Thoracic Sympathetic Nerve Research Articles

Peritoneal sepsis caused by Escherichia coli triggers brainstem inflammation and alters the function of sympatho-respiratory control circuits

BackgroundSepsis has a high mortality rate due to multiple organ failure. However, the influence of peripheral inflammation on brainstem autonomic and respiratory circuits in sepsis is poorly understood. Our working hypothesis is that peripheral inflammation affects central autonomic circuits and consequently contributes to multiorgan failure in sepsis.MethodsIn an Escherichia coli (E. coli)–fibrin clot model of peritonitis, we first recorded ventilatory patterns using plethysmography before and 24 h after fibrin clot implantation. To assess whether peritonitis was associated with brainstem neuro-inflammation, we measured cytokine and chemokine levels in Luminex assays. To determine the effect of E. coli peritonitis on brainstem function, we assessed sympatho-respiratory nerve activities at baseline and during brief (20 s) hypoxemic ischemia challenges using in situ-perfused brainstem preparations (PBPs) from sham or infected rats. PBPs lack peripheral organs and blood, but generate vascular tone and in vivo rhythmic activities in thoracic sympathetic (tSNA), phrenic and vagal nerves.ResultsRespiratory frequency was greater (p < 0.001) at 24 h post-infection with E. coli than in the sham control. However, breath-by-breath variability and total protein in the BALF did not differ. IL-1β (p < 0.05), IL-6 (p < 0.05) and IL-17 (p < 0.04) concentrations were greater in the brainstem of infected rats. In the PBP, integrated tSNA (p < 0.05) and perfusion pressure were greater (p < 0.001), indicating a neural-mediated pathophysiological high sympathetic drive. Moreover, respiratory frequency was greater (p < 0.001) in PBPs from infected rats than from sham rats. Normalized phase durations of inspiration and expiration were greater (p < 0.009, p < 0.015, respectively), but the post-inspiratory phase (p < 0.007) and the breath-by-breath variability (p < 0.001) were less compared to sham PBPs. Hypoxemic ischemia triggered a biphasic response, respiratory augmentation followed by depression. PBPs from infected rats had weaker respiratory augmentation (p < 0.001) and depression (p < 0.001) than PBPs from sham rats. In contrast, tSNA in E. coli-treated PBPs was enhanced throughout the entire response to hypoxemic ischemia (p < 0.01), consistent with sympathetic hyperactivity.ConclusionWe show that peripheral sepsis caused brainstem inflammation and impaired sympatho-respiratory motor control in a single day after infection. We conclude that central sympathetic hyperactivity may impact vital organ systems in sepsis.

Comparison of CT-guided thoracic sympathetic nerve block and radiofrequency in the treatment of primary palmar hyperhidrosis.

Primary palmar hyperhidrosis (PPH) is a condition marked by an overactive secretion of the hand's exocrine glands and is frequently hereditary. The profuse sweating associated with this condition can significantly impair the patient's daily activities and quality of life. The objective of this study was to compared the benefits and drawbacks of thoracic sympathetic block and thoracic sympathetic radiofrequency in the treatment of PPH. A retrospective analysis was conducted on 69 patients. They were divided into groups A and B according to their treatment. Group A (34 cases) received CT-guided percutaneous thoracic sympathetic nerve chain anhydrous alcohol chemical damage block, and group B (35 cases) received CT-guided percutaneous thoracic sympathetic nerve chain radiofrequency thermocoagulation. Palmar sweating disappeared immediately after the operation. The recurrence rates at 1, 3, 6, 12, 24, and 36 months were 5.88% vs. 2.86% (P > 0.05), 20.59% vs. 5.71% (P > 0.05), 32.35% vs. 11.43% (P < 0.05),32.35% vs. 11.43% (P < 0.05), 25% vs. 14.71% (P < 0.05), and 68.75% vs. 20.59% (P < 0.05), respectively. The incidence of intercostal neuralgia and compensatory hyperhidrosis was higher in group A compared with of group B (52.94% vs. 22.86%, P < 0.05; 55.88% vs. 22.86%, P < 0.05). Both methods were found to be effective in treating PPH, but thoracic sympathetic radiofrequency had a longer-term effect, a lower recurrence rate, and a lower incidence of intercostal neuralgia and compensatory hyperhidrosis than a thoracic sympathetic block.

Sympathetic dysregulation induced by postnatal intermittent hypoxia.

