Spinal relay neurons for central control of autonomic pathways in a photoperiodic rodent.

Location and distribution of spinal sympathetic preganglionic neurons projecting to the superior cervical ganglion were investigated in a rodent model organism for photoperiodic regulation, the Djungarian hamster (Phodopus sungorus). Upon unilateral injection of Fluoro-Gold into the superior cervical ganglia, retrograde neuronal tracing demonstrated labeled neurons ipsilateral to the injection site. They were seen in spinal segments C8 to Th5 of which the segments Th1 to Th3 contained about 98% of the labeled cells. Neurons were found in the spinal cord predominantly in the intermediolateral nucleus pars principalis and pars funicularis. At the same time, the central autonomic area and the intercalated region contained only very few labeled cells. In the intermediolateral nucleus, cells often were arranged in clusters, of which several were seen in each spinal segment. Selected sections were exposed to antibodies directed against arginine-vasopressin, neuronal nitric oxide synthase, neuropeptide Y, neurotensin, oxytocin or substance P. It was found that about two-thirds of sympathetic preganglionic neurons produced the gaseous neuroactive substance nitric oxide and that few contained small amounts of neuropeptide Y. Fibers of putative supraspinal origin immunopositive for either arginine-vasopressin, neuronal nitric oxide synthase, neuropeptide Y, neurotensin, oxytocin or, in particular, substance P were found in the vicinity of labeled sympathetic preganglionic neurons. These results demonstrate the location of relay neurons for autonomic control of cranial and cardial structures and provide further knowledge on neurochemical properties of sympathetic preganglionic neurons and related structures.

Ameliorating Effects of Transcutaneous Electrical Acustimulation Combined With Deep Breathing Training on Refractory Gastroesophageal Reflux Disease Mediated via the Autonomic Pathway.

AIMS: To investigate the effects and possible mechanisms of transcutaneous electrical acustimulation (TEA) combined with deep breathing training (DBT) on refractory gastroesophageal reflux disease (rGERD). METHODS: Twenty-one patients with rGERD were recruited and randomly assigned to receive either only esomeprazole (ESO, 20 mg bid) (group A, n = 7), TEA + DBT + ESO (group B, n = 7), or sham-TEA + DBT + ESO (group C, n = 7) in a four-week study. The reflux diagnostic questionnaire (RDQ) score and heart rate variability (HRV) were recorded and evaluated at baseline and at the end of each treatment. Blood samples were collected for the measurement of serum acetylcholine (Ach) and nitric oxide (NO). Esophageal manometry and 24-hour pH monitoring were performed before and after the treatment. RESULTS: After treatment, 1) the participants in group B had significantly lower scores of RDQ and DeMeester and increased lower esophageal sphincter pressure (LESP) than those in group C (all p < 0.05), suggesting the role of TEA; 2) low frequency band (LF)/(LF + HF) ratio in groups B and C was decreased, compared with group A (p = 0.010, p = 0.042, respectively); high frequency band (HF)/(LF + HF) ratio in B and C groups was significantly increased, compared with group A (p = 0.010, p = 0.042, respectively); 3) The serum Ach in groups B and C was significantly higher than group A (p = 0.022, p = 0.046, respectively); the serum NO in groups B and C was significantly lower than group A (p = 0.010, p = 0.027, respectively). CONCLUSIONS: TEA combined with the DBT can effectively improve the reflux symptoms in rGERD patients by increasing LESP and reducing gastroesophageal reflux, which may be mediated via the autonomic and enteric mechanisms.

The effects of arousal accompanying an apneic event on blood pressure and sympathetic nerve activity in severe obstructive sleep apnea.

