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The JT interval of the myocardial repolarization time can be divided into Jpoint to T-peak interval (JTp) and T-peak to T-end interval (Tpe). It is well known that the JT interval is dependent on the heart rate, but little is known regarding heart rate dependence for JTp and Tpe. The aim of the present study was to clarify the heart rate dependence of JTp and Tpe and to elucidate the interference of autonomic nervous activity with these parameters.We evaluated 50 prepubertal children (mean age: 6.4 ± 0.5 years; male:female, 22:28) without heart disease. JTp, Tpe, and the preceding RR intervals were measured using 120 consecutive beats (lead CM5). First, the relationships between the RR interval and JTp and Tpe were evaluated by Pearson's correlation coefficient. Second, to evaluate autonomic interference with JTp and Tpe, the degree of coherence between RR interval variability and JTp or Tpe variability was calculated using spectral analysis.Significant positive correlations were observed between the RR interval and JTp (y = 0.116x + 105.5; r = 0.594, p0.001) and between the RR interval and Tpe (y = 0.037x + 44.7; r = 0.432, p0.001). Tpe variability had a lower degree of coherence with RR interval variability (range: 0.039-0.5 Hz) than with JTp variability (0.401 [interquartile range, 0.352-0.460] vs. 0.593 [0.503-0.664], respectively; p0.001).Tpe had lower heart rate dependence and a lower degree of autonomic nervous interference than did JTp.

BACKGROUND CONTEXT Lumbar autonomic nerve injury is an underappreciated complication of anterior lumbar spinal surgery. A detailed description of lumbar autonomic nerve anatomy would be helpful for surgeons to minimize the risk of this complication. PURPOSE This study was designed to investigate the anatomical characteristics of lumbar autonomic nerves and provide a better understanding of these nerves for anterior lumbar spinal surgery. STUDY DESIGN A dissection-based study of 10 embalmed male cadavers. METHODS The lumbar autonomic nerves from 10 embalmed male cadavers were dissected in this study. The position of the lumbar sympathetic trunks was recorded. Distance between the initial sites of the lumbar splanchnic nerves (LSNs) and the corresponding lumbar vertebral inferior endplate, distance between the ipsilateral and adjacent LSNs, angles formed by the LSNs and the vertical axis were measured. This study has been supported by grants from Science and Technology Planning Project of Guangdong Province (CN) (Grant No. 2017B020210010 ) without potential conflict of interest-associated biases in the text of the paper. RESULTS In this study, a total of 72 LSNs were identified in the 10 human cadavers. On average, the investigation found that the initial sites of the first, second, third, and fourth LSNs were 9 mm distal, 5 mm distal, 9 mm proximal, and 9 mm distal to the inferior endplates of the L1, L2, L3, and L4 vertebrae, respectively, with variations from 6 to 11 mm for each nerve among specimens. There was no significant difference in the angle between each lumbar splanchnic nerve and the vertical axis (H=2.461, p=.482), with an angle of approximately 50°±6°. The distance between the first and the second LSNs, the second and the third LSNs, or the third and the fourth LSNs were 24±6 mm, 22±8 mm, and 55±11 mm, respectively. The bilateral lumbar sympathetic trunks (N=57, 95%) were more likely to be located in the first third of the sagittal plane at the level of the L2/3, L3/4, and L4/5 intervertebral discs. CONCLUSIONS The study found the same number and parallel courses of LSNs on each side, and on both the left and right side, the distance between the third and the fourth LSNs was much larger than the distance between the other two adjacent LSNs. The initial sites of 80.6% (n=58) of LSNs were superior to the inferior endplate of the L3 vertebra. Improved knowledge of lumbar autonomic nerve anatomy may be of great significance in reducing complications and improving surgical safety.

Imbalance of autonomic nerve is the cause of lots of cardiovascular and psychological diseases. Many studies have shown that Heart Rate Variability Biofeedback through respiratory training is an effective way to regulate the status of human autonomic nerves. However, due to the immature quantification of Respiratory Sinus Arrhythmia, the respiratory training process cannot be optimal personalized. In this paper, we propose the Cardiopulmonary Resonance Indices based on the Cardiopulmonary Coupling Model to calculate the personalized optimal breathing training frequency. Then the respiratory feedback training system is constructed to provide real-time audio-visual guidance for each subject. The results in the clinical trial of pregnant women in their third trimester showed that, compared to control group, with the intervention of personalized respiratory feedback training at home, pregnant women could stabilize their blood pressure and blood glucose, relieve mental stress, as well as exert positive effects on fetal development. This provides a new possibility of the autonomic imbalance treatment.

Objective Circumferential pulmonary vein isolation (CPVI) is a common procedure that is performed on patients with atrial fibrillation (AF). However, AF may recur in some patients after treatment. This study assesses the association between autonomic modulation and late recurrence after CPVI and between autonomic modulation and ablation lesion quality. Methods We prospectively enrolled 72 patients with paroxysmal AF who underwent CPVI from January 2017 to January 2018. Pre- and post-ablation 24 h electrocardiograms were performed to document heart rate variability (HRV), which represents cardiac autonomic function. The intraablation force-time integral (FTI) was used to indicate the extent of ablation injury. Patients were followed up for 12 months after the procedure and cases of AF recurrence were recorded. Results Changes in HRV decreased after the procedure, which was correlated with FTI (ΔSDNN: r = −0.26, P = 0.03; ΔrMMSD: r = −0.28, P = 0.02; ΔlnHF: r = −0.22, P = 0.04; ΔLnLF: r = −0.29, P = 0.01). Patients without AF recurrence had more pronounced ΔLF (−21.84 ± 33.21% vs. −8.68 ± 34.59%, P = 0.01) and ΔHF (−17.26 ± 16.61% vs. −1.28 ± 9.81%, P = 0.01) than patients with recurrence. Multivariate regression analysis showed that both ΔLF (HR: 1.07, P = 0.04) and ΔHF (HR: 1.11, P = 0.01) were associated with AF recurrence. After adjusting for FTI, ΔLF was no longer associated with AF recurrence (HR: 1.05, P = 0.10). ΔHF remained associated with AF recurrence (HR: 1.08, P = 0.03), but the correlation coefficient was decreased (HR: 1.08, P = 0.03). Conclusion Decreased autonomic nerve function is a valid predictor of AF recurrence and is indicated by the extent of ablation injury, which is independently associated with AF recurrence after CPVI.