Exposure to postnatal chronic intermittent hypoxia (pCIH), as experienced in sleep-disordered breathing, is a risk factor for developing cardiorespiratory diseases in adulthood. pCIH causes respiratory instability and motor dysfunction that persist until adult life. In this study, we investigated the impact of pCIH on the sympathetic control of arterial pressure in rats. Neonate male Holtzman rats (P0-1) were exposed to pCIH (6% O2 for 30 seconds, every 10 minutes, 8 h/day) during their first 10-15 days of life, while control animals were maintained under normoxia. In early adult life (P25-40), freely behaving pCIH animals (n = 13) showed higher baseline arterial pressure levels linked to augmented sympathetic-mediated variability than control animals (n = 12, p < 0.05). Using decerebrated in situ preparations, we found that juvenile pCIH rats exhibited a twofold increase in thoracic sympathetic nerve activity (n = 14) and elevated firing frequency of ventromedullary presympathetic neurons (n = 7) compared to control rats (n = 6-7, p < 0.05). This pCIH-induced sympathetic dysregulation was associated with increased HIF-1α (hypoxia-inducible factor 1 alpha) mRNA expression in catecholaminergic presympathetic neurons (n = 5, p < 0.05). At older age (P90-99), pCIH rats displayed higher arterial pressure levels and larger depressor responses to ganglionic blockade (n = 6-8, p < 0.05), confirming the sympathetic overactivity state. pCIH facilitates the vasoconstrictor sympathetic drive by mechanisms associated with enhanced firing activity and HIF-1α expression in ventromedullary presympathetic neurons. This excessive sympathetic activity persists until adulthood resulting in high blood pressure levels and variability, which contribute to developing cardiovascular diseases.

Efficacy of Radiofrequency Thermocoagulation of the Thoracic Sympathetic Nerve versus Chemical Excision in Pain Caused by Raynaud's Disease.

To investigate the effectiveness and safety of computed tomography (CT)-guided radiofrequency thermocoagulation (RFTC) of the thoracic sympathetic nerve versus chemical resection (CTS) for the treatment of pain caused by Raynaud's disease. Patients who underwent CTS or thoracic sympathetic nerve RFTC between March 2012 and March 2021 were enrolled in this retrospective study. There were 28 cases in the alcohol group (Group A) and 44 in the radiofrequency group (Group R). Visual analog scores (VAS) were collected from patients at different time points, as well as preoperative and postoperative finger end perfusion index (PI) and hand temperature (T). The efficiency, postoperative recurrence rate, complications, and improvement in postoperative quality of life were observed in both groups. Pain scores at different follow-up times after surgery decreased in both groups compared to the preoperative period (P < 0.05). Postoperative T and PI were higher in both groups than preoperatively all (P < 0.05). The recurrence rate was higher in the R group than in the A group. Postoperative complications were observed in 13.6% and 25% of patients in groups R and A, respectively. Meanwhile, the postoperative quality of life improved in both groups, but the radiofrequency (RF) group was better than the alcohol group in terms of improvement in quality of life (P < 0.05). Both CT-guided CTS and RFTC of the thoracic sympathetic nerve provided good treatment outcomes. However, the RF group was superior to the alcohol group in terms of complication rate and quality of life improvement.

Use of thoracoscopy for thoracic sympathetic nerve block in primary hyperhidrosis

Thoracic sympathetic nerve block (TSNB) has been widely used in the treatment of neuropathic pain. To reduce block failure rates, TSNB is assisted with several modalities including fluoroscopy, computed tomography, and ultrasonography. The present study describes our experience assessing the usefulness of thoracoscopy in TSNB for predicting compensatory hyperhidrosis before sympathectomy in primary hyperhidrosis. From September 2013 to October 2021, TSNB was performed under local anesthesia using a 2-mm thoracoscope in 302 patients with severe primary hyperhidrosis. Among the 302 patients, 294 were included for analysis. The target level of TSNB was T3 in almost all patients. The mean procedure time was 21 min. Following TSNB, the mean temperature of the left and right palms significantly changed from 31.5 to 35.3 °C and from 31.5 to 34.8 °C, respectively. With TSNB, primary hyperhidrosis was relieved in all patients. Pneumothorax occurred in six patients, in which no chest tube insertion was required. One patient developed hemothorax and was discharged the next day after small-bore catheter drainage. Transient ptosis developed in 10 patients and improved within a day in all patients. Our experiences showed that thoracoscopic TSNB is accurate, safe, and feasible to block the thoracic sympathetic nerve in patients with severe primary hyperhidrosis.

Norepinephrine/β2-Adrenergic Receptor Pathway Promotes the Cell Proliferation and Nerve Growth Factor Production in Triple-Negative Breast Cancer.

