Melatonin metabolism

Melatonin metabolism

There is a diurnal rhythm in the activity of serotonin N-acetyltransferase in the rat pineal gland. In the normal rat, the nocturnal enzyme activities are 15-to 30-fold greater than are daytime activities. This rhythm is abolished by decentralization or removal of the superior cervical ganglia, procedures that interrupt the only source of central neural input to the pineal gland. This effect of superior cervical sympathectomy on the N-acetyltransferase rhythm cannot be attributed to changes occurring in the denervated pineal parenchymal cells. When chronically denervated glands are placed in organ culture with norepinephrine, the neurotransmitter normally located in sympathetic terminals in the gland, N-acetyltransferase activity increases 10- to 20-fold. These data indicate that superior cervical sympathectomy abolishes the N-acetyltransferase rhythm by elimination of the input of central signals to the gland. These signals appear to regulate the N-acetyltransferase rhythm in the normal rat by regulation of the release of norepinephrine from the sympathetic terminals within the pineal gland.

by: DC Klein, JL Weller, RY Moore

Proceedings of the National Academy of Sciences of the United States of America, Vol. 68, No. 12. (December 1971), pp. 3107-3110.

Melatonin, serotonin

Cervical sympathetic nerves may affect blood adrenocorticotropic hormone (ACTH), cortisol (CS), melatonin or serotonin levels. We examined whether stellate ganglion block (SGB), which inhibits this nerve conduction, affects these substances.

During surgery, melatonin circadian rhythm and serotonin levels did not change, but melatonin increased only at night and serotonin decreased after surgery. These findings suggested that some stress stimuli are conducted via cervical sympathetic nerves to the hypothalamus, which is reduced by SGB, and to the pineal gland at night, which causes increased melatonin and decreased serotonin levels.

Authors: Iwama, Hiroshi; Son, Syoraku; Watanabe, Kazuhiro

Source: The Pain Clinic, Volume 13, Number 3, 2001 , pp. 233-244(12)

Publisher: Maney Publishing

Melatonin production abolished after sympathectomy

The amount of 6-sulphatoxymelatonin, the chief metabolite of melatonin, in the urine was measured in nine patients, who were subjected to
bilateral sympathectomy at the second thoracic ganglionic level for treatment of hyperhidrosis of the palms. All patients showed before surgery had a normal 6-sulphatoxymelatonin excretion with a peak in the excretion during the night time. After the sympathectomy, the high night time excretion
was clearly abolished in five patients but remained high in four patients. This indicates that the segmental locations of the preganglionic sympathetic perikarya in the spinal cord, stimulating the melatonin secretion in the pineal gland in humans, vary between individuals.
© 2006 Elsevier Ireland Ltd. All rights reserved.
Molecular and Cellular Endocrinology 252 (2006) 40–45


Melatonin
Melatonin is an important immunomodulator and is the principal means by which tissues are synchronized
to the daily cycle of light exposure and physical actity. Cortisol, on the other hand, is critical for
maintaining energy homeostasis and modulating immune function. Melatonin and cortisol tend to run opposite
to each other. That is, cortisol approaches its low point at bedtime, whereas melatonin reaches its peak a few
hours aft corti bottoms out (see Figure 1 below). Deviations from the normal patterns for these hormones can
have significant implications for overall health and future risk of cancer. In fact, research shows that low
melatonin and high cortisol are independently associated with some of the same health conditions.
Consequently, the balance between these two hormones is important to overall good healt. The melatonin-
cortisol index (MCI)s an innovative way of examining the balance between these two vital hormones. The MCI may be used to assess cancer risk and immune function, and may also aid in the assessment of depression, heart disease, osteoporosis and weight management issues.
Melatonin | Rocky Mountain Analytical Lab
http://www.rmalab.com/index.php?id=61

anaesthetic management of hypoxaemia during transthoracic endoscopic sympathectomy.

To present our experience and evaluate intraoperative arterial oxygen desaturation during anaesthesia for transthoracic endoscopic sympathectomy (TES). DESIGN: Prospective open study.
SETTING: University Hospital in Israel.
SUBJECTS: Consecutive series of patients (n = 210), suffering from upper limb hyperhidrosis, anaesthetised for TES.
MAIN OUTCOME MEASURES: Peripheral oxygen saturation (SpO2), haemodynamic status, complications, postoperative pain (n = 210) and arterial blood gases (n = 10).
RESULTS: 407 TES; 195 bilateral, 17 unilateral. Surgical time range 20-75 minutes. SpO2 decreased below 98% in 58 patients. Sudden hypotension and bradycardia in two patients. The mean PaO2 was significantly (p = 0.03) decreased during two-lung ventilation (TLV), after reinflation of the right lung, compared with TLV after endobronchial intubation. There was no significant difference in mean PaO2 during one-lung ventilation of both lungs. Lowest PaO2 observed during one-lung ventilation was less than 13.3 kPa in three sympathectomies. Postoperative pain, severe on awakening and mainly retrosternal, was relieved with i.v. opiates. CONCLUSION: Controlled ventilation with 100% inspired O2, SpO2 monitoring and one to two gentle manual ventilations when it decreases is the cornerstone of the management of hypoxaemia, a potentially serious complication of TES.
Eur J Surg Suppl. 1994;(572):23-5
PMID: 7524777 [PubMed - indexed for MEDLINE]

Risk of road traffic accidents associated with the prescription of drugs

Engeland A, Skurtveit S, Mørland J.

