Does bilateral thoracic sympathectomy predispose to reflex bronchospasm following tracheal intubation?

A 31 year old old non-smoking woman, 60 kg, withouth a history of allergy or asthma was scheduled for left knee arthroscopy. Two months previously she had an uneventful general anesthetic for bilateral thorascopic sympathectomy to treat essential hyperhidrosis.

Immediately following intubation, ventilation became difficult. Chest auscultation revealed bilateral expiratory wheezing associated with decreased air entry and increased airway pressure up to 60 cm H2O. Oxygen saturation, as monitored by pulse oximetry, decreased from 100% to 80%.

The severe bronchospams occured immediately following tracheal intubation, suggesting that it may have been a reflex response which was triggered by instrumentation of the airway under light level of anesthesia.

Sympathectomy results in a decrease of plasma norepinephrine, and parasympathetic predominance which may increase airway resistance.

Thus, patients with essential hyperhidrosis who have undergone bilateral thoracic sympathectomy, may be more liable to develop reflex bronchospams under light levels of anesthesia.

Ahed Zeidan MD
Nazih Nahle MD
Anis Baraka MD FRCA
Sahel General Hospital, American Universisty of Beirut Medical Center

Hypoxaemia is of a major concern during thorascopic sympathectomy

Hypoxaemia is of a major concern during thorascopic sympathectomy. However, the pathophysiology of hypoxaemia and consequent decrease in SpO2 differs between the two anaesthetic techniques. The normal physiological response to massive atelectasis is an increase in pulmonary vascular resistance (hypoxic pulmonary vasoconstriction) with re-routing of blood to well ventilated lung zones and consequent improvement in PaO2. HOWEVER, DURING ENDOBRONCHIAL ANAESTHESIA FOR THORACIC SYMPATHECTOMY THERE IS AN APPARENT FAILURE OF THIS COMPENSATORY MECHANISM. When more then 70% of the lung is atelectatic, compensation by hypoxic pulmonary vasoconstriction appears ineffective. During carbon dioxide insufflation using endobronchial intubation, Hartrey and colleagues reported a decrease in systolic arterial pressure of >20mm Hg in 21% of patients. Similarly we have reported sudden hypotension and bradycardia after injudicious carbon dioxide insufflation. Although extremely rare, sudden cardiac arrest has been reported after left T2-3 sympathetic nerve transection. While the exact pathophysiology of this occurence is unclear, it is postulated that before complete transection of the sympathetic trunk, continuous sympathetic stimulation to the stellate ganglions results in a reduction in the ventricular finrillation threshold, arrhythmia and cosequent cardiac arrest. In an iteresting study of the delayed cardiac effects of T2-$ symtpathectomy, Drott and colleagues demonstrated significantly reduced heart rate at rest, and during both exercise and the recovery phase of exercise. Changes is the electrical axis and shortening of the QT interval have also been reported. Irrespective of the technique used the reported incidence of postoperative pneumpthorax is variable, occuring in 2-15% of cases. In a study by Gothberg, Drott and Claes, postoperative chest x-ray after 1274 procedures, in 602 patients demonstrated that a small apical pneumothroax was a usual occurence. Conclusion: Because of the anaesthetic implications and possible surgical complications, many surgeons are reluctant to perform transthoracic sympathectomy. British Journal of Anaesthesia 1997; 79: 113-119 B. Fredman, D. Olsfanger and R. Jedeikin

Left, but not right, one-lung ventilation causes hypoxemia during endoscopic transthoracic sympathectomy

Anesth Analg 2000;90:28
© 2000 International Anesthesia Research Society

---

CARDIOVASCULAR ANESTHESIA

Sequential Changes of Arterial Oxygen Tension in the Supine Position During One-Lung Ventilation

Seiji Watanabe, MD, Eiko Noguchi, MD, Shinichi Yamada, MD, Nobuya Hamada, MD, and Tatsuhiko Kano, MD

Department of Anesthesiology, Kurume University School of Medicine, Fukuoka, Japan

Implications: Close observation and prompt counteractions including termination of one-lung ventilation (OLV) are crucial for patients under OLV in the supine position, because life-threatening hypoxemia frequently occurs approximately 10 min after starting OLV, even under 100% oxygen inhalation. The left semilateral decubitus position was as effective as the left lateral decubitus position in avoiding life-threatening hypoxemia during OLV.

Incidence of chest wall paresthesia after needlescopic video-assisted thoracic surgery for palmar hyperhidrosis

Alan D.L. Sihoe, Clement S.K. Cheung, Ho-Kei Lai, Tak-Wai Lee, Kin-Hoi Thung, Anthony P.C. Yim^*

Department of Surgery, Division of Cardiothoracic Surgery, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, Hong Kong SAR, China

Received 5 September 2004; received in revised form 28 September 2004; accepted 22 October 2004.

^* Corresponding author. Tel.: +86 852 2632 2629; fax: +86 852 2647 8273. (E-mail: yimap@cuhk.edu.hk).

Objective: Chest wall paresthesia is a reported sequela of thoracotomy and Video-Assisted Thoracic Surgery (VATS) which is distinct from wound pain. Although needlescopic VATS confers less post-operative pain and better cosmesis, the incidence of paresthesia after needlescopic VATS has not been quantified. Methods: For homogeneity of the patient cohort, we studied 50 patients who received bilateral needlescopic VATS sympathectomy (T2-T4 excision) for palmar hyperhidrosis using 2 or 3mm instruments during a 36-month period at a single institute. A standard questionnaire was administered by telephone interview, with 34 patents responding (68.0%). The median post-operative observation time was 16.5 months (range: 10–40 months). Collected data were compared with a historical group who received conventional VATS using 10mm ports. Results: Paresthetic discomfort distinguishable from wound pain was described by 17 patients (50.0%). The most common descriptions were of ‘bloating’ (41.2%), ‘pins and needles’ (35.3%), or ‘numbness’ (23.5%) in the chest wall. The paresthesia resolved in less than two months in 12 patients (70.6%), but was still felt for over 12 months in three patients (17.6%). Post-operative paresthesia and pain did not impact on patient satisfaction with the surgery, whereas compensatory hyperhidrosis in 24 patients (70.6%) did (P=0.001). The rates and characteristics of the paresthesia following needlescopic VATS are similar to those observed after conventional VATS. Conclusions: Chest wall paresthesia affects a significant but previously overlooked proportion of patients following needlescopic VATS

The effects of hypoxemia, G-6-PD deficiency and sympathectomy might all add to the development of acute pulmonary edema

Transaxillary endoscopic sympathectomy of thoracic ganglia (T₂-T₃) has recently gained wider acceptance as the treatment of choice for palmar hyperhidrosis. It requires one-lung ventilation to facilitate the surgery. One-lung ventilation, however, is not without complications, among which acute pulmonary edema has been reported. In this case report, we present a patient with palmar hyperhidrosis complicated by glucose-6-phosphate dehydrogenase (G-6-PD) deficiency, who received bilateral endoscopic sympathectomy under alternate one-lung anesthesia, and developed acute pulmonary edema immediately after recruitment of the successive collapsed lung. The effects of hypoxemia, G-6-PD deficiency and sympathectomy might all add to the development of acute pulmonary edema secondary to reexpansion of each individual lung after alternate one-lung ventilation. The possibilities of the inferred causes are herein discussed.

Source: Acta Anaesthesiologica Scandinavica, Volume 45, Number 1, January 2001

Haemodynamic changes during thoracoscopic surgery

Haemodynamic changes during thoracoscopic surgery: The effects of one-lung ventilation compared with carbon dioxide insufflation.