Invasive ductal carcinoma (IDC) accounts for 90% of triple-negative breast cancer (TNBC). IDC is mainly derived from the breast ductal epithelium which is innervated by the 4th to 6th thoracic sympathetic nerves. However, little is known about the contribution of the interactions between sympathetic nerves and breast cancer cells to the malignant progression of TNBC. The expression levels of the β2-adrenergic receptor (β2-AR, encoded by ADRB2 gene), nerve growth factor (NGF), and tropomyosin receptor kinase A (TrkA) were determined using immunohistochemistry (IHC). NGF expression levels in the serum were compared by enzyme-linked immunosorbent assay (ELISA). Cell proliferation was assessed using the Cell Counting Kit-8 assay. The β2-AR, NGF, p-ERK, and p-CERB expression levels were determined using western blotting. TNBC cells and neuronal cells of the dorsal root ganglion (DRG) in 2-day-old Sprague Dawley rats were co-cultured. Using norepinephrine (NE), NGF, and β2-AR, NGF/TrkA blocker pretreatments, the axon growth of each group of DRG neuron cells was detected by immunofluorescence analysis. The sympathetic adrenergic neurotransmitter NE activated the ERK signaling pathway in TNBC cells. NE/β2-AR signaling promotes NGF secretion. NGF further facilitates the malignant progression of TNBC by increasing sympathetic neurogenesis. In the co-culture assay, the sympathetic adrenergic NE/β2-AR signal pathway also enhanced NGF secretion. NGF binds TrkA in DRG neurons and promotes axonal growth. These results suggest that NE/β2-AR pathway promotes cell proliferation and NGF production in triple-negative breast cancer.

Efficacy and safety of sympathetic radiofrequency thermocoagulation in the treatment of cold hypersensitivity.

Cold hypersensitivity (CH) is a sensation of cold in the limbs and (or) body of a patient in an environment that is not considered cold by unaffected people, or a strong feeling of cold at a relatively low temperature. However, the currently available treatments are limited and often unsatisfactory. This study aimed to evaluate the clinical efficacy and safety of the sympathetic radiofrequency thermocoagulation (RF-TC) technique in patients with CH disorder. The study is a retrospective analysis. A total of 71 were entered into the final analysis and all patients underwent computed tomography-guided thoracic (lumbar) sympathetic nerve RF-TC on an elective basis. The values of terminal temperature (T) and perfusion index (PI) of patients before and after treatment were recorded. Patients were followed up clinically at regular intervals and their Visual Analog Scale (VAS) and Pittsburgh Sleep Quality Index (PSQI) scores were recorded to detect postoperative complications and assess patient satisfaction with the treatment. All patients completed the radiofrequency treatment. Compared with the preoperative period, VAS and PSQI scores were significantly lower at all postoperative time periods (P < 0.001). Patients had significantly higher postoperative terminal temperatures and perfusion indices on the right and left sides than before surgery (P < 0.001). The overall patient satisfaction score was 4 (3-5) at 3 years of postoperative follow-up. There were 20 recurrences (28.2%). The main postoperative complications were postoperative local pain and compensatory hyperhidrosis. No other adverse events or deaths were observed. RF-TC for CH could be a feasible, effective, and safe treatment option to improve patients' symptoms of cold sensation. Yet, more researches are needed to verify this potentially efficient and standardized treatment.

Generation, breakdown and responses of ATP in the carotid body

Purinergic signaling involving adenosine triphosphate (ATP) acting on P2X2/3 receptors modulates physiological carotid body (CB) afferent discharge and chemoreflex activation however, the upregulation of P2X3 receptors on petrosal sensory neurons is partly responsible for aberrant CB tonicity and hyperreflexia, and the increase in blood pressure in the Spontaneously Hypertensive rat (SHR). The enhanced chemoreflex occurs prior to the onset of hypertension and elevated CB activity is thought to contribute to the underlying pathophysiology of the disease but the exact mechanisms remain unclear. We hypothesize that there is greater release of ATP and/or decreased ATP breakdown in the pre‐hypertensive SHR CB compared with that in the Wistar rat, and this evokes an increase in the chemoreflex response and subsequent activation of the sympathetic nervous system. We performed three studies. (i) Using digital droplet PCR (ddPCR), we measured mRNA expression levels of enzymes involved in the breakdown of ATP in CBs extracted from male 4‐week‐old prehypertensive SHR and Wistar rats; these included: ectonucleotide pyrophosphatase/phosphodiesterase 1‐3 (Enpp1‐3), ectonucleoside triphosphate diphosphohydrolase 2‐3 (Entpd2‐3), and ecto‐5’‐nucleotidase (Nt5e). (ii) We quantified ATP release from CBs in vitro during baseline conditions and during cyanide‐evoked ATP release using a colorimetric assay (213‐579‐1 ‐ Millipore), comparing between male 4‐week‐old pre‐hypertensive SHR and Wistar rats. (iii) In an in situ working heart‐brainstem preparation of 4‐week‐old Wistar rats, simultaneous recordings were made from phrenic (PN), hypoglossal (HN), recurrent laryngeal (RLN), abdominal (ABN), and thoracic sympathetic nerves (tSNA). The peripheral chemoreceptors were stimulated with either potassium cyanide (KCN 20‐100 μL, 0.04%) or ATP at varying concentrations (10‐100 µL, 50 µM ‐ 2 mM) delivered via the internal carotid artery. In whole CB extracts, ddPCR revealed increased Enpp2‐3 and Nt5e expression (p&lt;0.05) in pre‐hypertensive SHRs relative to Wistar rats suggesting greater capacity to break down ATP in the pre‐hypertensive SHR CB. There were no differences in the expressions of Enpp1 or Entpd2‐3 between rat strains. However, the amount of ATP released from the CB in both baseline and during cyanide stimulation was two‐fold greater in the pre‐hypertensive SHR (P&lt;0.05). Stimulation of the CB with KCN evoked hyperpnoea, bradycardia and sympathoexcitation at all doses. In contrast, CB injection of low dose ATP increased PN rate with little effect on tSNA, whereas higher doses induced apnea accompanied by repetitive burst discharge of post‐inspiratory activity in the RLN with tonic elevations in the discharge of both ABN and tSNA. In sum, despite the upregulation of several ATP degrading enzymes in the CBs of the SHR, CB release of ATP is higher in this species. We hypothesize that the increase in ATP release in the SHR CB drives the CB hyperexcitability and that the shift towards an upregulation of ATP degrading enzymes even prior to the development of hypertension is compensatory to oppose the increase in ATP signaling. The dose‐dependent effect of exogenous ATP at supraphysiological levels evoking greater CB‐mediated expiratory and sympathetic outflow in the Wistar rat mimics aspects of pathophysiological CB chemoreflex signaling in the SHR.