Norwegian Institute of Public Health, University of Bergen, Norway. anders.engeland@isf.uib.no

The risk was markedly increased in users of natural opium alkaloids (2.0; 1.7-2.4), benzodiazepine tranquillizers (2.9; 2.5-3.5), and benzodiazepine hypnotics (3.3; 2.1-4.7). Somewhat increased or unchanged SIRs were found for nonsteroidal antiiflammatory drugs (1.5; 1.3-1.9), selective beta-2-adrenoreceptor agonists (i.e., antiasthmatics, 1.5; 1.0-2.1), calcium receptor antagonists (0.9; 0.5-1.5), and penicillin (1.1; 0.8-1.5). CONCLUSIONS: The increased risk of being involved in a road accident as driver while receiving prescribed opiates and benzodiazepines supported the results from other studies.

1: Ann Epidemiol. 2007 Aug;17(8):597-602. Epub 2007 Jun 18.
http://www.ncbi.nlm.nih.gov/pubmed/17574863

PMID: 17574863 [PubMed - indexed for MEDLINE]

Beta blockers as psychotropic drugs
Encephale. 1976;2(1):85-101.

CNS-related (side-)effects of beta-blockers with special reference to mechanisms of action
beta-Adrenoreceptor antagonists are liable to produce behavioural side-effects such as drowsiness, fatigue, lethargy, sleep disorders, nightmares, depressive moods, and hallucinations. These undesirable actions indicate that beta-blockers affect not only peripheral autonomic activity but also some central nervous mechanisms. In experimental animals beta-blockers have been found to reduce spontaneous motor activity, to counteract isolation-, lesion-, stimulation- and amphetamine-induced hyperactivity, and to produce slow-wave and paradoxical sleep disturbances. Furthermore, central effects such as tranquilizing influences are used for the treatment of conditions such as anxiety.
Peripherally mediated actions whereby beta-blockers induce changes in the autonomic activity in the periphery, which are relayed to the CNS to induce changes in activity of a variety of central systems.
1: Eur J Clin Pharmacol. 1985;28 Suppl:55-63
PMID: 2865151 [PubMed - indexed for MEDLINE]

Effect of betablockers on autonomic activation

Psychologist Alain Brunet of McGill University in Montreal (Canada) is looking for ways to make those improvements happen, through the use of an old-fashioned 'beta-blocker' drug called Propranolol. Primarily intended as heart medicine, beta blocker drugs like Propranolol have long been used "off label" to treat anxiety patients because they block or lessen "peripheral autonomic activation" (e.g., symptoms of anxiety occurring in the periphery of the body such as might be noticeable in the limbs e.g., clammy skin, sweating, shaking, etc.). A socially phobic patient who normally would freak out during a speech can take Propranolol and not notice their palms getting sweaty, etc. Because they are not distracted by arousal symptoms that do not occur (or occur with less force), they are better able to remain focused on their speaking task and to execute it without incident.

Propranolol may have another useful effect as well - in that it may suppress the long term storage of emotional memories. A Psychiatrist at Harvard, Dr. Roger Pitman, has shown that trauma patients treated with Propranolol immediately after traumas (accidents, rapes) show somewhat fewer PTSD-like symptoms than patients who did not receive Propranolol. The explanation for this is that Propranolol interferes with the formation of the strong emotional memories that might otherwise crystallize into true trauma memories.

The articles I've read about the Brunet and Pitman research suggest these researchers are thinking that the mechanism for the Propranolol effect lays in its ability to block the storage or re-storage of trauma memories. However, another explanation is also possible. It might be enough that the drug simply blunts the SNS arousal and activation that would normally occur when trauma memories are discussed.
Treating PTSD with Beta-Blockers
Posted by Mark Dombeck, Ph.D. on Tue, Apr 18th 2006

Reader's response to article: After reading your article I was greatly dismayed to note that you would class the memory suppression induced by beta blockers as beneficial. These drugs do not only 'supress' memory, they remove the emotional attatchment of memories both long and short term. They are also not selective about which memories will be be stripped of thier emotive content and can desensitise futher emotive responses, i.e. to graphic or disturbing imagery. Do you value the memory of your wife on your wedding day? The pivotal experiences through which you establish meaning in your life? Would you, for all your triumphs over adversity, through difficulties which have hindered you in some ways yet enriched your life in others think it worth it for them to be rendered obselete in a matter of hours? Is it a good thing to veiw images of injured and dying people and feel nothing? "If you disrupt those memories, remove continuity, what you have is an erosion of personhood." This was said by Dr. William B. Hurlbut, a consulting professor in biology at Stanford University and a member of the President's Council on Bioethics, I am deeply comforted that someone has the broad mindedness to consider the humanistic and ethical side of issues pertaining to the use of these drugs in an unbiased manner. I find the research alluded to in your article disturbing due to the casual nature in which it is expressed. An overdose or a mis-diagnoses due to oversensitivity to a beta-blocker such as propranolol can shatter somebodies life, or more to the point shatter somebody, leaving them with serious mental health difficulties and a complete inability to cope with the altered state in which they may find themselves.
http://www.mentalhelp.net/poc/view_doc.php?type=weblog&id=51&wlid=6&cn=1

lowering of heart can result in:

In a meta-analysis, lowering of heart rate was associated with increases in cardiac mortality, risk for nonfatal MI (Myocardial Infarction), and heart failure.