Main Articles

Anaesthesia. 55(1):10-16, January 2000.
Brock, H. 1; Rieger, R. 2; Gabriel, C. 3; Polz, W. 4; Moosbauer, W. 1; Necek, S. 5

Abstract:
Summary: We investigated the haemodynamic and respiratory effects of one-lung ventilation and carbon dioxide insufflation in 13 adult patients undergoing video-assisted thoracoscopy. Cardiorespiratory variables were determined during carbon dioxide insufflation at intrahemithoracic pressures of 5, 10 and 15 mmHg, and after 5 and 15 min of one-lung ventilation. Carbon dioxide insufflation was associated with a clear deterioration in circulatory function. The cardiac index decreased subsequent to increasing intrathoracic pressures. The mean cardiac index (SD) at pressures of 10 and 15 mmHg was 1.86 (0.39) and 1.52 (0.46), respectively, and may be compared with the reduced venous return consistent with tension pneumothorax. One-lung ventilation did not affect haemodynamic variables but reduced arterial oxygenation indices (PaO2/FIO2) from 424.29 (160.79) after induction of anaesthesia, to 207.72 (125.50) after 5 min and 172.04 (72.03) after 15 min of one-lung ventilation, respectively. The oxygenation index was not influenced by intrahemithoracic carbon dioxide insufflation. One-lung ventilation via a double-lumen endobronchial tube is safe and convenient for video-assisted thoracoscopic surgery. It has no further consequences on haemodynamic variables, whereas the compression of the lung by carbon dioxide insufflation may cause circulatory dysfunction.

one-lung ventilation causes hypoxemia during endoscopic transthoracic sympathectomy

Hypoxemia is an abnormal deficiency in the concentration of oxygen in arterial blood (Mosby's Medical Dictionary). A frequent error is made when the term is used to describe poor tissue diffusion as in hypoxia. It is possible to have a low oxygen content (e.g., due to anaemia) but a high PO₂ in arterial blood so incorrect use can lead to confusion.

Journal of Vascular Surgery : Reply - Published by Elsevier

2 Y Katz, E Zisman, S Isserles and B Rosenberg,
Left, but not right, one-lung ventilation causes hypoxemia during endoscopic transthoracic sympathectomy.

ETS sympathetically maintained pain, and vasospastic or ischemic vascular disease

Sympathectomy for Pain and Hyperhidrosis: Based on the Breakfast Seminar of April 24, 2001, at the 69th Annual Meeting of the American Association of Neurological Surgeons, Toronto, Ontario, Canada.

Article

Neurosurgery Quarterly. 12(2):89-99, June 2002.
Wilkinson, Harold A.

Abstract:
Summary: Surgical resections of sympathetic ganglia from the thoracic, splanchnic, and lumbar area have been carried out for more than 100 years. In the past decade, neurosurgeons have become more interested in surgery on the sympathetic nervous system as less invasive techniques have been developed. Percutaneous radiofrequency and video-assisted endoscopic techniques have largely replaced open surgical thoracic sympathectomy. Lumbar and splanchnic sympathetic ablation is commonly done by percutaneous chemical techniques or, occasionally, by radiofrequency ablation, but the open techniques are still widely used. Sympathectomy is most widely employed for pathologic hyperhidrosis (especially the palmar component), sympathetically maintained pain, and vasospastic or ischemic vascular disease. The less invasive techniques are especially attractive for treating the sympathetically mediated cardiac diseases, including Prinzmetal angina, "syndrome X," and congenital long Q-T interval syndrome.

Surgical complications are usually manageable, but deaths have occurred (even with endoscopic techniques).

Endoscopic sympathetic block in the treatment

In this study, endoscopic sympathetic block was useful in reducing the symptoms of
severe social phobia. Although the method is surgical and the effect hence mainly biolog-
ical, the psychological symptoms of social phobia were also significantly reduced. The
results are best if the main symptoms are blushing or palpitation, but even a smaller
reduction in the other symptoms is important if it helps the patient to break his isolation.
Knowledge of the elimination of embarrassing physical symptoms in social situations
helps the patient to expose himself to formerly impossible situations, and success in them
also causes psychological symptoms to subside. But the relief of psychological symp-
toms may also be due to direct a biological effect of the operation on the anxiety-mediat-
ing areas in the nervous system. The only meaningful side effect is compensatory sweat-
ing of the trunk, but not even that is significant when modern surgical method are used.
Clamping is as good as bilateral cauterisation, and the results may be equally good with
unilateral and bilateral clamping, but because there were only eight patients who had
undergone a unilateral clamping procedure, the material is not sufficient to allow definite
conclusions concerning that. The results remain unchanged over time, which shows that
they were not due to a placebo effect. In the future, it is important to compare this treat-
ment to traditional treatment in order to find out its place among the other, officially
approved methods of treating social phobia.

PÄIVI
POHJAVAARA
Faculty of Medicine,
Department of Psychiatry,
University of Oulu
OULU 2004

A qualitative study of the development of social phobia

PÄIVI POHJAVAARA
SOCIAL PHOBIA: AETIOLOGY, COURSE
AND TREATMENT WITH ENDOSCOPIC
SYMPATHETIC BLOCK (ESB)
A qualitative study of the development of social phobia
and its meaning in people's lives and a quantitative study
of ESB as its treatment
Academic Dissertation to be presented with the assent of
the Faculty of Medicine, University of Oulu, for public
discussion in the Väinö Pääkkönen Hall of the Department
of Psychiatry, on December 3rd, 2004, at 12 noon.

Thanks to modern research techniques, we know a lot of the location of attention, emo-
tion and arousal modulation in the brain. Arousal requires involvement of the brain stem,
the thalamus and the cortex, while attention is maintained by the function of the right
frontal lobe (Kaplan & Sadock 1998, Nagahama et al. 2001). The amygdala rates the
emotional importance of an experience, and the limbic system is the centre of human
drives, whose regulation appears to require an intact frontal cortex. Crude emotions are
produced and handled in the midbrain structures and the olfactory cortex, while distinct-
ly human emotions are generated in the cortex (Kaplan & Sadock 1998).

Homeostatic responses mediated by the autonomic
nervous system are achieved by altering the balance between the sympathetic, parasympa-
thetic and different hormonal systems (Mosqueda-Garcia 1996). The most apparent link
between the autonomic and endocrine systems is manifested by the interactions between
the adrenal cortex and the adrenal medulla.

The neuroanatomical circuits, which support fear and anxiety behaviour, are modulated
by a variety of chemical neurotransmitter systems (Charney 2003). These include the
peptidergic neurotransmitters, corticotrophin-releasing hormone (CRH), neuropeptide
Yand substance P, the monoaminergic transmitters, norepinephrine, serotonin and dopam-
ine, and the amino acid transmitters, gamma-aminobutyric acid and glutamate.
The connection between the sympathetic nervous system and the psyche is best seen in
anxiety and especially in social phobia. The observed usefulness of beta-adrenergic antag-
onists in performance phobia supports this hypothesis (Sutherland & Davidson 1995).

There are studies indicating possible supersensitivity of the central serotonin systems in
social phobia and schizophrenia patients (Tancer et al. 1995, Malhotra et al. 1998). It has
been shown using SPECT (Pirker et al. 2000) that, in a solitary case study, the decreased
5-HTT activity of a social phobic patient was normalized by a sympathetic block (Kuikka
et al. 2000). Among the many neurotransmitters implicated in social anxiety disorder, the
complex interactions between the noradrenergic and serotonergic systems and the HPA
axis overlap those found seen in fear and anxiety (Marcin & Nemeroff 2003).

The physical symptoms of social phobia might be treated by blocking the sympathetic
system at the upper thoracic level with a surgical procedure (Crozier 2001, Telaranta
1998). Sympathectomy was first used to treat the exophthalmos of Basedow disease
(Jonnesco 1896) and angina pectoris (Le Riche 1913, Jonnesco 1921) in the late 19th and
early 20th centuries. Its beneficial effect on the treatment of facial sweating was noticed
as early as the 1930s, and its impact on palmar sweating was reported in the 1950s, when
the procedure was already carried out endoscopically (Kux 1954).

