Role of sympathoadrenergic mechanisms in arrhythmogenesis

Role of sympathoadrenergic mechanisms in arrhythmogenesis

The NA content in the heart was not measured but it is likely to be small at least at the 10-day period. It is known that three days after chemical sympathectomy NA content is only 7% of normal value [6]. Second, the development of adrenoceptor supersensitivity in the transplanted heart was demonstrated clearly with enhanced heart rate responses to NA or propranolol (at Day 10) [1]. As dennervation sensitization increases the arrhythmia susceptibility [6], it is thus possible that, in the presence of receptor supersensitivity, adrenergic activation occurs by either increase in circulating catecholamines and possibly local release of residual NA, which might still have been sufficient to contribute to arrhythmia development.
Role of sympathoadrenergic mechanisms in arrhythmogenesis
Xiao-Jun Du* and Anthony M. Dart
Baker Medical Research Institute, Melbourne, Victoria, Australia
Cardiovascular Research 1999 43(4):832-834;

Surgeons should be aware of adverse effects such as bradycardia

The heart rate and systolic blood pressure de-
creased significantly after T2-T3ganglionectomy.
A prolonged QT interval was also recorded (p<> 0.05). The decrease was signifi-
cant in the sympathectomy group.
Our study also, it was revealed that
sympathectomy significantly prolonged the QT in-
terval.


Surgeons should be aware of adverse effects such as bradycardia during thoracic
sympathectomy. This study suggested that careful monitoring was required during thoracic sym-
pathectomy and early postoperative period.


Orhan YÜCEL, MD
GATA, Department of
Thoracic Surgery, Ankara,
TÜRKİYE/TURKEY

Sympathetic nervous system regulation of immunity

"suppressor T cells through an immune-privileged site requires an intact sympathetic nervous system."

Journal of Neuroimmunology
Volume 147, Issues 1-2, February 2004, Pages 87-90

Sympathectomy-induced alterations in immunity

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.
Brain, behavior and immunity ISSN 0889-1591
2002, vol. 16, n^o1, pp. 33-45 [13
CALLAHAN Tracy A. ; MOYNIHAN Jan A. ;

Reduced Heart Rate Variability associated with incresed mortality

These results support an association between CAN (cardiovascular autonomic neuropathy) and increased risk of mortality. The stronger association observed in studies defining CAN by the presence of two or more abnormalities may be due to more severe autonomic dysfunction in these subjects or a higher frequency of other comorbid complications that contributed to their higher mortality risk. Future studies should evaluate whether early identification of subjects with CAN can lead to a reduction in mortality.

1. Raelene E. Maser, PHD1,
2. Braxton D. Mitchell, PHD2,
3. Aaron I. Vinik, MD, PHD3 and
4. Roy Freeman, MD4

Sympathectomy also results in reduced heart rate variability

"Cardiovascular autonomic neuropathy (CAN) is the most prominent focus because of the life-threatening consequences and the availability of direct tests of cardiovascular autonomic function.. .CAN results from damage due to the autonomic nerve fibers that innervate the heart and blood vessels and results in abnormalities in heart rate control and vascular dynamics. Reduced heart variation is the earliest indicator of CAN."

"CAN is the most studied and clinically important form of DAN. Meta-analyses of published data demonstrate that reduced cardiovascular autonomic function as measured by heart rate variability (HRV) is strongly associated with an increased risk of silent myocardial ischemia and mortality. The determination of the presence of CAN is usually based on a battery of autonomic function tests..."

TECHNICAL REVIEW: Standard of Care - Diabetic Autonomic Neuropathy

Aaron I. Vinik, MD, PHD; Braxton D. Mitchell, PHD
Raelene E. Maser, PHD; Roy Freeman, MD

Skin denervation

Epidermal nerve fiber densities were significantly reduced in the skin of all patients, consistent with concomitant small-fiber neuropathies. Perivascular infiltration by T cells and macrophages was demonstrated by immunohistochemistry. All patients experienced neurologic improvement in muscle strength and alleviation of sensory symptoms after immunotherapy with corticosteroids, plasma exchange, or cyclophosphamide. Conclusions: Small-diameter sensory nerves are affected in vasculitis in addition to the well-known effect of vasculitis on large-diameter nerves. Significant inflammatory vasculopathy is present in the skin despite the absence of clinically active vasculitic lesions.
Archives of neurology ISSN 0003-9942 CODEN ARNEAS
2005, vol. 62, n^o10, pp. 1570-1573 [4 page(s) (article)] (24 ref.)

