Postganglionic Sympathetic Fibers Research Articles

Norepinephrine Reuptake Inhibition, an Emergent Treatment for Neurogenic Orthostatic Hypotension.

The NET (norepinephrine transporter) is situated in the prejunctional plasma membrane of noradrenergic neurons. It is responsible for >90% of the norepinephrine uptake that is released in the autonomic neuroeffector junction. Inhibitors of this cell membrane transporter, known as norepinephrine reuptake inhibitors (NRIs), are commercially available for the treatment of depression and attention deficit hyperactivity disorder. These agents increase norepinephrine levels, potentiating its action in preganglionic and postganglionic adrenergic neurons, the latter through activation of α-1 adrenoreceptors. Previous studies found that patients with neurogenic orthostatic hypotension can improve standing blood pressure and reduce symptoms of neurogenic orthostatic hypotension after a single administration of the selective NRI atomoxetine. This effect was primarily observed in patients with impaired central autonomic pathways with otherwise normal postganglionic sympathetic fibers, known as multiple system atrophy. Likewise, patients with normal or high norepinephrine levels may benefit from NRIs. The long-term efficacy of NRIs for the treatment of neurogenic orthostatic hypotension-related symptoms is currently under investigation. In summary, an in-depth understanding of the pathophysiology of neurogenic orthostatic hypotension resulted in the discovery of a new therapeutic pathway targeted by NRI.

Sprouting of afferent and efferent inputs to pelvic organs after spinal cord injury.

Neural plasticity occurs within the central and peripheral nervous systems after spinal cord injury (SCI). Although central alterations have extensively been studied, it is largely unknown whether afferent and efferent fibers in pelvic viscera undergo similar morphological changes. Using a rat spinal cord transection model, we conducted immunohistochemistry to investigate afferent and efferent innervations to the kidney, colon, and bladder. Approximately 3-4 weeks after injury, immunostaining demonstrated that tyrosine hydroxylase (TH)-labeled postganglionic sympathetic fibers and calcitonin gene-related peptide (CGRP)-immunoreactive sensory terminals sprout in the renal pelvis and colon. Morphologically, sprouted afferent or efferent projections showed a disorganized structure. In the bladder, however, denser CGRP-positive primary sensory fibers emerged in rats with SCI, whereas TH-positive sympathetic efferent fibers did not change. Numerous CGRP-positive afferents were observed in the muscle layer and the lamina propria of the bladder following SCI. TH-positive efferent inputs displayed hypertrophy with large diameters, but their innervation patterns were sustained. Collectively, afferent or efferent inputs sprout widely in the pelvic organs after SCI, which may be one of the morphological bases underlying functional adaptation or maladaptation.

Morphological signs of neurogenic inflammation in rat epicardial adipose tissue during aging

The aim of this work is to study the neuroinflammatory process in the epicardial adipose tissue (EAT) of the aorticpulmonary region of the rat heart during aging. The work was performed on Wistar rats aged 18-23 months (n=18). The adipose tissue of the pericardial region of rats was the object of study. Neuroimmunohistochemical markers (9.5 protein, tyrosine hydroxylase, synaptophysin) were used to study EAT innervation. The method of staining with toluidine blue and azure-eosin was used to study inflammation processes. Using histological and immunohistochemical methods, involutive and neurodegenerative changes in parasympathetic and sympathetic postganglionic nerve fibers were revealed in the white and brown adipose tissue of the heart of old rats (18-23 months old). A number of pathological changes were revealed in EAT: fibrosis, dystrophic changes and lysis of white adipocytes, disintegration of varicose axons of the terminal nerve plexus, as well as the formation of focal monocyticlymphoid infiltrates. It has been shown that the axons of the terminal nervous network are in close relationship with immune and inflammatory cells (lymphocytes, plasmablasts, monocyte-macrophage elements, mast cells). The noted morphological features indicate a neurogenic type of immune inflammation in the EAT of the heart. The identified changes may be the cause of chronic disorders of lipid metabolism during aging, leading to the development of pathological processes in the tissues of the main vessels of the aortic-pulmonary region of the heart, and also serve as prognostic indicators for clinical practice.