PURPOSE: Arousal plays an important protective role against life-threatening events by terminating the apneic events. However, arousal might also be considered as a contributor to obstructive sleep apnea (OSA) pathogenesis since ventilatory overshoot due to arousal leads to irregular breathing. Patients with OSA who have greater upper airway compensation, expressed by relatively high proportion of apneic events without arousal, could have less adverse events or consequences. Thus, our hypothesis was that the proportion of apneic events with or without arousal affects daytime systemic blood pressure and nocturnal sympathetic activity. METHODS: Subjects were consecutive 97 patients who had diagnostic polysomnography (PSG) and showed severe OSA (apnea-hypopnea index ≥ 30). The proportion of apnea-hypopneas with arousal among all apnea-hypopneas was calculated in each patient. Then, the association among the proportion of arousal accompanying apnea-hypopneas and a diagnosis of hypertension or heart rate variability during the PSG were investigated. RESULTS: The proportion of apnea-hypopneas with arousal among all apnea-hypopneas was higher in hypertensive patients (n = 47) than that in normotensive patients (n = 50) (mean ± standard deviation; 80.0 ± 12.8% vs. 73.7 ± 13.0%, p < 0.01). However, heart rate variability was not associated with the proportion of apnea-hypopneas with arousal. CONCLUSIONS: Apnea-hypopneas terminated by arousal are more often present in those with current systemic hypertension but independent of sympathetic nerve activity, compared with those whose apnea-hypopnea events do not have as many arousals. One could target an elevation in arousal threshold as a pathway for reducing daytime blood pressure.

Electrophysiology-based quality assurance of nerve-sparing in laparoscopic rectal cancer surgery: Is it worth the effort?

BACKGROUND: After low anterior resection for rectal cancer, visual assessment of pelvic autonomic nerve preservation can be difficult due to the complexity of neuroanatomy, as well as surgery- and patient-related factors. The present study aimed to evaluate nerve-sparing quality assurance using the laparoscopic neuromapping (LNM) technique. METHODS: We prospectively investigated a series of 30 patients undergoing laparoscopic low anterior resection. Nerve-sparing was evaluated both visually and electrophysiologically. LNM was performed using stimulation of pelvic autonomic nerves under simultaneous cystomanometry and processed electromyography of the internal anal sphincter. Urogenital and anorectal functions were evaluated using validated and standardized questionnaires preoperatively, at short-term follow-up, and at mid-term follow-up at a median of 9 months (range 6-12 months) after surgery. RESULTS: One patient reported new onset of urinary dysfunction, and another patient reported new onset of anorectal dysfunction. Of the 20 sexually active patients, five reported sexual dysfunction. Visual assessment by laparoscopy confirmed complete nerve preservation in 28 of 30 cases. For prediction of urinary and anorectal function, LNM sensitivity, specificity, positive and negative predictive value, and overall accuracy were each 100 %. LNM with combined assessment for prediction of sexual function yielded a sensitivity of 80 %, specificity of 93 %, positive predictive value of 80 %, negative predictive value of 93 %, and overall accuracy of 90 %. CONCLUSIONS: LNM is an appropriate method for reliable quality assurance of laparoscopic nerve-sparing.

The impact of concussion on cardiac autonomic function: A systematic review.

PRIMARY OBJECTIVE: To evaluate the evidence regarding the effect of concussion on cardiac autonomic function (CAF). INCLUSION CRITERIA: Original research; available in English; included participants with concussion or mild traumatic brain injury (mTBI) and a comparison group; included measures of heart rate (HR) and/or heart rate variability (HRV) as outcomes. Studies of humans (greater than 6 years old) and animals were included. Critical appraisal tools: The Downs and Black (DB) criteria and Structured Effectiveness Quality Evaluation Scale (SEQES). RESULTS: Nine full-length articles and four abstracts were identified. There is conflicting evidence regarding CAF at rest following concussion. There is evidence of elevated HR and reduced HRV with low-intensity, steady-state exercise up to 10 days following concussion. There was no significant difference in HRV during isometric handgrip testing or HR while performing cognitive tasks following concussion. The validity of current literature is limited by small sample sizes, lack of female or paediatric participants, methodological heterogeneity and lack of follow-up. CONCLUSIONS: While there is some evidence to suggest CAF is altered during physical activity following concussion, methodological limitations highlight the need for further research. Understanding the effect of concussion on CAF will contribute to the development of more comprehensive concussion management strategies.

Ameliorating effects and autonomic mechanisms of needle-less transcutaneous electrical stimulation at ST36 on stress-induced impairment in gastric slow waves.

