Clinical and Immune Responses of Peripheral Chemical Sympathectomy in Enterovirus 71 Infection.

The activation of the sympathetic nervous system, release of norepinephrine (NE), and adrenergic receptor signaling participate in and regulate the complicated enterovirus 71 (EV71) brainstem encephalitis (BE). The neurotoxin 6-hydroxydopamine (6-OHDA) selectively ablates sympathetic nerves and markedly depletes NE in innervated organs. Changes in the plasma levels of NE, severity score, cytokine profiles, and percentages of immunophenotype expression in 7-day-old Bltw : CD1 (ICR) mice infected with EV71, with or without 6-OHDA treatment, were compared. The survival rate (76.9%) of EV71-infected and 6-OHDA (30 µg/g)-treated mice was increased significantly. The clinical scores were decreased markedly on days 8-12 in MP4-infected and 6-OHDA-treated mice compared to those without treatment. The results showed that the plasma levels of NE, epinephrine, and dopamine were decreased on days 4-8 after 6-OHDA treatment and at most on day 8. The plasma levels of interleukin (IL)-12p70, tumor necrosis factor, IL-6, and IL-10 did not change significantly after 6-OHDA treatment. Interferon-γ levels decreased evidently on days 4, 6, and 8 after 6-OHDA treatment. The absolute events of CD3+CD4+, CD3+CD8+, and CD3+NK1.1+ cells of peripheral blood mononuclear cells were increased significantly in MP4-infected and 6-OHDA-treated mice compared to those without treatment. In splenocytes, the absolute cells of CD3-NK1.1+, CD3+NK1.1+ and CD11b+Gr-1+ cells of EV71-infected mice were increased significantly after 6-OHDA treatment. These findings suggested that 6-OHDA may be used a probe to explore clinical improvements and immune responses in the complicated EV71 infection. Taken together, peripheral chemical sympathectomy contribute to further understand the immunopathogenesis of EV71 BE with autonomic nervous system dysregulation.

A case of migraine treatment in a patient with a clinical diagnosis of CHARGE syndrome using onabotulinum toxin A.

CHARGE syndrome is a genetic disorder that affects multiple organ and sensory systems. Cranial nerve involvement is one of the key clinical diagnostic criteria. We present the case of an 8-year-old girl with CHARGE syndrome, associated right-sided facial palsy, and chronic severe migraines, that were intractable to medical treatment. At age 6, onabotulinum toxin A was used to weaken the contralateral non-paralyzed side of her face to address her stigmatizing asymmetry. Onabotulinum toxin A chemodenervation was performed on the left lower lip depressors to relax the muscles and improve left lower lip position. Coincidentally, it was noted that with these treatments, migraine symptoms resolved. As the chemodenervation subsided over the next 3-4 months, the severe migraines returned. Continued treatment with onabotulinum toxin A injections every 3 months has resulted in ongoing improvements in facial symmetry and migraine control. Onabotulinum toxin A is a well-known treatment of chronic migraine. Injections are usually directed to the occipitalis, frontalis, and corrugator muscles. The literature has no reports of injections to the lower lip depressors as a useful therapy for migraine, making the results from this case unique.

Renal Sympathetic Denervation by Image-Guided Percutaneous Ethanol Injection - Histopathologic Characteristics, Efficacy and Safety.