Patterns of cardio-respiratory motor outputs during acute and subacute exposure to chlorpyrifos in an ex-vivo in situ preparation in rats

While a considerable body of literature has characterized the clinical features induced by organophosphate pesticides, the field lacks scrutiny into cardio-respiratory changes in different phases of poisoning. Herein, we evaluated the impact of chlorpyrifos (CPF) and its active metabolite chlorpyrifos-oxon (CPO) on the cardiorespiratory system during acute and subacute phases of poisoning using an in situ experimental rodent model. CPF (30 mg/kg) was injected intraperitoneally to rats beforehand (24 h) whereas CPO (15 mg/kg) was added into the perfusate reservoir to evaluate the effects on the motor outputs throughout the three phases of the respiratory cycle: inspiration, post-inspiration and late expiration. Phrenic, recurrent laryngeal (RLN) and thoracic sympathetic nerve activity (tSNA) were recorded. Heart rate was derived from the electrocardiogram (ECG) and the baro- and chemo-reflexes tested. CPF and CPO led to a time-dependent change in cardiorespiratory motor outputs. In the acute phase, the CPO induced bradypnea, transiently reduced the inspiratory time (TI), and increased the amplitude of phrenic. Post-inspiratory (PI) discharge recorded from the RLN was progressively reduced while tSNA was increased. CPO significantly depressed the chemoreflex but had no effect on baroreflex. During subacute phase, CPF prolongated TI with no effect on respiratory rate. Both the RLN PI discharge, the chemoreflex and the baroreflex sympathetic gain were reduced. In addition, both CPF and CPO shifted the cardiac sympatho-vagal balance towards sympathetic dominance. Our data show that different phases of poisoning are associated with specific changes in the cardio-respiratory system and might therefore demand distinct approaches by health care providers.

S1440 Novel Neuromodulation Treatment Using Repetitive Magnetic Stimulation for Diabetic Gastroparesis: Preliminary Results From a Proof-of-Concept Study

Introduction: Diabetic gastroparesis (DGp) is chartacterized by autonomic neuropathy, for which there are limited effective treatments. Stimulation of thoracic sympathetic and parasympathetic nerves may improve symptoms in patients with diabetic gastroparesis by enhancing gastric contractility. Our aim was to assess safety and feasibility of a novel, non-invasive treatment, Thoracic Splanchnic Magnetic Neuromodulation Therapy (ThorS-MagNT,) for refractory DGp in a proof-of-concept study. Methods: DGp patients, who required hospital admission and without known GI mucosal disease, were included. A mapping procedure in the left and right posterior mid-thoracic regions, using a single-pulse circular 90 mm coil (MAGSTIM, Whitland, UK) determined the location and minimum intensity required to achieve a motor evoked response (MEP) of 10 µV with 50% of trials (resting motor threshold) in the upper rectus abdominis and external oblique muscles. ThorS-MagNT was administered at 50% intensity above motor threshold, using a 70 mm double air film self-cooling coil (MAGSTIM Rapid2) positioned over bilateral pre-determined locations to deliver a total of 1200 stimulations at 1 Hz. Treatments were administered twice daily for five consecutive days. Safety and tolerability data were collected. ANMS GCSI-DD was assessed at baseline and throughout the treatment period. Patients who completed all ten treatments were defined as per protocol. Results: Seven DGp patients (6F; 1M) were enrolled . All subjects tolerated administered treatment sessions. One DGp patient experienced medication-related hypotension-a serious adverse event unrelated to study treatment. After resuscitation and missing one treatment, this subject completed 4 subsequent treatments. One patient reported self-limited tingling and numbness, which resolved after treatment. No other adverse events occurred. In four per protocol subjects, an average of 68.25% reduction in ANMS GCSI-DD score from baseline was observed (Table 1). Two other subjects had an average of 13.95% reduction in ANMS GCSI-DD and one study subject dropped out. Conclusion: ThorS-MagNT appears to be feasible, safe and a promising novel treatment for refractory DGp. Further studies are needed in larger samples to assess its effects on symptoms, hospitalization duration, gastric emptying and safety. Acknowledgement: Supported by the NIDDK Diabetic Complications Consortium grants DK076169 & DK115255.Table 1.: ANMS GCSI-DD scores at baseline versus during treatment.