BACKGROUND AND AIM: Stress has long been documented to alter gastrointestinal motility. The effects of electroacupuncture (EA) on stress and gastric motility are relatively well known; however, whether EA has an ameliorating effect on stress-induced dysmotility remained unclear. This study aims to investigate the effects and mechanisms of needle-less transcutaneous electroacupuncture (TEA) on stress-induced impairment in gastric slow waves. METHODS: A watch-size digital stimulator was developed. Ten healthy volunteers were involved in a four-session study (control, cold stress, TEA, and sham TEA). Electrogastrograpy was used to assess gastric slow waves, and electrocardiogram was recorded for the assessment of autonomic functions. The recordings were made in each session with/without stress and with TEA at ST36 or sham points. RESULTS: The results are as follows: (i) Cold stress-induced gastric dysrhythmia and impaired normal slow waves (P < 0.01). TEA showed a preventive effect on cold stress-induced impairment in gastric slow waves. TEA at ST36, but not sham TEA, normalized slow waves (P = 0.03 vs stress; P = 0.44 vs control), attributed to the suppression of gastric dysrhythmia; (ii) Postprandially, there was a decrease in vagal activity in both control (P = 0.004) and stress (P = 0.002) sessions; this decrease was prevented with TEA (P < 0.05). Similarly, there was a postprandial increase in sympathetic activity in both control (P = 0.01) and stress (P = 0.002) sessions, and this increase was suppressed with TEA. CONCLUSIONS: Needle-less TEA at ST36 using a watch-size stimulator is able to improve stress-induced impairment in gastric slow waves, possibly mediated via the autonomic mechanism. Home-based needle-less TEA may be a viable therapy for stress-induced impairment in gastric motility functions.

[Glucose homeostasis and gut-brain connection]. / Contrôle de la glycémie par l'axe nerveux intestin-cerveau.

Since the XIX(th) century, the brain has been known for its role in regulating food intake (via the control of hunger sensation) and glucose homeostasis. Further interest has come from the discovery of gut hormones, which established a clear link between the gut and the brain in regulating glucose and energy homeostasis. The brain has two particular structures, the hypothalamus and the brainstem, which are sensitive to information coming either from peripheral organs or from the gut (via circulating hormones or nutrients) about the nutritional status of the organism. However, the efforts for a better understanding of these mechanisms have allowed to unveil a new gut-brain neural axis as a key regulator of the metabolic status of the organism. Certain nutrients control the hypothalamic homeostatic function via this axis. In this review, we describe how the gut is connected to the brain via different neural pathways, and how the interplay between these two organs drives the energy balance.

Role of exercise training on autonomic changes and inflammatory profile induced by myocardial infarction.

The cardiovascular autonomic imbalance in patients after myocardial infarction (MI) provides a significant increase in mortality rate, and seems to precede metabolic, hormonal, and immunological changes. Moreover, the reduction in the parasympathetic function has been associated with inflammatory response in different pathological conditions. Over the years, most of the studies have indicated the exercise training (ET) as an important nonpharmacological tool in the management of autonomic dysfunction and reduction in inflammatory profile after a myocardial infarction. In this work, we reviewed the effects of ET on autonomic imbalance after MI, and its consequences, particularly, in the post-MI inflammatory profile. Clinical and experimental evidence regarding relationship between alterations in autonomic regulation and local or systemic inflammation response after MI were also discussed.

Laparoscopic neuromapping in pelvic surgery: scopes of application.