— Mark S. Link, MD

Published in Journal Watch Cardiology December 10, 2008




A review of 22 studies published in the medical journal The Lancet in January may suggest another reason to be wary of beta-blockers for high blood pressure. The review concluded that diuretics and beta-blocker treatments may increase the chances of developing type 2 diabetes.
http://www.news-medical.net/?id=22051

Dual innervation of the cerebral arteries

There has been considerable controversy concerning the motor innervation of cerebral arteries. Bayliss et aL (1) and Hill and MacLeod (2) reported no evidence of any vascular response suggesting the existence of vasomotor nerves supplying the vessels of the brain. Dumke and Schmidt (3) also found
little effect of sympathetic stimulation on cerebral blood flow, as did Carlyle and Grayson (4), who concluded that non-nervous autoregulation is the most important factor in the control of cerebral blood flow. The view of these authors (1-4) and others that vasomotor nerves are of minor importance in the
regulation of cerebral blood flow has been supported in recent reviews (5-7), but these conclusions have been recently challenged by James et al. (8), who implicated vasomotor nerves in the responses of cerebral vessels to changes in blood CO2 levels. Earlier than this, Hiirthle (9) and Forbes and Cobb (10) had observed clear responses of cerebral arteries to motor nerve stimulation. Forbes and Cobb observed a constriction of cerebral arteries in response to sympathetic stimulation and a
dilatation, which was blocked by atropine, in response to parasympathetic stimulation.
Meyer et al (11), using a preparation similar to that of Dumke and Schmidt (3), recently
observed a 22 to 30% reduction in internal carotid blood flow when the cervical sympathetic nerve was stimulated.

This work has clearly shown a dual
adrenergic and nonadrenergic innervation of
the anterior cerebral arteries of the rat. Two
types of nerve fiber can be distinguished by
their vesicle inclusions in tissue fixed in
permanganate or, after treatment with 6-
OHDA, in osmium or glutaraldehyde. The
first type contained many small granular
vesicles and degenerated after cervical sympa-
thectomy. Fluorescent, noradrenaline-contain-
ing fibers were detected around the cerebral
arteries; after sympathectomy, these fibers also
degenerated. This suggests that the axons
containing small granular vesicles are adrener-
gic.

Copyright © 1970 American Heart Association. All rights reserved. Print ISSN: 0009-7330. Online ISSN:
TX 72514
Circulation Research is published by the American Heart Association. 7272 Greenville Avenue, Dallas, 1970;26;635-646
Circ. Res.T. IWAYAMA, J. B. FURNESS and G. BURNSTOCK
From the Department of Zoology, University of
Melbourne, Parkville 3052, Victoria, Australia.

This investigation was supported by grants from the
National Heart Foundation of Australia and the
Australian Research Grants Committee.
Dr. Iwayama's permanent address is Department of
Anatomy, Faculty of Medicine, Kyushu University,
Fukuoka, Japan.
Received January 5, 1970. Accepted for publication
March 9, 1970.

Catecholamine influences and sympathetic neural modulation of immune responsiveness

K S Madden, V M Sanders, D L Felten
Department of Neurobiology and Anatomy, University of Rochester School of Medicine and Dentistry, New York 14642, USA.
Primary and secondary lymphoid organs are innervated extensively by noradrenergic sympathetic nerve fibers. Lymphocytes, macrophages, and other cells of the immune system bear functional adrenoreceptors. Norepinephrine fulfills criteria for neurotransmission with cells of the immune system as targets. In vitro, adrenergic agonists can modulate all aspects of an immune response (initiative, proliferative, and effector phases), altering such functions as cytokine production, lymphocyte proliferation, and antibody secretion. In vivo, chemical sympathectomy suppresses cell-mediated (T helper-1) responses, and may enhance antibody (T helper-2) responses. Noradrenergic innervation of spleen and lymph nodes is diminished progressively during aging, a time when cell-mediated immune function also is suppressed. In animal models of autoimmune disease, sympathetic innervation is reduced prior to onset of disease symptoms, and chemical sympathectomy can exacerbate disease severity. These findings illustrate the importance of the sympathetic nervous system in modulating immune function under normal and disease states.

the third ventricular floor of the rat following cervical sympathectomy

Various investigators have shown that unilateral ganglionectomy or transection
of the internal and external carotid nerves leads to a regenerative response in
the ipsilateral superior cervical ganglion and to uninjured mature sympathetic
neurons sprouting into bilaterally innervated shared target organs. In this study
changes in the supraependymal neuronal network following unilateral and bi-
lateral cervical sympathectomy on the infundibular floor of the third ventricle
were studied by scanning electron microscopy in comparison with normal and
sham-operated control animals. After unilateral cervical sympathectomy there
was a great increase in the number of varicose nerve fibres on the infundibular
floor as compared to the normal and sham-operated control animals. Not only
was there an increase in the number of nerve fibres, but also their varicosities
were substantially larger than those normally present on the ependymal surface.
This study indicates the possible sympathetic projections from the superior cer-
vical ganglia to the ependymal surface of the third cerebral ventricle.