PURPOSE: Evaluation of the efficacy and safety of chemical renal denervation by image-guided periarterial ethanol injection in pigs with emphasis on histopathological characteristics. MATERIALS AND METHODS: Unilateral renal periarterial ethanol injection under general anesthesia was performed in 16 animals with the contralateral kidney serving as the control. All interventions were performed in an open MRI system under real-time multiplanar guidance. In 10 pigs an ethanol-carbostesin contrast agent mixture was injected with amounts of 5 ml (6 animals, group I) and 10 ml (4 animals, group II). 6 pigs (group III) were treated with 10 ml of an ethanol-polyacrylic (2 %) mixture. Four weeks after treatment, all animals underwent MRI including MRA. After euthanasia, macroscopic and histologic examination of the kidneys, renal arteries and periarterial tissue was performed to assess nerve injury and potential side effects. Furthermore, the norepinephrine concentration (RTNEC) in the renal tissue was determined as a surrogate parameter of efficacy. RESULTS: Histologic signs of nerval degeneration with various degrees of severity and circumferential distribution were found in all groups. Injury depths ranged up to 7.6 mm. In groups II and III the nerve count was significantly lower on the treated side. Renal artery stenosis was not observed in any pig. In all pigs of group II treatment resulted in neural degeneration with a mean RTNEC reduction of 53 % (p < 0.02). In groups I and III significant changes in RTNEC were not observed. CONCLUSION: Image-guided percutaneous periarterial ethanol injection was efficient and safe for renal denervation. The detected variations in histologic outcome underlined the importance of the preclinical optimization of the technique in order to maximize treatment effects in humans. KEY POINTS: · Renal denervation by percutaneous periarterial ethanol injection is an effective and potentially safe procedure.. · The percutaneous approach is less prone to anatomical and procedural limitations compared to catheter-based procedures.. · The achievable nerve injury depth lies beyond those of current RFA-probes.. · Efficacy depends on amount, concentration, viscosity and periarterial distribution of the ethanol-mixture.. · Establishing an optimal balance between these parameters is mandatory for a maximum treatment effect at minimum risk for sensitive adjacent structures.. CITATION FORMAT: · Freyhardt P, Haage P, Walter A et al. Renal Sympathetic Denervation by Image-Guided Percutaneous Ethanol Injection - Histopathologic Characteristics, Efficacy and Safety. Fortschr Röntgenstr 2020; 192: 549 - 560.

Pharmacological properties of ß-adrenoceptors mediating rat superior mesenteric artery relaxation and the effects of chemical sympathetic denervation.

AIMS: ß-Adrenoceptors (ß-ADRs) mediating the relaxation of rat superior mesenteric arteries (SMAs) were pharmacologically identified, and the effects of chemical sympathetic denervation on ß-ADR-mediated relaxation were examined. MAIN METHODS: The tension changes of endothelium-denuded SMAs were isometrically recorded and the mRNA of endothelium-denuded SMA ß-ADR was detected using RT-PCR. KEY FINDINGS: In endothelium-denuded SMAs contracted with ≥10-7 M phenylephrine (an α1-ADR agonist), isoprenaline (a ß-ADR agonist)-induced relaxation was competitively inhibited by 3 × 10-9-10-8 M propranolol (a ß1,2-ADR antagonist), but not further affected by ≥10-8 M propranolol. Although isoprenaline-induced relaxation was not affected by ICI-118,551 (10-9-10-8 M; a ß2-ADR antagonist), it was competitively inhibited by atenolol (10-7-3 × 10-7 M; a ß1-ADR antagonist) in the presence of ICI-118,551. In the presence of 10-7 M propranolol, isoprenaline- and CGP-12177A (a ß3-ADR partial agonist)-induced relaxation was competitively inhibited by high concentrations of bupranolol (a ß1,2,3-ADR antagonist), with pA2 values of 6.49 and 5.76, respectively. We detected the mRNA of ß1- and ß3-ADRs in endothelium-denuded SMAs. Treatment with 6-hydroxydopamine (a catecholaminergic neurotoxin) reduced maximal isoprenaline-induced relaxation in the presence and absence of 10-7 M propranolol, but not CGP-12177A-induced relaxation. SIGNIFICANCE: Isoprenaline-induced relaxation of rat SMAs is mediated by ß1- and ß3-ADRs. ß-ADR-mediated relaxation of rat SMAs is shown to be attenuated by chemical sympathetic denervation. The differences in the effects of bupranolol and chemical sympathetic denervation on the responses to isoprenaline and CGP-12177A in rat SMAs might be explained by the possible presence of multiple ß3-ADRs with different pharmacological properties.

Chemical sympathectomy attenuates lipopolysaccharide-induced increase of plasma cytokine levels in rats pretreated by ACTH.