BACKGROUND: New developments in intraoperative electrophysiological neuromonitoring for conventional surgery are providing further insights into functional neuroanatomy and nerve-sparing in the minor pelvis. The aim of this study was to open up potential scopes of application in laparoscopy. METHODS: Ten patients with different indications for surgery (presacral tumor excision, n = 2; resection rectopexy. n = 2; low anterior rectal resection, n = 2; proctocolectomy. n = 2; abdomino-perineal excision of the rectum, n = 2) were investigated prospectively. The pelvic autonomic nerves were bilaterally mapped by laparoscopic electric stimulation under simultaneous electromyography of the internal anal sphincter and manometry of the bladder. Stimulation results were compared to patients' anorectal and urogenital functional outcome. RESULTS: In all the operations laparoscopic neuromapping (LNM) was technically feasible. Laparoscopy enabled excellent visibility of pelvic neural structures for simple and differentiated electric stimulation. In all cases LNM resulted in significantly evoked electromyographic potentials and intravesical pressure rises. The technique facilitated electrophysiological determination of functional neuroanatomical topography in the minor pelvis. The stimulation results were suitable to confirm laparoscopic nerve-sparing and compatible with patients' anorectal and urogenital functional outcome. CONCLUSIONS: LNM is technically feasible and opens up a new dimension for verification of functional nerve integrity. Further developments and investigations are mandatory to evaluate its role for laparoscopic nerve-sparing procedures.

Effects of stimulation by three-dimensional natural images on prefrontal cortex and autonomic nerve activity: a comparison with stimulation using two-dimensional images.

Empirical evidence suggests that three-dimensional (3D) images of nature promote physiological relaxation in humans by providing more realistic effects compared with two-dimensional (2D) images. However, no studies have evaluated the physiological relaxation effects of nature-derived 3D images on prefrontal cortex and autonomic nerve activity. The present study aimed to clarify the physiological relaxation effects of visual stimulation by 3D flower images on prefrontal cortex and autonomic nerve activity. Nineteen male university students (22.2 ± 0.6 years) were presented with 3D and 2D images of the water lily for 90 s. Prefrontal cortex activity was measured using near-infrared spectroscopy, while autonomic nerve activity was measured using heart rate variability (HRV). Psychological effects were determined using a modified semantic differential method (SD). Compared with visual stimulation by 2D images, that by 3D images resulted in a significant decrease in oxyhemoglobin concentration in the right prefrontal cortex, lower sympathetic activity as calculated by the ratio of the low-frequency to high-frequency HRV component, and a significantly greater realistic feeling as evidenced by higher SD ratings. In conclusion, visual stimulation by realistic 3D floral images promotes physiological relaxation more effectively than the corresponding 2D image.

[Autonomic regulation of cardiac rhythm in elderly patients with bronchial asthma].

Evaluation of independent and combined interrelations of bronchial obstruction and autonomic regulation of cardiac rhythm in elderly patients with bronchial asthma was carried out. Positive correlation of the extent of bronchial obstruction and decrease of absolute indices of cardiac rhythm variability was established.

The anterior cingulate cortex may enhance inhibition of lateral prefrontal cortex via m2 cholinergic receptors at dual synaptic sites.

The anterior cingulate cortex (ACC) and dorsolateral prefrontal cortices (DLPFC) share robust excitatory connections. However, during rapid eye movement (REM) sleep, when cortical activity is dominated by acetylcholine, the ACC is activated but DLPFC is suppressed. Using pathway tracing and electron microscopy in nonhuman primates (Macaca mulatta), we tested the hypothesis that the opposite states may reflect specific modulation by acetylcholine through strategic synaptic localization of muscarinic m2 receptors, which inhibit neurotransmitter release presynaptically, but are thought to be excitatory postsynaptically. In the ACC pathway to DLPFC (area 32 to area 9), m2 receptors predominated in ACC axon terminals and in more than half of the targeted dendrites of presumed inhibitory neurons, suggesting inhibitory cholinergic influence. In contrast, in a pathway linking the DLPFC area 46 to DLPFC area 9, postsynaptic m2 receptors predominated in targeted spines of presumed excitatory neurons, consistent with their mutual activation in working memory. These novel findings suggest that presynaptic and postsynaptic specificity of m2 cholinergic receptors may help explain the differential engagement of ACC and DLPFC areas in REM sleep for memory consolidation and synergism in awake states for cognitive control.

Cholinergic regulation of bone.