Changes in the autonomic and respiratory patterns of mice submitted to short‐term sustained hypoxia

Short-term sustained hypoxia (SH) in rats induces changes in sympathetic-respiratory coupling and sympathetic overactivity, which seems to be linked to hypertension. However, there is no previous experimental data about the effects of SH on the autonomic and respiratory pattern in mice. In the present study we tested the hypothesis that mice submitted to SH present autonomic and respiratory changes similarly to rats. To reach this goal we evaluated the effects of 24-hour SH exposure on cardiovascular, respiratory and autonomic parameters in baseline conditions and upon chemoreflex activation.C57BL/6J mice (7-8 weeks old, ~25g) were deeply anesthetized for femoral artery and jugular vein catheterization. Four days later, they were submitted to SH (24h, FiO2 0.1) or normoxia. At the end of SH protocol, arterial pressure, heart rate and ventilation were recorded in vivo. Peripheral chemoreflex was activated via KCN injection (0.16 mg/Kg, i.v.). In another experimental group, we performed in situ recordings of phrenic (PN), abdominal, (AbN), cervical vagus (cVN) and thoracic sympathetic (tSN) nerves activities of SH mice using the working heart-brainstem preparation. All experimental protocols were approved by the Institutional Ethics Committee (#140/2019 and #163/2019). In the in vivo approach, although SH mice (n=13) presented a significant decrease in baseline HR (510 ± 22 vs 633 ± 16 beats min-1; P = 0.002) compared with the controls (n=17), no differences were observed in mean arterial pressure levels (109 ± 2 vs 106 ± 2 mmHg; P=0.443). SH mice (n=14) also showed significantly increased respiratory frequency [(fR) 277 ± 8 vs 203 ± 6 breaths.min-1; P <0.0001], tidal volume [(VT) 14 ± 1 vs. 12 ± 1mL.Kg1; P = 0.0019)], and ventilation [(VE) 3927 ± 164 vs 2390 ± 104 mL.Kg-1.min-1; P < 0.0001)] compared with controls (n=17). The magnitudes of bradycardic responses to chemoreflex activation were greater in SH mice (n=8) than in controls (n=11; -329 ± 36 vs -210 ± 30 beats min-1, P=0.02). In the in situ approach, baseline PN discharge (PND) frequency was significantly reduced in SH mice (n=11) in relation to controls (n=26) (0.69 ± 0.06 vs 1.13 ± 0.10 Hz, P=0.0154). The incidence of Late-E bursts in AbN activity in SH mice (n=10) was significantly increased in relation to controls (n=20) (83.3 ± 7.7 vs 24.3 ± 8.0%, P<0.0001). The duration of expiration in SH mice (n=11) was longer than in controls (n=22) (1.13 ± 0.16 vs 0.67 ± 0.07s, P= 0.0002) due to an increase in the duration of post-inspiration (0.78 ± 0.12 vs 0.35 ± 0.04s, P= 0.0032). tSNA in the SH group (n=10) was significantly reduced during late-expiration (E2) compared with the control group (n=16) (19.0 ± 4.3 vs 39.7 ± 4.2%, P= 0.0203). The data are showing that 24-h SH protocol in mice produces: a) an increase in parasympathetic tone to the heart, which seems to be related to changes in their breathing pattern; and b) prolonged expiration and active expiration associated with a reduction in sympathetic activity during E2. This autonomic imbalance favoring the parasympathetic componente may explain why mice, different of rats, do not develop hypertension after SH.

Changes in the autonomic and respiratory patterns in mice submitted to short-term sustained hypoxia.