Immunohistochemical study of the sympathetic innervation of the colon in chronic slow-transit constipation

The purpose of this study is to determine the distribution and features of sympathetic innervation of the tissues of the human colon wall in chronic slow-transit constipation using immunohistochemical methods. Materials and methods. Immunohistochemical study of large intestine segments (colon and sigmoid colon) obtained as a result of surgical treatment of patients with chronic slow-transit constipation was carried out using neural markers (PGP 9.5 protein, tyrosine hydroxylase, synaptophysin). Results. It has been shown that the majority of postganglionic sympathetic nerve fibers are localized in the Auerbach and Meissner plexuses. Their terminal axons form pericellular synaptic apparatuses around cholinergic neurons. Another part of the sympathetic fibers is involved in the innervation of the muscular plate of the mucous membrane and the walls of the venous vessels of the submucosa; their terminal varicose axons can be seen on smooth muscle cells as distant synapses en passant. Significant features of sympathetic innervation disorders of the large intestine of the studied patients were established; morphological evidence for the reactive, dystrophic and degenerative changes in the sympathetic apparatuses in the ganglionic plexuses were found. The regularities of the absence of sympathetic innervation in two muscle layers (longitudinal and circular), as well as in the mucous membrane, were revealed. Sympathetic neurons were not found in the studied sections of the large intestine. Conclusion. It is assumed that the identified pathological changes in sympathetic innervation in chronic slow-transit constipation can serve as one of the main causes of disruption of normal bowel functions.

Role of the P2 × 4 Receptor in Sympathetic-mediated Inflammatory Low Back Pain

The sympathetic nervous system mediates various pain conditions including inflammatory low back pain. To better understand the underlying mechanisms, we developed a surgical procedure named localized microsympathectomy (mSYMPX) in rats and mice, which consists of cutting the grey rami containing postganglionic sympathetic fibers as they enter the spinal nerves near the lumbar dorsal root ganglia (DRG). We reported that mSYMPX attenuated pain behaviors in several preclinical pain models including a mouse model of chemotherapy-induced peripheral neuropathy (CIPN model). Under pathological conditions release of ATP from sympathetic nerve endings locally in the DRG activates purinergic receptor P2 × 4 in macrophages resulting in a more M1/pro-inflammatory polarization. In this study we asked whether the macrophage-enriched P2 × 4 receptors are involved in sympathetic-mediated inflammatory low back pain/radiculopathy produced by intravertebral injection of the immune activator zymosan, causing mechanical hypersensitivity (LID model). Our previous microarray study in rats showed upregulation of the macrophage cell marker Iba1 and purinergic receptor (P2rx4) after LID. As previously reported in rats, we found that mice showed mechanical hypersensitivity assessed by calibrated von Frey filaments and transcriptional upregulation of Iba1 and P2rx4 three days after LID. Interestingly, mSYMPX prevented mechanical hypersensitivity, and also caused significant transcriptional upregulation of Iba1 and a trend towards downregulation of P2rx4 three days after LID. The enhancement of P2 × 4 signaling with the allosteric modulator ivermectin reduced expression of the M2 marker in cultured peritoneal macrophages. Conversely, blocking P2 × 4 signaling with PSB12062 in M1 skewed macrophages mitigated the expression of M1 marker. Furthermore, the mechanical hypersensitivity in the LID model was reversed by intrathecal injection of the P2 × 4 antagonist (PSB12062) three days after LID. These findings suggest P2 × 4 receptor as a potential therapeutic target for managing inflammatory low back pain/radiculopathy. Funded by NS045594 and the HEAL supplement to NINDS grant NS045594 (J-M Z).