Background Renal artery catheter ablation has been reported as a possible therapeutic option for drug-refractory ventricular arrhythmias (VAs) associated with structural heart diseases. Objective To further clarify its therapeutic background, we examined the relationship between electrical nerve stimulation (ENS)–induced blood pressure (BP) elevation and occurrence of VAs by using an acute canine model of renal artery ablation. Methods Using a decapolar electrode catheter, ENS was successively applied from the distal, mid, and proximal segments of the renal artery in 8 beagles. The same ENS was repeated after accomplishment of radiofrequency ablation at the ostial site of the renal artery by using an irrigation catheter. Results Before ablation, ENS increased BP from 140 ± 11/77 ± 11 to 167 ± 20/98 ± 16 mm Hg and heart rate from 100 ± 21 to 131±33 beats/min as well as induced VAs in 20 of the 45 ENS applications. Occurrence of VAs was associated with a greater magnitude of sympathetic nerve augmentation, and VAs were more frequently observed by ENS at the distal (67%) rather than mid/proximal segments of the renal artery (33%). Renal artery ablation was accomplished without any angiographic stenosis, and ENS-induced BP elevation, heart rate acceleration, and VAs occurrence were attenuated not only at the close segment (proximal) but also at the remote segments (mid/distal) of the renal artery. Conclusion The renal autonomic nerves are considered as one of the therapeutic targets for suppression of frequent VAs because its activation has arrhythmogenic potential and induces premature ventricular beats.

Aims It is known that autonomic nerve activity (ANA) affects glucose metabolism by regulating the secretion of insulin and glucagon. Sympathetic nerve stimulation results in increased blood glucose levels. ANA also showed a circadian variation, and sympathetic nerve activity was minimal at night and began to rise at arousal. Therefore, a drastic alteration in ANA around wake-up would be associated with glycemic variability (GV) known risk factor for cardiovascular disease. We investigated the relation between ANA around wake-up and either morning or daily GV. Methods We simultaneously performed Holter ECG and continuous glucose monitoring system in 41 patients with type 2 diabetes (T2D). ANA was assessed by heart rate variability (HRV) analysis. Delta (Δ) wake-up was defined as the difference between the maximum and minimum value during 1 h before and after wake-up time, before breakfast. Results Δ of low frequency/high frequency (LF/HF) around wake-up time (Δ LF/HF wake-up) was positively associated with Δ glucose wake-up, standard deviation (SD) glucose wake-up, the mean amplitude of glucose excursions (MAGE24h), and SD glucose24h after adjustment for age, sex, BMI, the duration of diabetes, and the prevalence of diabetic polyneuropathy (β = 0.47, p = 0.011, β = 0.48, p = 0.009, β = 0.54, p = 0.002 and β = 0.41, p = 0.0025, respectively). No association was found between Δ LF/HFwake-up and either mean blood glucose for 24 h, or HbA1c as parameters of chronic hyperglycemia. Conclusions In T2D, the fluctuation in fasting sympathetic nerve activity around wake-up was positively associated with not only morning but also daily GV.

Paragangliomas are rare and highly vascularized neuroendocrine tumors originating from neural crest-derived paraganglionic tissue surrounding the autonomic nerve. In this case, we report a nonfunctional paraganglioma located in the right supraclavicular fossa. Both computed tomography and paraffin-embedded sections diagnosed paraganglioma. The paraganglioma was presumed to be derived from the paraganglia of the right cervical parasympathetic nerve and primarily supplied by the right subclavian artery. Because of the abundant blood supply, we performed arterial embolization before the operation. This ectopic paraganglioma is considered a rare report of a paraganglioma supplied by the subclavian artery. Keywords: Ectopic paraganglioma, Subclavian artery, Embolization

Background Imbalanced activation of the cardiac autonomic nervous system triggers postoperative atrial fibrillation (POAF). Neuronal calcium overload induces apoptosis. We hypothesize that epicardial injection of timed-release nanoformulated CaCl2 (nCaCl2) into left atrial ganglionic plexi (GP) modulates autonomic function and suppresses POAF. Objective The purpose of this study was to determine whether nCaCl2 GP therapy suppresses POAF. Methods We used a novel canine model of POAF with implanted radiotelemetry to record nerve activity (NA) from the left stellate ganglion (SNA), left cardiac vagus nerve, and GP. At week 3, nCaCl2 (n = 7) or vehicle control (sham; n=3) was injected into left pulmonary vein GP (LGP), followed by right pulmonary vein GP at week 4. Atrial effective refractory period (AERP) and atrial fibrillation vulnerability (AFV) were assessed in vivo. Resting and exercise NA and heart rate (HR) were assessed before and after LGP treatment. Results AERP decreased (P Conclusion Epicardial injection of nCaCl2 into left atrial GP induced neuroapoptosis and modulated autonomic function. This reversed a postoperative reduction in AERP and suppressed POAF.

In the mechanisms of acupuncture analgesia, an important aspect often overlooked is the anti-inflammatory effect of acupuncture, which is mainly attained through the self-limiting inflammatory response-inflammatory reflex and its regulation of hypothalamic-pituitary-adrenal(HPA) axis and autonomic nerve system (the vagus nerve and the sympathetic postganglionic fiber). The significance of anti-inflammatory effect of acupuncture in analgesia is manifested twofold: The first, inflammatory nociceptive pain is a major type of chronic pain. The second, neurogenic inflammation is the mechanism by which certain acupoints or acu-reflex points (ARPs) are formed at the body surface and have short-cut connections to the pathological focus. Selecting ARPs and applying appropriate sensory stimulation or local microtrauma (affected by different needling means or stimulation parameters), combined with low-frequency electrical stimulation or the vagus stimulation in the concha region, are helpful to strengthen the anti-inflammatory and analgesic effect of acupuncture.

Objective To observe the differences in the effects and mechanisms on chronic gastritis treated by ginger-isolated moxibustion at Zusānlĭ (足三里ST 36) and Neiguān (内关PC 6). Methods A total of 60 eligible patients of chronic gastritis were randomized into two groups, a ST 36 group (ginger-isolated moxibustion at ST 36, 30 cases) and a PC 6 group (ginger-isolated moxibustion at PC 6, 30 cases). Before and after 6 treatments, the total variability of heart rate (TV) and the scores in Scale for gastrointestinal diseases of traditional Chinese medicine were determined and recorded. Using correlation analysis, the hidden correlation condition that affects the therapeutic outcomes was excavated from the data. With least square method, the gradient curve (K value) of TV in treatment was estimated and the correlation between the effect mechanism and autonomic nerve regulation was excavated. Results ① In ST 36 group, the duration of sickness, severity of disease and the activity of autonomic nerve before treatment presented the underlying correlation with the therapeutic effects. In contrast, the hidden correlation in PC 6 group was not clear. ② In ST 36 group, the higher K value of TV in treatment was, the more significant the therapeutic effects were, but in PC group, K value was reversely related to the therapeutic effects. Conclusion The therapeutic effects of ginger-isolated moxibustion at single acupoint are correlated with the duration and severity of sickness. The therapeutic effects in ST 36 group were improved by the modulation of autonomic nerve activity and the effects in PC 6 group were negatively correlated with autonomic nerve activity. It is deduced that the effect mechanisms are different on single acupoint for chronic gastritis between the two points.

