:478-485). Vasoconstriction events were detected by applying an algorithm that found reductions in PPGa from local baseline that exceeded a threshold level of change. The changes in RRI from the pre-vasoconstriction baseline were also computed (Fig 1). The duration, average magnitude (Mvasoc) and area under the curve of PPGa were extracted from each significant vasoconstriction. The median values of these compact descriptors were taken to represent the nocturnal vasoconstriction characteristics of each participant. A participant was classified to be in the high- or low-pain event category if they were hospitalized for severe pain at least two times or less than 2 times within a 1-year window from 6 months before to 6 months after the PSG, respectively. Multiple logistic regression analysis was applied, using pain category as the outcome variable, and vasoconstriction descriptors, arousal index, obstructive apnea-hypopnea index, age, sex and hemoglobin level as predictor variables. Pain category was strongly associated with magnitude of vasoconstriction (Mvasoc; p=0.0058), with larger Mvasoc predicting high-pain, after accounting for age, sex and hemoglobin level (Hgb). Figure 2 displays the adjusted Mvasoc (mean ± SE) in the high-pain and low/no-pain groups. Mvasoc was strongly correlated with arousal index (p=0.0073). However, none of the traditional measures of sleep-disordered breathing, including arousal index, were associated with pain category. Age was the only other predictor of severe pain. These findings, showing that propensity for a high degree of microvascular vasoconstriction is associated with the temporal relationship of severe pain requiring hospitalization, validate on a macro scale the model that increased microvascular transit time promotes entrapment of sickled red blood cells, elevating the risk of severe vaso-occlusive pain. Our data reveals for the first time, a mechanistic link between the patient's symptoms and the triggering of transition from steady state to acute severe pain. The fact that individuals have intrinsic vasoreactivity phenotypes, that can be identified by analysis of the photoplethysmogram, provides yet another factor in acute vaso-occlusive pain. Autonomic balance and vasoreactivity likely contribute to known variability of the incidence rate of severe pain and represent another plausible target for therapeutic intervention. Disclosures Coates: apo pharma: Consultancy, Honoraria, Speakers Bureau; vifor: Consultancy, Honoraria; agios pharma: Consultancy, Honoraria; celgene: Consultancy, Honoraria, Other: steering committee of clinical study.

Low-Intensity Exercise Training Increases Heart Rate Variability in Patients With Peripheral Artery Disease

Patients with peripheral artery disease (PAD), consistent with others with atherosclerotic occlusive disorders, have autonomic dysfunction (as measured by low heart rate variability [HRV]) that predisposes them to sympathetically mediated cardiac arrhythmias and sudden death. Exercise therapy has been shown to increase HRV in patients with coronary artery disease by increasing parasympathetic modulation of heart rate. This study quantified the circulatory and autonomic effects of a progressive, 12-week home-based, low-intensity (pain-free walking) exercise program in PAD and intermittent claudication. Participants (N = 33, mean age 67.8 8.1 years) were randomly assigned to either a walking group (n = 18), whose members performed a structured, 12-week, progressive walking program 5 days/week for 12 weeks, or a comparison group (n = 15), whose members performed usual activities. Circulatory measures (heart rate, blood pressure, and rate pressure product) and autonomic measures (HRV) were obtained at the beginning (Week 1) and end (Week 12) of the study. Minimal change in circulatory measures occurred. However, spectral analysis of HRV revealed that autonomic function improved significantly in members of the walking group; specifically, there was an increase in parasympathetic and a decrease in sympathetic modulation. Members of the walking group also significantly increased maximal walking distance. These findings suggest that a structured, low-intensity, high-frequency walking program improves autonomic function by increasing HRV in patients with PAD.

Elastase-2, a Tissue Alternative Pathway for Angiotensin II Generation, Plays a Role in Circulatory Sympathovagal Balance in Mice.