Endoscopic sympathicotomy and endoscopic sympathetic block strongly influence typical symptoms of patients with social phobia

Social phobia is an anxiety disorder which causes fear and anxiety in social interaction or performance situations and can in its worst forms be very debilitating. The patients tend to isolate themselves and suffer from comorbid disorders such as depression, other anxiety disorders and drug and alcohol abuse. Traditional treatment methods such as medication and psychotherapy cause improvement in only 50–70% of patients. METHODS: 164 patients who had been suffering from social phobia for at least 5 years and who were resistant to conservative treatment (medication and/or psychotherapy) were enrolled in this open, uncontrolled, prospective follow-up study. 71 patients underwent endoscopic sympathicotomy (cauterisation); 93 underwent endoscopic sympathetic block (clamping) of the T2–T3 ganglia. Severity of psychic and physical symptoms was assessed by a modified version of Davidson’s brief social phobia scale and patients’ satisfaction was evaluated 1, 6, and 12 months postoperatively. RESULTS: Fear of observation, performance anxiety and embarrassment were alleviated and alertness increased. Likewise, palpitations, trembling of hands and heads, blushing and hyperhidrosis were relieved. All changes were statistically significant. Patients’ satisfaction was high and remained stable over time. Gender, age, and education did not influence satisfaction rates. CONCLUSIONS: Endoscopic sympathicotomy and endoscopic sympathetic block strongly influence typical symptoms of patients with social phobia.

JournalEuropean Surgery
Volume 37, Number 3 / June, 2005

http://www.springerlink.com/content/w986882515290647/

During Thoracoscopic sympathectomy hypotension occurs frequently.

Background : During Thoracoscopic sympathectomy hypotension occurs frequently. In this study we compared propofol with etomidate as a main anesthetic agent for thoracoscopic sympathectomy by observing intraoperative vital signs, postoperative
recovery
and side effects.
Methods : Thirty adult patients scheduled for both thoracoscopic sympathectomy were allocated to groups P (propofol) or E (etomidate). P-deletion test (PDT) was dome and plasma cortisol level was measured. In group P (n = 16), anesthesia was
induced
with fentanyl 100 μg, propofol target controlled infusion (TCI) and vecuronium. Anesthesia was maintained with N2O (60%)-propofol. MAP, HR and bispectral index were measure before induction, right after positioning, at the beginning of
right
and left sympathectomy. In group E(n = 14), anesthesia was induced and maintained with etomidate instead of propofol. Postoperative recovery was assessed on the basis of modified Aldrete scoring system at 5, 15, 30, 60 minutes postoperatively. PDT
was
performed at 1, 2 hours postoperatively. Plasma cortisol level was measured 2 h and 3 days after operation. Occurrence of myoclonic movement and nausea was recorded.
Results : MAP was lover in group P (P < 0.05). There was no difference between groups in HR, plasma cortisol concentration. The values of BIS, PDT, recovery score of group P were higher than those of group E (P< 0.05). The incidence of nausea was significantly higher in group E (P < 0.05). Conclusions : Etomidate anesthesia provided more stable vital signs during thoracoscopic sympathectomy compared to propofol anesthesia. However, in terms of recovery and nausea, better outcome was suggested in propofol anesthesia.

http://kmbase.medric.or.kr/Main.aspx?d=KMBASE&m=VIEW&i=0858220000040040262

Sympathetic regulation of Autoimmune Disease

In animal models of human autoimmune disease, alterations in sympathetic innervation, NE concentration and lymphocyte AR expression have been demonstrated. ....reduced splenic noradrenergic innervation and decreased splenic NE concentration were apparent before the onset os disease symptoms. In myelin basic protein-induced EAE and MS-like disease, a reduction in splenic NE concentration was reported at the time of maximal antigen-induced lymphocyte proliferation and was accompanied by an increase in the density of of splenic lymphocyte beta-AR. In chronic/relapsing EAE (CREAE) induced in rats, splenocyte beta-AR density correlated positively with the severity of CREAE. Removal of noradrenergic innervation by chemical sympathectomy with 6-OHDA enhanced the severity of symptoms in EAE...

Neuropsychiatry

By Randolph B. Schiffer, Stephen M. Rao, Barry S. Fogel
Published 2003
Lippincott Williams
& Wilkins

Alterations in autonomic activity have been reported in RA and MS

Neuropsychiatry

By Randolph B. Schiffer, Stephen M. Rao, Barry S. Fogel

The SNS may elicit different, and often opposing functions at different anatomic sites. Localized denervation of draining lymph nodes, with sparing of the nerves innervating the joint, exacerbated joint pathology, but sympathetic removal of sympathetic input, either by beta-AR blockade or chemical sympathectomy with 6-OHDA or guanethidine reduced arthritic symptoms. These results suggest that noradrenergic innervation of draining lymph nodes inhibits the generation of antigen-specific T cells but promotes inflammation of the joints. A similar complexity was demonstrated after beta-agonist administration. Administration of a high dose of EPI reduced the severity of experimental arthritis by an alpha2-AR-mediated mechanism, but a low dose of EPI exacerbated joint injury. These results indicate that care must be used in manipulating the SNS therapeutically in complex diseases.
The SNS may also influence autoimmune processes in humans. Alterations in autonomic activity have been reported in RA and MS, but it is not known whether these changes are induced in response to disease or whether alterations in the SNS play a role in initiating the disease. In children with juvenile RA, increased sympathetic activity and autonomic hyporesponsiveness were associated with disease exacerbation.

Published 2003
Lippincott Williams
& Wilkins

a possible mechanism for sympathectomy-induced adrenal hypertrophy

Journal of Hypertension. 17(7):933-940, July 1999.
Qiua, Jingxin 1; Nelsona, Sharon H. 1; Spethb, Robert C. 2; Wanga, Donna H. 1,3

Abstract:
Objective: Previous studies indicate that the adrenal gland plays a compensatory role in the maintenance of blood pressure in chemically sympathectomized rats. However, the mechanisms responsible for compensatory adrenal responses are poorly understood. This study examined the regulation of adrenal growth and type 1A, 1B, and type 2 angiotensin II (Ang II) receptor (AT1A, AT1B and AT2) expression in the adrenal gland induced by sympathectomy.

Methods: Five-week-old male Sprague-Dawley rats were treated with either guanethidine (50 mg/kg per day, intraperitoneally) or vehicle for 5 weeks. Norepinephrine and epinephrine levels in the atrium of the heart were measured by high-pressure liquid chromatography. Plasma renin activity was determined by radioimmunoassay. Adrenal AT1 and AT2 receptor density was determined by radioligand binding assay. Adrenal AT1A, AT1B and AT2 mRNA levels were determined by Northern blot analysis.

Results: Norepinephrine and epinephrine levels in the atrium of the heart were decreased 86% (P <>0.05), were increased in guanethidine-treated rats compared with vehicle (P < r =" 0.9," r =" 0.6," r =" 20.01,"> 0.05) expression.

Conclusions: Impairment of the sympathetic nervous system with guanethidine withdraws the normal stimulation of this system on the circulating renin-angiotensin system, but upregulates the expression of adrenal Ang II receptors. Increased expression of adrenal AT2 and AT1A receptors may play an important role in adaptive adrenal hypertrophy and hormonal responses to sympathectomy.

Associations between neuropeptide Y nerve terminals and intraparenchymal microvessels in rat and human cerebral cortex

Neuropeptide Y (NPY) can influence local brain perfusion, possibly via direct relationships with the microvascular bed. To evaluate this possibility, the authors quantitatively analyzed by light and electron microscopy the morphological associations between immunostained NPY neuronal elements and intraparenchymal microvessels in the rat and human cerebral cortex. At the light microscopic level in the rat frontoparietal cortex, about 16% of NPY neurons and large proximal processes as well as a subset of nerve terminals not affected by double sympathectomy were associated with penetrating arterioles and local microvessels. In human temporal cortex, a dense network of NPY nerve fibers was observed, many of which approached and/or contacted intracortical vessels. At the ultrastructural level, 14% of NPY axonal varicosities in the rat cerebral cortex were considered perivascular and associated with capillaries (70%) or microarterioles (30%). They were particularly enriched in the immediate vicinity (<0.25 src="http://www3.interscience.wiley.com/giflibrary/12/mgr.gif" align="absbottom" border="0">m) of the microvessels, where the perivascular astrocytic leaflets represented a frequent target. In human cerebral cortex, NPY varicosities were observed in proximity to microvessels corresponding primarily to capillaries. Perivascular NPY varicosities never established synaptic junctions with vascular or astroglial elements. The results show that central NPY nerve terminals associate with microvessels and perivascular astroglial cells in the rat and human cerebral cortex. Thus, NPY released from these nerves could possibly influence (via a parasynaptic mode of action) vascular and/or astrocytic functions depending on the distribution of NPY receptors in these cellular compartments. These results provide morphological support for the effects of NPY on brain perfusion and homeostasis. J. Comp. Neurol. 388:444-453, 1997. © 1997 Wiley-Liss, Inc.
Roger Abounader, Edith Hamel ^*Laboratory of Cerebrovascular Research, Montreal Neurological Institute, Montréal, Québec H3A 2B4, Canada

clear association between the head pain and the release of the neuropeptide calcitonin gene-related peptide (CGRP)

In support, there is a clear association between the head pain and the release of the neuropeptide calcitonin gene-related peptide (CGRP) from the trigeminovascular system. In cluster headache there is, in addition, release of the parasympathetic neuropeptide vasoactive intestinal peptide (VIP) that is coupled to facial vasomotor symptoms. Triptan administration, activating the 5-HT_1B/1D receptors, causes the headache to subside and the levels of neuropeptides to normalise, in part through presynaptic inhibition of the cranial sensory nerves. These data suggest a central role for sensory and parasympathetic mechanisms in the pathophysiology of primary headaches. The positive clinical trial with a CGRP receptor antagonist offers a new promising way of treatment.