Study Objective To describe the anatomical and technical highlights of a novel nerve-sparing surgery for deep endometriosis (DE) using near-infrared (NIR) fluorescence technology and indocyanine green (ICG). Design Stepwise demonstration of a technique. Setting An urban general hospital. ICG is a fluorescent dye that allows accurate, intraoperative, real-time assessment of tissue vascularization, once excited with light of a specific wavelength in the near-infrared spectrum. NIR fluorescence technology and ICG have been confirmed as feasible, safe, and useful tools to guide surgery in several settings, including colorectal and urologic surgeries. However, no reports have discussed pelvic autonomic nerve-sparing surgery using this tool in the gynecological field. Patients or Participants Stage IV endometriosis patients with parametrial involvement. Interventions An intravenous injection of 0.25mg/kg body weight of ICG for intraoperative NIR fluorescence imaging. Pelvic autonomic nerves were highlighted by ICG because these nerves are surrounded by many capillaries. Measurements and Main Results Evaluation of blood perfusion of DE nodules and achieving better visualization of anatomical relationship to the pelvic autonomic nerves. We could easily identify ischemic nodules which included DE and fibrosis under NIR fluorescence imaging, beyond the limits of macroscopic disease. Endometriosis or fibrosis was confirmed pathologically from all resected tissues, and resection margins of these tissues were negative for disease. These results suggest that this technique might be feasible for objectively identifying the border between DE lesions and healthy tissue. Furthermore, the hypogastric nerve and inferior hypogastric plexus were strongly highlighted by ICG and objectively preserved with assessment of perfusion. The patients developed no perioperative complications, including postoperative bladder or rectal dysfunction after surgery. Conclusion Application of ICG with NIR fluorescence appears potentially useful, not only to remove DE, but also to improve nerve-sparing. To our knowledge, this is the first reported use of ICG during pelvic autonomic nerve-sparing surgery for gynecologic disease.

The heart rate variability (HRV) signals can well reflect the effect of exercise on cardiac autonomic nerve function, which can be used as the theoretical index for the development of the best physical exercise program. In this paper, we used multifractal detrended fluctuation analysis (MF-DFA), mass index spectrum and multifractality spectrum to analyze the heart rate variability signals, which have been obtained in these states, such as before, during and after exercise. The purpose is to establish the relationship between the nonlinear parameter of the signals and the autonomic nerve regulation, reveal the physiological mechanism for the effect of circadian rhythm. The result shows that exercise can decrease the correlation and increase the multifractality of heart rate variability signals. In different periods, the diversity of correlation and multifractality among different signals are obviously. The result shows that the correlation of heart rate variability signals was negatively correlated with sympathetic nerve regulation and positively correlated with vagus nerve regulation; the multifractality was positively correlated with sympathetic nerve regulation and negatively correlated with vagus nerve regulation. Further studies show that the function of heart system and the balance of autonomic nerve in the afternoon are more suitable for high-intense physical exercise.

Objective We used functional magnetic resonance imaging to provide a longitudinal description of cortical plasticity caused by electroacupuncture (EA) of sciatic nerve transection and direct anastomosis in rats. Methods Sixteen rats in a sciatic nerve transection and direct anastomosis model were randomly divided into intervention and control groups. EA intervention in the position of ST-36, GB-30 was conducted continuously for 4 months in the intervention group. Functional magnetic resonance imaging and gait assessment were performed every month after intervention. Results The somatosensory area was more activated in the first 2 months and then deactivated in the rest 2 months when EA was applied. The pain-related areas had the same activation pattern as the somatosensory area. The limbic/paralimbic areas fluctuated more during the EA intervention, which was not constantly activated or deactivated as previous studies reported. We attributed such changes in somatosensory and pain-related areas to the gradual reduction of sensory afferentation. The alterations in limbic/paralimbic system might be associated with the confrontation between the upregulating effect of paresthesia or pain and the downregulating effect of EA intervention through the autonomic nerve system. The gait analysis showed significantly higher maximum contact mean intensity in the intervention group. Conclusions The alterations in the brain brought about by the long-term therapeutic effect of EA could be described as a synchronized activation pattern in the somatosensory and pain-related areas and a fluctuating pattern in the limbic/paralimbic system.

The brain activity involved mental stress can increase the risk of sudden cardiac death in patients with organic and ischemic heart disease. Thus, the interaction between the senior nerve and autonomic nerve has recently been given more attention. The purpose of this study was to analyze the cortico-cortical functional coupling and direction of information flow between the brain and heart during a mental arithmetic (MA) task. Forty-three healthy male volunteer participated in the study. Functional coupling patterns of cerebral cortex and heart activity were determined by directed transfer function (DTF) and corrected conditional entropy (CCE). The experimental results showed that sympathetic activity increased, parasympathetic activity and heart rate variability (HRV) decreased, and the heart rate increased during the was quickened by MA task. Furthermore, a reciprocal pattern was observed in the changes of the autonomic nervous system. Meanwhile, cortico-cortical functional coupling was stronger during the MA task. Activity directed to post-central areas of brain and heart localized to the C4 and Cz regions. Our findings suggest that a stress-inducing mental task may cause an increase in the coupling of brain regions and an increase in heart rate though the increase of sympathetic activity.

Background Salivary gland maturation and function are modulated by the nervous system. Nevertheless, little is known about salivary gland innervation during development, particularly minor salivary glands. This study investigated the development of the innervation of the palatine glands of rat. Materials and methods Frozen sections of rat palatine glands at different stages were immunohistochemically labeled for detection of the general nerve markers protein gene product 9.5 (PGP 9.5) and growth associated protein 43 (GAP-43), and the autonomic nerve markers calcitonin gene-related peptide (CGRP) and neuropeptide Y (NPY). Results PGP 9.5 and GAP-43-immunoreactive fibers (IRF) were present in the mesenchyme and in association with developing acini, ducts and blood vessels. GAP-43-IRF were more abundant and diffuse than PGP 9.5-IRF at early stages, but showed similar distribution with growth, ramifying out from thick bundles in connective tissues until encircling the secretory units observed around postnatal day 21 (PN21). CGRP-IRF were detected in the mesenchyme at embryonic day 20 (E20) and PN0. CGRP-IRF became numerous around PN7 and PN10. They then decreased to the adult level at PN21, mainly located around ducts and infrequently blood vessels. NPY-IRF were sparsely detected in the mesenchyme at E20, then detected in close proximity to acini in addition to blood vessels at PN3. NPY-IRF increased till reaching the adult stage, and were mainly associated with blood vessels and around mucous cells and some serous demilunes. Conclusion The findings indicated a developmental modification of the sensory and autonomic innervation which may play a role in the functional maturation of the palatine salivary glands.