In vitro and ex vivo experiments indicate that elastase-2 (ELA-2), a chymotrypsin-serine protease elastase family member 2A, is an alternative pathway for angiotensin II (Ang II) generation. However, the role played by ELA-2 in vivo is unclear. We examined ELA-2 knockout (ELA-2KO) mice compared to wild-type (WT) mice and determined whether ELA-2 played a role in hemodynamics [arterial pressure (AP) and heart rate (HR)], cardiocirculatory sympathovagal balance and baroreflex sensitivity. The variability of systolic arterial pressure (SAP) and pulse interval (PI) for evaluating autonomic modulation was examined for time and frequency domains (spectral analysis), whereas a symbolic analysis was also used to evaluate PI variability. In addition, baroreflex sensitivity was examined using the sequence method. Cardiac function was evaluated echocardiographically under anesthesia. The AP was normal whereas the HR was reduced in ELA-2KO mice (425 ± 17 vs. 512 ± 13 bpm from WT). SAP variability and baroreflex sensitivity were similar in both strains. The LF power from the PI spectrum (33.6 ± 5 vs. 51.8 ± 4.8 nu from WT) and the LF/HF ratio (0.60 ± 0.1 vs. 1.45 ± 0.3 from WT) were reduced, whereas the HF power was increased (66.4 ± 5 vs. 48.2 ± 4.8 nu from WT) in ELA-2KO mice, indicating a shift toward parasympathetic modulation of HR. Echocardiographic examination showed normal fractional shortening and an ejection fraction in ELA-2KO mice; however, the cardiac output, stroke volume, and ventricular size were reduced. These findings provide the first evidence that ELA-2 acts on the sympathovagal balance of the heart, as expressed by the reduced sympathetic modulation of HR in ELA-2KO mice.

Nonlinear causal influences assessed by mutual compression entropy

Abstract Autonomic control of the heart rate was demonstrated to be complex and nonlinear. Respiratory sinus arrhythima plays a crucial role in heart rate vagal modulation. Here we present an approach of assessing nonlinear causal relationships in bivariate time series, called mutual compression entropy (MCE). We applied MCE to cardiorespiratory data of 29 patients with acute schizophrenia and 29 matched controls. The method is based on data compression and estimates to which extend a (target) time series can be compressed regarding another time series (driver). In schizophrenia an elevated sympathetic and reduced parasympathetic heart rate modulation was found. The nonlinear influence of respiration on heart rate variability was demonstrated by a highly significant reduction of MCE (0.816 vs. 0.808, p¡0.01). In healthy subjects MCE was mainly related to sympathovagal balance. We conclude, that this index has the potential to uncover physiological information beyond linear measures.

Autonomic Findings in Takotsubo Cardiomyopathy

Takotsubo cardiomyopathy (TC) often occurs after emotional or physical stress. Norepinephrine levels are unusually high in the acute phase, suggesting a hyperadrenergic mechanism. Comparatively little is known about parasympathetic function in patients with TC. We sought to characterize autonomic function at rest and in response to physical and emotional stimuli in 10 women with a confirmed history of TC and 10 age-matched healthy women. Sympathetic and parasympathetic activity was assessed at rest and during baroreflex stimulation (Valsalva maneuver and tilt testing), cognitive stimulation (Stroop test), and emotional stimulation (event recall, patients). Ambulatory blood pressure monitoring and measurement of brachial artery flow-mediated vasodilation were also performed. TC women (tested an average of 37 months after the event) had excessive pressor responses to cognitive stress (Stroop test: p <0.001 vs baseline and p = 0.03 vs controls) and emotional arousal (recall of TC event: p = 0.03 vs baseline). Pressor responses to hemodynamic stimuli were also amplified (Valsalva overshoot: p <0.05) and prolonged (duration: p <0.01) in the TC women compared with controls. Plasma catecholamine levels did not differ between TC women and controls. Indexes of parasympathetic (vagal) modulation of heart rate induced by respiration and cardiovagal baroreflex gain were significantly decreased in the TC women versus controls. In conclusion, even long after the initial episode, women with previous episode of TC have excessive sympathetic responsiveness and reduced parasympathetic modulation of heart rate. Impaired baroreflex control may therefore play a role in TC.