Bone remodeling is regulated by the two branches of the autonomic nervous system: the adrenergic and the cholinergic branches. Adrenergic activity favors bone loss, whereas cholinergic activity has been recently shown to favor bone mass accrual. In vitro studies have reported that cholinergic activity induces proliferation and differentiation of bone cells. In vivo studies have shown that the inhibition of cholinergic activity favors bone loss, whereas its stimulation favors bone mass accrual. Clinical studies have shown that bone density is associated with the function of many cholinergic-regulated tissues such as the hypothalamus, salivary glands, lacrimal glands and langerhans cells, suggesting a common mechanism of control. Altogether, these observations and linked findings are of great significance since they improve our understanding of bone physiology. These discoveries have been successfully used recently to investigate new promising therapies for bone diseases based on cholinergic stimulation. Here, we review the current understanding of the cholinergic activity and its association with bone health.

Perinatal taurine exposure programs patterns of autonomic nerve activity responses to tooth pulp stimulation in adult male rats.

Perinatal taurine excess or deficiency influences adult health and disease, especially relative to the autonomic nervous system. This study tests the hypothesis that perinatal taurine exposure influences adult autonomic nervous system control of arterial pressure in response to acute electrical tooth pulp stimulation. Female Sprague-Dawley rats were fed with normal rat chow with 3% ß-alanine (taurine depletion, TD), 3% taurine (taurine supplementation, TS), or water alone (control, C) from conception to weaning. Their male offspring were fed with normal rat chow and tap water throughout the experiment. At 8-10 weeks of age, blood chemistry, arterial pressure, heart rate, and renal sympathetic nerve activity were measured in anesthetized rats. Age, body weight, mean arterial pressure, heart rate, plasma electrolytes, blood urea nitrogen, plasma creatinine, and plasma cortisol were not significantly different among the three groups. Before tooth pulp stimulation, low- (0.3-0.5 Hz) and high-frequency (0.5-4.0 Hz) power spectral densities of arterial pressure were not significantly different among groups while the power spectral densities of renal sympathetic nerve activity were significantly decreased in TD compared to control rats. Tooth pulp stimulation did not change arterial pressure, heart rate, renal sympathetic nerve, and arterial pressure power spectral densities in the 0.3-4.0 Hz spectrum or renal sympathetic nerve firing rate in any group. In contrast, perinatal taurine imbalance disturbed very-low-frequency power spectral densities of both arterial pressure and renal sympathetic nerve activity (below 0.1 Hz), both before and after the tooth pulp stimulation. The power densities of TS were most sensitive to ganglionic blockade and central adrenergic inhibition, while those of TD were sensitive to both central and peripheral adrenergic inhibition. The present data indicate that perinatal taurine imbalance can lead to aberrant autonomic nervous system responses in adult male rats.

Endogenous brain-derived neurotrophic factor in the nucleus tractus solitarius tonically regulates synaptic and autonomic function.

Brain-derived neurotrophic factor (BDNF) and its receptor, TrkB, are highly expressed in the nucleus tractus solitarius (nTS), the principal target of cardiovascular primary afferent input to the brainstem. However, little is known about the role of BDNF signaling in nTS in cardiovascular homeostasis. We examined whether BDNF in nTS modulates cardiovascular function in vivo and regulates synaptic and/or neuronal activity in isolated brainstem slices. Microinjection of BDNF into the rat medial nTS (mnTS), a region critical for baroreflex control of sympathetic outflow, produced dose-dependent increases in mean arterial pressure (MAP), heart rate (HR), and lumbar sympathetic nerve activity (LSNA) that were blocked by the tyrosine kinase inhibitor K252a. In contrast, immunoneutralization of endogenous BDNF (anti-BDNF), or microinjection of K252a alone, decreased MAP, HR, and LSNA. The effects of anti-BDNF were abolished by blockade of ionotropic glutamate receptors, indicating a role for glutamate signaling in the response to BDNF. In vitro, BDNF reduced the amplitude of miniature EPSCs as well as solitary tract (TS) evoked EPSC amplitude and action potential discharge (APD) in second-order nTS neurons. BDNF effects on EPSCs were independent of GABAergic signaling and abolished by AMPA receptor blockade. In contrast, K252a increased spontaneous EPSC frequency and TS evoked EPSC amplitude. BDNF also attenuated APD evoked by injection of depolarizing current into second-order neurons, indicating reduced intrinsic neuronal excitability. Our data demonstrate that BDNF signaling in mnTS plays a tonic role in regulating cardiovascular function, likely via modulation of primary afferent glutamatergic excitatory transmission and neural activity.