Radical resection for rectal cancer with total mesorectal excision has been widely recognized in mid-low rectal cancer. Although such surgery reduced the tumor recurrence rate and improved the survival rate of patients, the rate of urinary and sexual dysfunction was high after rectal cancer surgery, which might be attributed to pelvic autonomic nerve injury. The present study found that the pelvic autonomic nerves never exist alone. These are always surrounded by tiny capillaries and adipose tissue and covered by a thin layer of membranous tissue, leading to a continuous plane that should be preserved pelvic autonomic nerve from thermal damage, ischemic injury, nerve stretching, and chemical factors produced by local inflammatory effects. However, the completeness of the continuous plane is easily damaged intraoperatively in routine total mesorectal excision in rectal cancer. Postoperative urinary and sexual dysfunction might be closely associated with the injury of continuous plane. Therefore, the continuous plane should be protected and considered as the optimal surgical plane for rectal cancer surgery.

Obstructive sleep apnea (OSA) is a serious sleep disorder, which leads to changes in autonomic nerve function and increases the risk of cardiovascular disease. Heart rate variability (HRV) has been widely used as a non-invasive method for assessing the autonomic nervous system (ANS). We proposed the two-dimensional sample entropy of the coarse-grained Gramian angular summation field image (CgSampEn2D) index. It is a new index for HRV analysis based on the temporal dependency complexity. In this study, we used 60 electrocardiogram (ECG) records from the Apnea-ECG database of PhysioNet (20 healthy records and 40 OSA records). These records were divided into 5-min segments. Compared with the classical indices low-to-high frequency power ratio (LF/HF) and sample entropy (SampEn), CgSampEn2D utilizes the correlation information between different time intervals in the RR sequences and preserves the temporal dependency of the RR sequences, which improves the OSA detection performance significantly. The OSA screening accuracy of CgSampEn2D (93.3%) is higher than that of LF/HF (80.0%) and SampEn (73.3%). Additionally, CgSampEn2D has a significant association with the apnea-hypopnea index (AHI) (R = −0.740, p = 0). CgSampEn2D reflects the complexity of the OSA autonomic nerve more comprehensively and provides a novel idea for the screening of OSA disease.

Introduction To establish an animal model for diabetic peripheral neuropathy (DPN) at an earlier stage, we performed functional and pathophysiological evaluations in Spontaneously Diabetic Torii (SDT) fatty rats before 16 weeks of age. Methods Male SDT fatty rats were treated with vehicle or phlorizin (100 to 150 mg/kg/day) from 5 to 16 weeks. Sprague-Dawley (SD) rats were used as age-matched controls. Body weights and biochemical parameters were measured over time. During the treatment period, the sensory and motor nerve conduction velocity (SNCV and MNCV) of the sciatic nerve, blood pressure, pupil size, and electrocardiograms were measured. At 16 weeks, the rats were sacrificed and sural nerves and intraepidermal nerves were sampled for histological studies, electron microscopic analysis and assessments of nerve fiber density. Results Functional abnormalities, such as delays of SNCV, increase of blood pressure, reduced pupillary reactivity, and decrease of the coefficient of variance of R-R intervals were observed in SDT fatty rats. Histopathologically, decreased intraepidermal nerve fiber density, mitochondrial abnormalities of small myelinated fibers, and vacuolation and mitochondrial swelling of unmyelinated fibers were found in SDT fatty rats. These changes were prevented by well-controlled blood glucose with phlorizin treatment. Discussion Male SDT fatty rats can help future work on DPN in diabetes with obesity, since this rat exhibited functional and pathological abnormalities in somatic and autonomic nerve from an early stage of diabetes.

Highlights • Cardiovascular autonomic nerve function (i.e. E/I ratio) deteriorates over time in type 1 diabetes. • HSP27, MIF and PAI-1 concentrations do not correlate with cardiovascular autonomic nerve function. • The change in HbA1c correlates negatively with the change in E/I over time. • Higher HbA1c is associated with worse cardiovascular autonomic nerve function., Aim Diabetes mellitus type 1 (T1D) has numerous complications including autonomic neuropathy, i.e. dysfunction of the autonomous nervous system. This study focuses on Heat Shock Protein 27 (HSP27), Macrophage Migration Inhibitory Factor (MIF), Plasminogen Activator Inhibitor-1 (PAI-1) and HbA1c and their possible roles in effects of diabetes on the autonomic nervous system. Methods Patients with T1D (n = 32, 41% women) were recruited in 1985 and followed up on four occasions (1989, 1993, 1998, and 2005). Autonomic function was tested using expiration/inspiration (E/I-ratio). Blood samples, i.e. HSP27 (last three occasions), MIF, PAI-1 (last two occasions) and HbA1c (five occasions), were analyzed. Results Autonomic nerve function deteriorated over time during the 20-year-period, but levels of HSP27, MIF, and PAI-1 were not associated with cardiovascular autonomic neuropathy. MIF and PAI-1 were lower in T1D than in healthy controls in 2005. Increased HbA1c correlated with a decrease in E/I-ratio. Conclusions Neither the neuroprotective substance HSP27 nor the inflammatory substances, MIF and PAI-1 were associated with measures of cardiovascular autonomic nerve function, but a deterioration of such function was observed in relation to increasing HbA1c in T1D during a 20-year follow-up period. Improved glucose control might be associated with protection against autonomic neuropathy in T1D.

Aims To investigate whether the expression of nerve growth factor precursor (proNGF) changes during cardiopulmonary bypass (CPB) and whether neutralizing interleukin-6 (IL-6) during CPB has cardiac benefits. Main methods Thirty patients undergoing CPB were recruited and their serum proNGF and troponin-I (TNI) were detected. In addition, rats were divided into three groups: CPB group, CPB with cardiac ischemia–reperfusion (IR) group, and a control group. The pre-CPB standard deviation of N-N intervals (SDNN) and post-CPB SDNN were compared. At the end of CPB, nerve peptide Y (NPY), acetylcholinesterase, cell apoptosis, and proNGF protein expression were measured in the heart and hypothalamus. Another rat cohort undergoing CPB was divided into two groups: an anti-IL-6 group with IL-6 antibody and a control group with phosphate buffer solution. At the end of CPB, serum hs-troponin-T and cardiac caspases 3 and 9 were detected. NPY and proNGF in the heart and hypothalamus were detected. Key findings In patients, serum proNGF increased during CPB, and the concentration was positively correlated with TNI. In rats, cardiac autonomic nervous function was disturbed during CPB. More apoptotic cells and higher levels of proNGF were found in the heart and hypothalamus in the CPB groups than in the control groups. Neutralizing IL-6 was beneficial to lower cardiac injury by decreasing proNGF and apoptosis. Significance CPB induced changes in proNGF in the heart and hypothalamus. Suppressing inflammation attenuated myocardial apoptosis and autonomic nerve function disturbance in CPB rats, likely due in part to regulation of proNGF in the heart and hypothalamus.