An Exploration of the Sympathetic Component of the Recurrent Laryngeal Nerve

INTRODUCTIONHigh interest in the recurrent laryngeal nerve (RLN) morphology has been dictated by the frequent iatrogenic injures that can result in multifaceted functional losses such as dysphagia, voice alteration, and breathing. Thus, RLN has been extensively studied on the macroscopic and histological levels. According to the literature, RLN is a mixed nerve carrying motor, sensory, and preganglionic parasympathetic fibers to the larynx and displays asymmetry in branching from the vagus nerve. Even though gross anastomoses between RLN and the cervical sympathetic trunk have been observed, the presence of sympathetic postganglionic fibers within RLN have not been addressed. The present study was conducted to determine if catecholaminergic fibers are present within the RLN using immunohistochemical analysis for tyrosine hydroxylase (TH).METHODSRLN samples were obtained from 19 formalin‐preserved adult human cadavers (male n=11, female n=8). Anastomoses with sympathetic structures were noted and documented before obtaining tissue samples for histological examination. Samples were collected one centimeter distal to the RLN branching site. All sections were prepared using Luxol fast blue staining to reveal the presence of myelinated and unmyelinated fibers and TH antibody staining was used to determine the presence of catecholaminergic fibers. Histological slides were then photographed and quantitative analysis of the images was conducted with ImageJ software by measuring of the effective surface area (ESA), TH‐positive, myelinated, and unmyelinated. We reported results as mean ± SEM.RESULTSNeural communications between right RLNs and sympathetic ganglia were observed in two whole‐body donors. No statistically significant differences in the number of the fascicles, ESA, myelinated, and unmyelinated fibers between right and left RLNs were found. TH‐positive fibers were detected bilaterally or unilaterally in 89.5% of examined donors. Bilateral absence of TH activity throughout the effective surface area was observed in two cases. TH‐positive nerve fiber area within the RLNs varied from 0% to 22.14% (Figure 1). The average of TH‐positive fibers on the right was 0.045 ± 0.011 mm2 (4.47% ± 1.1% of ESA) and 0.05 ± 0.015 mm2 (5.03±1.5% of ESA) on the left. A positive correlation between the number of unmyelinated fibers and TH‐positive component was found (P=0.022 and P=0.0026 on the right and left, respectfully). All parameters, such as fascicles, ESA, myelinated, unmyelinated, and TH‐positive fibers, occurred independently of age, gender, or conditions (p>0.05).CONCLUSIONSympathetic postganglionic fibers within RLN nerve exist; however, there is a considerable difference in their number between individuals. However, the origin and functions of this component are ambiguous.SIGNIFICANCEKnowledge of the sympathetic component of RLN could assist in better understanding the physiological effects and adverse responses of vagus nerve stimulation therapy and the sequala of the RLN injury.

The Origin of Sympathetic Postganglionic Fibers in the Cervical Region of the Vagus Nerve

IntroductionThe vagus nerve (VN) is a cranial nerve that is mainly known for its parasympathetic function. Although a communication between the VN and sympathetic ganglia was described as early as 1858 by Henry Gray, the existence of sympathetic fibers within the VN is still under debate. Studies utilizing immunohistochemical verification with anti‐Tyrosine Hydroxylase (TH) antibody have found variable distribution of catecholaminergic activity in the cervical and thoracic trunks of the VN, ranging from 0% to 21.63%. We aimed to elucidate the presence and distribution of the postganglionic sympathetic element within the cervical region of the VN using immunohistochemical analysis with anti‐TH antibody. We evaluated macroscopic neural communications between cervical sympathetic chain ganglia (SCG) and the cervical VN as a potential source of intravagal catecholaminergic fibers.MethodsDissection of the VN, cervical chain ganglia, and any communicating branches was performed bilaterally on 20 fully embalmed cadavers (male n=11, female n=9) using standard dissection tools. All communications were histologically validated to confirm neural tissue and cervical VN samples were collected bilaterally in two locations. Tissue sections were stained with anti‐TH antibody and Luxol Fast Blue. Histological slides were viewed and photographed with a Leica DM 500 compound microscope. All images underwent quantitative analysis with ImageJ software to measure effective surface area (ESA) and TH‐positive areas.ResultsTwenty pairs of VN and SCG with associated neural communications were identified. Interconnections were found in 11 donors (55%), resulting in 13 total neural anastomoses between the VN and either the superior, middle, or inferior cervical ganglia. All measurements are reported as mean ± SEM. When comparing the right and left superior cervical vagus nerve ESA, the right side had a larger ESA than the left (2.27±0.26mm2 and 1.82±0.15mm2; p=0.039). TH Immunoreactivity was detected in all donors bilaterally. We observed TH positive fibers in three distribution patterns (Figure 1). There was a significant interaction of location and gender on the percentage of TH‐positive fibers. Females expressed a higher percentage of TH‐positive fibers on the right side (3.0 ±1.22% in females and 1.2 ±0.37% in males; p=0.044). The average ESA of communications on the right side was 0.15±0.07 mm2 and 0.04±0.009 mm2 on the left (p>0.05). The number of fascicles within each communication varied from one to seven (2.77±0.4956). Most fibers stained positive for TH, occupying 91.86% ±4.1% of the total ESA. Presence or size of communications did not influence number of TH positive fibers within the VN. We identified ganglion cells within the superior and inferior samples of the cervical VN (Figure 2).ConclusionTH‐positivity within the cervical VN and its communications with the SCG suggests a ganglionic sympathetic source. However, identification of ganglion cells within the VN suggests a postganglionic source that warrants further study. Investigating sympathetic activity of the VN and its source, aids in understanding its physiologic role.