The sympathetic nervous system participates significantly in the regulation of immune functions. In support of this, data indicate that besides vagal afferent and efferent pathway, sympathetic nerves represent crucial component of inflammatory reflex. In addition, it was shown that efferent arm of this reflex might be activated by ACTH. Therefore, we investigated the effect of chemical sympathectomy on lipopolysaccharide (LPS)-induced increases in plasma IL-1ß, IL-6, and TNF-α levels in rats. Plasma IL-10 and corticosterone levels were also evaluated. We also investigated the effect of sympathectomy in rats pretreated with ACTH (1-24). We found that sympathectomy significantly attenuated LPS-induced increases of plasma IL-1ß levels. Administration of ACTH (1-24) reduced LPS-induced increases of plasma IL-1ß and IL-6 and exaggerated the rise of IL-10. In animals treated with ACTH (1-24) sympathectomy attenuated LPS-induced increases of IL-1ß, IL-6, and IL-10 plasma levels. Plasma levels of TNF-α and corticosterone were not affected by any interventions. These data indicate that during acute immune challenge, sympathetic nerves stimulate the immune response. In addition, our data indicate that sympathetic nerves are not significantly involved in the anti-inflammatory effect of ACTH (1-24) and that the anti-inflammatory effect of ACTH (1-24) is independent of plasma corticosterone levels.

Cardiac Afferent Denervation Abolishes Ganglionated Plexi and Sympathetic Responses to Apnea: Implications for Atrial Fibrillation.

Background The autonomic nervous system response to apnea and its mechanistic connection to atrial fibrillation (AF) are unclear. We hypothesize that sensory neurons within the ganglionated plexi (GP) play a role. We aimed to delineate the autonomic response to apnea and to test the effects of ablation of cardiac sensory neurons with resiniferatoxin (RTX), a neurotoxic TRPV1 (transient receptor potential vanilloid 1) agonist. Methods Sixteen dogs were anesthetized and ventilated. Apnea was induced by stopping ventilation until oxygen saturations decreased to 80%. Nerve recordings from bilateral vagal nerves, left stellate ganglion, and anterior right GP were obtained before and during apnea, before and after RTX injection in the anterior right GP (protocol 1, n=7). Atrial effective refractory period and AF inducibility on single extrastimulation were assessed before and during apnea, and before and after intrapericardial RTX administration (protocol 2, n=9). GPs underwent immunohistochemical staining for TRPV1. Results Apnea increased anterior right GP activity, followed by clustered crescendo vagal bursts synchronized with heart rate and blood pressure oscillations. On further oxygen desaturation, a tonic increase in stellate ganglion activity and blood pressure ensued. Apnea-induced effective refractory period shortening from 110.20±31.3 ms to 90.6±29.1 ms ( P<0.001), and AF induction in 9/9 dogs versus 0/9 at baseline. After RTX administration, increases in GP and stellate ganglion activity and blood pressure during apnea were abolished, effective refractory period increased to 126.7±26.9 ms ( P=0.0001), and AF was not induced. Vagal bursts remained unchanged. GP cells showed cytoplasmic microvacuolization and apoptosis. Conclusions Apnea increases GP activity, followed by vagal bursts and tonic stellate ganglion firing. RTX decreases sympathetic and GP nerve activity, abolishes apnea's electrophysiological response, and AF inducibility. Sensory neurons play a role in apnea-induced AF.

The effects of retinol oral supplementation in 6-hydroxydopamine dopaminergic denervation model in Wistar rats.

Vitamin A (retinol) is involved in signaling pathways regulating gene expression and was postulated to be a major antioxidant and anti-inflammatory compound of the diet. Parkinson's disease (PD) is a progressive neurodegenerative disorder, characterized by loss of nigral dopaminergic neurons, involving oxidative stress and pro-inflammatory activation. The aim of the present study was to evaluate the neuroprotective effects of retinol oral supplementation against 6-hydroxydopamine (6-OHDA, 12 µg per rat) nigrostriatal dopaminergic denervation in Wistar rats. Animals supplemented with retinol (retinyl palmitate, 3000 IU/kg/day) during 28 days exhibited increased retinol content in liver, although circulating retinol levels (serum) were unaltered. Retinol supplementation did not protect against the loss of dopaminergic neurons (assessed through tyrosine hydroxylase immunofluorescence and Western blot). Retinol supplementation prevented the effect of 6-OHDA on Iba-1 levels but had no effect on 6-OHDA-induced GFAP increase. Moreover, GFAP levels were increased by retinol supplementation alone. Rats pre-treated with retinol did not present oxidative damage or thiol redox modifications in liver, and the circulating levels of TNF-α, IL-1ß, IL-6 and IL-10 were unaltered by retinol supplementation, demonstrating that the protocol used here did not cause systemic toxicity to animals. Our results indicate that oral retinol supplementation is not able to protect against 6-OHDA-induced dopaminergic denervation, and it may actually stimulate astrocyte reactivity without altering parameters of systemic toxicity.