What is the central question of this study? Do mice submitted to sustained hypoxia present autonomic and respiratory changes similarly to rats? What is the main finding and its importance? Arterial pressure in the normal range, reduced baseline heart rate and tachypnoea were observed in behaving sustained hypoxia mice. Recordings in the in situ preparation of mice submitted to sustained hypoxia show an increase in cervical vagus nerve activity and a simultaneous reduction in thoracic sympathetic nerve activity correlated with changes in the respiratory cycle. Therefore, mice are an important model for studies on the modulation of sympathetic activity to the cardiovascular system and the vagus innervation of the upper airways due to changes in the respiratory network induced by sustained hypoxia. Short-term sustained hypoxia (SH) in rats induces sympathetic overactivity and hypertension due to changes in sympathetic-respiratory coupling. However, there are no consistent data about the effect of SH on mice due to the different protocols of hypoxia and difficulties associated with the handling of these rodents under different experimental conditions. In situ recordings of autonomic and respiratory nerves in SH mice have not been performed yet. Herein, we evaluated the effects of SH ( =0.1 for 24h) on baseline mean arterial pressure (MAP), heart rate (HR), respiratory frequency (fR ) and responses to chemoreflex activation in behaving SH mice. A characterization of changes in cervical vagus (cVN), thoracic sympathetic (tSN), phrenic (PN) and abdominal (AbN) nerves in SH mice using the in situ working heart-brainstem preparation was also performed. SH mice presented normal MAP, significant reduction in baseline HR, increase in baseline fR , as well as increase in the magnitude of bradycardic response to chemoreflex activation. In in situ preparations, SH mice presented a reduction in PN discharge frequency, and increases in the time of expiration and incidence of late-expiratory bursts in AbN activity. Nerve recordings also indicated a significant increase in cVN activity and a significant reduction in tSN activity during expiration in SH mice. These findings make SH mice an important experimental model for better understanding how changes in the respiratory network may impact on the modulation of vagal control to the upper airways, as well as in the sympathetic activity to the cardiovascular system.

The role of glycinergic inhibition in respiratory pattern formation and cardio-respiratory coupling in rats.

Cardio-respiratory coupling is reflected as respiratory sinus arrhythmia (RSA) and inspiratory-related bursting of sympathetic nerve activity. Inspiratory-related inhibitory and/or postinspiratory-related excitatory drive of cardiac vagal motoneurons (CVMs) can generate RSA. Since respiratory oscillations may depend on synaptic inhibition, we investigated the effects of blocking glycinergic neurotransmission (systemic and local application of the glycine receptor (GlyR) antagonist, strychnine) on the expression of the respiratory motor pattern, RSA and sympatho-respiratory coupling. We recorded heart-rate, phrenic, recurrent laryngeal and thoracic sympathetic nerve activities (PNA, RLNA, t-SNA) in a working-heart-brainstem preparation of rats, and show that systemic strychnine (50–200 ​nM) abolished RSA and triggered a shift of postinspiratory RLNA into inspiration, while t-SNA remained unchanged. Bilateral strychnine microinjection into the ventrolateral medullary area containing CVMs and laryngeal motoneurons (LMNs) of the nucleus ambiguus (NA/CVLM), the nucleus tractus solitarii, pre-Bötzinger Complex, Bötzinger Complex or Kölliker-Fuse nuclei revealed that only NA/CVLM strychnine microinjections mimicked the effects of systemic application. In all other target nuclei, except the Bötzinger Complex, GlyR-blockade attenuated the inspiratory-tachycardia of the RSA to a similar degree while evoking only a modest change in respiratory motor patterning, without changing the timing of postinspiratory-RLNA, or t-SNA. Thus, glycinergic inhibition at the motoneuronal level is involved in the generation of RSA and the separation of inspiratory and postinspiratory bursting of LMNs. Within the distributed ponto-medullary respiratory pre-motor network, local glycinergic inhibition contribute to the modulation of RSA tachycardia, respiratory frequency and phase duration but, surprisingly it had no major role in the mediation of respiratory-sympathetic coupling.

Selective Peripheral Chemoreceptor Hyperreflexia Evoked after Sympathetic Stimulation

Previous studies have demonstrated that the integrity of the carotid bodies is essential for the development and maintenance of hypertension. In this condition, both increased tonicity and hyperreflexia are displayed by chemosensitive neurons in the petrosal ganglia of spontaneous hypertensive rats (SHR). However, what drives carotid body hyper‐excitability is not known. We hypothesised this was triggered by the sympathetic nerves innervating the carotid body, which originate from the superior cervical ganglion (SCG). The aim of our study was test if activation of the SCG could modulate carotid body activity. Experiments were carried out in 6 juvenile Wistar rats (60–80g) using the decerebrated in situ working heart‐brainstem preparation (WHBP). Simultaneous recordings of phrenic (PN) and thoracic sympathetic nerves (tSNA) were obtained using glass suction electrodes. Heart rate (HR) was derived from the electrocardiogram (ECG). Chemoreflex was activated using NaCN (50μL, 0.04%, i.a.) and the SCG was stimulated electrically (ES; 30Hz, 2 ms, 10V) using a Grass SD9 stimulator via a bipolar microelectrode. The chemoreflex was evoked before and immediately after ES of the SCG. Changes in sympathetic activity, perfusion pressure, phrenic and heart rate were analysed quantitatively. Data are displayed as mean ± SEM with a level of significance set at P&lt;0.05; differences were tested using paired student‐t test.The only component of the chemoreflex augmented by SCG stimulation was the evoked increase in sympathetic activity. In Wistars, the control response of 29.3 ± 3.2% from baseline was augmented to 46.04 ± 3.58% after ES (P=0.006). Within 10 min of the stimulation, the sympatho hyperreflexia had returned to control (20.24 ± 5.96%). SHR also presented sympatho hyperreflexia (43.0 ± 6.3 vs 62.9 ± 9.2 %, P= 0.015) but the change of sensitization was of similar magnitude between rat strains. The SCG induced carotid body hyperreflexia was prevented by application of lignocaine into the SCG. We conclude that stimulation of the efferent sympathetic nerves innervating the carotid body can increase the gain of the chemoreflex symathoexcitatory response. We are currently assessing whether chemoreflex hyperreflexia observed in neurogenic hypertension is mediated by sympathetic nerves innervating the carotid body.Support or Funding InformationHealth Research Council of New Zealand