Lars Edvinsson^{a, ,} and Rolf Uddman^b

^aDepartment of Internal Medicine, University Hospital, S-221 85 Lund, Sweden

^bDepartment of Otorhinolaryngology, Malmö University Hospital, Malmö, Sweden

Accepted 8 September 2004.

Available online 18 November 2004.

Blocks the nerve responsible for narrowing blood vessels

Sympathectomy uses procedures that block or remove the nerve responsible for narrowing blood vessels in the hand.

http://health.nytimes.com/health/guides/disease/scleroderma/treatment-for-raynaud's-phenomenon.html

Review

A 2003 systematic review [1] looked at sympathectomy for facial blushing and the authors concluded:

We did not identify any controlled trials or cohort studies. The evidence about effectiveness, based on three case series, was therefore very limited. The main weakness of these studies was their lack of a comparison group and their resulting inability to exclude a placebo response to surgery. In addition, the methods of assessing outcome were poorly described and not validated, and the range of outcomes assessed was limited. The studies provided very limited evidence that sympathectomy improves blushing. Side effects were common.

A 2007 systematic review [2] of endoscopic thoracic sympathectomy for excessive sweating and facial blushing concluded:

The evidence of the effectiveness of ETS is weak due to a lack of randomized trials. The intervention leads to severe immediate complications in some of the patients, and to persistent side-effects for many of the patients.

http://www.clinicalanswers.nhs.uk/index.cfm?question=6881

Gustatory facial sweating subsequent to upper thoracic sympathectomy

MDShanker Nesathurai^a, , MDDavid T. Harvey^b and MDStanley W. Schatz^c

^aDepartment of Physical Medicine and Rehabilitation, McMaster University, Canada

^bMcMaster University Clinic, Hamilton Civic Hospitals, Henderson General Division, Canada

^cDepartment of Neurosurgery, McMaster University Clinic-Hamilton General Hospital, Hamilton, Ontario, Canada

Received 3 February 1994;

accepted 8 July 1994

Gustatory facial sweating has been described as a consequence of upper thoracic sympathectomy. Patients may also develop compensatory hyperhidrosis, sensory deficits, nipple hypersensitivity, and Horner's syndrome. In this article, we have reviewed three patients with reflex sympathetic dystrophy who developed gustatory facial sweating subsequent to endoscopic T2 and T3 ganglionectomy. This article also discusses the possible mechanisms of gustatory facial sweating.

keyterms: dysesthetic pain, vasomotor instability, hyperhidrosis, denervation supersensitivity.

A dysesthetic syndrome can occur after sympathectomy

Eugenia-Daniela Hord, MD, Instructor, Departments of Anesthesia and Neurology, Massachusetts General Hospital Pain Center, Harvard Medical School

A dysesthetic syndrome can occur after sympathectomy; it usually is transient but sometimes can be persistent.
Chemical sympathectomy is transient and should be used initially for diagnostic purposes to
establish the involvement of SNS and hence inhibition of sympathetic activity (eg, increased limb
temperature or ocular Horner signs) without evidence of sensory somatic blockade (eg,
hypoesthesia to pinprick and cold stimuli).

For chemical sympathectomy, 2 basic techniques are used.
Injections of local anesthetic around sympathetic paravertebral ganglia that project to the
affected body part (sympathetic ganglion block): This will affect all components of the
sympathetic outflow to an extremity (adrenergic vasoconstrictor, cholinergic sudomotor, and adrenergic pilomotor).

Intravenous regional block: This will prevent the release of only norepinephrine from the sympathetic terminals within the region of application (ie, distal to the tourniquet).

Effect of sympathetic denervation on the rate of protein synthesis

Rates of protein synthesis were investigated in skeletal muscles from rats submitted to chemical and surgical sympathectomy. Three models of sympathetic denervation were used: 1) treatment with guanethidine (100 mg·kg^-1·day^-1 sc); 2) lumbar sympathetic denervation (surgical excision of the second and third lumbar ganglia of the sympathetic chain, from which arises the postganglionic fibers to the skeletal muscles of rat hindlimb); and 3) adrenodemedullation. Protein synthesis was estimated in isolated soleus muscle by the rate of incorporation of [¹⁴C]tyrosine (0.1 mM, 0.05 µCi/ml) into total protein. Soleus isolated after 2 and 4 days of chemical sympathectomy or after 3 days of lumbar denervation showed a 17-20% statistically significant decrease in in vitro rates of protein synthesis. These effects were reverted by addition of 10^-5 M isoproterenol or epinephrine in vitro. Neither clenbuterol nor isoproterenol (10^-7, 10^-6, or 10^-5 M) in vitro affected the rate of protein synthesis in soleus from normal rats. On the other hand, clenbuterol or epinephrine (10^-5 M) increased by 20% the rate of protein synthesis in soleus muscles from adrenodemedullated rats and prevented its decrease in muscles from fasted rats. The data suggest that the sympathetic nervous system stimulates protein synthesis in oxidative muscles, probably through the activation of ₂-adrenoceptors, especially in situations of hormonal or nutritional deficiency.
Luiz Carlos C. Navegantes, Neusa M. Z. Resano, Amanda M. Baviera, Renato H. Migliorini, and Isis C. Kettelhut
Am J Physiol Endocrinol Metab 286: E642-E647, 2004

Evaluation of long-term chemical sympathectomy

AJP - Heart and Circulatory Physiology, Vol 238, Issue 4 527-H532, Copyright © 1980 by American Physiological Society

K. Fronek

Administration of 6-hydroxydopamine (6-OHDA) will produce long-term sympathectomy in newborn animals. This investigation was designed to determine whether or not a long-term sympathectomy can be achieved by repeated administration of 6-OHDA in adult rabbits. Chronic treatment with 6-OHDA lowered blood pressure on average of 9 mmHg; the carotid sinus reflex was depressed, in contrast to the pressure response to intravenously administered epinephrine, which was doubled. In a constant-flow hindlimb preparation, the response to norepinephrine (NE) in 6-OHDA-treated rats was 50% larger and lasted 3 times longer. NE uptake in vitro, which is proportional to the number of adrenergic nerve endings, was found to be diminished by 80-85% in aortas from 6-OHDA-treated animals, and the dose-response curve for NE was slightly shifted to the left. The number of ganglionic cells in the superior cervical ganglia in treated animals was decreased by 80%. In conclusion, results from 6-OHDA-treated adult animals were entirely consistent with the effects of long-term sympathectomy.

Effects of 6-hydroxydopamine on dopamine and noradrenaline content

Naunyn-Schmiedeberg's Archives of Pharmacology

Volume 329, Number 3 / May, 1985

P. Soares-da-Silva¹ and R. Davidson¹

(1)	Laboratorio de Farmacologia, Faculdade de Medicina, P-4200 Porto, Portugal

Received: 29 October 1984 Accepted: 27 January 1985

6-OHDA and pargyline plus 6-OHDA induced a parallel decrease of the noradrenaline and dopamine content in the main trunk of the mesenteric artery, femoral artery and heart. In the proximal branches of the mesenteric artery, renal and splenic arteries 6-OHDA selectively reduced noradrenaline (by 50%) without changes in dopamine levels. Previous treatment with pargyline abolished this selectivity and depleted the tissue levels of both noradrenaline and dopamine by 75%.