CT-Guided Chemical Thoracic Sympathectomy versus Botulinum Toxin Type A Injection for Palmar Hyperhidrosis.

BACKGROUND: The present study aimed to evaluate and compare the efficacy of botulinum toxin type A (BTX-A) injection versus thoracic sympathectomy for idiopathic palmar hyperhidrosis. METHODS: Fifty-one patients with idiopathic palmar hyperhidrosis were treated with either BTX-A injection or thoracic sympathectomy between March 2013 and April 2016. The severity of palmar hyperhidrosis was qualitatively measured via the Hyperhidrosis Disease Severity Scale (HDSS). All patients completed a questionnaire that detailed the time taken for the treatment to work, local or systemic adverse effects, and pre- and post-treatment severity of hyperhidrosis. The efficacy and adverse effects of the two treatments were compared and analyzed. RESULTS: Hyperhidrosis-related quality of life improved quickly and significantly in the BTX-A group (26 patients) and the sympathectomy group (25 patients). Compared with pre-treatment, the HDSS score significantly reduced after treatment in both groups (p < 0.05). All patients in the sympathectomy group had cessation of sweating of the hands after treatment, and this curative effect lasted for 12 months. In contrast, the treatment took more time to work in the BTX-A group, and the curative effect lasted for a much shorter period (3 months). The sympathectomy group had a significantly lesser mean HDSS score than the BTX-A group at 1 week, 3 months, 6 months, 9 months, and 12 months after treatment (p < 0.05). The sympathectomy group experienced more complications than the BTX-A group. CONCLUSION: For palmar hyperhidrosis, thoracic sympathectomy is more effective and has a longer lasting curative effect than BTX-A injection, but thoracic sympathectomy has more complications.

Chemical lumbar sympathectomy in the treatment of recalcitrant erythromelalgia.

OBJECTIVE: Erythromelalgia is highly disabling and treatment is often very challenging. There have been solitary case reports that it might benefit from sympathectomy. This study sought to evaluate the short-term and long-term efficacy of chemical lumbar sympathectomy (CLS) for treatment of recalcitrant erythromelalgia and try to identify a CLS-responsive subset. METHODS: Patients with recalcitrant erythromelalgia were recruited from a tertiary hospital over a 10-year period. L3 to L4 CLS was performed using 5% phenol. The pain intensity score (visual analog scale [VAS] 0-10) was assessed before CLS and at 1 day, 1 week, 3 months, 6 months, 1 year, and 2 years after CLS. A VAS decrease of 90%-100% is defined as complete response, 60%-89% as major partial response. Relapse was defined by a return of a VAS score of 5 or higher. SCN9A gene mutations were screened. RESULTS: Thirteen patients were enrolled, with a median age of 15 years. The mean follow-up was 6.2 ± 3.8 years. SCN9A gene mutation was identified in five patients having family histories. The VAS was 8.2 ± 2.0 at baseline; it decreased to 4.9 ± 2.7 at 1 day and 1.9 ± 3.0 at 1 week after CLS. Nine patients (69.2%) achieved complete response at 1 week after CLS, including three patients with SCN9A gene mutation. Among the three complete response patients having the gene mutation, two reverted to major partial response and one relapsed at 2 years after CLS. Among the six complete response patients without mutation, five maintained complete response and one relapsed. Among the four patients who did not achieve complete response, one patient died at 3.5 months and one patient had an amputation performed at 4 months after CLS. CONCLUSIONS: CLS provides a valid option for the treatment of recalcitrant erythromelalgia. It takes about 1 week to achieve full efficacy. Relapse may occur, especially in patients with an SCN9A gene mutation.

Targeted ablation of cardiac sympathetic neurons improves ventricular electrical remodelling in a canine model of chronic myocardial infarction.