Nerve-sparing Robot-assisted Retroperitoneal Lymph Node Dissection: The Monoblock Technique

BackgroundRetroperitoneal lymph node dissection (RPLND) is a treatment option for men with stage 1 or 2 testis cancer and the standard of care for men with postchemotherapy retroperitoneal residual disease. Given the morbidity of RPLND, four important surgical modifications have been proposed: minimally invasive access, nerve-sparing resection, template resection, and en-bloc resection. ObjectiveTo describe the surgical steps and perioperative outcomes of robotic nerve-sparing unilateral template RPLND with en-bloc resection (roboRPLND-NS+). Design, setting, and participantsFrom 2017 to 2019, five patients with suspicion of retroperitoneal metastatic testicular cancer on abdominopelvic computed tomography underwent roboRPLND-NS+ at a single referral center. All surgeries were carried out by a single surgeon who has performed more than 500 extended and more than 50 super-extended robot-assisted lymph node dissections. Surgical procedureA lateral transperitoneal robotic approach with a da Vinci Xi Surgical System (Intuitive Surgical, Sunnyvale, CA, USA) in six-arm configuration was used. The sympathetic chains, postganglionic sympathetic fibers, and hypogastric plexus were preserved as much as possible to ensure a nerve-sparing procedure. The template borders consisted of the renal vein cranially, the ureter laterally, the interaortocaval space medially, the common iliac artery caudally, and the psoas muscle dorsally for the right and left modified RPLND templates. Lymph nodes and the surrounding fatty tissue were progressively resected from the common iliac vessels and the abdominal aorta using the split-and-roll technique, and all of the template tissue was resected as a single specimen. Intraoperative and postoperative complications were recorded. MeasurementsLymph node yield and perioperative and postoperative oncological and functional outcomes were measured. Results and limitationsThe median patient age was 38 yr (interquartile range [IQR] 32–41) and the median operative time was 274 min (IQR 238–280). Node metastases were pathologically confirmed in three patients. The median number of lymph nodes removed was 19 (IQR 18–21), and the median number of positive lymph nodes was 2 (IQR 1–3). No patient experienced intraoperative or postoperative complications. The postoperative hospital stay was either 3 or 4 d. Maintenance of antegrade ejaculation was achieved in all patients. After median follow-up of 15 mo (IQR 14–30), all patients were alive and no recurrence was observed. Limitations include the low number of patients and the single surgeon experience. ConclusionsRoboRPLND-NS+ is a safe and feasible technique that allows removal of a high number of lymph nodes with good functional outcomes. Short-term survival outcomes were excellent, with no recurrences or deaths recorded. Patient summaryWe describe a feasible and safe robot-assisted surgical procedure for removal of lymph nodes in patients with testicular cancer. Our technique has potential to decrease the medical problems arising as side effects of the surgery while achieving good cancer control.

Physiology of cholinergic and adrenergic synapses. Role in pharmacology and practical significance

The transmission of signals between cholinergic neurons and from neurons to muscle cells (neuro-neuronal and neuromuscular transduction) occurs through synapses. They are formed by the membranes of two contacting cells, presynaptic and postsynaptic, which are separated by a narrow synaptic gap. The review article provides up-to-date information about the physiological processes in cholinergic and adrenergic synapses. The role of these synapses in pharmacology and their practical significance are presented. The transmission of excitation in cholinergic synapses occurs with the help of acetylcholine. The stages of synthesis, storage and release of acetylcholine are the same in all cholinergic neurons. The specific effects of acetylcholine mediated through cholinergic synapses depend mainly on the type of synaptic cholinergic receptors. In the system of efferent innervation, adrenergic synapses are formed by the endings of postganglionic sympathetic (adrenergic) fibers and cells of effector organs.

Review of the external carotid plexus: anatomy, function, and clinical manifestations.

The external carotid plexus is a combination of postganglionic sympathetic fibers derived from the superior cervical ganglion. This plexus travels along the external carotid artery and continues onto the artery’s branches. The external carotid plexus plays an important role in innervating the mid and lower face. Therefore, implications to the plexus may result in facial abnormalities. Herein, we review the anatomy, function, and review its clinical applications.