The present findings suggest: an independent dopamine presence in the proximal branches of the mesenteric artery, renal artery and splenic artery; that noradrenaline and dopamine are in one and the same structure in the heart, femoral artery and the main trunk of the mesenteric artery; the saphenous vein is more resistant to chemical sympathectomy than arterial blood vessels; the changes in plasma catecholamine concentrations are probably related to a compensatory mechanism initiated at the adrenal medulla.

Alteration of antioxidant status following sympathectomy: Differential effects of modified plasma levels of adrenaline and noradrenaline

Molecular and Cellular Biochemistry
Volume 152, Number 1 / November, 1995
Philip M. Toleikis¹ and David V. Godin
Department of Pharmacology and Therapeutics, The University of British Columbia, V6T 1Z3 Vancouver, B.C., Canada

Differences between adrenalectomy and 6-OH treatment on antioxidant components are suggestive of differential actions of adrenaline and noradrenaline on tissue antioxidant status which may have important implications under conditions associated with elevations in levels of these catecholamines including chronic stress and myocardial infarction.

Sympathectomy improves skin blood flow at the thermoregulatory but not the nutritive level

These results indicate that in case of lower limb ischemia, sympathectomy improves skin blood flow at the thermoregulatory but not the nutritive level of skin microcirculation. This may be related to the fact that the thermoregulatory vessels are mainly sympathetically controlled, whereas the nutritive capillaries are mainly controlled by local (nonneural) factors.

François M.H. van Dielen¹, Harrie A.J.M. Kurvers¹, Ruben Dammers¹, Mirjam G.A. oude Egbrink², Dick W. Slaaf³, Jan H.M. Tordoir¹ and Peter J.E.H.M. Kitslaar¹

(1)	Department of General Surgery, Cardiovascular Research Institute Maastricht and University Hospital Maastricht, PO Box 5800, 6202 AZ Maastricht, The Netherlands, NL

(2)	Department of Physiology, Cardiovascular Research Institute Maastricht, PO Box 616, 6200 MD Maastricht, The Netherlands, NL

(3)	Department of Biophysics, Cardiovascular Research Institute Maastricht, PO Box 616, 6200 MD Maastricht, The Netherlands, NL World Journal of Surgery Volume 22, Number 8 / August, 1998

Imbalance of regional cerebral blood flow

Imbalance of regional cerebral blood flow and oxygen consumption: effect of vascular alpha adrenoceptor blockade.

Neuropharmacology. 1993 Mar;32(3):297-302.
Weiss HR, Sinha AK.

Department of Physiology and Biophysics, University of Medicine and Dentistry of New Jersey, Robert Wood Johnson Medical School, Piscataway 08854-5635.

the regulation of cerebrovascular tone

Brain perfusion is tightly coupled to neuronal activity, is commonly used to monitor normal or pathological brain function, and is a direct reflection of the interactions that occur between neuronal signals and blood vessels. Cerebral blood vessels at the surface and within the brain are surrounded by nerve fibers that originate, respectively, from peripheral nerve ganglia and intrinsic brain neurons. Although of different origin and targeting distinct vascular beds, these "perivascular nerves" fulfill similar roles related to cerebrovascular functions, a major one being to regulate their tone and, therein, brain perfusion. This utmost function, which underlies the signals used in functional neuroimaging techniques and which can be jeopardized in pathologies such as Alzheimer's disease, stroke, and migraine headache, is thus regulated at several levels. Recently, new insights into our understanding of how neural input regulate cerebrovascular tone resulted in the rediscovery of the functional "neurovascular unit." These remarkable advances suggest that neuron-driven changes in vascular tone result from interactions that involve all components of the neurovascular unit, transducing neuronal signals into vasomotor responses not only through direct interaction between neurons and vessels but also indirectly via the perivascular astrocytes. Neurovascular coupling is thus determined by chemical signals released from activated perivascular nerves and astrocytes that alter vascular tone to locally adjust perfusion to the spatial and temporal changes in brain activity.
Edith Hamel

Laboratory of Cerebrovascular Research, Montreal Neurological Institute, McGill University, Montréal, Québec, Canada

J Appl Physiol 100: 1059-1064, 2006; doi:10.1152/japplphysiol.00954.2005

Dopaminergic regulation of cerebral cortical microcirculation

Nature Neuroscience 1, 286 - 289 (1998)
doi:10.1038/1099
Leonid S. Krimer¹, E. Christopher Muly III², Graham V. Williams¹ & Patricia S. Goldman-Rakic¹

¹ Section of Neurobiology, Yale University School of Medicine, New Haven, Connecticut 06510, USA

² Department of Psychiatry, Yale University School of Medicine, New Haven, Connecticut 06510, USU

Functional variations in cerebral cortical activity are accompanied by local changes in blood flow, but the mechanisms underlying this physiological coupling are not well understood. Here we report that dopamine, a neurotransmitter normally associated with neuromodulatory actions, may directly affect local cortical blood flow. Using light and electron-microscopic immunocytochemistry, we show that dopaminergic axons innervate the intraparenchymal microvessels. We also provide evidence in an in vitro slice preparation that dopamine produces vasomotor responses in the cortical vasculature. These anatomical and physiological observations reveal a previously unknown source of regulation of the microvasculature by dopamine. The findings may be relevant to the mechanisms underlying changes in blood flow observed in circulatory and neuropsychiatric disorders.

Disturbance of sympathetic cardiovascular regulation is involved in CFS

Wyller VB, Saul JP, Walloe L, Thaulow E "...our results suggest that CFS patients suffer from a more comprehensive disturbance of sympathetic cardiovascular regulation than previously acknowledged, supporting the hypothesis that dysautonomia may be a central etiologic component of CFS (Freeman and Komaroff 1997). Specifically, the sympathetic nervous system is more activated at rest, and seems to have an enhanced response to orthostatic stress, but has a reduced response to the addition of isometric exercise. These abnormalities may account for the high prevalence of orthostatic symptoms among CFS patients.

recent reports have linked cerebral hypoperfusion to abnormalities in cholinergic metabolism

Dr Faisel Khan, Vascular Diseases Research Unit,
University Department of Medicine, Ninewells
Hospital and Medical School, Dundee DD1 9SY, UK

accepted 30 April 2003

Although the aetiology of chronic fatigue syndrome (CFS) is unknown, there have
been a number of reports of blood flow abnormalities within the cerebral circulation
and systemic blood pressure defects manifesting as orthostatic intolerance. Neither
of these phenomena has been explained adequately, but recent reports have linked
cerebral hypoperfusion to abnormalities in cholinergic metabolism. Our group has
previously reported enhanced skin vasodilatation in response to cumulative doses of
transdermally applied acetylcholine (ACh), implying an alteration of peripheral
cholinergic function. To investigate this further, we studied the time course of ACh-
induced vasodilatation following a single dose of ACh in 30 patients with CFS and
30 age- and gender-matched healthy control subjects. No differences in peak blood
flow was seen between patients and controls, but the time taken for the ACh
response to recover to baseline was significantly longer in the CFS patients than in
control subjects. The time taken to decay to 75% of the peak response in patients and
controls was 13Æ7 ± 11Æ3 versus 8Æ9 ± 3Æ7 min (P
1⁄4 0Æ03), respectively, and time
taken to decay to 50% of the peak response was 24Æ5 ± 18Æ8 versus 15Æ1 ± 8Æ9 min
(P
1⁄4 0Æ03), respectively. Prolongation of ACh-induced vasodilatation is suggestive
of a disturbance to cholinergic pathways, perhaps within the vascular endothelium
of patients with CFS, and might be related to some of the unusual vascular
symptoms, such as hypotension and orthostatic intolerance, which are characteristic
of the condition.

Regional temperature rises within the CNS can lead to alteration of membrane properties.