Eyeball Pressure Stimulation Unveils Subtle Autonomic Cardiovascular Dysfunction in Persons with a History of Mild Traumatic Brain Injury.

After mild traumatic brain injury (mTBI), patients have increased long-term mortality rates, persisting even beyond 13 years. Pathophysiology is unclear. Yet, central autonomic network dysfunction may contribute to cardiovascular dysregulation and increased mortality. Purely parasympathetic cardiovascular challenge by eyeball pressure stimulation (EP), might unveil subtle autonomic dysfunction in post-mTBI patients. We investigated whether mild EP shows autonomic cardiovascular dysregulation in post-mTBI patients. In 24 patients (34 ± 12 years; 5-86 months post-injury) and 27 controls (30 ± 11 years), we monitored respiration, electrocardiographic RR intervals (RRI), systolic and diastolic blood pressure (BPsys, BPdia) before and during 2 min of 30 mm Hg EP, applied by an ophthalmologic ocular pressure device (Okulopressor(®)). We calculated spectral powers of RRI in the mainly sympathetic low frequency (LF; 0.04-0.15 Hz) and parasympathetic high frequency (HF; 0.15-0.5 Hz) ranges, and of BP in the sympathetic LF range, the RRI-LF/HF ratio as index of the sympathetic-parasympathetic balance, normalized (nu) RRI-LF- and HF-powers, and LF- and HF-powers after natural logarithmic transformation (ln). Parameters before and during EP in post-mTBI patients and controls were compared by repeated measurement analysis of variance with post hoc analysis (p < 0.05). During EP, BPsys and BPdia increased in post-mTBI patients. Only in controls but not in post-mTBI patients, EP increased RRI-HFnu-powers and decreased RRI-LF-powers, RRI-LFnu-powers, BPsys-LF-powers, BPsys-lnLF-powers and BPdia-lnLF-powers. RRI-LF/HF ratios slightly increased in post-mTBI patients but slightly decreased in controls upon EP. Even with only mild EP, our controls showed normal EP responses and shifted sympathetic-parasympathetic balance towards parasympathetic predominance. In contrast, our post-mTBI patients could not increase parasympathetic heart rate modulation but increased BP upon EP, indicating a paradox sympathetic activation. The findings support the hypothesis that central autonomic dysfunction might contribute to an increased cardiovascular risk, even years after mTBI.

Glycogen Synthase Kinase-3β Inhibition Ameliorates Cardiac Parasympathetic Dysfunction in Type 1 Diabetic Akita Mice

Decreased heart rate variability (HRV) is a major risk factor for sudden death and cardiovascular disease. We previously demonstrated that parasympathetic dysfunction in the heart of the Akita type 1 diabetic mouse was due to a decrease in the level of the sterol response element–binding protein (SREBP-1). Here we demonstrate that hyperactivity of glycogen synthase kinase-3β (GSK3β) in the atrium of the Akita mouse results in decreased SREBP-1, attenuation of parasympathetic modulation of heart rate, measured as a decrease in the high-frequency (HF) fraction of HRV in the presence of propranolol, and a decrease in expression of the G-protein coupled inward rectifying K+ (GIRK4) subunit of the acetylcholine (ACh)-activated inward-rectifying K+ channel (IKACh), the ion channel that mediates the heart rate response to parasympathetic stimulation. Treatment of atrial myocytes with the GSK3β inhibitor Kenpaullone increased levels of SREBP-1 and expression of GIRK4 and IKACh, whereas a dominant-active GSK3β mutant decreased SREBP-1 and GIRK4 expression. In Akita mice treated with GSK3β inhibitors Li+ and/or CHIR-99021, Li+ increased IKACh, and Li+ and CHIR-99021 both partially reversed the decrease in HF fraction while increasing GIRK4 and SREBP-1 expression. These data support the conclusion that increased GSK3β activity in the type 1 diabetic heart plays a critical role in parasympathetic dysfunction through an effect on SREBP-1, supporting GSK3β as a new therapeutic target for diabetic autonomic neuropathy.