Neurodegenerative disorders affecting the autonomic nervous system: Pure autonomic failure and multiple system atrophy

AbstractPure autonomic failure (PAF) and multiple system atrophy (MSA) are representative neurodegerative diseases present with a severe autonomic dysfunction in the urinary, cardiovascular, and pupillary systems, as well as the gastrointestinal tract and skin/sweat glands. Clinically PAF is characterized by chronic progressive pure autonomic dysfunction occasionally associated with parkinsonism or cognitive dysfunction (Lewy body disease), whereas MSA is associated with cerebellar manifestation and/or parkinsonism. Pathology of both PAF and MSA is characterized by α‐synuclein deposition, but in PAF major involvement exists in the sympathetic ganglion and postganglionic autonomic nerve fibers, whereas MSA mainly affects the central autonomic system, such as the vagal nerve lateral nucleus, locus coeruleus, spinal cord medial lateral nucleus, and sacral Onuf's nucleus. Therefore, it is necessary to evaluate whether peripheral or central autonomic function is predominantly affected by the differential diagnosis of PAF and MSA. Autonomic dysfunction is also frequently present in patients with Parkinson's disease, but usually not so severe as in PAF or MSA. This review summarizes features of autonomic dysfunction in PAF and MSA.

AIDA directly connects sympathetic innervation to adaptive thermogenesis by UCP1.

The sympathetic nervous system-catecholamine-uncoupling protein 1 (UCP1) axis plays an essential role in non-shivering adaptive thermogenesis. However, whether there exists a direct effector that physically connects catecholamine signalling to UCP1 in response to acute cold is unknown. Here we report that outer mitochondrial membrane-located AIDA is phosphorylated at S161 by the catecholamine-activated protein kinase A (PKA). Phosphorylated AIDA translocates to the intermembrane space, where it binds to and activates the uncoupling activity of UCP1 by promoting cysteine oxidation of UCP1. Adipocyte-specific depletion of AIDA abrogates UCP1-dependent thermogenesis, resulting in hypothermia during acute cold exposure. Re-expression of S161A-AIDA, unlike wild-type AIDA, fails to restore the acute cold response in Aida-knockout mice. The PKA-AIDA-UCP1 axis is highly conserved in mammals, including hibernators. Denervation of the sympathetic postganglionic fibres abolishes cold-induced AIDA-dependent thermogenesis. These findings uncover a direct mechanistic link between sympathetic input and UCP1-mediated adaptive thermogenesis.

Distribution and morphology of sensory and autonomic fibres in the subendocardial plexus of the rat heart.

Cardiac reflexes originating from sensory receptors in the heart ensure blood supply to vital tissues and organs in the face of constantly changing demands. Atrial volume receptors are mechanically sensitive vagal afferents which relay to the medulla and hypothalamus, affecting vasopressin release and renal sympathetic activity. To date, two anatomically distinct sensory endings have been identified which may subserve cardiac mechanosensation: end‐nets and flower‐spray endings. To map the distribution of atrial receptors in the subendocardial space, we have double‐labelled rat right atrial whole mounts for neurofilament heavy chain (NFH) and synaptic vesicle protein 2 (SV2) and generated high‐resolution maps of the rat subendocardial neural plexus at the cavo‐atrial region. In order to elucidate the nature of these fibres, double labelling with synaptophysin (SYN) and either NFH, calcitonin gene‐related peptide (CGRP), choline acetyltransferase (ChAT) or tyrosine hydroxylase (TH) was performed. The findings show that subendocardial nerve nets are denser at the superior cavo‐atrial junction than the mid‐atrial region. Adluminal plexuses had the finest diameters and stained positively for synaptic vesicles (SV2 and SYN), CGRP and TH. These plexuses may represent sympathetic post‐ganglionic fibres and/or sensory afferents. The latter are candidate substrates for type B volume receptors which are excited by stretch during atrial filling. Deeper nerve fibres appeared coarser and may be cholinergic (positive staining for ChAT). Flower‐spray endings were never observed using immunohistochemistry but were delineated clearly with the intravital stain methylene blue. We suggest that differing nerve fibre structures form the basis by which atrial deformation and hence atrial filling is reflected to the brain.