Aims: The purpose of this study was to evaluate the cardiac electrophysiologic effects of targeted ablation of cardiac sympathetic neurons (TACSN) in a canine model of chronic myocardial infarction (MI). Methods and results: Thirty-eight anaesthetized dogs were randomly assigned into the sham-operated, MI, and MI-TACSN groups, respectively. Myocardial infarction-targeted ablation of cardiac sympathetic neuron was induced by injecting cholera toxin B subunit-saporin compound in the left stellate ganglion (LSG). Five weeks after surgery, the cardiac function, heart rate variability (HRV), ventricular electrophysiological parameters, LSG function and neural activity, serum norepinephrine (NE), nerve growth factor (NGF), and brain natriuretic peptide (BNP) levels were measured. Cardiac sympathetic innervation was determined with immunofluorescence staining of growth associated protein-43 (GAP43) and tyrosine hydroxylase (TH). Compared with MI group, TACSN significantly improved HRV, attenuated LSG function and activity, prolonged corrected QT interval, decreased Tpeak-Tend interval, prolonged ventricular effective refractory period (ERP), and action potential duration (APD), decreased the slopes of APD restitution curves, suppressed the APD alternans, increased ventricular fibrillation threshold, and reduced serum NE, NGF, and BNP levels. Moreover, the densities of GAP43 and TH-positive nerve fibres in the infarcted border zone in the MI-TACSN group were lower than those in the MI group. Conclusion: Targeted ablation of cardiac sympathetic neuron attenuates sympathetic remodelling and improves ventricular electrical remodelling in the chronic phase of MI. These data suggest that TACSN may be a novel approach to treating ventricular arrhythmias.

First Clinical Experience With Targeted REnal Nerve Demodulation (TREND-1) Using a Neurotropic Agent for the Treatment of Sympathetic Hypertension.

AIMS: To evaluate the feasibility and safety of a novel targeted neuromodulatory treatment for sympathetic hypertension involving a one-time local injection of neurotropic agents near renal nerves. METHODS AND RESULTS: Seven patients suffering from uncontrolled hypertension per ESH-ESC guidelines were treated using a single dose of NW2013, a neurotropic Na+/K+ ATPase antagonist. A microneedle catheter was used to administer 1.2 mL of NW2013 (0.6 mL per artery) to the perivascular space surrounding renal arteries using percutaneous endovascular procedures under fluoroscopic guidance. All patients were successfully treated without any procedural complications. Patients were followed for 12 months post procedure, and office and 24-hour ambulatory blood pressure measurements were made. Both office and ambulatory blood pressures were lower at 24 hours, 1 month, and 3 months after treatment. The decrease in office blood pressure was greater than the decrease in ambulatory blood pressure. A reduction in medication regimen was also observed in 2 patients. One patient suffered a cerebrovascular event after 6-month follow-up and died from stroke, unrelated to the treatment. Overall, the reduction in office and ambulatory blood pressure was sustained over the course of 12 months. CONCLUSIONS: Treatment of hypertension using local administration of NW2013 near renal nerves appears to be feasible and safe. Large, controlled, randomized, and blinded clinical studies with monitoring of patient compliance to daily oral medication are recommended to further establish the efficacy of this novel treatment.

Lumbar Sympathetic Neurolysis: How to and When to Use?

Lumbar sympathectomy was historically a mainstay of treatment for arterial occlusive disease and other vasospastic disorders, before the development of contemporary arterial reconstructive procedures either by surgical or endovascular means. Today, percutaneous methods of sympathetic blockade are possible using chemical neurolytic or ablative modalities. Lumbar sympathetic neurolysis is generally reserved for those patients with ischemic rest pain in the setting of nonreconstructable arterial occlusive disease, although patients with complex regional pain syndrome, peripheral neuralgia, vasospastic disorders, and various other disease states such as plantar hyperhydrosis may also benefit. A working knowledge of procedural anatomy and physiology, accompanied by appropriate patient selection, serve to maximize procedural success and minimize complications, which although infrequent may cause significant morbidity. A review of technique with a focus on traditional fluoroscopy is described, with attention drawn to intraprocedural and immediate postprocedural findings, as well as discussion of expected outcomes.

Nonoperative Management of Chronic Exertional Compartment Syndrome: A Systematic Review.

Although nonoperative treatment options for chronic exertional compartment syndrome (CECS) are often used in clinical practice, supporting evidence is limited. The objective of this study was to systematically review the literature for nonsurgical treatment options for CECS of the lower leg. The literature search identified seven articles describing in total four different treatment options: massage, gait changes, chemodenervation, and ultrasound-guided (USG) fascial fenestration. Pertinent studies were in the form of case series and one case report, which limited the robustness of the data. Nevertheless, all four treatment options have little to no reported adverse effect profiles and can be considered in clinical practice. In addition, gait changes and USG fascial fenestration were found to have continued effect at 1 and 1.5 years, respectively.