Objectives Surviving long lasting cardiac arrest following accidental hypothermia has been reported after treatment with extra corporeal life support (ECLS), but there is a risk of neurologic injury. Most surviving hypothermia patients have a prolonged stay in the intensive care unit, where most patients experience polyneuropathy. Theoretically, accidental hypothermic cardiac arrest may in itself contribute to polyneuropathy. This study was designed to examine the impact of three hours of cardiac arrest at a core temperature of 20 °C followed by reanimation of peripheral nerve function. Methods Seven pigs were cannulated for ECLS and cooled to a core temperature of 20 °C followed by three hours of circulatory arrest where the extremities were packed with ice. After three hours, ECLS was started and rewarming was performed. During the process, neural testing of the ulnar nerve (a somatic nerve) and of the vagus nerve (an autonomic nerve) were performed and blood was drawn for analysis of p-potassium, serum-neuron-specific enolase, and S100b protein. Results The ulnar nerve was cooled from 34.9±1.6 °C to 12.8±3.8 °C and the vagus nerve from 36.2±1.2 °C to 15.4±1.4 °C. Physiologic function of both somatic and autonomic nerves were strongly affected by cooling, but recovered to almost normal levels during rewarming, even after three hours of hypothermic cardiac arrest. P-potassium rose from 3.9 (3.6–4.6) mmol/l to 8.1 (7.2–9.1) mmol/l after three hours of cardiac arrest, but normalized after recirculation. There was no rise in serum-neuron-specific enolase, but a slight rise in S100b protein during three hours of hypothermic cardiac arrest was observed. All pigs obtained return of spontaneous circulation (ROSC). Conclusions Reanimation after three hours of hypothermic cardiac arrest using ECLS was possible with no or, if present, minor damage to the two nerves tested.

Background Autonomic remodeling, characterized by sympathetic activation and vagal withdrawal, contributes to heart failure (HF) progression. However, the exact mechanism(s) responsible for vagal withdrawal in HF remain(s) unclear, and whether HF causes epicardial autonomic nerve remodeling is unknown. Methods and results Myocardial infarction (MI) was produced in 14 Sprague–Dawley rats, and 10 sham surgery rats served as the control. MI–HF was confirmed 2 months after the surgery by echocardiography and hemodynamic measurement. Cervical vagal nerve stimulation was delivered to examine the heart rate slowing effect. Whole heart acetylcholinesterase histochemistry was used to examine the epicardial autonomic nerve remodeling at dorsal ventricles (remote from the infarcted area). Compared with the control animals, the same vagal nerve stimulation had less heart rate slowing effect in MI–HF group. Both epicardial nerve bundle length-density (2.56±0.60 μm/mm 2 versus 1.68±0.46 μm/mm 2 , P =.001) and branching point-density (1.24±0.25 points/mm 2 versus 0.66±0.18 points/mm 2 , P Conclusions Whole heart acetylcholinesterase histochemistry revealed a decreased ventricular epicardial vagal nerve density in MI–HF rats, which may contribute to impaired cardiac vagal control in HF.

This study developed a new method using radiopaque markers under X-ray to measure rat colonic transit by geometric center repeatedly and/or over a time series in the same individually. Additionally, the utility of this method was shown by elucidating the innervation of the autonomic nerve on colonic transit in detail with a pharmacological technique in conscious rats. An in-dwelling silastic cannula was inserted into the cecum and the proximal part was moved through the abdominal wall, where it was fixed to the posterior neck skin. Twenty markers were administered from the cannula to the proximal colon with saline on the fifth day after surgery. The markers were observed with soft X-ray before required repeated short anesthesia. Experimentation 1: Rats were measured colonic transit twice over 2 days with no administration. Experimentation 2: Rats were administered saline on the first day and pharmacology on the second day intraperitoneally before measurement. Experimentation 1: The markers administrated from the cannula and transited from proximal colon to distal colon over a time series. It showed no significant difference in complication rates between 2 days. Experimentation 2: The colonic transit was increasingly accelerated by neostigmine and phentolamine but not propranolol. Significant changes in 1.0 mg/kg atropine were noted although no differences were found between control and 0.05 mg/kg atropine and between each other's. We have presented the method using radiopaque markers under X-ray with short anesthesia for evaluating the colonic transit. The methods could show rat colonic transit changes in detail with a pharmacological technique.

Low-level carotid baroreflex stimulation (LL-CBS) appears to have a potential antiarrhythmogenic effect.The purpose of this study was to investigate effects of short-term LL-CBS on an atrial fibrillation (AF) canine model.Group 1 (LL-CBS in the 6 hour-rapid atrial pacing model): Anesthetized dogs underwent 6 hours of rapid atrial pacing (RAP) with concomitant LL-CBS in last 3 hours (LL-CBS group; n = 7) or without (control group; n = 6). Effective refractory period (ERP), ERP dispersion, and window of vulnerability to AF were determined. Left stellate ganglion (LSG) neural activity and heart rate variability were analyzed. Group 2 (LL-CBS on electrically or mechanically induced AF with acetylcholine): In subgroup 1, sustained AF was induced by injecting acetylcholine (Ach; 10 mM) into the anterior right ganglionated plexus at baseline and after 3-hour LL-CBS (n = 7) or sham operation (n = 6). In subgroup 2, Ach was applied onto the right atrial appendage. The time of duration of AF and the average AF cycle length were determined in both subgroups.Group 1: LL-CBS reversed the RAP-induced ERP shortening and increase in ERP dispersion and window of vulnerability (P.05). The activation of LSG, decrease in high frequency, and increase in low frequency and low frequency/high frequency ratio induced by RAP were also reversed by LL-CBS (P.05). After 6-hour RAP, plasma norepinephrine and angiotensin II concentrations were significantly lower in the LL-CBS group than in the control group (P.05). Group 2: The AF duration was shortened and the average AF cycle length was prolonged markedly in both subgroups (P.01) by LL-CBS.LL-CBS can reverse RAP-induced atrial electrical remodeling and suppress electrically or mechanically induced AF with Ach, and the anti-AF effect is attributed to attenuation of autonomic nerve remodeling, including inhibition of the LSG activity.

Background CO 2 -pneumoperitoneum can cause sympathetic nerve activity increased and is likely to causes severe stress-related homeostatic disorders. Objective Patients undergoing elective laparoscopic cholecystectomy were administered type-B ultrasound-guided stellate ganglion block (SGB) to observe the effects on autonomic nervous system during CO 2 - pneumoperitoneum. Design A randomized, double-blinded, and placebo-controlled study. Setting University-affiliated teaching hospital. Patients Eighty patients (aged 32-75 years; weight, 45-80 kg; American Society of Anesthesiologists (ASA) physical status classification, class I or II) undergoing elective laparoscopic cholecystectomy. Interventions The RSGB group was administered lidocaine 1% 7 ml under ultrasound guidance. Main outcome measures The low frequency (LF), high frequency (HF), total power (TP) and LF/HF ratio were recorded before the block (T 0 ), 5 min (T 1 ) and 30 min (T 2 ) following pneumoperitoneum, 5 min after deflation of pneumoperitoneum (T 3 ) and after surgery (T 4 ). The low-frequency normalized unit (LFnu) and high-frequency normalized units (HFnu) were calculated. Results Compared with T 0 , LF, LFnu and LF/HF ratio were significantly elevated at T 1 - 4 (all P 2 - 4 in control group ( P P P 1 - 4 in RSGB group. Compared with control group, the LF, LFnu and LF/HF ratio were significantly decreased ( P P 1 - 4 in RSGB group. Conclusion Ultrasound-guided RSGB inhibited CO 2 -pneumoperitoneum-induced sympathetic neural excitation, upregulated vagal nerve stimulation and maintained stable autonomic nervous function.