Исследование иннервации двенадцатиперстной кишки крысы с использованием нейральных иммуногистохимических маркеров

The purpose of the work is to study the topography, morphology, and mediator status of the nerve apparatus of the rat duodenum using immunohistochemical methods. The use of markers selective for the peripheral nervous system (PGP 9.5, synaptophysin (Syn), serotonin (5HT) and tyrosine hydroxylase (TH) made it possible to reveal in the tissues of the intestinal wall, in addition to the two main submucosal and myienteral ganglionic nerve plexuses), the third plexus is the mucous epithelium villous. Using comparative immunohistochemical analysis, it was found that most of the nerve structures (neurons, nerve fibers, interneuronal and neuromuscular synapses in the ganglion plexuses) are PGP 9.5-immunopositive and cholinergic. There are no catecholaminergic and serotonergic (5HT +) neurons in the studied ganglion plexuses. It is assumed that postganglionic sympathetic fibers enter the duodenum from the outside. They participate in the innervation of the muscle layers of the intestinal wall and arterial vessels, form pericellular synapses on the bodies and dendrites of parasympathetic neurons. A large number of terminal varicose axons were found in the connective tissue of the villi using PGP 9.5, and single bipolar neuron-like cells were found in the epithelium. Sympathetic elements in the villi were not identified. A reaction to serotonin revealed a large number of serotonin-containing cells that were morphologically similar to enterochromaffinocytes.

Innervation of the thoracolumbar fascia.

The aim of the study was to obtain information on the sensory functions of the thoracolumbar fascia (TLF). The types of nerve fibres present in the TLF were visualized with specific antibodies to neuropeptides and sympathetic fibres. Most data were obtained from the TLF in rats, but some findings from the human fascia are also included. The only receptive nerve ending found was the free nerve ending, i.e. no corpuscular receptors existed in our specimen. An exclusive innervation with free nerve endings speaks for a nociceptive function, but the TLF may also fulfill proprioceptive functions, since many of the free nerve endings have a low mechanical threshold. Most of the fibres could be visualized with antibodies to CGRP [calcitonin gene- related peptide (CGRP)] and SP [substance P (SP)]. The latter ones most likely were nociceptors. The TLF contained a great proportion of postganglionic sympathetic fibres, which may be vasoconstrictors. A comparison between an inflamed and intact fascia showed an increase of the CGRP- and SP-positive fibres in the inflamed TLF. This finding could be one explanation for the low back pain of many patients, since practically all lesions of the fascia are accompanied by a sterile inflammation.

Neural Responses of the Cervical Sympathetic Chain to Barorecepter Activation and to Hypoxic Challenge in Sprague‐Dawley Rats

The superior cervical ganglion (SCG) and cervical sympathetic chain (CSC) contain cell bodies that project to the cerebral arteries, and to peripheral structures such as the carotid bodies and upper airways. Despite the importance of these pathways, little is known about how the CSC responds to baroreceptor stimuli and to hypoxic challenges that mimic upper airway obstruction and central apneas. To characterize sensory control of CSC activity, we anesthetized male Sprague‐Dawley rats (275–300g) with isoflurane (2%) and placed bipolar recording electrodes under the CSC at approximately 3 mm caudal to the SCG, and a blood pressure catheter into the left femoral artery (Telemetry Research, model TR56SP). A catheter was placed in the left femoral vein for intravenous (IV) injections. Heart rate, blood pressure (BP), and multi‐fiber CSC neural activity were recorded during 10% oxygen challenge, tracheal occlusion, and during IV drug administration. At the end of the protocol, the rats were euthanized to determine background noise activity. In on‐going studies (n = 4), we found that CSC recordings yielded typical sympathetic responses to phenlyephrine (2.5 μg) and sodium nitroprusside (2.5 μg). For phenyephrine, BP increased by 24 ± 5 mmHg with CSC decreases of 100% baseline to 69 ± 11%. For sodium nitroprusside, BP decreased by 26 ± 3 mmHg with CSC increases of 100% to 111 ± 14%. Ganglionic blockade with hexamethonium (10 mg/kg) decreased BP by 49 ± 2 mmHg and lowered CSC activity by 69 ± 8%. Temporary occlusion of the tracheal airway decreased BP by 16 ± 4 mmHg and increased CSC activity from 100% to 120 ± 17%. Finally, a 1 min 10% oxygen challenge lowered BP by 33 ± 9 mmHg but did not alter CSC activity (100% to 103 ± 5%). These findings indicate that the CSC, just caudal to the SCG, contains approximately 69% post‐ganglionic sympathetic nerve fibers. These nerve fibers respond appropriately to baroreceptor loading and unloading, and show increased activity to temporary upper airway occlusion.Support or Funding InformationThis work was supported in part by NIH award 3OT2OD023680‐01S2 and Galvani BioelectronicsThis abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Evidence for differential control of muscle sympathetic single units during mild sympathoexcitation in young, healthy humans.