Folia Morphol.
Vol. 66, No. 2, pp. 94–99
Copyright © 2007 Via Medica
ISSN 0015–5659
www.fm.viamedica.

Adrenergic sympathectomy ablates unmyelinated fibers in the rat 'preganglionic' cervical sympathetic trunk

Classical anatomical depictions of the cervical sympathetic trunk label it as a cholinergic preganglionic structure. We studied the cervical sympathetic trunk of the rat following daily injection for 5 weeks of guanethidine monosulphate, a regimen known to selectively destroy adrenergic neurons outside of the blood-brain barrier leaving cholinergic systems and preganglionic structures intact. The drug-treated animals were compared with a group of physiologic saline-injected animals. In the drug-treated animals, there was an approximately 40% reduction in the numbers of unmyelinated fibers per unit area compared to controls. The finding of swollen and degenerative appearing unmyelinated fibers at 7 days of drug treatment confirmed that the fiber loss resulted from active axonal degeneration. The pattern of unmyelinated fiber loss was expressed as a reduction of fibers per Schwann cell-basement membrane profile with an appearance of 'empty profiles', and a conversion of large profiles (with large numbers of fibers per profile) to smaller size categories. There were no differences in axon diameters, fascicular areas, and numbers of microvessels between the groups. Microvessels were dilated in the drug-treated animals. These findings suggest that a large component of the cervical sympathetic chain in the rat consists of postganglionic adrenergic fibers which appear to intermingle with preganglionic cholinergic axons coursing through the chain.
Brain Res. 1989 Oct 2;498(2):221-8.

http://www.ncbi.nlm.nih.gov/pubmed/2790480?dopt=Abstract

Parasympathetic varicosity proliferation after sympathectomy

Parasympathetic innervation to eyelid smooth muscle inhibits sympathetic neurotransmission pre-junctionally without appreciable direct post-junctional effects. However, 5 weeks after sympathectomy, parasympathetic stimulation elicits substantial cholinergically mediated contractions. This study examined ultrastructural changes accompanying the conversion to parasympathetic excitation. In intact muscles, 64±9 nerve varicosities were encountered per 104 μm2. Most were close to muscle cells and not fully enclosed by supporting cells. Axo–axonal synapses were observed occasionally. Two days following sympathectomy, varicosity numbers were reduced by 97% and, relative to controls, remaining varicosities were farther from muscle cells and more frequently fully enclosed by supporting cells, but contained greater numbers of small spherical and large dense vesicles. By 6 weeks post-sympathectomy, numbers of varicosities per unit muscle volume increased to 14% of controls. These varicosities differed from those at 2 days in being closer to smooth muscle cells, less frequently enclosed, and having fewer small vesicles. These findings indicate that intact eyelid smooth muscle varicosities are predominantly sympathetic, but a small number of parasympathetic varicosities are present, some of which may form pre-junctional synapses with sympathetic nerves. Between 2 days and 6 weeks post-sympathectomy, varicosities increased in number and established appositions with smooth muscle cells. This suggests that parasympathetic nerves are capable of re-innervating an atypical smooth muscle target after sympathectomy, and that parasympathetic synaptogenesis is likely to contribute to conversion from pre-junctional inhibition to post-junctional excitation after sympathectomy.
Brain Research
Volume 786, Issues 1-2, 9 March 1998, Pages 171-180

Ultrastructural changes in the nerves innervating the cerebral artery after sympathectomy

The ultrastructure of the innervation of the anterior cerebral artery of the rat was studied in control animals and in animals after superior cervical ganglionectomy.
Fluorescence histochemistry shows a periarterial network of intensely fluorescent fibers which are divided into two groups, adventitial and periadventitial. The fluorescence begins to decrease 26 hours after, and completely disappears about 32 hours after, ganglionectomy.
Fine structural changes are first observed 18 hours after ganglionectomy, when the axoplasm of degenerating axons becomes electron dense. This density gradually increases up to about 32 hours. By 32 hours most axons with disintegrating axolemmas become inclusion bodies of the Schwann cells. At this stage, synaptic vesicles can still be distinguished as less dense areas, but the membrane structures of synaptic vesicles and mitochondria are difficult to recognize. The degenerating axons are gradually absorbed and by 38 hours dense, residual bodies are observed in the Schwann cells. Generally speaking, the degeneration occurs first in the adventitial fibers and then in the periadventitial fibers. The transient appearance of small, granular vesicles is noticed in axon terminals about 18 hours after denervation, although very few small, granular vesicles are seen in control tissue or at later stages of degeneration.
Cell and Tissue Research
Publisher Springer Berlin / Heidelberg
ISSN 0302-766X (Print) 1432-0878 (Online)
Issue Volume 109, Number 4 / December, 1970

Sypathetic nervous system (SNS) modulation of immunity

Sypathetic nervous system (SNS) modulation of immunity. The role of the sympathetic nervous system in regulation of immunity is examined in mice that are chemically-denervated by injection of the neurotoxin 6-hydroxydopamine (6-OHDA). This results in a strain-dependant elevation of Th1 and Th2 cytokines and antibody titers. Denervation also results in a robust, but transient, expression of central Fos protein and corticotrophin releasing hormone, as well as an elevation in corticosterone levels in denervated mice. The interrelationships of this HPA axis activation, loss of peripheral sympathetics, and altered immune function is being explored.