Background Catheter ablation of the renal artery can be performed without apparent angiographic stenosis. This suggests that renal nerve function can be attenuated with minor structural damage to the renal artery. Objective To clarify this hypothesis, we examined the relationship between electrical nerve stimulation (ENS)–induced blood pressure (BP) response and severity of histological injury of the renal artery using an acute canine model of renal artery ablation. Methods An irrigation catheter was inserted into the renal arteries of 8 dogs, and radiofrequency current was delivered at 15, 20, or 25 W. ENS was applied to each artery before and after ablation. Results Before ablation, ENS increased the BP and heart rate from 145 ± 15/86 ± 13 to 189 ± 21/111 ± 19 mm Hg and from 116 ± 9 to 130 ± 6 beats/min, respectively. Heart rate variability indices and serum catecholamine levels were elevated concomitantly. After ablation, the ENS-induced increase in BP and heart rate were markedly attenuated after 15 W ablation and those were nearly completely inhibited after 20 or 25 W ablation. An increase in heart rate variability indices and serum catecholamine levels became insignificant regardless of the applied energy. Renal artery angiograms revealed stenotic lesions only after 25 W ablation procedures. Histological studies showed mild to moderate injury of the arterial wall and autonomic nerves caused by 20 and 25 W ablation procedures, whereas only minor changes caused by 15 W ablation. Conclusion Functional renal autonomic nerve ablation is potentially performable with the guidance of ENS.

Sudden cardiac death as a result of lethal ventricular arrhythmias is a major cause of death in cardiac diseases such as heart failure and prior myocardial infarct. Activity of the autonomic nervous system is often abnormal where sympathetic activity is upregulated and vagal activity reduced in these conditions. The abnormal autonomic state has been shown to be a strong prognostic marker of increased mortality and propensity to lethal arrhythmias, for which there is no effective prevention. Research effort over the years has established good evidence for a causal link between autonomic disturbance and ventricular arrhythmias. However, the detailed electrophysiological mechanisms by which ventricular fibrillation occurs are still not clear and molecular processes which are modulated by autonomic nerve influences that either predispose the heart to or protect it from these arrhythmias are not fully understood. This review presents data from studies investigating the link between activity of the autonomic nervous system and ventricular arrhythmias, from seminal findings in classical studies to ongoing investigations, in the quest for a better understanding of the arrhythmogenic mechanisms underlying neurocardiac interactions with a view to the development of effective preventative and therapeutic strategies which are very much needed.

Aims Osteopontin (OPN) and osteoprotegerin (OPG) are bone metabolism biomarkers potentially associated with nerve function. We evaluated the association of cardiovascular autonomic nerve function, OPN, and OPG in 50 individuals with type 2 diabetes mellitus (T2DM). Methods RR-variation during deep breathing (i.e., mean circular resultant (MCR) and expiration/inspiration (E/I) ratio) was used to assess parasympathetic nerve function. Participants' demographics, HbA1c, 25-hydroxyvitamin D (25(OH)D), BMI, HOMA-IR, calcium, parathyroid hormone, creatinine, OPN, and OPG were determined. Results Using stepwise multiple linear regression analysis with MCR or E/I ratio as the dependent variable, OPN was independently associated with reduced autonomic function. A previous report showed a significant association of cardiovascular autonomic function with age, 25(OH)D insufficiency, and the interaction of age×25(OH)D insufficiency. Here we report a novel association for OPN and its interaction with age indicating that for those who are younger, elevated OPN levels are related to a greater loss of autonomic function (MCR model R 2 =0.598, p 2 =0.594, p Conclusion Our results suggest that OPN is associated with reduced parasympathetic function, particularly in younger individuals with T2DM. Further studies are needed to determine if OPN is neuroprotective, involved in the pathogenesis of autonomic dysfunction, or a bystander.

Despite therapy advances in the management of heart failure, symptomatic congestion and low cardiac output in acute heart failure is a leading cause of mortality and morbidity. The purpose of this study was to investigate transvenous cardiac autonomic nerve stimulation (CANS) effects on in-hospital hemodynamics and signs and symptoms of congestion. The study was a single-center, observational, clinical investigation of CANS. Twelve subjects with left ventricular ejection fraction (LVEF)

The effects of continuous vagal nerve stimulation (VNS) on atrial neural remodeling during atrial fibrillation (AF) remain unclear.To test the hypothesis that VNS affects atrial neural remodeling and reduces AF inducibility.Twenty rabbits were randomly divided into two groups: rapid atrial pacing (RAP) group and RAP with VNS group. AF inducibility studies and atrial histologic analyses were performed after 4 weeks.Five rabbits of RAP group (5/10) in the RAP group developed sustained AF. None of rabbits in RAP with VNS group had developed AF. The incidence of sustained AF in VNS group was significant lower than that in rapid pacing group (P.01). Treatment with VNS resulted in a significant reduction in atrial neural remodeling and AF duration (P.01).Atrial neural remodeling plays an important role in the initiation and maintenance of AF. Modulating autonomic nerve function with VNS can contribute to AF control.

Motor abnormalities of the small and large intestine are common in both functional and organic gastrointestinal disorders. However, the presence of some of these patterns of dysmotility in healthy controls, the absence of correlation with symptoms, and the poor response to treatments has raised questions as to whether these are epiphenomena rather than pathophysiologically relevant events. This is especially the case in functional disorders, such as irritable bowel syndrome and slow-transit constipation, where disturbances of sensitivity and autonomic nerve activity are also important. In motility disorders with an organic basis, such as chronic intestinal pseudo-obstruction and Hirschsprung's disease, the presence of predictable abnormalities of colonic and small bowel motility has helped define the condition. Radiological proof of dilated small bowel remains the diagnostic gold standard of these conditions but serial MRI techniques are proving increasingly useful in the diagnosis and measurement of small bowel motility. The advent of prokinetic drugs that target gut serotonin may lead to the specific reduction of dysmotility and the symptoms it causes. Furthermore, recognition of the interplay between motility and sensory function in functional and organic gastrointestinal disorders has suggested a therapeutic role for electrical neuromodulation of spinal and gut reflexes.

