Bepridil Inhibits Premature Ventricular Complexes Induced by Cardio-Sympathetic Nerve Stimulation in a Canine Experimental Model.

Sympathetic nerve activity has arrhythmogenic potential for ventricular arrhythmias associated with structural heart diseases. However, a sufficient amount of beta-blockers occasionally cannot be prescribed in some patients.An experimental study was performed to clarify the therapeutic effects of bepridil, a multiple ionic current inhibitor that does not affect beta-adrenergic receptors, for premature beats occurring during enhanced sympathetic nerve activity. Cardio-sympathetic nerve activity was augmented via stellate-ganglion (SG) stimulation in a canine model (n = 8), and the arrhythmogenic potential and anti-arrhythmic effects of bepridil (2 and 4 mg/kg intravenously) were assessed. For safe use, vagal-stimulation-induced slow HR and programmed electrical stimulation were applied to evaluate possible pro-arrhythmic effects of the drug. Heart rate variability (HRV) indexes were used to estimate cardio-autonomic nerve activity.Either side of the SG-stimulation increased BP and HR. Premature beats were induced in 10/16 SG-stimulations and it was more frequent in left (8/8) rather than right stimulation (2/8). Following 2 mg/kg drug administration, premature beats were still inducible in 8/16 stimulations (7/8 in left and 1/8 in right), but burden of the premature beats decreased from 87.1 ± 46.8 to 62.1 ± 42.6 beats. After 4 mg/kg administration, premature beats were inducible in one SG-stimulation. Proarrhythmic effects were not observed in all experiments. Steady-state HRV indexes and percent increases in SG-stimulation-induced BP-elevation and HR-acceleration were similar among the 3 periods (before, 2 and 4 mg/kg of the drug).Bepridil may be an option for ventricular arrhythmias developed during enhanced cardio-sympathetic nerve activity with minimal effect on autonomic nerve responses.

Regional differences in facial skin blood flow responses to thermal stimulation.

PURPOSE: The facial skin blood flow (SkBF) shows regional differences in the responses to a given stimulation. The facial SkBFs, especially in the eyelid and nose exhibit unique response to physiological and psychological stimuli, but the mechanisms inducing those regional differences remain unclear. To investigate whether the regional differences in the local control of vasomotion in facial vessels correspond to the regional differences in facial SkBF response, we monitored the relative change of facial SkBF to regional thermal stimulation. We hypothesized that heat stimulation dilates the cutaneous vessels in the eyelid, while cold stimulation constricts those in the nose, which was based on previous findings METHODS: A thermal stimulator was used to apply temperature increase (from 20 to 40 °C at 2 °C/min) and decrease (from 40 to 20 °C at 2°C/min) in a randomized order to the right eyelid, nose, right cheek, and forehead of 14 healthy young males. The facial SkBF was measured for 10 s using laser-speckle flowgraphy when temperatures of 20 °C, 30 °C, and 40 °C had been applied for 30 s in both trials. RESULTS: The SkBF in the eyelid did not change significantly during any thermal stimulation, and the nasal SkBF did not decrease significantly during cold stimulation. The SkBFs in the cheek and forehead increased significantly with the applied temperature. CONCLUSIONS: These findings indicate that a large regional variation exists in facial skin blood flow response to local heating or cooling and that the regional variation did not correspond to the unique SkBF responses in the previous studies.

Effects of cigarette smoking on ambulatory blood pressure, heart rate, and heart rate variability in treated hypertensive patients.