Jan A. Moynihan
Associate Professor of Psychiatry, Microbiology and Immunology and of Oncology

Rice PA, Boehm GW, Moynihan JA, Bellinger DL, Stevens SY. Chemical sympathectomy alters numbers of splenic and peritoneal leukocytes. Brain Behav Immun. 16:62-73, 2002.

Rice PA, Boehm GW, Moynihan JA, Bellinger DL, Stevens SY. Chemical sympathectomy increases the innate immune response and decreases the specific immune response in the spleen to infection with Listeria monocytogenes. J Neuroimmunol 114:19-27, 2001.

Safety and Ethics in Healthcare

"...professionals may adopt unreasonable practices. Practices may develop in professions, particularly as to disclosure, not because they serve the interests of the clients, but because they protect the interests or convenience of members of the profession. The court has an obligation to scrutinize professional practices to ensure that they accord with the standard of reasonableness imposed by the law."
Incresingly, the question is not whether the defendant's conduct conforms with the practices of the profession, but whether it conforms with standards of reasonableness. (p. 150)

The right of patients self-determination is well entrenched both in law and in ethical codes. Respect for patient autonomy now occupies centre stage in medical ethics. In considerin patient autonomy one needs to think about truth telling, confidentiality, privacy, disclosure of information and consent. Each is important and all have important implications for healthcare professionals. (p. 167)

Safety and Ethics in Healthcare: A Guide to Getting it Right

By Bill Runciman, Alan Merry

Published by Ashgate Publishing, Ltd., 2007

ISBN 0754644375, 9780754644378

Some secondary effects of sympathectomy; with particular reference to disturbance of sexual function

N Engl J Med. 1951 Jul 26;245(4):121-30.
WHITELAW GP, SMITHWICK RH.

PMID: 14853048 [PubMed - indexed for MEDLINE]

causes of autonomic dysfunction

Patients with progressive autonomic dysfunction (including diabetes) have little or no increase in plasma noradrenaline and this correlates with their orthostatic intolerance (Bannister, Sever and Gross, 1977). In patients with pure autonomic failure, basal levels of noradrenaline are lower than in normal subjects (Polinsky, 1988). Similar low values are observed in patients with sympathectomy and in patients with tetraplegia. (p.51)

The finger wrinkling response is abolished by upper thoracic sympathectomy. The test is also abnormal in some patients with diabetic autonomic dysfunction, the Guillan-Barre syndrome and other peripheral sympathetic dysfunction in limbs. (p.46)

Other causes of autonomic dysfunction without neurological signs include medications, acute autonomic failure, endocrine disease, surgical sympathectomy . (p.100)

Anhidrosis is the usual effect of destruction of sympathetic supply to the face. However about 35% of patients with sympathetic devervation of the face, acessory fibres (reaching the face through the trigeminal system) become hyperactive and hyperhidrosis occurs, occasionally causing the interesting phenomenon of alternating hyperhidrosis and Horner's Syndrome (Ottomo and Heimburger, 1980). (p.159)

Disorders of the Autonomic Nervous System

By David Robertson, Italo Biaggioni

Edition: illustrated

Published by Informa Health Care, 1995

ISBN 3718651467, 9783718651467

Hyperhidrosis is more than sympathetic overactivity

Our overall findings suggest that essential hyperhidrosis is a complex autonomic dysfunction rather than sympathetic overactivity, and parasympathetic system seems to be involved in pathogenesis of this disorder.

Annals of Noninvasive Electrocardiology

Volume 10 Issue 1, Pages 1 - 6

Published Online: 13 Jan 2005

Journal compilation © 2009 Wiley Periodicals, Inc.

interrupting sympathetic efferent fibers innervating the heart and baroreflex

The results suggest that cardiac sympathectomy induced by epidural anesthesia can suppress partially baroreceptor function by interrupting sympathetic efferent fibers innervating the heart during high levels of epidural anesthesia, but that lumbar sympathectomy during epidural anesthesia is unlikely to affect baroreceptor activity.
Baroreflex control of heart rate during cardiac sympathectomy by epidural anesthesia in lightly anesthetized humans.

Dohi S, Tsuchida H, Mayumi T
Anesth Analg 1983; 62:815-20.

Baroreflex sensitivity, measured as cardiac acceleration in response to nitroglycerin, was significantly lower (p < 0.01) in groups 1 and 2 (1.8 and 1.5 ms.mmHg-1 respectively) compared with group 3 (3.5 ms.mmHg-1) with no differences between the two bupivacaine concentrations. The results suggest that baroreflex-mediated response to decreases in arterial pressure is dependent on the integrity of the sympathetic nervous system.

Baroreflex control of heart rate during high thoracic epidural anaesthesia. A randomised clinical trial on anaesthetised humans.
Goertz A, Heinrich H, Seeling W
Anaesthesia 1992; 47:984-7.

How sympathetic tone maintains or alters arterial pressure

After chronic sympathectomy or sinoaortic denervation (SAD), arterial pressure (AP) becomes extremely unstable, especially because of movement-related depressor episodes. The simultaneous measurement of AP and regional blood flows in sympathectomized and SAD rats indicates that these depressor episodes are accompanied by strong regional vasodilations, possibly involving an autoregulatory component.