Regional temperature rises within the
CNS can lead to an alteration of mem-
brane properties. For example, enzyme
activity – ornithine decarboxylase – is in-
creased when calcium flows into the cell
via a temperature-sensitive mechanism.
Interestingly, one study observed an acti-
vation of this enzyme after EMF exposure,
subsequently resulting in a temporary per-
meability increase of the BBB.

On the other hand, also a tempo-
rary blood pressure rise could cause an
increase of BBB permeability.

Privatdozent Dr. med. Florian Stögbauer,
University of Münster

Hyperpigmentation after sympathectomy

Hyperpigmentation after sympathectomy

• CLAIRE SAMUEL,**Departments of Surgery, Royal Infirmary, Bristol BS2 8HW
• D.R. BIRD¹¹Departments of Dermatology, Royal Infirmary, Bristol BS2 8HW AND
• J.L. BURTON¹¹Departments of Dermatology, Royal Infirmary, Bristol BS2 8HW

• ¹Departments of Dermatology, Royal Infirmary, Bristol BS2 8HW *Departments of Surgery, Royal Infirmary, Bristol BS2 8HW

• Clinical and Experimental Dermatology

  Volume 5 Issue 3 Page 349-350, September 1980

Avoidance learning

Chemical sympathectomy and two-way escape and avoidance learning in the rat.

Six experiments are reported on the effects of 2,4,5-trihydroxyphenylethyl-amine (6-hydroxydopamine) on two-way escape and avoidance learning. Rats were tested on either escape or avoidance learning at 80 days of age after chemical sympathectomy at birth or 40 or 80 days of age. Neonatal and chronic sympathectomy (at 40 days), but not acute sympathectomy (at 80 days), resulted in depressed escape learning. Avoidance learning was affected by neonatal sympathectomy and partially by acute sympathectomy. The results have implications for the role of the autonomic nervous system in escape-avoidance learning.
Lord BJ, King MG, Pfister HP
J Comp Physiol Psychol 1976; 90:303-16.

alteration of carbohydrate and lipid metabolism following sympathectomy

Recent Adv Stud Cardiac Struct Metab 1976; 9:259-67.
Imbach A

These results indicate an important alteration of carbohydrate and lipid metabolism after chemical sympathectomy, thus supporting a role of the sympathetic nervous system in their regulation.

sympathectomy on insulin receptors and insulin action

Insulin receptors and effects of insulin on lipolysis, lipogenesis and glucose transport were investigated in fat cells obtained from rats chemically sympathectomized with 6-hydroxydopamine. Four days after a single injection of 6-hydroxydopamine (50 mg/kg), the norepinephrine content of the epididymal adipose tissue was reduced by 97.5%. The number of high-affinity insulin binding sites was increased moderately (16%). In parallel, the sensitivity to insulin of the isoprenaline-stimulated lipolysis was increased as judged from insulin concentrations yielding half-maximal inhibition which were lower (40%) in the treated group. Glucose metabolism, however, was inhibited by chemical sympathectomy: the glucose transport rate was significantly reduced and fatty acid synthesis was nearly totally abolished. Insulin was still effective in stimulating both parameters but failed to restore normal levels. The results suggest that the sympathetic innervation of adipose tissue may exert an inhibitory effect on the number of high-affinity insulin receptors as well as on the sensitivity of the lipolysis to insulin, as both parameters were increased by sympathectomy. To explain the inhibitory effect of 6-hydroxydopamine treatment on glucose transport and fatty acid synthesis, a possible trophic effect of the sympathetic innervation is discussed as well as indirect mechanism counteracting the effects of the chemical sympathectomy.

Effects of chemical sympathectomy on insulin receptors and insulin action in isolated rat adipocytes.
Joost HG, Quentin SH J Pharmacol Exp Ther 1984; 229:839-44.

relevant to the pathogenesis of human dysautonomias.

Brimijoin, S, Lennon, V A

Systemic injection of monoclonal antibodies to neural acetylcholinesterase in adult rats caused a syndrome with permanent, complement-mediated destruction of presynaptic fibers in sympathetic ganglia and adrenal medulla. Ptosis, hypotension, bradycardia, and postural syncope ensued. In sympathetic ganglia, acetylcholinesterase activity disappeared from neuropil but not from nerve cell bodies. Choline acetyltransferase activity and ultrastructurally defined synapses were also lost. Electrical stimulation of presynaptic fibers to the superior cervical ganglion ceased to evoke end-organ responses. On the other hand, direct ganglionic stimulation remained effective, and the postganglionic adrenergic system appeared intact. Motor performance and the choline acetyltransferase content of skeletal muscle were preserved, as was parasympathetic (vagal) function. This model of selective cholinergic autoimmunity represents another tool for autonomic physiology and may be relevant to the pathogenesis of human dysautonomias.

Norepinephrine depletion commonly is the desired effect, other neurotransmitters (eg ATP, NPY and enkephalins) are depleted by sympathectomy

The term Sympathectomy used in this discussion refers mainly to the lesioning of postganglionic noradrenergic (NA) neurons and fibers except where noted. Although norepinephrine depletion commonly is the desired effect, other costored neurotransmitters (eg ATP, NPY and enkephalins) are depleted by sympathetic denervation. The multitude of research studying the effects of sympathetic loss is made possible by the morphologically defined anatomy of the postganglionic sympathetic chains, the sensitivity of postganglionic NA neurons to nerve growth factor (NGF) deprivation, and the phenotypic specialty of these neurons that allows for the selective uptake of neurotoxins.

Primer on the Autonomic Nervous System

By David Robertson
Published 2004

Serum Dopamine-β -Hydroxylase: Decrease after Chemical Sympathectomy

Dopamine-β -hydroxylase is an enzyme that is localized to catecholamine-containing vesicles in sympathetic nerves and the adrenal medulla, and is also found in the serum. Treatment of rats with 6-hydroxydopamine, a drug which destroys sympathetic nerve terminals, leads to a decrease in serum dopamine-β -hydroxylase activity.

		Weinshilboum, Richard; Axelrod, Julius
Publication:		Science, Volume 173, Issue 4000, pp. 931-934
Publication Date:		09/1971
Origin:		JSTOR

In the adrenal medulla, AChE-rich presynaptic fibers disappeared within 3 days

In the adrenal medulla, AChE-rich presynaptic fibers disappeared within 3 days
Autoimmune Preganglionic Sympathectomy Induced by Acetylcholinesterase Antibodies
Stephen Brimijoin and Vanda A. Lennon
Proceedings of the National Academy of Sciences of the United States of America, Vol. 87, No. 24 (Dec., 1990), pp. 9630-9634 (article consists of 5 pages)
Published by: National Academy of Sciences
• 
  

intact adrenal medulla was essential for SHR groups to achieve many of the adaptations associated with training.

Responses of SHR to combinations of chemical sympathectomy, adrenal demedullation, and training

C. M. Tipton, M. S. Sturek, R. A. Oppliger, R. D. Matthes, J. M. Overton and J. G. Edwards

The single and combined influences of exercise training, chemical sympathectomy (SYMX), and surgical adrenal demedullation (D) were examined in four separate spontaneously hypertensive rat (SHR) groups. SYMX was accomplished by subcutaneous injections of antinerve growth factor (ANGF) over a 5-day period after birth followed by 20 separate injections of guanethidine sulfate during a 27-day period. Measurements of urine, plasma, or tissue levels of catecholamines indicated that these experimental procedures were effective. The animals were exercise trained (T) for 10 wk or longer at 40-60% of their VO2max capacity, and all T groups exhibited longer run times or higher muscle cytochrome oxidase activity; however, only the SHR + T subgroup had a significantly higher VO2max value than its control (NT). Training lowered resting systolic blood pressure (SBP) in the SHR subgroup but normalization of SBP occurred only with SYMX. Interestingly, only the SYMX + T subgroup with intact adrenal glands also had lower SBP values than the NT. The SHR + T and SYMX + T subgroups but not the SYMX + D + T had less cardiac acceleration after ip injections of atropine than their controls. Heavier heart weights were observed only in the SHR + T subgroup; SYMX was associated with lighter heart weights regardless of whether the rats had been T or D. These collective findings demonstrated again the importance of the sympathetic nervous system to an exercise response, suggesting that an intact adrenal medulla was essential for SHR groups to achieve many of the adaptations associated with training.
Am J Physiol Heart Circ Physiol 247: H109-H118, 1984;
0363-6135/84 $5.00

no one has examined the effects of sympathectomy, adrenergic blockade, or adrenal demedulation

Thus, until proven otherwise, we suggest that many, if not all, of the anti-inflammatory effects associated with efferent vagal stimulation are due to the concurrent activation of the adrenal medulla and the sympathetic nervous system. It is surprising that no one has examined the effects of sympathectomy, adrenergic blockade, or adrenal demedulation on the inhibition of TNF-� and inflammation produced by efferent vagal stimulation.