Two subpopulations of muscle sympathetic single units with opposite discharge characteristics have been identified during low-level cardiopulmonary baroreflex loading and unloading in middle-aged adults and patients with heart failure. The present study sought to determine whether similar subpopulations are present in young healthy adults during cardiopulmonary baroreflex unloading ( study 1) and rhythmic handgrip exercise ( study 2). Continuous hemodynamic and multiunit and single unit muscle sympathetic nerve activity (MSNA) data were collected at baseline and during nonhypotensive lower body negative pressure (LBNP; n = 12) and 40% maximal voluntary contraction rhythmic handgrip exercise (RHG; n = 24). Single unit MSNA responses were classified as anticipated or paradoxical based on whether changes were concordant or discordant with the multiunit MSNA response, respectively. LBNP and RHG both increased multiunit MSNA burst frequency (∆5 ± 3 bursts/min, P < 0.001; ∆5 ± 8 bursts/min, P = 0.005), burst amplitude (∆5 ± 7%, P = 0.04; ∆13 ± 14%, P < 0.001), and total MSNA (∆302 ± 191 AU/min, P = 0.001; ∆585 ± 556 AU/min, P < 0.001). During LBNP and RHG, 43 and 64 muscle single units were identified, respectively, which increased spike frequency (∆9 ± 11 spikes/min, P < 0.001; ∆10 ± 19 spikes/min, P < 0.001) and the probability of multiple spike firing (∆10 ± 12%, P < 0.001; ∆11 ± 26%, P = 0.001). During LBNP and RHG, 36 (84%) and 39 (61%) single units possessed anticipated firing responses (∆12 ± 10 spikes/min, P < 0.001; ∆19 ± 19 spikes/min, P < 0.001), whereas 7 (16%) and 25 (39%) single units exhibited paradoxical reductions (∆-3 ± 1 spikes/min, P = 0.003; ∆-4 ± 5 spikes/min, P < 0.001). The observation of divergent subpopulations of muscle sympathetic single units in healthy young humans during two mild sympathoexcitatory stressors supports differential control at the fiber level as a fundamental characteristic of human sympathetic regulation. NEW & NOTEWORTHY The activity of muscle sympathetic single units was recorded during cardiopulmonary baroreceptor unloading and rhythmic handgrip exercise in young healthy humans. During both stressors, the majority of single units (84% and 61%) exhibited anticipated behavior concordant with the integrated muscle sympathetic response, whereas a smaller proportion (16% and 39%) exhibited paradoxical sympathoinhibition. These results support differential control of postganglionic muscle sympathetic fibers as a characteristic of human sympathetic regulation during mild sympathoexcitatory stress. Listen to this article's corresponding podcast at https://ajpheart.podbean.com/e/differential-control-of-sympathetic-outflow-in-young-humans/ .

Assessing changes in tissue oxygenation by near-infrared spectroscopy following brachial plexus block for arteriovenous fistula surgery: A prospective observational pilot study.

Near-infrared spectroscopy (NIRS) can be used to measure tissue oxygen saturation (StO2) in different sites and in a wide range of clinical scenarios. Peripheral regional anaesthesia induces vascular changes causing increased arterial blood flow and venodilatation, but its effect on StO2 is still under debate. This is especially so for patients undergoing arteriovenous fistula surgery, wherein latest data suggest an improved outcome under brachial plexus block (BPB) compared with local anaesthesia, but no data are available. The aim of this study was to investigate changes in StO2 following BPB prior to arteriovenous fistula surgery using NIRS. A prospective observational study. A secondary teaching hospital from August 2016 to March 2017. Fifteen patients undergoing arteriovenous fistula surgery. Ultrasound-guided BPB in 15 patients undergoing arteriovenous fistula surgery. StO2 at baseline and compared with baseline and the contralateral arm following BPB measured using NIRS of the thenar eminence (NIRSth). Baseline values of StO2 assessed by NIRSth were 42.6 ± 7.7% in the arteriovenous fistula arm and 42.7 ± 9.7% in the contralateral arm. There was no significant difference between the two. Five minutes after BPB, there was a significant increase in StO2 of the blocked arm, compared with the control arm expressed as difference of absolute values (7.1 ± 9.7%). At 60 min, an absolute difference of 21.0 ± 13.5% was reached. The absolute increase in StO2 of the blocked arm compared with baseline reached significance after 5 min (8.8 ± 4.6%) and increased up to 23.2 ± 8.2% after 60 min. NIRSth indicates that BPB significantly increases StO2 of the arteriovenous fistula arm in patients undergoing haemodialysis. Clinicaltrials.gov: NCT03044496.