Liraglutide increases 24-h heart rate by reducing the cardiac parasympathetic activity of patients with type 2 diabetes: power spectral analysis of heart rate variability on 24-h Holter ECG recordings

The effects of liraglutide, a glucagon-like peptide 1 receptor agonist, on heart rate over a 24-h period (24-h heart rate) and on parasympathetic modulation of heart rate among patients with type 2 diabetes were investigated by 24-h power spectral analysis (PSA) of heart rate variability. Seven consecutive male patients with type 2 diabetes received once-daily subcutaneous injection of liraglutide (0.9 mg). We performed 24-h Holter electrocardiographic recording at baseline and after treatment for 24 weeks. PSA revealed that R–R variability data were distributed in two bands: low-frequency (LF) and high-frequency (HF) power. Compared with baseline, heart rate after treatment for 24 weeks was higher at every hour, with a significant difference for 15 of the 24 h time points. LF power was significantly reduced at two measurement points, and HF power was significantly reduced at four points. In addition, heart rate was significantly increased at all points at which LF or HF power was significantly reduced after treatment with liraglutide for 24 weeks. In conclusion, liraglutide increases 24-h heart rate after treatment for 24 weeks, possibly by inhibiting cardiac parasympathetic (vagal) activity.

Relationship of Heart Rate Variability to Sleepiness in Patients with Obstructive Sleep Apnea with and without Heart Failure

Many patients with severe obstructive sleep apnea (OSA) do not complain of excessive daytime sleepiness (EDS), possibly due to increased sympathetic nervous activity (SNA) and accompanying heightened alertness. We hypothesized that in patients with OSA, those without subjective EDS (Epworth Sleepiness Scale, ESS score < 11) would have higher very low frequency (VLF) heart rate variability (HRV) during sleep, reflecting greater sympathetic heart rate modulation than patients with an ESS score ≥ 11. Patients with severe OSA (AHI ≥ 30: 26 with and 65 without heart failure) were divided into those with and without EDS. Heart rate (HR) signals were acquired in stage 2 sleep during periods of recurrent apneas and hypopneas and submitted to coarse graining spectral analysis, which extracts harmonic, neurally mediated contributions to HRV from total spectral power. Because the apnea-hyperpnea cycle entrains muscle SNA at VLF (0 to 0.04 Hz), VLF power was our principal between-group comparison. Subjects without EDS had higher harmonic VLF power (944 ± 839 vs 447 ± 461 msec(2), p = 0.003) than those with EDS, irrespective of the presence or absence of heart failure (1218 ± 944 vs 426 ± 299 msec(2), p = 0.043, and 1029 ± 873 vs 503 ± 533 msec(2), p = 0.003, respectively). ESS scores correlated inversely with VLF power in all (r = -0.294, p = 0.005) and in heart failure subjects (r = -0.468, p = 0.016). Patients with severe OSA but without EDS have higher VLF-HRV than those with EDS. This finding suggests that patients with severe OSA but without EDS have greater sympathetic modulation of HRV than those with EDS that may reflect elevated adrenergically mediated alertness. Taranto Montemurro L; Floras JS; Picton P; Kasai T; Alshaer H; Gabriel JM; Bradley TD. Relationship of heart rate variability to sleepiness in patients with obstructive sleep apnea with and without heart failure.