Control of breathing by raphe obscurus serotonergic neurons in mice.

We used optogenetics to determine the global respiratory effects produced by selectively stimulating raphe obscurus (RO) serotonergic neurons in anesthetized mice and to test whether these neurons detect changes in the partial pressure of CO(2), and hence function as central respiratory chemoreceptors. Channelrhodopsin-2 (ChR2) was selectively (∼97%) incorporated into ∼50% of RO serotonergic neurons by injecting AAV2 DIO ChR2-mCherry (adeno-associated viral vector double-floxed inverse open reading frame of ChR2-mCherry) into the RO of ePet-Cre mice. The transfected neurons heavily innervated lower brainstem and spinal cord regions involved in autonomic and somatic motor control plus breathing but eschewed sensory related regions. Pulsed laser photostimulation of ChR2-transfected serotonergic neurons increased respiratory frequency (fR) and diaphragmatic EMG (dEMG) amplitude in relation to the duration and frequency of the light pulses (half saturation, 1 ms; 5-10 Hz). dEMG amplitude and fR increased slowly (half saturation after 10-15 s) and relaxed monoexponentially (tau, 13-15 s). The breathing stimulation was reduced ∼55% by methysergide (broad spectrum serotonin antagonist) and potentiated (∼16%) at elevated levels of inspired CO(2) (8%). RO serotonergic neurons, identified by their entrainment to short light pulses (threshold, 0.1-1 ms) were silent (nine cells) or had a low and regular level of activity (2.1 ± 0.4 Hz; 11 cells) that was not synchronized with respiration. These and nine surrounding neurons with similar characteristics were unaffected by adding up to 10% CO(2) to the breathing mixture. In conclusion, RO serotonergic neurons activate breathing frequency and amplitude and potentiate the central respiratory chemoreflex but do not appear to have a central respiratory chemoreceptor function.

Enhanced catabolism to acetaldehyde in rostral ventrolateral medullary neurons accounts for the pressor effect of ethanol in spontaneously hypertensive rats.

We have previously shown that ethanol microinjection into the rostral ventrolateral medulla (RVLM) elicits sympathoexcitation and hypertension in conscious spontaneously hypertensive rats (SHRs) but not in Wistar-Kyoto (WKY) rats. In this study, evidence was sought to implicate the oxidative breakdown of ethanol in this strain-dependent hypertensive action of ethanol. Biochemical experiments revealed significantly higher catalase activity and similar aldehyde dehydrogenase (ALDH) activity in the RVLM of SHRs compared with WKY rats. We also investigated the influence of pharmacological inhibition of catalase (3-aminotriazole) or ALDH (cyanamide) on the cardiovascular effects of intra-RVLM ethanol or its metabolic product acetaldehyde in conscious rats. Compared with vehicle, ethanol (10 µg/rat) elicited a significant increase in blood pressure in SHRs that lasted for the 60-min observation period but had no effect on blood pressure in WKY rats. The first oxidation product, acetaldehyde, played a critical role in ethanol-evoked hypertension because 1) catalase inhibition (3-aminotriazole treatment) virtually abolished the ethanol-evoked pressor response in SHRs, 2) intra-RVLM acetaldehyde (2 µg/rat) reproduced the strain-dependent hypertensive effect of intra-RVLM ethanol, and 3) ALDH inhibition (cyanamide treatment) uncovered a pressor response to intra-RVLM acetaldehyde in WKY rats similar to the response observed in SHRs. These findings support the hypothesis that local production of acetaldehyde, due to enhanced catalase activity, in the RVLM mediates the ethanol-evoked pressor response in SHRs.

Neuromodulation targets intrinsic cardiac neurons to attenuate neuronally mediated atrial arrhythmias.