We investigated the influence of cigarette smoking on the levels and circadian patterns of blood pressure (BP), heart rate (HR), and HR variability (HRV) in hypertensive patients. Sixteen hypertensive smokers (57 ± 2 years old) receiving antihypertensive treatments participated in this study. Ambulatory monitoring of BP, HR, and electrocardiograms was performed every 30 min for 24 hours on a smoking day and nonsmoking day in a randomized crossover manner. Average 24-hour BP and daytime BP were significantly higher in the smoking period than in the nonsmoking period. No significant differences were observed in nighttime BP between the two periods. Average 24-hour and daytime HR, but not nighttime HR, were also higher in the smoking period than in the nonsmoking period. The daytime high frequency (HF) component of HRV was attenuated more in the smoking period than in the nonsmoking period. No significant differences were observed in the low frequency (LF) components of HRV or LF/HF ratio between the two periods. These results demonstrated that cigarette smoking increased the daytime and average 24-hour BP and HR, and the increases observed in daytime BP and HR were associated with the attenuation of parasympathetic nerve activity.

Crossover trial of the effects of a far-infrared heater that heats the feet with ceramic balls on autonomic nervous activity and mood states.

INTRODUCTION: The accumulation of fatigue and stress creates problems, including reductions in quality of life and productivity. OBJECTIVES: To investigate the effects of a far-infrared heater that heats the feet with ceramic balls on autonomic nervous activity and mood states. METHODS: This study was performed as a crossover trial. Participants comprised 20 women. On different days, each participant underwent 15 min of foot warming with the far-infrared heater (far-infrared group) or remained seated for 15 min (control group). Autonomic nervous activity (low-frequency component/high-frequency component, high-frequency) and mood states scales (Profile of Mood States Second Edition and Two-Dimensional Mood Scale for Self-monitoring and Self-regulation of Momentary Mood States) during the study intervention were measured and compared between groups. RESULTS: Low-frequency/high-frequency was significantly higher in the control group 10 min after the start of intervention than at baseline (P = .033). Low-frequency/high-frequency was significantly lower in the far-infrared group than in the control group at 5 min (P = .027), 10 min (P = .011), and 15 min (P = .015). High-frequency was significantly higher in the far-infrared group at 5 min (P = .008), 10 min (P = .004), and 15 min (P = .015) than at baseline. High-frequency 5 min after the start of intervention was significantly higher in the far-infrared group than in the control group (P = .033). POMS2 scores improved significantly more in the far-infrared group than in the control group, including in fatigue-inertia (P = .019), tension-anxiety (P = .025), and total mood disturbance (P = .019). Finally, the far-infrared group showed greater improvements in Two-Dimensional Mood Scale-Short Term scores such as stability (P = .002) and pleasure (P = .013). CONCLUSION: Using the far-infrared heater to heat the feet with ceramic balls stabilized and improved mood, reduced Fatigue-Inertia and Tension-Anxiety, and alleviated total mood disturbance. Parasympathetic nervous system activation was observed from 5 min after the start of heating, suggesting that short-duration heat stimulation of the feet is effective.

C-fos expression in the solitary nucleus medial region and reaction to acute hemorrhage in streptozotocin-stimulated diabetic rats.

Examination of circulatory dynamics and autonomic nerve activity in acute hemorrhage in diabetic (DM) rats revealed that despite decreased receptor sensitivity to arterial blood pressure, the DM rats experienced a decline in the heart rate and acceleration of the parasympathetic nerve activity at the sympathoinhibitory phase in response to bleeding (Bezold-Jarisch [B-J] reflex). To elucidate the involvement of the B-J reflex as a reaction to acute hemorrhage in DM rats by assessing c-Fos-positive cell (c-Fos) expression in the nucleus of the solitary tract (SolM), the primary relay nucleus of the baroreflex, Streptozotocin-induced DM and non-DM rats underwent controlled-graded bleeding or continuous phenylephrine infusion under conscious state. Changes in hemodynamics and autonomous nervous system caused by acute hemorrhage and continuous phenylephrine infusion were examined by analyzing blood pressure-heart rate variability. Furthermore, effects of hemorrhage and phenylephrine infusion on the expression of c-Fos in SolM were examined. DM rats showed increased c-Fos expression in response to acute blood loss in the SolM. Non-DM rats showed the same phenomenon in response to continuous phenylephrine infusion in the SolM. Significant interactions between DM and Non-DM rats were observed among hemodynamic and autonomic response to acute hemorrhage and continuous phenylephrine infusion. DM rats were sensitive to acute blood loss, and the circulatory system easily collapsed with accelerating parasympathetic activity in the form of the B-J reflex.