Caloric restriction may reverse age‐related autonomic decline in humans

Caloric restriction (CR) retards aging in laboratory rodents. No information is available on the effects of long-term CR on physiologic markers of aging and longevity in humans. Heart rate variability (HRV) is a marker for cardiac autonomic functioning. The progressive decline in HRV with aging and the association of higher HRV with better health outcomes are well established. Heart rate variability assessment is a reliable tool by which the effects of CR on autonomic function can be assessed. Time- and frequency-domain analyses compared 24-h HRV in 22 CR individuals aged 35-82 years and 20 age-matched controls eating Western diets (WD). The CR group was significantly leaner than the WD group. Heart rate was significantly lower, and virtually, all HRV values were significantly higher in the CR group than in the WD group (P < 0.002). Heart rate variability in the CR individuals was comparable with published norms for healthy individuals 20 years younger. In addition, when differences in heart rate (HR) and HRV between CR and WD were compared with previously published changes in HRV induced in healthy adults given atenolol, percent differences in each measure were generally similar in direction and magnitude and suggested declines in sympathetic and increases in parasympathetic modulation of HR and increased circadian variability associated with CR. These findings provide evidence that CR has direct systemic effects that counter the expected age-associated changes in autonomic function so that HRV indexes in CR individuals are similar to those of individuals 20 years younger eating WDs.

Relationship between social support and autonomic function during a stress protocol in ulcerative colitis patients in remission

The relationship of psychological stress to relapse in ulcerative colitis (UC) is inconsistent. This may be due to a failure to identify patient characteristics, such as social support, which moderate the transduction of stress from the central nervous system to the immune system. In this study we tested the hypothesis that social support enhances parasympathetic modulation of heart rate in UC. An indirect measure of autonomic function (heart rate variability; HRV) was measured in 108 patients with UC in remission during a standard protocol involving periods of stress, paced breathing, and relaxation. Social support was measured with the Social Support Questionnaire. After controlling for age, which is strongly related to HRV, both satisfaction with social support (F = 5.7, significance = 0.002) and its interaction with age (F = 7.8, significance <0.001) were associated with high-frequency HRV, which measures parasympathetic modulation of heart rate. Social support was associated with higher levels of high-frequency HRV at almost all points in the stress protocol. Neither age nor social support was associated with differences in the LF/HF ratio, which measures sympathetic modulation of heart rate. Social support is related to parasympathetic activity in UC. Given previous evidence of an antiinflammatory role for the parasympathetic nervous system, this suggests that autonomic function could serve as a mediating link between social support and reduced inflammatory activity.

Relationship between Malocclusion and Heart Rate Variability Indices in Young Adults

Heart rate variability (HRV) has been used to assess sympathetic and parasympathetic modulation of heart rate. Chronic stress relates to reduced HRV. Malocclusion has effects on quality of life, which can lead to chronic stress. Therefore, we hypothesized that malocclusion, as chronic stress, may contribute to reduced HRV. The aim of this study was to investigate the relationship between malocclusion and HRV indices in healthy young adults. Thirty-seven non-smoking healthy subjects, aged 22 to 25 years, were examined. Malocclusion was defined by Angle classification. HRV indices included root mean square of successive differences, low frequency (LF), high frequency (HF) and ratio of LF to HF. The effects of malocclusion on quality of life and mental health were assessed using self-reported questionnaires, the condition-specific Oral Impacts on Daily Performances index (CS-OIDP) and the Hopkins Symptoms Checklist (HSCL), respectively. Significantly lower score of HF and higher heart rate (HR) level and CS-OIDP score were observed in subjects with malocclusion (n = 17) compared to those in the control subjects (n = 20) ( P <0.05). There was a positive correlation between HR and score of "anxiety" in HSCL ( P <0.05). The data showed an association between malocclusion and lower HRV. Based on our results, orthodontic treatment might contribute not only to improvement of oral esthetic and functional problems but also to improvement of stress and HRV indices.