sympathetic vascular innervation in sympathectomized patients

We measured arterial and venous plasma catecholamines and used laser-Doppler flowmetry to measure cutaneous microcirculatory flow in the sympathectomized and in the intact limbs of 3 patients who had undergone regional sympathectomies. Venous concentrations of norepinephrine, the sympathetic neurotransmitter, exceeded arterial concentrations in the intact limbs--a normal finding--but invariably were less than arterial in the sympathectomized limbs of the same patients, both during baseline conditions and during sympathetic stimulation using tilt, standing and the cold pressor test (mean arteriovenous decrement about 40%). Arterial epinephrine levels exceeded venous levels with or without sympathectomy. Skin microvascular flow rapidly decreased during the cold pressor test and the Valsalva maneuver in the intact but not in the sympathectomized limbs, and spontaneous flow oscillations occurred in the sympathectomized limbs. The results suggest that an arteriovenous increment in plasma norepinephrine reflects local release of norepinephrine from sympathetic nerve endings, whereas removal of circulating catecholamines can occur with or without sympathetic neural impulses. Laser-Doppler flowmetry can measure reflexive sympathetically mediated responses of skin microvascular flow and so can detect sympathetic denervation.
PMID: 3517118 [PubMed - indexed for MEDLINE

Impaired skin vasomotor reflexes

Not surprisingly, diminished vasoconstrictor responses, similar to the current findings, have been found
in patients with sympathetic dystrophies [26], dysautomias [27], post-regional sympathectomy [28] and
diabetic neuropathies [11].


Additionally, there have been a few reports of EM patients benefitting from sympathectomy or neurolitic
irreversible blocks of the lumbar sympathetic ganglia [22,23], while others have found the symptoms of EM to
be aggravated by such treatment [24,25], possibly as a result of denervation supersensitivity.
Clinical Science (1999) 96, 507ñ512 (Printed in Great Britain)
Roberta C. LITTLEFORD, Faisel KHAN and Jill J. F. BELCH
University Department of Medicine, Section of Vascular Medicine and Biology, Ninewells Hospital and Medical School,
Dundee DD1 9SY, Scotland, U.K.

Peripheral Nervous System Disease

Combined with loss of active vasodilation, anhidrosis places tetraplegic patients at risk for hyperthermia.

Peripheral Nervous System Disease

With normal aging, thermoregulatory sweat output declines due to peripheral neural and eccrine glandular factors, which vary in degree depending on genetic predisposition and level of physical conditioning.^[75] Extensive anhidrosis may also accompany disease of the peripheral nervous system. When exposed to an elevated ambient temperature or physical exercise, these individuals may present with symptoms of heat intolerance, dizziness, weakness, flushing, dyspnea, or palpitations and may be at risk for heat exhaustion and hyperthermia.

Peripheral Neuropathy

Distal anhidrosis, although often subclinical, is detectable by clinical sudomotor testing in many patients with peripheral neuropathy.^[76,77] Diabetes mellitus, the most common cause of autonomic neuropathy in the developed world, typically impairs thermoregulatory sweating in a stocking and glove distribution.^[78] As the neuropathy progresses, asymmetric truncal anhidrosis or global anhidrosis may develop.^[76]

Some immune-mediated neuropathies selectively target the autonomic neuron. Autoimmune autonomic neuropathy typically presents with sicca complex, anhidrosis, gastrointestinal hypomotility, orthostatic hypotension, abnormal pupillary light reflexes, and neurogenic bladder that may be subacute or insidious in onset. Autoantibodies to the ganglionic acetylcholine receptor have been demonstrated in these patients.^[29,79,80] Subacute autonomic neuropathy may signal an occult malignancy, most commonly small cell lung carcinoma. The dysautonomia in paraneoplastic autonomic neuropathy can be manifested mainly by cholinergic failure presenting as gastrointestinal dysfunction and anhidrosis.