A Workcation Improves Cardiac Parasympathetic Function during Sleep to Decrease Arterial Stiffness in Workers.

A "Workcation" (combining work and vacation) has become increasingly common. Traditionally, the workcation focus has been on productivity; however, data showing associations between workcations and improvements in employees' health are lacking. Therefore, this study examines the effects of a workcation on blood pressure, arterial stiffness, heart rate, autonomic nervous system function, and physical activity. Twenty healthy employees participating in a five-day workcation project at a large private company agreed to participate in this study. Data on arterial stiffness, heart rate, autonomic nerve activity, and physical activity were collected before, during, and after the workcation. Arterial stiffness, blood pressure, and heart rate significantly decreased (p < 0.05); meanwhile, physical activity levels and parasympathetic function during sleep significantly increased during the workcation (p < 0.05). Thus, a workcation implies a new way of working that improves employees' cardiovascular indices and parasympathetic function during sleep.

Vagal nerve stimulation preserves right ventricular function in a rat model of right ventricular pressure overload.

Vagal nerve stimulation (VNS) ameliorates pulmonary vascular remodeling and improves survival in a rat model of pulmonary hypertension (PH). However, the direct impact of VNS on right ventricular (RV) function, which is the key predictor of PH patients, remains unknown. We evaluated the effect of VNS among the three groups: pulmonary artery banding (PAB) with sham stimulation (SS), PAB with VNS, and control (no PAB). We stimulated the right cervical vagal nerve with an implantable pulse generator, initiated VNS 2 weeks after PAB, and stimulated for 2 weeks. Compared to SS, VNS increased cardiac index (VNS: 130 ± 10 vs. SS: 93 ± 7 ml/min/kg; p < 0.05) and end-systolic elastance assessed by RV pressure-volume analysis (VNS: 1.1 ± 0.1 vs. SS: 0.7 ± 0.1 mmHg/µl; p < 0.01), but decreased RV end-diastolic pressure (VNS: 4.5 ± 0.7 vs. SS: 7.7 ± 1.0 mmHg; p < 0.05). Furthermore, VNS significantly attenuated RV fibrosis and CD68-positive cell migration. In PAB rats, VNS improved RV function, and attenuated fibrosis, and migration of inflammatory cells. These results provide a rationale for VNS therapy as a novel approach for RV dysfunction in PH patients.

The Elevated Central Chemosensitivity in Obstructive Sleep Apnea Patients with Hypertension.

Purpose: Hypertension is a common comorbidity in obstructive sleep apnea (OSA), in which dysfunction of the autonomic nervous system plays an integral part. Chemoreflex is essential for ventilatory control and cardiovascular activity. This study aimed to determine whether central chemosensitivity was increased in OSA patients with hypertension and the potential role of the autonomic nerve activity in this relationship. Patients and Methods: A total of 77 men with OSA were included in this cross-sectional study. We measured hypercapnic ventilatory response (HCVR) by the rebreathing method under isoxic hyperoxia to test the central ventilatory chemosensitivity since hyperoxia silences the peripheral chemoreceptors' response to CO2. To elevate the autonomic nerve activity, time-domain, frequency-domain, and non-linear variables of heart rate variability were calculated over 5-min records. Univariate and multivariate linear regression analyses were used to find the determinants of HCVR. Results: The median HCVR was 2.3 (1.8, 3.3), 2.1 (1.6, 3.0), and 3 (2.2, 3.7) L/min/mmHg in all participants, OSA patients, and OSA patients with hypertension, respectively. Hypertension was significantly associated with elevated HCVR after adjusting for age, central obesity, OSA severity, daytime sleepiness, and diabetes mellitus. Compared with OSA patients, OSA patients with hypertension had higher body mass index, worse nocturnal hypoxia, and lower time-domain variables and frequency-domain variables. After adjusting for age, apnea-hypopnea index, central obesity, and beta-blocker usage, approximate entropy was independently negatively associated with HCVR in OSA patients with hypertension. Conclusion: This study demonstrated elevated central chemosensitivity in OSA patients with hypertension. Compared with OSA patients, OSA patients with hypertension had attenuated parasympathetic nerve activity. This study preliminarily illustrated that elevated central chemosensitivity might be associated with weak adaptability of the cardiac autonomic nervous system in OSA patients with hypertension.