Superior Cervical Ganglionectomy alters Glomus Cell Potassium‐Channel Properties in Response to Hypoxia

The carotid body (CB) chemosensory glomus (type I) cells respond to changes in blood PO2, PCO2, and pH by releasing neurotransmitters that increase action potential discharge of chemosensory afferent fibers within the carotid sinus nerve (CSN). The CSN then signals to the nucleus tractus solitarius (NTS) within the dorsal brainstem, which leads to a compensatory increase in ventilation in order to restore blood gas levels and pH. Along with the CSN, the ganglioglomerular nerve (GGN) also innervates the carotid body. The GGN consists of post‐ganglionic sympathetic fibers, which originate from the superior cervical ganglion (SCG). Stimulation of the GGN causes an increase in CB chemosensory afferent discharge. However, it is unknown whether loss of sympathetic input to the CB directly alters the chemosensitivity of glomus cells. Our objective was to characterize electrophysiological properties of CB glomus cell potassium (K+) channels in response to acute hypoxia following superior cervical ganglionectomy (SCGx). Sprague Dawley (SD) male rats postnatal (P) 21 were subjected to unilateral (right) SCGx. The left SCG was identified, but not removed. Four days post surgery at P25 the right and left carotid bodies were removed, and primary glomus cells were isolated and plated on coverslips. Glomus cell K+ channel properties were then recorded using the whole‐cell perforated patch‐clamp technique. Our preliminary results reveal that following unilateral (right) SCGx, glomus cells respond to hypoxia with significant reductions (P&lt;0.05 to P&lt;0.01) in outward K+ current amplitudes over the test potential range +10 to +60 mV. The mean maximal effect, a reduction in K+ amplitude of 64.9 ± 18.5% (mean ± SD, n = 3 cells), occurred at a Vtest of +30 mV. In contrast, wild‐type control CB glomus cells respond to hypoxia with a significant reduction (P&lt;0.05) in outward K+ current amplitude at only a Vtest of +60 mV (n = 4 cells). In addition, glomus cells from SCGx rats appear to respond to hypoxia via a different population of K+ channels that do not appear to be presently active in wild‐type glomus cells when exposed to hypoxia. These findings demonstrate that loss of sympathetic input from the SCG increases CB glomus cell sensitivity to hypoxia, and modulates the O2‐sensing capabilities of glomus cell K+ channels.Support or Funding InformationNIH‐SPARC 1OT2OD023860‐02 SJLewisThis abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

A Preliminary Study Into Meniscal Innervation in 2 Horses With Different Degrees of Chondropathy in the Femorotibial Joint

Osteoarthritis is a painful degenerative disease, sometimes responsible for the premature ending of the careers of sporting horses. In humans, meniscal neurogenesis has been suggested to contribute to pain in osteoarthritis. To the best of our knowledge, no study on this subject has been performed in equine species. The aim of this report was to compare the density of the nociceptive and sympathetic nerves in the menisci of two 11- and 13-year-old mares, one presenting a “low-chondropathy grade” in its stifle and the other a “high-chondropathy grade”. The cranial horns of the medial menisci, a commonly reported site of equine meniscal injuries, were harvested after a maximum of 48 hours postmortem. A macroscopic and microscopic grading system was established using a modified Pauli score. Nociceptive fibers were highlighted by immunohistochemical staining with an antibody against Substance P (SP) and postganglionic sympathetic fibers with an antibody against tyrosine hydroxylase (TH). Descriptive statistics were calculated, and a nonparametric statistical test was used to analyze the data. The meniscus from the “high-chondropathy horse (HCH)” showed a higher density and frequency of postganglionic sympathetic nerves compared with the meniscus of the “low-chondropathy horse (LCH)”. No difference was observed regarding nociceptive nerves. This report shows possible meniscal sympathetic efferent-mediated pain in a “highly chondropathic horse”. Although these results cannot be extended to the equine population as a whole because of the small sample size, they are nevertheless interesting as they provide new information regarding the possible etiology of the pain in equine stifle osteoarthritis.