Prevention of pneumothorax in CT-guided thoracic sympathetic nerve block

Objective To explore the measures for prevention of pneumothorax in CT-guided thoracic sympathetic block. Methods The clinical data of 769 patients with hyperhidrosis or Raynaud syndrome treated with CT-guided chemical destructive block of thoracic sympathetic nerve chain in Jiaxing First Hospital from January 2010 to December 2017 were retrospective analyzed. The CT-guided thoracic sympathetic nerve block puncture was performed with a special blunt needle outside the wall pleura above the caput costae following the principle of safe distance and advance only. After exclusion of pneumothorax by CT scan, 2.5 ml of absolute ethanol mixed with 30% iohexol 0.25 ml was injected on both sides of thoracic sympathetic nerve chain. Results The punctures were successfully performed in all 769 patients (1 538 nerve chain segments) and no pneumothorax occurred. After treatment with absolute ethanol injection, Horner syndrome occurred in 31 patients, which disappeared after injecting saline into the stellate ganglion; and intercostal neuralgia occurred in 188 patients after surgery, which was healed in 1 to 3 months. Conclusion It is suggested that pneumothorax can be avoided through CT guidance, using appropriate needles and puncture techniques during the procedure of thoracic sympathetic nerve chain block. Key words: Sympathectomy, chemical; Ganglia, sympathetic, thoracic; Intraoperative complications; Pneumothorax

The evaluation of clinical efficacy with radiofrequency ablation of thoracic sympathetic nerve in the treatment of cardiac dysfunction

The evaluation of clinical efficacy with radiofrequency ablation of thoracic sympathetic nerve in the treatment of cardiac dysfunction

Pectoral Nerve Block and Erector Spinae Plane Block and Post-Breast Surgery Complications

Background: The use of regional methods in various types of surgery such as mastectomy is very popular today. Various methods, including Pecs I-II block, erector spinae, epidural thoracic, and paravertebral block have been used in these operations, each with its own advantages and disadvantages. Recent studies on the effect of μ receptor stimulation on the likelihood of recurrence and metastasis have been published, which make the use of a suitable regional approach with low complications and high efficacy attractive. Among the side effects of breast surgery in patients with cancer are nausea and vomiting, the risk of which is reduced through regional procedures that reduce the need for opioids. Methods: We randomly divided 64 patients into two pectoralis block (Pecs B) and erector spinae block (ESB) groups. Visual analogue scale (VAS) scores at 2, 4, 6, and 10 hours, nausea and vomiting, need for opioids, and hemodynamic changes were recorded. Results: The analyses showed that pain score was significantly higher in the Pecs B group compared to the ESB group, while VAS score, as well as the frequency of opioid use, were lower, which could be due to medial branch of the anterior intercostal nerve. Hemodynamic changes were also significantly greater in the ESB group, which could be due to the proximity of the block to the thoracic sympathetic nerves and spinal cord. Conclusions: Despite the statistically significant differences in analgesia and hemodynamic changes, the seemingly superiority of the Pecs B is not clinically significant and the use of both types of the block is selective. Regarding the need for opioids and nausea, Pecs B showed a tangible advantage over ESB.

Computed Tomography (CT)-Guided Percutaneous Thoracic Sympathetic Chain Radiofrequency Thermocoagulation for Raynaud Disease.