It is concluded that both stability and normal variability of AP critically depend on the baroreflex control of the sympathetic vascular tone.
Fundam Clin Pharmacol. 1995;9(4):343-9. PMID: 8566933 [PubMed - indexed for MEDLINE]

Endoscopic thoracic sympathectomy suppressed the baroreflex control of heart rate during pressor and depressor tests in patients with palmar or axillary hyperhidrosis.
We conclude that baroreflex responses are suppressed in patients who receive ETS.

Anesth Analg. 2004 Jan;98(1):37-9, table of contents.

PMID: 14693579 [PubMed - indexed for MEDLINE]

Autonomic neuropathy simulating the effects of sympathectomy

Autonomic neuropathy simulating the effects of sympathectomy as a complication of diabetes mellitus. Diabetes 1955;4:92-97.
Odel HM, Roth GM, Keating FR,

Dysautonomias: Clinical Disorders of the Autonomic Nervous System

The term dysautonomia refers to a change in autonomic nervous system function that adversely affects health. The changes range from transient, occasional episodes of neurally mediated hypotension to progressive neurodegenerative diseases; from disorders in which altered autonomic function plays a primary pathophysiologic role to disorders in which it worsens an independent pathologic state; and from mechanistically straightforward to mysterious and controversial entities. In chronic autonomic failure (pure autonomic failure, multiple system atrophy, or autonomic failure in Parkinson disease), orthostatic hypotension reflects sympathetic neurocirculatory failure from sympathetic denervation or deranged reflexive regulation of sympathetic outflows. Chronic orthostatic intolerance associated with postural tachycardia can arise from cardiac sympathetic activation after "patchy" autonomic impairment or blood volume depletion or, as highlighted in this discussion, from a primary abnormality that augments delivery of the sympathetic neurotransmitter norepinephrine to its receptors in the heart. Increased sympathetic nerve traffic to the heart and kidneys seems to occur as essential hypertension develops. Acute panic can evoke coronary spasm that is associated with sympathoneural and adrenomedullary excitation. In congestive heart failure, compensatory cardiac sympathetic activation may chronically worsen myocardial function, which rationalizes treatment with ß-adrenoceptor blockers. A high frequency of positive results on tilt-table testing has confirmed an association between the chronic fatigue syndrome and orthostatic intolerance; however, treatment with the salt-retaining steroid fludrocortisone, which is usually beneficial in primary chronic autonomic failure, does not seem to be beneficial in the chronic fatigue syndrome. Dysautonomias are an important subject in clinical neurocardiology.
David S. Goldstein, MD, PhDModerator:; David Robertson, MDDiscussants:; Murray Esler, MD; Stephen E. Straus, MD; and Graeme Eisenhofer, PhD

5 November 2002 | Volume 137 Issue 9 | Pages 753-763

NIH CONFERENCE

PMID: 12416949 [PubMed - indexed for MEDLINE]

Exaggerated responses to drugs

Exaggerated responses to drugs following nervous system lesions were described in the medical literature more than a century ago. Although the phenomenon of supersensitivity is still not completely understood, studies in experimental animals have clarified the distinction between denervation and decentralization (for review see Trendelenberg, 1963). These characteristic pharmacologic abnormalities form the basis for distinguishing pre-, and post-ganglionic noradrenergic involvement.
Chronic postgangliionic denervation increases the pressor response to NA, while the effects of indirect symphatomimetics are reduced. Decentralization causes more modest changes in the blood pressure response and is not associated with loss of neuronal NA stores; the increase in pressor sensitivity is non-specific.

Disorders of the Autonomic Nervous System

By David Robertson, Italo Biaggioni

Published by Informa Health Care, 1995

ISBN 3718651467, 9783718651467

Peripheral SNS and Cerebral Blood Flow

Immediately following experimentation the cerebral vessels were examined
for the presence of noradrenergic fibers. The results of the study demonstrate that: (1) superior
cervical ganglionectomy produces a significant reduction in the noradrenergic innervation of ip-
silateral extraparenchymal arteries; (2) the peripheral sympathetic nervous system contributes
to overall cerebral vascular resistance primarily by affecting resistance in extraparenchymal
arteries; and (3) as a result, it determines the contribution of the extraparenchymal arteries tooverall cerebral blood flow autoregulation.
1975;6;284-292 Stroke

Regulation of peripheral inflammation

It is clear that the spinal adenosine effect requires intact somatic connectivity. Information on pain and inflammation in the periphery is transmitted to the nervous system, where increased spinal adenosine levels can suppress peripheral inflammation.
Experimental Neurology
Volume 184, Issue 1, November 2003, Pages 162-168

Thoracoscopy performed under sedation-assisted local anesthesia is associated with significant hypoventilation

Thoracoscopy performed under sedation-assisted local anesthesia is associated with significant hypoventilation. Combined measurement of Spo₂ and Pcco₂ during thoracoscopy is a novel approach in the monitoring of ventilation, enhancing patient safety, and might allow to guide the administration of sedation in a better way.