Lumbar Sympathetic Block with Botulinum Toxin Type B for Complex Regional Pain Syndrome: A Case Study.

Lumbar sympathetic block (LSB) is an effective method for relief of sympathetically mediated pain in the lower extremities. To prolong the sympathetic blockade, sympathetic destruction with alcohol or radiofrequency has been used. The pre-ganglionic sympathetic nerves are cholinergic, and botulinum toxin (BTX) has been found to inhibit the release of acetylcholine at the cholinergic nerve terminals. Moreover, BTX type B (BTX-B) is more convenient to use than BTX type A. Based on these findings, we performed LSB on the 2 patients with complex regional pain syndrome (CRPS) in the lower extremity. Levobupivacaine 0.25% 5 mL mixed with BTX-B 5,000 IU was given under fluoroscopic guidance. Two months after LSB with BTX-B, pain intensity and the Leeds assessment of neuropathic symptoms and signs (LANSS) score were significantly reduced. Allodynia and coldness disappeared and skin color came back to normal. In conclusion, BTX-B can produce an efficacious and durable sympathetic blocking effect on patients with CRPS.

Chemical lumbar sympathectomy in the treatment of idiopathic livedo reticularis.

OBJECTIVE: Livedo reticularis (LR) is a reticulated discoloration of the skin, particularly on lower extremities. Few treatment options are reported. This study investigated the efficacy and safety of chemical lumbar sympathectomy (CLS) in idiopathic LR. The key technique points of CLS are also illustrated in detail. METHODS: Patients with idiopathic LR with a strong desire for treatment were recruited during a 2.5-year period. L3-4 CLSs were performed with 5% phenol (2 mL) in each injection site. The needle tip extends to approximately one-third of the vertical dividing line of the vertebral body. The contrast along the psoas muscle fibers indicates targeting on gray rami communicans instead of the sympathetic trunk. The primary efficacy variable was achieving "clear or almost clear" of LR lesions staying >1 hour in a 24°C air-conditioned room. Safety assessments included monitoring and recording of all adverse events and tolerability to treatment. The follow-up period was 2.5 to 4.7 years. RESULTS: Ten women (median age, 22 years) were enrolled. Seven patients achieved "clear or almost clear" of LR lesions after CLS. The postoperative skin surface temperature increase was 7.4°C ± 2.6°C. Two patients achieved "major partially resolved," and one patient achieved "minor partially resolved." Two of the seven with "clear or almost clear" results reported recurrence ≤1 year during the follow-up, CLS was repeated, and they then achieved "clear or almost clear" again. Two patients reported mild pain localized to the thigh area, which resolved spontaneously by the second day. CONCLUSIONS: This study showed CLS provides a valid option for the treatment of idiopathic LR. The efficacy of CLS can be long-lasting, and CLS can be repeated if LR recurs. Targeting at gray rami communicans, rather than the sympathetic trunk, is comparably effective and safer for sympathetic interruption.

Norepinephrine Regulates Condylar Bone Loss via Comorbid Factors.

Degenerative changes of condylar subchondral bone occur frequently in temporomandibular disorders. Although psychologic stresses and occlusal abnormalities have been implicated in temporomandibular disorder, it is not known if these risks represent synergistic comorbid factors that are involved in condylar subchondral bone degradation that is regulated by the sympathetic nervous system. In the present study, chronic immobilization stress (CIS), chemical sympathectomy, and unilateral anterior crossbite (UAC) were sequentially applied in a murine model. Norepinephrine contents in the subjects' serum and condylar subchondral bone were detected by ELISA; bone and cartilage remodeling parameters and related gene expression in the subchondral bone were examined. Subchondral bone loss and increased subchondral bone norepinephrine level were observed in the CIS and UAC groups. These groups exhibited decreased bone mineral density, volume fraction, and bone formation rate; decreased expressions of osterix, collagen I, and osteocalcin; but increased trabecular separation, osteoclast number and surface, and RANKL expression. Combined CIS + UAC produced more severe subchondral bone loss, higher bone norepinephrine level, and decreased chondrocyte density and cartilage thickness when compared to CIS or UAC alone. Sympathectomy simultaneously prevented subchondral bone loss and decreased bone norepinephrine level in all experimental subgroups when compared to the vehicle-treated counterparts. Norepinephrine also decreased mRNA expression of osterix, collagen I, and osteocalcin by mesenchymal stem cells at 7 and 14 d of stimulation and increased the expression of RANKL and RANKL/OPG ratio by mesenchymal stem cells at 2 h. In conclusion, CIS and UAC synergistically promote condylar subchondral bone loss and cartilage degradation; such processes are partially regulated by norepinephrine within subchondral bone.