The characteristics and efficacy of catheter ablation of focal atrial tachycardia arising from an epicardial site.

BACKGROUND: Although epicardial structures around the atrium such as adipose tissue possess arrhythmogenicity, little is known about atrial tachycardias (ATs) originating from epicardial sites (Epi-ATs). This study aimed to elucidate the prevalence, characteristics, and outcome after radiofrequency catheter ablation (RFCA) of Epi-ATs and to reveal the association between Epi-ATs and the epicardial structures. METHODS: The electrocardiographic, electrophysiologic, and anatomical properties and results of RFCA were analyzed in 42 patients with a total of 49 ectopic ATs. RESULTS: Six Epi-ATs (12%) were observed in six patients (14%). Four of six were respiratory cycle-dependent ATs and one was a swallowing-induced AT. The Epi-AT origins were adjacent to a pulmonary vein (five cases) and vein of Marshall (one case). A Valsalva maneuver or atropine infusion to define the arrhythmia mechanism affected the appearance of the Epi-ATs. The congruity rate between epicardial adipose tissue and the AT origin was significantly higher (100% vs. 44%, p = .045), and the epicardial adipose tissue volume of the atrium was significantly larger (104.1 vs. 64.6 ml, p = .04) in the Epi-AT group. Endocardial RFCA targeting the AT foci resulted in acute success in five of five cases. However, electrical isolation including of the AT foci resulted in acute failures (two of three cases) or a recurrence (one of one case). CONCLUSIONS: Six Epi-ATs were associated with thoracic veins and epicardial arrhythmogenic structures. The main cause provoking the Epi-ATs was associated with autonomic nerve activity.

Effects of ethyl hexanoate on activities of sympathetic nerves innervating the brown and white adipose tissues, body temperature, and plasma fatty acids.

The autonomic nervous system (ANS) is implicated in maintaining homeostasis of the internal environment in mammals. Therefore, changes occurring in the ANS can cause alterations of physiological phenomena. Ethyl hexanoate (EH) is known as the aroma component of apples. To study the action of ethyl hexanoate on physiological phenomena, we examined the effect of an intragastric (IG) injection of 1 mL/kg body weight of 0.1 ppm EH solution on sympathetic nerve activity innervating the brown adipose tissue (BAT) and white adipose tissue (WAT) in anesthetized rats. Consequently, IG administration of EH increased activity of the sympathetic nerves innervating both the BAT and WAT. In addition, the effects of the IG injection on body temperature above the interscapular BAT and plasma free fatty acid (FFA) concentration were also examined in conscious rats. In this attempt IG injection of EH elevated both the body temperature and plasma FFA levels. Furthermore, subdiaphragmatic vagotomy eliminated the effects of EH on sympathetic nerves innervating BAT and WAT. These findings suggest that EH causes excitations of sympathetic nerves innervating BAT and WAT, and enhances thermogenesis and lipolysis via the afferent vagus nerve. Thus, these present findings also suggest the possibility that EH might have anti-obesity effects.

ß-eudesmol, an oxygenized sesquiterpene, affects efferent adrenal sympathetic nerve activity via transient receptor potential ankyrin 1 in rats.