PubMed articles by:
Autonomic Innervation and Regulation of the Immune System
(1987-2007)
Dwight M. Nance and Virginia M. Sanders
Brain Behav Immun. 2007 August; 21(6): 736–745.


Madden KS, Felten SY, Felten DL, Sundaresan PR, Livnat S.
Sympathetic neural modulation of the immune system. I.
Depression of T cell immunity in vivo and in vitro following chemical sympathectomy. Brain Behav.Immun.
1989;3:72–89. [PubMed]

HYPOTHALAMUS:

RECENT STUDIES ON THE HYPOTHALAMUS:
K. E. COOPER
TEMPERATURE REGULATION AND THE HYPOTHALAMUS
Br. Med. Bull., September 1966; 22: 238 - 242.
......pathway is necessary for the complete febrile response in cats was shown by Knkston (1935), who found that complete bilateral sympathectomy greatly reduced the pyrogenic response, and by Douglas (1954), who showed the importance of ear vasoconstriction in the......

Role of Dopamine

Dopamine has moved from being an insignificant intermediary in the formation of noradrenaline in 1957 to its present-day position as a major neurotransmitter in the brain. This neurotransmitter is involved in the control of movement and Parkinson's disease, the neurobiology and symptoms of schizophrenia and attention deficit hyperactivity disorder. It is also considered an essential element in the brain reward system and in the action of many drugs of abuse. This evolution reflects the ability of several famous names in neuropharmacology, neurology and psychiatry to apply new techniques to ask and answer the right questions. There is now excellent knowledge about the metabolism of dopamine, dopamine receptor systems and the structural organisation of dopamine pathways in the brain. Less is known about the function of the different receptors and how the various dopamine pathways are organised to produce normal behaviour, which exhibits disruption in the disease states mentioned. In particular, we have very limited information as to why and how the dopamine system dies or becomes abnormal in Parkinson's disease or a neurodevelopmental disorder such as schizophrenia. Dopamine neurones account for less than 1% of the total neuronal population of the brain, but have a profound effect on function. The future challenge is to understand how dopamine is involved in the integration of information to produce a relevant response rather than to study dopamine in isolation from other transmission systems. This integrated approach should lead to greater understanding and improved treatment of diseases involving dopamine.
Charles A Marsden
1
School of Biomedical Sciences, Institute of Neuroscience, Medical School, Queen's Medical Centre, University of
Nottingham, Nottingham NG7 2UH

mental stress is abolished by sympathectomy

AUTONOMIC NERVOUS SYSTEM:
C. LOVATT EVANS
SWEATING IN RELATION TO SYMPATHETIC INNERVATION
Br. Med. Bull., September 1957; 13: 197 - 201.
*......or to mental stress is abolished by sympathectomy, but apocrine emotional sweating in...axilla is stated not to be abolished by sympathectomy (Shelley & Hurley, 1952). 4. The Sympathetic...according to the results of operations for sympathectomy, there are sudomotor as well as pilomotor......

bizarre phenomena

AUTONOMIC NERVOUS SYSTEM:
J. G. MURRAY and J. W. THOMPSON
COLLATERAL SPROUTING IN RESPONSE TO INJURY OF THE AUTONOMIC NERVOUS SYSTEM, AND ITS CONSEQUENCES
Br. Med. Bull., September 1957; 13: 213 - 219.
......after sympathec- tomy, e.g., surgical sympathectomy of thoracicolumbar region and upper...syndrome (Haxton, 1948; Young, 1956) Post-sympathectomy pain (Tracy & Cockett, 1957) After...reflex autonomic function after surgical sympathectomy, and (ii) bizarre phenomena. The operation......

Autonomic innervation of the heart and vasculature

As shown in the following table, activation of sympathetic efferent nerves to the heart increases heart rate (positive chronotropy), contractility (positive inotropy), rate of relaxation (increased lusitropy), and conduction velocity (positive dromotropy). Parasympathetic effects are opposite. Parasympathetic effects on inotropy are weak in the ventricle, but relatively strong in the atria. Physiologically, whenever the body activates the sympathetic system, it down regulates parasympathetic activity, and visa versa, so that the activities of these two branches of the autonomic nervous system respond reciprocally.

In blood vessels, sympathetic activation constricts arteries and arterioles (resistance vessels), which increases resistance and decreases distal blood flow. Sympathetic-induced constriction of veins (capacitance vessels) decreases venous compliance and blood volume, and thereby increases venous pressure. Most blood vessels in the body do not have parasympathetic innervation. However, parasympathetic nerves do innervate salivary glands, gastrointestinal glands, and genital erectile tissue where they cause vasodilation.

The overall effect of sympathetic activation is to increase cardiac output, systemic vascular resistance (both arteries and veins), and arterial blood pressure. Enhanced sympathetic activity is particularly important during exercise, emotional stress, and during hemorrhagic shock.

Cardiac function is altered by neural activation. Sympathetic stimulation increases heart rate (positive chronotropy), inotropy and conduction velocity (positive dromotropy), whereas parasympathetic stimulation of the heart has opposite effects. Sympathetic and parasympathetic effects on heart function are mediated by beta-adrenoceptors and muscarinic receptors, respectively.

Sympathetic adrenergic nerves travel along arteries and nerves and are found in the adventitia (outer wall of a blood vessel). Varicosities, which are small enlargements along the nerve fibers, are the site of neurotransmitter release. Capillaries receive no innervation. Activation of vascular sympathetic nerves causes vasoconstriction of arteries and veins mediated by alpha-adrenoceptors.

Richard E. Klabunde, Ph.D.

loss of myocardial sympathetic-nerve terminals

"The classification of dysautonomias has been confusing, and the pathophysiology obscure. We examined sympathetic innervation of the heart in patients with acquired, idiopathic dysautonomias using thoracic positron-emission tomography and assessments of the entry rate of the sympathetic neurotransmitter norepinephrine into the cardiac venous drainage (cardiac norepinephrine spillover). We related the laboratory findings to signs of sympathetic neurocirculatory failure (orthostatic hypotension and abnormal blood-pressure responses associated with the Valsalva maneuver), central neural degeneration, and responsiveness to treatment with levodopa–carbidopa (Sinemet)."

"The results of 6-[¹⁸F]fluorodopamine positron-emission tomography and neurochemical analyses support a new clinical pathophysiologic classification of dysautonomias, based on the occurrence of sympathetic neurocirculatory failure, signs of central neurodegeneration, and responsiveness to levodopa–carbidopa."

Sympathetic Cardioneuropathy in Dysautonomias

David S. Goldstein, M.D., Ph.D., Courtney Holmes, C.M.T., Richard O. Cannon, M.D., Graeme Eisenhofer, Ph.D., and Irwin J. Kopin, M.D.