Hypohidrosis commonly occurs in the autonomic neuropathy associated with Sjögren's syndrome.^[83,84] Hypohidrosis also accompanies neuropathies due to amyloidosis, alcoholism, Tangier disease, vasculitis, and Fabry's disease.^[85] Focal areas of hypohidrosis may be found in patients with leprosy.^[86]

Anhidrosis is a prominent feature of hereditary sensory and autonomic neuropathies type IV and V (congenital insensitivity to pain with anhidrosis), in which absent skin innervation is associated with mutations of the NTRK1 gene encoding the neurotrophic tyrosine kinase receptor type 1.^[30]

^{http://www.medscape.com/viewarticle/473206_3}

Link between skin innervation and neuropathic pain

Nerve conduction studies for large-diameter motor and sensory nerves were normal. This report documents a pure small-fibre sensory neuropathy after prolonged use of linezolid, and the relationship between skin innervation and corresponding neuropathic pain.

Journal of Neurology, Neurosurgery, and Psychiatry 2008;79:97-99

Some patients demonstrate unexpected responses

The indications for neurolytic or surgical sympathectomy are uncertain. There is no clear correlation between the degree or duration of pain relief and the actual period of sympathetic blockade and the same patient may show variable responses on different occasionsv (Loh et al 1980). Some patients demonstrate unexpected responses such as contralateral or delayed blocks and some are made worse (Purcell-Jones &Justins 1988, Evans et al 1980, Kleiman 1954)

Neurological Rehabilitation

by R. Greenwood
"All neurological diseases can cause short- and long-term disability..."

• Publisher: Psychology Press; New edition edition (February 1, 1997)
• Language: English
• ISBN-10: 0863774849

Nerve 'injury' and consequences well observed in animals

Ligation injury of the L5/L6 nerve roots in rats produces behavioral signs representative of clinical conditions of neuropathic pain, including tactile allodynia and thermal and mechanical hyperalgesia.

Anesthesiology:

January 1997 - Volume 86 - Issue 1 - pp 196-204

Laboratory Investigation

the ablated segment becomes hypersensitive to acetylcholine

The injured tissue distal to the ablated segment becomes hypersensitive to acetylcholine. This can explain why CH may appear very early after sympathectomy.

All patients except one suffered from compensatory sweating, which was the main cause of patients' dissatisfaction postoperatively. Seventeen percent of the patients (12 of 72 patients) experienced new symptoms of gustatory sweating (facial sweating associated with eating). Twenty-one patients experienced other complications, including pneumothorax, Horner's syndrome, nasal obstruction, and intercostal neuralgia.

CONCLUSION: Transthoracic endoscopic sympathectomy is an effective and simple modality to treat palmar hyperhidrosis. However, all patients need to be warned of the common complications, particularly compensatory hyperhidrosis, before surgery.

by MC Kao - 1998

Neurosurgery:

July 1997 - Volume 41 - Issue 1 - pp 110-115

sympathectomy abolished the Psychogalvanic Reflex

Some P.G.R. studies in a female subject who had bilateral cervical sympathectomy were described. It was found that sympathectomy abolished P.G.R. and that intra-arterial infusion of acetylcholine evoked marked P.G.R. changes in the sympathectomized limb. These findings support the theory that the P.G.R. is mediated through the cholinergic fibres of the sympathetic nervous system.

Submitted on May 22, 1967
The British Journal of Psychiatry (1968) 114: 639-642. doi: 10.1192/bjp.114.510.639
© 1968 The Royal College of Psychiatrists

Sympathetic Innervation of Cerebral Arteries: Prejunctional Supersensitivity to Norepinephrine After Sympathectomy

© 1975 American Heart Association, Inc.

Cold Hypersensitivity after Sympathectomy for Raynaud's Disease

Scandinavian Cardiovascular Journal, Volume 14, Issue 1 1980 , pages 109 - 111

augmented cholinergic preponderance in cardiac dynamics

In the majority of 16 non-cardiac and in two angina pectoris patients, unilateral
or bilateral endoscopic transthoracic sympathectomy (method of Kux) was followed
by signs of augmented cholinergic preponderance in cardiac dynamics (especially
prolongation of the Isometric period of the left ventricle).

The findings obtained in 16 non-cardiac patients concerning the length
of the isometric or tension period (TP), heart rate and pulse pressure
are represented in Table 1.
In response to transthoracic sympathectomy, all three parameters
varied from person to person in wide ranges in both directions. However,
when the tests were repeated in the same patients at different time inter-
vals after the operation (with or without a second contralateral syrn-
pathectomy inbetween), their qualitative pattern of response (either
upward or downward) remained the same in nearly all instances, as
far as the TP and pulse pressure were concerned. The responses of the
heart rate, on the other hand, were less striking percentage-wise and
varied in quite an irregular fashion in identical individuals.
No significant relationship existed between the magnitude of the pre-
operative average values and the type (positive or negative) or degree
of the postoperative deviations in either one of the three recorded pa-
rameters.