Chemical sympathectomy restores baroreceptor-heart rate reflex and heart rate variability in rats with chronic nitric oxide deficiency.

Nitric oxide (NO) plays a crucial role not only in regulation of blood pressure but also in maintenance of cardiac autonomic tone and its deficiency induced hypertension is accompanied by cardiac autonomic dysfunction. However, underlying mechanisms are not clearly defined. We hypothesized that sympathetic activation mediates hemodynamic and cardiac autonomic changes consequent to deficient NO synthesis. We used chemical sympathectomy by 6-hydroxydopamine to examine the influence of sympathetic innervation on baroreflex sensitivity (BRS) and heart rate variability (HRV) of chronic N(G)-nitro-L-arginine methyl ester (L-NAME) treated adult Wistar rats. BRS was determined from heart rate responses to changes in systolic arterial pressure achieved by intravenous administration of phenylephrine and sodium nitroprusside. Time and frequency domain measures of HRV were calculated from 5-min electrocardiogram recordings. Chronic L-NAME administration (50 mg/kg per day for 7 days orally through gavage) in control rats produced significant elevation of blood pressure, tachycardia, attenuation of BRS for bradycardia and tachycardia reflex and fall in time as well as frequency domain parameters of HRV. Sympathectomy completely abolished the pressor as well as tachycardic effect of chronic L-NAME. In addition, BRS and HRV improved after removal of sympathetic influence in chronic L-NAME treated rats. These results support the concept that an exaggerated sympathetic activity is the principal mechanism of chronic L-NAME hypertension and associated autonomic dysfunction.

Retroperitoneal hemorrhage from an unrecognized puncture of the lumbar right segmental artery during lumbar chemical sympathectomy: diagnosis and management.

Lumbar chemical sympathectomy has been performed using fluoroscopic guidance for needle positioning. An 84 year old woman with atherosclerosis obliterans was referred to the pain clinic for intractable cold allodynia of her right foot. A thermogram showed decreased temperature of both feet compared with temperatures above both ankles. The patient agreed to undergo lumbar chemical sympathectomy using fluoroscopy after being informed of the associated risks of nerve injury, hemorrhage, infection, transient back pain, and transient hypotension. During the procedure and three hours afterward, no abnormal signs or symptoms were found except an increase in right leg temperature. The patient was ambulatory after the procedure. However, one day after undergoing lumbar chemical sympathectomy, she visited our emergency department for abdominal discomfort and postural dizziness. Her blood pressure was 80/50 mmHg, and flank tenderness was noted. Retroperitoneal hemorrhage from the second right lumbar segmental artery was shown on computed tomography and angiography. Vital signs were stabilized immediately after embolization into the right lumbar segmental artery.

Chemical renal denervation by vincristine: the role of the flow rate of delivery.

PURPOSE: Vincristine has been proven promising regarding its safety and efficacy for the renal artery denervation both in experimental models and in humans. The aim of the study was to compare in an experimental model the efficacy of constant versus random flow rate delivery of vincristine on renal sympathetic denervation. METHODS: We used 10 juvenile Landrace swine. After the introduction of a 7F sheath into the femoral artery, a guide wire was advanced into the distal part of the renal artery. Then the first delivery balloon catheter, which delivers vincristine in random flow rate, was advanced at the proximal part of the artery, and the balloon was inflated in order to locally deliver vincristine to the media of the renal artery. The process was repeated in the contralateral renal artery, with the use of the double balloon catheter that delivers vincristine with a constant flow rate. Euthanasia of the animals was performed at 28 days. All sections were processed for histological and immunohistochemical analysis. RESULTS: The delivery of vincristine with both catheters was successful and uncomplicated. Immunohistochemistry showed that the mean number of intact nerves in all sections was significantly lower in the group of vincristine delivered with constant flow catheter compared to the group that the delivery was performed in a random fashion. (1.48 ± 0.37 vs. 1.70 ± 0.41, p = 0.04). CONCLUSION: Chemical renal denervation with vincristine by a constant flow rate catheter is more effective compared to the denervation performed by a catheter that delivers vincristine in a random fashion.