The New England Journal of Medicine , March 6, 1997

Clinical Investiation

To validate the method, healthy volunteers underwent 6-¹⁸F-fluorodopamine scanning of the head, thorax, and abdomen, with or without treatment with desipramine to block sympathoneural uptake of catecholamines. ¹³N-Ammonia scanning was used to address possible group differences in 6-¹⁸F-fluorodopamine delivery by blood perfusion. Results: Desipramine treatment was associated with decreased 6-¹⁸F-fluorodopamine–derived radioactivity in the heart, renal cortex, and thyroid gland but not in the liver, spleen, renal pelvis, or salivary glands. Both the PD+OH group and the PAF group had decreased 6-¹⁸F-fluorodopamine–derived radioactivity in the heart (P <> (P = 0.02 and P = 0.005, respectively). The PD+OH group also had decreased radioactivity in the thyroid gland (P = 0.01). Neither group had decreased radioactivity in the other organs, after correction for ¹³N-ammonia–derived radioactivity. Conclusion: 6-¹⁸F-Fluorodopamine scanning visualizes sympathetic innervation in the heart, renal cortex, and thyroid gland. Both PD+OH and PAF involve decreased noradrenergic innervation that is most prominent in the heart but is also detectable in extracardiac organs.
Dnyanesh N. Tipre, MPharm, PhD and David S. Goldstein, MD, PhD

Clinical Neurocardiology Section, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland

JNM 2005 46

Heterogenous cardiac sympathetic innervation - cause of sudden cardiac death

Recently, a colony of German shepherd dogs with inherited spontaneous cardiac arrhythmias and associated sudden death has been developed and characterized. Due to the median age of onset of the arrhythmia (4.5 months), the tendency for the arrhythmia to occur during REM sleep or after exercise, and the absence of structural heart disease, we hypothesized a developmental abnormality of the sympathetic innervation to the heart. METHODS AND RESULTS: We studied 11 dogs from this colony, ranging in age from 6 months to 6 years, and four 7-month-old German shepherd dogs unrelated to the colony as controls. We imaged the distribution of functional myocardial sympathetic innervation and perfusion with [123I]metaiodobenzylguanidine (MIBG) and 201Tl, respectively. Sympathetic nerve distribution was evaluated morphologically by immunocytochemical localization of tyrosine hydroxylase. All of the hearts showed evidence of a regional decrease in MIBG uptake, ranging from 5.3% to 53.4% of the myocardium, whereas control dogs showed homogeneous MIBG uptake. Immunocytochemical studies on sections from regions with decreased MIBG uptake showed a striking paucity of nerves compared with regions with normal MIBG uptake, confirming denervation. When the dogs were grouped into those with (n=6) and without (n=5) evidence of ventricular tachycardia on ambulatory ECG, the group with ventricular tachycardia showed 35+/-16.5% denervation, whereas the group without ventricular tachycardia showed 12+/-5.6% denervation (P<.02). CONCLUSIONS: Abnormal heterogeneous sympathetic innervation exists in these dogs with inherited ventricular arrhythmia and sudden cardiac death. Mechanisms relating the presence and extent of regional denervation to the incidence of ventricular arrhythmia remain to be defined.

Loss of sympathetic innervation to the eye

Loss of sympathetic innervation caused a significant increase in steady state mRNA levels of fibronectin and a 15% increase in laminin-ß1 mRNA 3 weeks after surgical sympathectomy. Protein expression also increased at this point. In addition, capillary basement membrane thickness increased significantly. NG2 proteoglycan staining decreased significantly in pericytes in the sympathectomized rat retina. Steady state mRNA for PDGF-BB decreased significantly 6 weeks after surgery.
Sympathetic nerves may be compromised in diabetes, and these findings suggest that they may regulate some complications of diabetic retinopathy. Gene expression levels of fibronectin and laminin-ß1 changed between 1 and 3 weeks. These data are supported by electron microscopy, which showed the increase in basement membrane thickness in vivo. Loss of sympathetic innervation to the eye also caused a decrease in the number of pericytes. Steady state mRNA expression of PDGF-BB was reduced, suggesting a mechanism for the loss of pericytes in the sympathectomized retina. Overall, these results suggest that sympathetic nerve alterations may function in some complications observed in diabetic retinopathy, and this may be a suitable model to investigate therapies for this disorder.
(Investigative Ophthalmology and Visual Science. 2005;46:744-748.)
© 2005 by The Association for Research in Vision and Ophthalmology, Inc.
DOI: 10.1167/iovs.04-1023

Coronary artery calcification

Ludman et al. have reported the prevalence of coronary artery calcification in heart transplant recipients and examined risk factors for calcifi- cation[1]. The authors noted that in some patients calcification was present despite angiographically trivial disease. One possible explanation to consider is that in cardiac transplant recipients, the usual close correlation between coronary artery calcification
and atheroma may not hold true.
Specifically, denervation might result in calcification of the media of coronary vessels. Medial calcification cannot easily be distinguished from intimal calcification with electron beam CT scanning.
Autopsy studies of unselected patients show that coronary calcification is atherosclerosis-related and intimal and this is the basis for using the calcification score as a proxy foratheroma burden. However, calcification of the media in in peripheral vessels is commonin diabetic patients in whom it is closely related to autonomic neuropathy and there are case reports of medial calcification in coronary vessels of diabetic patients.
Lumbar sympathectomy can also result in medial calcification
of peripheral vessels. Thus given that the transplanted heart is denervated
it is at least possible that some of the calcification detected
by Ludman et al is medial.
H.M. COLHOUN
Circ 1994; 90: 1786–93.

Clinical Lecturer in
Epidemiology and Public Health,
University College,
London, U.K.

Ablation of the sympathetic nervous system by chemical sympathectomy is a standard model for the study of sympathetic nervous system regulation of imm

Ablation of the sympathetic nervous system by chemical sympathectomy is a standard model for the study of sympathetic nervous system regulation of immune function. We have previously documented that chemical denervation results in enhanced antigen-specific, but suppressed mitogen-induced, cytokine production by spleen cells. In our investigation into the mechanisms of sympathectomy-induced immune alterations, we first evaluated the peritoneal environment into which the protein antigen keyhole limpet hemocyanin is administered. Denervation resulted in increased production of tumor necrosis factor- by peritoneal exudate cells and these cells appeared to have enhanced antigen presenting capability. We hypothesized that nerve terminal destruction may be inducing an inflammatory response by monocyte/macrophages and other cell types throughout the periphery that could differentially alter subsequent mitogen versus antigen-specific responses. However, no evidence of sympathectomy-induced systemic or local splenic inflammatory responses was observed, as indicated by measuring the proinflammatory cytokines tumor necrosis factor- and interleukin-1. These experiments indicate that an inflammatory response is not likely to be responsible for sympathectomy-induced immune alterations, eliminating a potential confounding factor in interpreting sympathectomy studies. Copyright 2001 Elsevier Science (USA).

Authors: Callahan T.A.^{1, 2}; Moynihan J.A.^{1, 2, 3, 4, 5}

Source: Brain, Behavior, and Immunity, Volume 16, Number 1, February 2002 , pp. 33-45(13)

Effects of antidepressants on cytokine production and actions

There are intriguing analogies between many features of depression and physiological and behavioral responses to infection, which are mediated by the brain effects of cytokines. These observations suggest that depression can be considered as a psychoneuroimmunological disorder where a central increase of pro-inflammatory cytokines, may have adverse consequences on the functional activity of the neurochemical and neuroendocrine systems implicated in the symptoms of the disorder. According to this hypothesis, the therapeutic effects of antidepressants should be at least partly exerted by attenuating the brain expression and/or actions of pro-inflammatory cytokines. Despite their inherent limitations, animal models of depression that are based on behavioral and pharmacological analogies with the symptoms observed in humans, represent the best available tool to test this hypothesis and to investigate the action mechanisms of the immune effects of antidepressants. Treatment with different classes of antidepressants indeed conferred protection against cytokine-induced depressive-like biological and behavioral changes. This ‘anti-inflammatory’ profile may be due to alterations of the pro-/anti-inflammatory cytokine balance. The mechanisms underlying these effects of antidepressants are presently unknown, but the available literature suggests several possibilities, including actions on different molecules representing potential mediators of mood disorders induced by cytokines. The studies summarized in this review have opened up new vistas in both the pathophysiology of depression and the pharmacology of antidepressants. Whether their demonstrated immune effects are a side effect or a significant part of their clinical activity still remains to be elucidated.

Nathalie Castanon^{, , a}, Brian E. Leonard^b, Pierre J. Neveu^a and Raz Yirmiya^c

^a INRA-INSERM U394, Neurobiologie Integrative, Institut François Magendie, Rue Camille Saint-Saëns, Bordeaux Cedex 33077, France

^b Pharmacology Department, National University of Ireland, Galway, Ireland

^c Department of Psychology, The Hebrew University, Mount Scopus, Jerusalem 91905, Israel

Received 9 July 2001.

Available online 1 October 2002.