Our objective was to determine whether atrial fibrillation (AF) results from excessive activation of intrinsic cardiac neurons (ICNs) and, if so, whether select subpopulations of neurons therein represent therapeutic targets for suppression of this arrhythmogenic potential. Trains of five electrical stimuli (0.3-1.2 mA, 1 ms) were delivered during the atrial refractory period to mediastinal nerves (MSN) on the superior vena cava to evoke AF. Neuroanatomical studies were performed by injecting the neuronal tracer DiI into MSN sites that induced AF. Functional studies involved recording of neuronal activity in situ from the right atrial ganglionated plexus (RAGP) in response to MSN stimulation (MSNS) prior to and following neuromodulation involving either preemptive spinal cord stimulation (SCS; T(1)-T(3), 50 Hz, 200-ms duration) or ganglionic blockade (hexamethonium, 5 mg/kg). The tetramethylindocarbocyanine perchlorate (DiI) neuronal tracer labeled a subset (13.2%) of RAGP neurons, which also colocalized with cholinergic or adrenergic markers. A subset of DiI-labeled RAGP neurons were noncholinergic/nonadrenergic. MSNS evoked an ∼4-fold increase in RAGP neuronal activity from baseline, which SCS reduced by 43%. Hexamethonium blocked MSNS-evoked increases in neuronal activity. MSNS evoked AF in 78% of right-sided MSN sites, which SCS reduced to 33% and hexamethonium reduced to 7%. MSNS-induced bradycardia was maintained with SCS but was mitigated by hexamethonium. We conclude that MSNS activates subpopulations of intrinsic cardiac neurons, thereby resulting in the formation of atrial arrhythmias leading to atrial fibrillation. Stabilization of ICN local circuit neurons by SCS or the local circuit and autonomic efferent neurons with hexamethonium reduces the arrhythmogenic potential.

An educational training simulator for advanced perfusion techniques using a high-fidelity virtual patient model.

The operation of cardiopulmonary bypass procedure requires an advanced skill in both physiological and mechanical knowledge. We developed a virtual patient simulator system using a numerical cardiovascular regulation model to manage perfusion crisis. This article evaluates the ability of the new simulator to prevent perfusion crisis. It combined short-term baroreflex regulation of venous capacity, vascular resistance, heart rate, time-varying elastance of the heart, and plasma-refilling with a simple lumped parameter model of the cardiovascular system. The combination of parameters related to baroreflex regulation was calculated using clinical hemodynamic data. We examined the effect of differences in autonomous-nerve control parameter settings on changes in blood volume and hemodynamic parameters and determined the influence of the model on operation of the control arterial line flow and blood volume during the initiation and weaning from cardiopulmonary bypass. Typical blood pressure (BP) changes (hypertension, stable, and hypotension) were reproducible using a combination of four control parameters that can be estimated from changes in patient physiology, BP, and blood volume. This simulation model is a useful educational tool to learn the recognition and management skills of extracorporeal circulation. Identification method for control parameter can be applied for diagnosis of heart failure.

Continuous intraoperative monitoring of autonomic nerves during low anterior rectal resection: an innovative approach for observation of functional nerve integrity in pelvic surgery.

PURPOSE: The aim of this study was to develop a methodological setup for continuous intraoperative neuromonitoring with intent to improve nerve-sparing pelvic surgery. METHODS: Fourteen pigs underwent low anterior rectal resection. Continuous stimulation of pelvic autonomic nerves was carried out with a newly developed tripolar surface electrode during lateral, anterolateral, and anterior mesorectal dissection. Neuromonitoring was performed under electromyography of the autonomic innervated internal anal sphincter. RESULTS: Continuous neuromonitoring resulted in significantly increased electromyographic amplitudes of the internal anal sphincter, confirming intact innervation throughout the whole dissection in each animal (median 0.9 µV, interquartile range 0.5; 1.5 vs. median 3.4 µV, interquartile range 2.1; 4.7) (p < 0.001). The median dissection time in each animal was 10 min within a median number of ten (range 8-13) tripolar electric stimulations. CONCLUSION: The present study is the first to demonstrate that continuous intraoperative monitoring of pelvic autonomic nerves during low anterior rectal resection is feasible.