An α2A-adrenergic agonist guanfacine improves autonomic imbalance in attention-deficit hyperactivity disorder, suggesting that it may be useful to correct autonomic imbalance in chronic heart failure (CHF) patients. To investigate the effects of guanfacine on cardiac autonomic nerve activities, a microdialysis technique was applied to anesthetized rabbit heart. Acetylcholine (ACh) and norepinephrine (NE) concentrations in atrial dialysates were measured as indices of cardiac autonomic nerve activities. Guanfacine at a dose of 100 μg/kg significantly decreased heart rate and increased dialysate ACh concentration without decreasing sympathetic NE release. Guanfacine may be useful for vagal activation therapy in CHF patients.

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.

The relationship between cardiac autonomic nerve activity and blood pressure (BP) changes in ambulatory dogs is unclear.The purpose of this study was to test the hypotheses that simultaneous termination of stellate ganglion nerve activity (SGNA) and vagal nerve activity (VNA) predisposes to spontaneous orthostatic hypotension and that specific β₂-adrenoceptor blockade prevents the hypotensive episodes.We used a radiotransmitter to record SGNA, VNA, and BP in eight ambulatory dogs. Video imaging was used to document postural changes.Of these eight dogs, five showed simultaneous sympathovagal discharges in which the minute-by-minute integrated SGNA correlated with integrated VNA in a linear pattern (group 1). In these dogs, abrupt termination of simultaneous SGNA-VNA at the time of postural changes (as documented by video imaging) was followed by abrupt (20 mm Hg over four beats) drops in BP. Dogs without simultaneous on/off firing (group 2) did not have drastic drops in pressure. ICI-118,551 (ICI, a specific β₂-blocker) infused at 3 µg/kg/h for 7 days significantly increased BP from 126 mm Hg (95% confidence interval 118-133) to 133 mm Hg (95% confidence interval 125-141; P = .0001). The duration of hypotension (mean systolic BP100 mm Hg) during baseline accounted for 7.1% of the recording. The percentage was reduced by ICI to 1.3% (P = .01).Abrupt simultaneous termination of SGNA-VNA was observed at the time of orthostatic hypotension in ambulatory dogs. Selective β₂-adrenoceptor blockade increased BP and reduced the duration of hypotension in this model.

Evidence from a canine experimental acute myocardial infarction (MI) model shows that until the seventh week after MI, the relationship between stellate ganglion nerve activity (SGNA) and vagal nerve activity (VNA) progressively increases.The purpose of this study was to evaluate how autonomic nervous system activity influences temporal myocardial repolarization dispersion at this period.We analyzed autonomic nerve activity as well as QT and RR variability from recordings previously obtained in nine dogs. From a total of 48 short-term ECG segments, 24 recorded before and 24 recorded 7 weeks after experimentally-induced MI, we obtained three indices of temporal myocardial repolarization dispersion: QTe (from Q-wave to T-wave end), QTp (from Q-wave to T-wave peak), and Te (from T-wave peak to T-wave end) variability index (QTeVI, QTpVI, TeVI). We also performed heart rate variability power spectral analysis on the same segments.After MI, all the QT variables increased QTeVI (median [interquartile range]) (from -1.76[0.82] to -1.32[0.68]), QTeVI (from -1.90[1.01] to -1.45[0.78]), and TeVI (from -0.72[0.67] to -0.22[1.00]), whereas all RR spectral indices decreased (P.001 for all). Distinct circadian rhythms in QTeVI (P.05,) QTpVI (P.001) and TeVI (P.05) appeared after MI with circadian variations resembling that of SGNA/VNA. The morning QTpVI and TeVI acrophases approached the SGNA/VNA acrophase. Conversely, the evening QTeVI acrophase coincided with another SGNA/VNA peak. After MI, regression analysis detected a positive relationship between SGNA/VNA and TeVI (R(2): 0.077; β: 0.278; p0.001).Temporal myocardial repolarization dispersion shows a circadian variation after MI reaching its peak at a time when sympathetic is highest and vagal activity lowest.

To analyze the distribution of autonomic nerves and blood and lymphatic vessels in the uterosacral ligament, elucidate detailed anatomy at a surgical level and provide pathobiological evidence for improvement of nerve-sparing radical hysterectomy.Surgical samples were collected from 15 patients who underwent radical hysterectomy for early stage cervical cancer (FIGO Ib1-IIa). Twenty-nine fresh specimens were divided into cervical, intermediate and sacral sections, and then subdivided into superficial and deep portions from the middle: the medial surface and lateral surface were also subdivided in order to analyze lymphatic vessels. The numbers of nerve branches in each section or portion of the section were analyzed. The lengths of the uterosacral ligaments were measured and immunohistochemistry staining was studied. Autonomic nerves, blood vessels and lymphatic vessels were quantitatively analyzed using image analysis software and biological stereology.The volume density of sympathetic nerves in the deep portion was significantly higher than in the superficial portion (p0.05), and the number of nerves was greatest in the cervical section (p0.05). The volume density of blood vessels was not significantly different between the two portions (p0.05) or among the three sections (p0.05), and the volume density of the lymphatic vessels was greater in the medial surface (p0.05), with most of them in the cervical section (p0.05).Our study provides systematic mapping of the location and distribution of autonomic nerve branches, blood vessels and lymphatic vessels in the uterosacral ligament.

We thank Dr. Madias for the valuable comments and totally agree with the idea of combining optogenetic neuromodulation (ON) with direct monitoring of sympathetic autonomic nerve activity (SANA) for precision therapy. Left stellate ganglion (LSG) plays an important role in modulating ventricular

Video Objective Comprehension of structure of pelvic autonomic nerve system is mandatory for constant preservation of voiding function while maintaining oncological outcome of radical hysterectomy. Setting 47 years old, cervical cancer T1bN0M0. Total laparoscopic nerve sparing radical hysterectomy is presented. Interventions Superior hypogastric nerve plexus and inferior hypogastric nerves are in the same layer between pararectal space of Latzko and Okabayashi. Two subperitoneal fasciae are identified in pelvic retroperitoneal space: pre-hypogastric nerve fascia in ventral side, ureterohypogastric fascia in dorsal side of ureter and hypogastric nerves. Pelvic splanchnic nerves are identified in lateral side of pre-hypogastric nerve fascia, so preservation of these fasciae during operation result in protection of hypogastric and pelvic splanchnic nerves. Pelvic nerve plexus is identified in dorsal side of deep uterine vein and superior vesical vein. Careful slice up of these veins and preserve underlying fasciae result in protection of pelvic nerve plexus. Vesical nerve branch is identified in caudal side of posterior leaf of vesicouterine ligament (VUL). Division of posterior leaf of VUL is required to visualize vesical nerve branch, but constant preservation of voiding function is feasible once location of vesical nerve branch is understood. Outline of surgical procedure to identify and preserve hypogastric nerves and vesical nerve branch is presented in the video of TLRH for cervical cancer stage 1B1. Conclusion Once visualization of pelvic autonomic nerve system is experienced, stable preservation of voiding function in radical hysterectomy is realized.