The autonomic nervous system innervates various peripheral tissue functions. Various external stimuli affect autonomic nerve activity, however, there is little information about the involvement of sensory receptors in the responses. The TRPA1 is a calcium-permeable non-selective cation channel which plays a crucial role in the susceptibility to various stimuli. ß-Eudesmol, an oxygenated sesquiterpene found in hop essential oil and beer, activates the TRPA1. Intragastric administration of ß-eudesmol decreased efferent adrenal sympathetic nerve activity (ASNA) in rats, whereas subcutaneous administration did not. ASNA suppression by ß-eudesmol was not observed in TRPA1 knockout rats. The ß-eudesmol derived ASNA suppression was partially, but significantly, eliminated by subdiaphragmatic vagotomy in rats, suggesting the afferent vagal nerve from the gastrointestinal tract to the brain is involved in the effect of ß-eudesmol on ASNA. Our results indicate that ß-eudesmol suppresses ASNA, partly through TRPA1 and the afferent vagus nerve. These findings introduce the physiological significance of the TRPA1 in the control of ASNA.

Effect of ghrelin on autonomic activity in healthy volunteers.

Ghrelin is a novel growth hormone (GH)-releasing peptide originally isolated from the stomach. Recently, we have shown that ghrelin suppresses cardiac sympathetic activity and prevents early left ventricular remodeling in rats with myocardial infarction. In the present study, we evaluated the effect of ghrelin on autonomic nerve activity in healthy human subjects. An intravenous bolus of human synthetic ghrelin (10µg/kg) was administered to 10 healthy men (mean age, 33 years). Holter monitoring assessment was performed before and during 2h after the ghrelin therapy. The standard deviation of normal RR intervals (SDNN), square root of the mean of the sum of the squares of differences between adjacent RR intervals (rMSSD), high-frequency power (HF), and low-frequency power (LF) were analyzed. Blood samples were also obtained before and after the therapy. A single administration of ghrelin decreased both heart rate and blood pressure. Interestingly, ghrelin significantly decreased the LF and LF/HF ratio of heart rate variability and increased the SDNN, rMSSD, and HF. Ghrelin also elicited a marked increase in circulating GH, but not insulin-like growth factor-1. These data suggest that ghrelin might suppress cardiac sympathetic nerve activity and stimulate cardiac parasympathetic nerve activity.

"Effect of ""brisk walking"" on male elderly with hypertension in community-based health centers" / 上海交通大学学报（医学版）

Objective · To explore the effects of brisk walking on blood pressure, body mass index (BMI), and autonomic nerve activity of male elderly with hypertension in community-based health centers in Shanghai. Methods · A total of 630 elderly men received brisk walking treatment (>10000 steps/d) voluntarily, who were selected from six community-based health centers in Pudong New Area of Shanghai. Among them, 210 people stick to training for 12 weeks. According to whether suffering from hypertension, the people were assigned to hypertension intervened group (intervention group, n=110) and normal intervened group (control group 1, n=100). Blood pressure, BMI, heart rate and autonomic nerve activity before and after the training were compared. Results · After 12 weeks of training, systolic blood pressure (SBP), diastolic blood pressure (DBP) and sympathetic nerve activity of intervention group were significantly lower than those before the training (P0.05). Conclusion · Brisk walking treatment lasting for 12 weeks can decrease blood pressure and sympathetic nerve activity in elderly men with hypertension. It is worthy to be popularized in the community.