Mean baseline Pcco₂ measurement was 39.1 ± 7.2 mm Hg (± SD) [range, 27.5 to 50.5 mm Hg], and peak measurement during the procedure was 52.3 ± 10.3 mm Hg (range, 37.2 to 77 mm Hg) [p < class="sc">co₂ measurement from baseline were 13.0 mm Hg and 13.2 ± 5.3 mm Hg (range, 5.5 to 27.8 mm Hg), respectively. Mean fall in Spo₂ during the procedure was 4.6 ± 3.2% (range, 1 to 14%).

(The Paratrend 7 monitoring system (PT7), which was used in our study, is a widely validated and accepted method of continuous intraarterial blood gas measurement with good accuracy and performance. Apart from our own results in patients undergoing thoracoscopic interventions with one-lung ventilation (2), this device has been validated in an experimental study (3). In the intensive care unit (4), and during cardiac surgery (5). Furthermore, this device was used by two other groups, and their results have also been published (6,7). Nevertheless, in our study, we provided ample data on the good agreement of PT7 data with laboratory blood gas analyses. In fact, whenever a laboratory blood gas analysis was performed, PT7 values were recorded simultaneously and used for bias/precision analysis. We found an overall limit of agreement for bias/precision of -3.4/15.9 mm Hg in the clinically most important range of PaO₂ values <100> a PaO₂ value of 65 mm Hg obtained by PT7 could be as low as 45.7 mm Hg or as high as 77.5 mm Hg. However, both values clearly indicate hypoxemia under an inspired oxygen fraction of 1.0 and, thus, represent a critical medical condition.)

Detection of Hypoventilation During Thoracoscopy^*

Combined Cutaneous Carbon Dioxide Tension and Oximetry Monitoring With a New Digital Sensor

1. Prashant N. Chhajed, MD, FCCP,
2. Bruno Kaegi,
3. Rajeevan Rajasekaran, and
4. Michael Tamm, MD

CHEST February 2005 vol. 127 no. 2 585-588

Substantial changes in arterial blood gases during thoracoscopic surgery

Zaugg M, Lucchinetti E, Zalunardo M, et al. Substantial changes in arterial blood gases during thoracoscopic surgery can be missed by conventional intermittent laboratory blood gas analysis. Anesth Analg. 1998;87:647-653.

Substantial and clinically relevant changes in arterial blood gases are likely to occur during thoracoscopic surgery with one-lung ventilation (OLV). We hypothesized that they may be missed when using the conventional intermittent blood gas sampling practice. Therefore, during 30 thoracoscopic procedures with OLV, the sampling intervals between consecutive intermittent laboratory blood gas analyses (BGA) were evaluated with respect to changes of PaO2, PaCO2, and pHa ([H+]) using a continuous intraarterial blood gas monitoring system.
Extreme fluctuations of PaO2 (37-625 mm Hg), PaCO2 (27-56 mm Hg), and pHa (7.24-7.51) were observed by continuous blood gas monitoring. During 63% of all sampling intervals, PaO2 decreased >20% compared with the preceding BGA value, which remained undetected by intermittent analysis. In 10 patients with a continuously measured minimal PaO2 value < or =" 60"> overestimated this minimal PaO2 by > 47%. Correspondingly, PaCO2 increases of > 10% were observed in 35% of all sampling intervals, and [H+] increases of > 10% were observed in 24% of all sampling intervals. Because these blood gas changes were not reliably detected by using noninvasive monitoring and their magnitude is not predictable during OLV, intermittent BGA with short sampling intervals is warranted. In critical cases, continuous blood gas monitoring may be helpful.
http://www.anesthesia-analgesia.org/cgi/content/abstract/87/3/647

Arterial oxygen desaturation during only one of two similar thoracoscopic procedures on the same patient

PFITZNER J. ⁽¹⁾ ; FOWLIE J. A. ⁽¹⁾ ; KISHORE M. ⁽¹⁾ ; MICHAEL A. S. ⁽¹⁾ ; LANCE D. G. ⁽¹⁾ ;

⁽¹⁾ Department of Anaesthesia and Thoracic Surgery Unit, The Queen Elizabeth Hospital, Woodville, South Australia, AUSTRALIE
Because acute hypoxia had developed during one-lung ventilation on the first occasion, serial blood gases were taken during the second. Also, whereas on the first occasion the non-ventilated lung had been left open to air when one-lung ventilation was initiated, on the second it was connected to an ambient pressure oxygen source with the object of theoretically enabling apnoeic oxygenation during lung collapse. It is argued that this fundamental difference in anaesthetic practice may have contributed to the improved oxygenation that was recorded during the second thoracoscopy.

Anaesthesia and intensive care ISSN 0310-057X CODEN AINCBS
2005, vol. 33, n^o6, pp. 805-807 [3 page(s) (article)] (16 ref.)