Nicotinic receptor activation in the airways evokes airway defensive reflexes including cough. These reflexes are the direct result of bronchopulmonary afferent nerve activation, which may occur directly, through activation of nicotinic receptors expressed on the terminals of airway sensory nerves, or indirectly, secondary to the end organ effects associated with autonomic nerve stimulation. The irritating effects of nicotine delivered topically to the airways are counterbalanced by an inhibitory effect of nicotinic receptor activation in the central nervous system. We present evidence that these nicotinic receptors are components of essential transducing and encoding mechanisms regulating airway defense.

Research on the therapeutic modulation of cardiac autonomic tone by electrical stimulation has yielded encouraging early clinical results. Vagus nerve stimulation has reduced the rates of morbidity and sudden death from heart failure, but therapeutic vagus nerve stimulation is limited by side effects of hypotension and bradycardia. Sympathetic nerve stimulation that has been implemented in the experiment may exacerbate the sympathetic-dominated autonomic imbalance. In contrast, concurrent stimulation of both sympathetic and parasympathetic cardiac nerves increases myocardial contractility without increasing heart rate. This review assesses the current state of electrical stimulation of the cardiac autonomic nervous system to treat heart failure.

Obesity often results from hyperphagia and involves rhythm disorder. Circadian feeding pattern is suggested to be implicated in energy homeostasis while its disorder in obesity. However, the mechanism underlying circadian feeding is little known. PVN is considered a regulatory center for feeding and circadian activities of hormone release and autonomic nerve. Nucleobindin2 (NUCB2) and its processing product nesfatin-1 (NUCB2/nesfatin-1) are localized in the hypothalamic paraventricular nucleus (PVN) and implicated in regulation of feeding. This study aimed to clarify whether the PVN NUCB2/nesfatin-1 expression exhibits diurnal rhythm and, if so, whether it is related to circadian feeding. Here we show that NUCB2 mRNA expression in the PVN rises during early light phase (LP) in parallel with suppression of food intake. Immunoneutralization of PVN NUCB2/nesfatin-1 with anti-nesfatin-1 IgG during LP, but not dark phase, increased food intake. PVN-selective shRNA-induced knockdown of NUCB2 mRNA expression elevated food intake. Furthermore, the rise of PVN NUCB2 mRNA during LP was blunted in Zucker-fatty obese rats which exhibited LP-preferential hyperphagia. The increases in food intake during LP and 24h were significantly corrected by intracerebroventricular injection of nesfatin-1 during LP. These results reveal the diurnal rhythm of PVN NUCB2 mRNA expression characterized by early LP rise, which may serve as a factor to limit LP food intake, contributing to circadian feeding. Furthermore, impaired NUCB2/nesfatin-1 rhythm may be related to dysregulated feeding pattern and hyperphagia in Zucker-fatty rats.

Background End-to-side nerve repair is a new tool in managing certain nerve injuries. In previous studies, it was limited to somatic nerves. Herein, we evaluate the feasibility of anorectal reinnervation after end-to-side coaptation of autonomic nerve to somatic nerve. Materials and methods Forty adult male Sprague-Dawley rats were randomly divided into three groups: end-to-side coaptation group (n = 16), the left L6 and S1 spinal nerves were transected, and the distal stump of L6 ventral root (L6VR) was sutured to L4VR (L4VR) through end-to-side neurorrhaphy; no coaptation group (n = 12), rats received the same operation as the end-to-side coaptation group but without coaptation; and control group (n = 12), rats received the same operation as the end-to-side coaptation group but the L6VR was preserved. At 16 wk, using double retrograde tracing and histomorphological technique and anorectal manometry, morphological and functional properties of regenerated nerve were investigated. Results Retrograde tracing indicated that the new neural pathway was established and the main nerve regeneration mechanism was axon collateral sprouting. Histology showed good axonal regeneration with end-to-side neurorrhaphy. The wet weight and morphology of left tibialis anterior muscles appeared no detrimental effect on donor nerve. Anorectal manometry showed good anorectal functional recovery. Conclusions These results suggest that the somatic motor axon ingrowth into autonomic nerve could be through collateral sprouting after end-to-side coaptation of autonomic nerve to somatic nerve. Our innovative technique of end-to-side coaptation may be of great value in anorectal reinnervation without functional impairment of the donor somatic nerve.

When mammals are exposed to an odor, that odor is expected to elicit a physiological response in the autonomic nervous system. An unpleasant aversive odor causes non-invasive stress, while a pleasant odor promotes healing and relaxation in mammals. We hypothesized that pleasant odors might reduce a stress response previously induced by an aversive predator odor. Rats were thus exposed to pleasant and unpleasant odors in different orders to determine whether the order of odor exposure had an effect on the physiological response in the autonomic nervous system. The first trial examined autonomic nerve activity via sympathetic and parasympathetic nerve response while the second trial examined body temperature response. Initial exposure to a pleasant odor elicited a positive response and secondary exposure to an unpleasant odor elicited a negative response, as expected. However, we found that while initial exposure to an unpleasant odor elicited a negative stress response, subsequent secondary exposure to a pleasant odor not only did not alleviate that negative response, but actually amplified it. These findings were consistent for both the autonomic nerve activity response trial and the body temperature response trial. The trial results suggest that exposure to specific odors does not necessarily result in the expected physiological response and that the specific order of exposure plays an important role. Our study should provide new insights into our understanding of the physiological response in the autonomic nervous system related to odor memory and discrimination and point to areas that require further research.

Obesity is associated with autonomic imbalance. With respect to cardiovascular autonomic dysfunction, this is characterized by reduced heart rate variability (HRV). Our objective was to determine the effect of surgically induced weight loss on cardiovascular autonomic nerve fiber function in subjects with severe obesity and examine whether an association with reduced insulin resistance exists. The setting was a hospital and private practice in the United States.A total of 32 morbidly obese patients (body mass index 51 ± 11 kg/m(2)) underwent laparoscopic Roux-en-Y gastric bypass. Measures of HRV (e.g., power spectral analysis, RR variation during deep breathing) were used to evaluate autonomic function before and 6 months after surgery. The homeostasis model assessment of insulin resistance index (HOMA-IR) was used to assess insulin resistance.At 6 months after bariatric surgery, the patients had lost 58% excess body mass index with improvement in the HOMA-IR (3.0 ± 1.4 versus 1.1 ± .7; P.001). Measures of RR variation during deep breathing and total spectral power, low frequency (LF) power (influenced by sympathetic and parasympathetic activity), and high frequency (HF) power (parasympathetic activity) increased with weight loss. The LF/HF ratio was lower (1.5 ± 1.5 versus .9 ± .7, P.05) with a reduction in weight. Spectral analysis of HRV combined with spectral analysis of respiratory activity generated the respiration frequency area (RFA) and low frequency area. The RFA was increased, and the LFA/RFA ratio was reduced with weight loss. HOMA-IR and HRV did not correlate.Surgically induced weight loss has a favorable effect on autonomic function, but it does not appear to be directly attributable to reduced insulin resistance.