BACKGROUND We introduce a minimally invasive technique for the treatment of Raynaud disease - CT-guided percutaneous thoracic sympathetic chain radiofrequency thermocoagulation. MATERIAL AND METHODS Under CT guidance, the radiofrequency needle was punctured from the upper edge of the costotransverse joint to the anterior superior edge of the 4th capitulum costae and the lateral parietal pleura. After sensorial (1.5 mA, 50 Hz) and motorial (1.5 mA, 2Hz) testing to determine that there was no nerve innervation zone with muscle numbness and twitches, radiofrequency coagulation was set at 95°C for 300 s. RESULTS A total of 17 patients were enrolled in the treatment group. All the patients underwent CT-guided percutaneous thoracic sympathetic chain puncture of the needles to the upper edge of the 4th capitulum costae on both sides. The perfusion index (PI) of the fingers began to rise 30 s after radiofrequency thermocoagulation, and the palm temperature (T) began to rise after 90 s. At the end of treatment, PI increased by an average of 4.6-fold, and the T average rose by 3.6°C. Postoperative cold-water stimulation testing could no longer induce Raynaud disease. Follow-up was conducted for 1 to 15 months. Two patients were found to have recurrence at 9 months and 13 months, respectively. CONCLUSIONS CT-guided percutaneous thoracic sympathetic nerve chain radiofrequency coagulation can effectively treat Raynaud disease.

Carotid bodies contribute to sympathoexcitation induced by acute salt overload.

What is the central question of this study? Does carotid body input contribute to the hyperosmotic responses? What is the main finding and its importance? The response to NaCl overload is sympathorespiratory excitation. Eliminating the carotid body input reduced sympathoexcitation but did not affect the increase in phrenic burst frequency, whereas eliminating the hypothalamus prevented the tachypnoea and sympathoexcitation. We conclude that the carotid body inputs are essential for the full expression of the sympathetic activity during acute NaCl overload, whereas the tachypnoea depends on hypothalamic mechanisms. Acute salt excess activates central osmoreceptors, which trigger an increase in sympathetic and respiratory activity. The carotid bodies also respond to hyperosmolality of the extracellular compartment, but their contribution to the sympathoexcitatory and ventilatory responses to NaCl overload remains unknown. To evaluate their contribution to acute NaCl overload, we recorded thoracic sympathetic (tSNA), phrenic (PNA) and carotid sinus nerve activities in decorticate insitu preparations of male Holtzman rats (60-100g) while delivering intra-arterial infusions of hyperosmotic NaCl (0.17, 0.3, 0.7, 1.5 and 2.0moll-1 ; 200μl infusion over 25-30 s, with a 10min time interval between solutions) or mannitol (0.3, 0.5, 1.0, 2.7 and 3.8moll-1 ) progressively. The cumulative infusions of hyperosmotic NaCl increased the perfusate osmolality to 341± 5mosmol (kgwater)-1 and elicited an immediate increase in PNA and tSNA (n= 6, P< 0.05) in sham-denervated rats. Carotid body removal attenuated sympathoexcitation (n= 5, P< 0.05) but did not affect the tachypnoeic response. A precollicular transection disconnecting the hypothalamus abolished the sympathoexcitatory and tachypnoeic responses to NaCl overload (n= 6, P< 0.05). Equi-osmolar infusions of mannitol did not alter the PNA and tSNA in sham-denervated rats (n= 5). Sodium chloride infusions increased carotid sinus nerve activity (n= 10, P< 0.05), whereas mannitol produced negligible changes (n= 5). The results indicate that carotid bodies are activated by acute NaCl overload, but not by mannitol. We conclude that the carotid bodies contribute to the increased sympathetic activity during acute NaCl overload, whereas the ventilatory response is mainly mediated by hypothalamic mechanisms.

Interaction between the retrotrapezoid nucleus and the parafacial respiratory group to regulate active expiration and sympathetic activity in rats.

The retrotrapezoid nucleus (RTN) contains chemosensitive cells that distribute CO2-dependent excitatory drive to the respiratory network. This drive facilitates the function of the respiratory central pattern generator (rCPG) and increases sympathetic activity. It is also evidenced that during hypercapnia, the late-expiratory (late-E) oscillator in the parafacial respiratory group (pFRG) is activated and determines the emergence of active expiration. However, it remains unclear the microcircuitry responsible for the distribution of the excitatory signals to the pFRG and the rCPG in conditions of high CO2. Herein, we hypothesized that excitatory inputs from chemosensitive neurons in the RTN are necessary for the activation of late-E neurons in the pFRG. Using the decerebrated in situ rat preparation, we found that lesions of neurokinin-1 receptor-expressing neurons in the RTN region with substance P-saporin conjugate suppressed the late-E activity in abdominal nerves (AbNs) and sympathetic nerves (SNs) and attenuated the increase in phrenic nerve (PN) activity induced by hypercapnia. On the other hand, kynurenic acid (100 mM) injections in the pFRG eliminated the late-E activity in AbN and thoracic SN but did not modify PN response during hypercapnia. Iontophoretic injections of retrograde tracer into the pFRG of adult rats revealed labeled phox2b-expressing neurons within the RTN. Our findings are supported by mathematical modeling of chemosensitive and late-E populations within the RTN and pFRG regions as two separate but interacting populations in a way that the activation of the pFRG late-E neurons during hypercapnia require glutamatergic inputs from the RTN neurons that intrinsically detect changes in CO2/pH.