The Effect of Air Pollution on Spatial Dispersion of Myocardial Repolarization in Healthy Human Volunteers

We tested the hypothesis that exposure to concentrated ambient particles (CAP) and/or ozone (O(3)) would increase dispersion of ventricular repolarization. Elevated levels of air pollution are associated with cardiac arrhythmias through mechanisms yet to be elucidated. Each of 25 volunteers (18 to 50 years of age) had four 2-h exposures to 150 μg/m(3) CAP; 120 parts per billion O(3); CAP + O(3); and filtered air (FA). Exposure-induced changes (Δ = 5-min epochs at end-start) in spatial dispersion of repolarization were determined from continuous 12-lead electrocardiographic recording. Spatial dispersion of repolarization assessed by corrected ΔT-wave peak to T-wave end interval increased significantly for CAP + O(3) (0.17 ± 0.03, p < 0.0001) exposure only, remaining significant when factoring FA (CAP + O(3) - FA) as control (0.11 ± 0.04, p = 0.013). The influence on repolarization was further verified by a significant increase in ΔQT dispersion (for CAP + O(3) compared with FA (5.7 ± 1.4, p = 0.0002). When the low-frequency to high-frequency ratio of heart rate variability (a conventional representation of sympathetic-parasympathetic balances) was included as a covariate, the effect estimate was positive for both corrected ΔT-wave peak to T-wave end interval (p = 0.002) and ΔQT dispersion (p = 0.038). When the high-frequency component (parasympathetic heart rate modulation) was included as a covariate with corrected ΔT-wave peak to T-wave end interval, the effect estimate for high frequency was inverse (p = 0.02). CAP + O(3) exposure alters dispersion of ventricular repolarization in part by increasing sympathetic and decreasing parasympathetic heart rate modulation. Detection of changes in repolarization parameters, even in this small cohort of healthy individuals, suggests an underappreciated role for air pollutants in urban arrhythmogenesis.

Differential Effects of Statins ( Pravastatin or Simvastatin) on Ventricular Ectopic Complexes: Gα i2, a Possible Molecular Marker for Ventricular Irritability

Retrospective studies suggest that statins might exert an antiarrhythmic effect on the heart. The mechanism of this effect is unclear. Parasympathetic stimulation of the heart has been shown to protect against ventricular arrhythmias. The goal of this study was to determine the effect of statins on ventricular arrhythmias and its correlation with changes in parasympathetic responsiveness and Galpha(i2) expression. Patients were randomized to pravastatin and simvastatin in a double-blind crossover design. Ventricular arrhythmias were determined by analysis of 24-hour Holter recordings. Spectral RR interval analysis of Holter studies determined peak high-frequency power fraction, which reflects parasympathetic modulation of heart rate. Expression of Galpha(i2), a molecular component of the parasympathetic response pathway, was determined by Western blots of patients' lymphocytes. Pravastatin treatment decreased the incidence of ventricular premature complexes by 22.5 + or - 3.4% (n = 20, p <0.05), couplets, and runs of 3 to 6 beats of nonsustained ventricular tachycardia from 9.8 + or - 2.67 to 3.9 + or - 1.25 events/patient/24 hours (n = 12, p <0.05). Pravastatin increased peak high-frequency fraction by 29.8 + or - 4.3% (n = 33, p <0.001), while Galpha(i2) expression increased by 51.3 + or - 22.5% (n = 21, p <0.05). Effects of simvastatin on ventricular premature complexes and nonsustained ventricular tachycardia were not significant. Relative changes in couplets and nonsustained ventricular tachycardia in pravastatin-treated patients correlated negatively with changes in Galpha(i2) and high-frequency fraction (rho = -0.588 and rho = -0.763, respectively, n = 12, p <0.05). In conclusion, these data suggest that pravastatin might decrease cardiac irritability via an increase in parasympathetic responsiveness and that changes in Galpha(i2) expression might serve as a molecular marker for this effect, which might play a role in the molecular mechanism of the antiarrhythmic effect of statins.