Effect of autonomic nerve activity on emotion experience: an empirical study / 中华行为医学与脑科学杂志

Objective To study the effect of autonomic nerve activity on emotion experience.Methods 71 healthy males were asked to see a neutral film STICK and conduct a computer game,then evaluated emotion experience.All participants were recorded skip temperature,skin conduction,heart rate,LF and HF during baseline and game periods.Results (1) There was significant difference in fear experience among high,middle and low synchronous groups (2.64 ± 2.05,2.50 ± 2.01,4.46 ± 2.41; P＜ 0.01),and low synchronous group was significantly higher than high synchronous group (P ＜ 0.01).The main effects of three periods were significant in basis of three response types of autonomic nerve activity(skin conduction:F(2.68) =76.083,P＜0.01; heart rate:F(2.68) =71.692,P ＜ 0.01),and skip temperature,skin conduction and heart rate were no significant difference among three response types.Types and periods had no significant interaction.(2) Different response modes of autonomic nervous system has different distributions in high fear and low fear groups (x2 =9.763,P ＜ 0.01).Skip temperature,skin conduction and heart rate were no significant difference between high fear group and low fear group.Conclusion The modes of autonomic nervous system have an effect on intensity of fear experience,but not the same in skip temperature,skin conduction and heart rate.

Obesity and cardiac autonomic nerve activity in healthy children: Results of the toyama birth cohort study.

OBJECTIVES: To determine the relationship between obesity and cardiac autonomic nerve activity in healthy children. METHODS: 16 healthy male children comprising of 9 nonobese and 7 obese subjects (body mass index > 19.1 kg/m(2)) aged 8-9 years were selected. Electrocardiograms were measured for 10 min. under controlled ventilation (0.25 Hz) in the supine position. Consecutive 256-second RR interval data were transformed by the Fast Fourier Transform method into power spectral data. Very low frequency (VLF; 0.003-0.04 Hz), low frequency (LF; 0.04-0.15Hz), high frequency (HF; 0.15-0.40Hz), and total power (TP; 0.003-0.40Hz) were calculated and transformed into a natural logarithm (In). Normalized units (nu) were also calculated as follows: LFnu=LF/(TP-VLF)x100. HFnu=HF/(TP-VLF)x100. Low/high-frequency ratio (LHR) was calculated as LF divided by HF. Unpaired t test was performed to compare the 2 groups. RESULTS: TP In and HFnu, reflecting cardiac parasympathetic nerve activity, in obese children were significantly lower than those in nonobese children. In contrast, LFnu and LHF, reflecting cardiac sympathetic nerve activity, in obese children were significantly higher than those in nonobese children. CONCLUSIONS: These findings suggest that obese children have higher sympathetic nerve activity and lower parasympathetic nerve activity than nonobese children.

Obesity and Cardiac Autonomic Nerve Activity in Healthy Children: Results of the Toyama Birth Cohort Study

Objectives: To determine the relationship between obesity and cardiac autonomic nerve activity in healthy children. Methods: 16 healthy male children comprising of 9 nonobese and 7 obese subjects (body mass index > 19.1 kg/m2) aged 8−9 years were selected. Electrocardiograms were measured for 10 min. under controlled ventilation (0.25 Hz) in the supine position. Consecutive 256-second RR interval data were transformed by the Fast Fourier Transform method into power spectral data. Very low frequency (VLF; 0.003−0.04 Hz), low frequency (LF; 0.04−0.15 Hz), high frequency (HF; 0.15−0.40 Hz), and total power (TP; 0.003−0.40 Hz) were calculated and transformed into a natural logarithm (ln). Normalized units (nu) were also calculated as follows: LFnu = LF / (TP - VLF) x 100. HFnu = HF / (TP - VLF) x 100. Low/high-frequency ratio (LHR) was calculated as LF divided by HF. Unpaired t test was performed to compare the 2 groups. Results: TP ln and HFnu, reflecting cardiac parasympathetic nerve activity, in obese children were significantly lower than those in nonobese children. In contrast, LFnu and LHF, reflecting cardiac sympathetic nerve activity, in obese children were significantly higher than those in nonobese children. Conclusions: These findings suggest that obese children have higher sympathetic nerve activity and lower parasympathetic nerve activity than nonobese children.