Venous Versus Arterial Forearm Catecholamines as an Index of Overall Sympatho-Adrenomedullary Activity

The metabolism of norepinephrine (NE) and epinephrine (EPI) in peripheral tissues limits the use of venous plasma levels of these parameters as an index of overall sympathetic or adreno-medullary activity. Therefore venous (deep antecubital vein) and arterial (brachial artery) concentrations of NE and EPI were compared in 16 hypertensive subjects. NE and EPI were determined after 30 min supine rest, and immediately before and after isometric exerise, cold provocation, head-up tilting (OST) and Stroop's colour word test (CWT). At rest venous NE exceeds arterial NE. Assuming similar fractional extractions (FE) of NE and EPI, 46±14% (mean±SD) of venous NE appeared to be produced locally. Despite this considerable local production venous and arterial levels of NE were closely correlated (r=0.92). At rest venous EPI was 42±13% lower than arterial EPI, but since the interindividual variation of the FE of EPI was relatively small and independent of arterial levels, venous and arterial levels were also closely correlated (r=0.82). All four tests caused an increase in arterial and venous NE, whereas EPI did not change. Responses of arterial and venous NE were only correlated after OST and CWT. It is concluded that at rest, but not invariably so during different forms of sympatho-adrenal activation, arterial plasma concentrations of NE and EPI can be substituted for by their respective venous equivalents. Clinical and Experimental Hypertension, Volume 11, Issue S1 1989 , pages 345 - 351

Antibody responses

Chemical sympathectomy of peripheral nerves has been demonstrated to augment antibody response following immunization with specific antigen.

Surgery: Basic Science and Clinical Evidence

By Jeffrey A. Norton, R. Randall Bollinger

Contributor Jeffrey A. Norton

Edition: illustrated

Published by Springer, 2001

ISBN 038798447X, 9780387984476

Norepinephrine response to mental challenge

DS Goldstein, G Eisenhofer, FL Sax, HR Keiser and IJ Kopin
Hypertension-Endocrine Branch, National Heart, Lung, and Blood Institute, Bethesda, MD 20892.

We simultaneously infused tracer-labeled norepinephrine (NE) and isoproterenol (ISO) intravenously into 14 subjects to measure forearm and total body NE pharmacokinetics at rest and in response to mental challenge (video game or cognitive task). Mental challenge was associated with significantly increased heart rate (24%), systolic blood pressure (13%), cardiac output (impedance cardiography, 9%), forearm blood flow (38%), and the rate of release of endogenous NE into arterial blood (total body NE spillover, 29%), but not with changes in cardiac output (r = 0.68) and systolic blood pressure (r = 0.60), whereas those of antecubital venous NE were not. Forearm extraction of NE was related inversely to forearm blood flow both at rest (r = -0.80) and during mental challenge (r = -0.81), and total body clearance of NE was positively related to cardiac output at rest (r = 0.78) and during mental challenge (r = 0.54). The results indicate that mental challenge is associated with generally increased sympathetically-mediated NE release that determines the hemodynamic responses. Because of regional changes in sympathetic activity and blood flow during psychological stress, changes in antecubital venous NE and even arterial NE may not reflect accurately sympathetic nerve activity. Measurement of total body and regional NE pharmacokinetics avoids these difficulties.
Psychosomatic Medicine, Vol 49, Issue 6 591-605, Copyright © 1987 by American Psychosomatic Society

The integrative relationship between insulin and insulin-like growth factor 1-induced cardiovascular responses and sympathetic nervous responses

Lumbar sympathectomy caused greater increase in skeletal muscle blood flow in response to both insulin and IGF-1 when hypoglycemia occurred. But when hypoglycemia was prevented, IGF-1 induced increase in blood flow was suppressed in sympathetic denervated iliac artery. We concluded that insulin and IGF-1 have both similar and distinct effects on cardiovascular system and sympathetic nervous system. They both may act directly on vasculature to elicit vasodilation thus decrease MAP Insulin can selectively increase sympathetic nerve activity, while IGF-1 decreases sympathetic nerve activity.
Zhengbo Duanmu, Wayne State University

Vasoconstrictor responses to immersion of the hand in ice water in the sympathetically denervated forearm were abolished

Vasoconstrictor responses to immersion of the hand in ice water in the sympathetically denervated forearm were abolished; during the second minute of the cold pressor test, vascular resistance had increased by 48±20 percent in the innervated limb, whereas it had decreased by 17±5 percent in the denervated limb (P<0.02> limbs).

Figs. 1 and 2 show that L-NMMA infusion evoked a roughly 3-fold larger increase in vascular resistance in the denervated forearm than in the innervated calf. In the forearm, vascular resistance increased by 58±10 percent during L-NMMA infusion whereas in the calf, it increased only by 21±6 percent (P<0.001, forearm vs. calf). The L-NMMA induced vasoconstriction was reversed by L-arginine, but not by D-arginine, infusion (Table 1). In contrast to L-NMMA, infusion of an equipressive dose of phenylephrine increased the vascular resistance comparably in the denervated and the innervated limb (by 24±3 and 26±7 percent, respectively; P>0.5, forearm vs. calf).

Here we used subjects having undergone thoracic sympathectomy for hyperhydrosis, to probe the role of the peripheral sympathetic nervous system in the modulation of the vascular responsiveness to nitric oxide synthase inhibition. We found that sympathectomy markedly potentiated the vasoconstrictor effect of L-NMMA infusion. The L-NMMA induced vasoconstrictor effect was almost three times larger in the denervated than in the innervated limb. These findings provide the first evidence for an important interplay between the peripheral sympathetic nervous system and the L-arginine–nitric-oxide system in the regulation of the vascular tone in humans, and indicate that sympathetic innervation attenuates the vasoconstrictor effect of nitric oxide synthase inhibition.

Cardiovascular Research 1999 43(3):739-743; doi:10.1016/S0008-6363(99)00084-X
© 1999 by European Society of Cardiology

Posted by Mia 0 comments