DOI 10.1378/chest.38.4.423
1960;38;423-428
Dis Chest
W. RAAB, E. KUX and H. MARCHET
Effect of Transthoracic Endoscopic Sympathectomy
on the Cardiac Neurovegetative Equilibrium
and on Angina Pectoris

not found any improvement in ulcer healing with sympathectomy

We have not found any improvement in ulcer healing with sympathectomy as compared with local wound care and have not performed upper extremity sympathectomy for upper extremity ischemia in over a decade.

Noninvasive Vascular Diagnosis:

A Practical Guide to Therapy

By Ali F. AbuRahma, John J. Bergan
2nd ed., 2007
ISBN: 978-1-84628-446-5

sympathectomy severs both vasomotor and sensory fibres

CUTANEOUS INNERVATION IN MAN BEFORE AND AFTER LUMBAR SYMPATHECTOMY: EVIDENCE FOR INTERRUPTION OF BOTH SENSORY AND VASOMOTOR NERVE FIBRES.
ANZ Journal of Surgery. 73(1-2):14-18, January 2003.
COVENTRY, BRENDON J. BM BS, PhD, FRACS *; WALSH, JOHN A. MD, FRACS +

INFLUENCES OF SHORT-TERM SYMPATHECTOMY ON THE COMPOSITION OF PROTEINS

The protein constituents in parasympathetically evoked saliva from normal and short-term sympathectomized parotid glands were compared. There was a reduction in all proline-rich proteins (PRP) in the saliva following sympathectomy. The decrease was quantified for acidic PRP by high-performance ion-exchange chromatography, which showed an increase in the ratio of amylase to other proteins. These results suggest that sympathetic impulses influence the synthesis of PRP and amylase in opposite directions.
http://ep.physoc.org/content/73/1/139.abstract

Enhanced vascular reactivity

In conclusion, we showed that sympathectomy produces complex alterations of vascular reactivity both in vivo and in isolated vessels, which shift the balance of the sensitivity of the vessel between vasoconstrictor and vasodilating agents towards an increased constriction. These results are unlikely to simply reflect denervation supersensitivity; their underlying receptor, post-receptor and/or contractile mechanisms are yet to be identified.

Journal of Hypertension:

August 2000 - Volume 18 - Issue 8 - p 1041-1049

An adrenergic sensitivity in nociceptive afferents might contribute to pain and hyperalgesia

Normal inhibitory influences on pain during sympathetic arousal are compromised in the majority of patients with CRPS. The augmented vasoconstrictor response in the symptomatic limb during sympathetic arousal is consistent with adrenergic supersensitivity. An adrenergic sensitivity in nociceptive afferents might contribute to pain and hyperalgesia during sympathetic arousal in certain patients with CRPS.

Drummond PD, Finch PM, Skipworth S, Blockey P.

School of Psychology, Murdoch University, Perth, Western Australia. drummond@central.murdoch.edu.au

PMID: 11591852 [PubMed - indexed for MEDLINE

Persistence of pain induced by startle and forehead cooling after sympathetic blockade

J Neurol Neurosurg Psychiatry. 2004 Jan;75(1):98-102.

These findings suggest that stimuli arousing sympathetic activity act by a central process to exacerbate pain in some patients, independent of the peripheral sympathetic nervous system. This may account for the lack of effect of peripheral sympathetic blockade on pain in some CRPS patients.

Drummond PD, Finch PM. School of Psychology, Murdoch University, Perth, Western Australia,
PMID: 14707316 [PubMed - indexed for MEDLINE

enhanced hyperalgesic response following sympathectomy

We report on the ability of a delayed sympathectomy after a prolonged hyperalgesia to result in a subsequent enhanced hyperalgesic response. Sympathectomy was performed one day after injection of prostaglandin E₂ plus rolipram, which induces a prolonged sympathetically-maintained hyperalgesia [Aley K. O. and Levine J. D. (1995) Eur. J. Pharmac. 273, 107-112].
http://cat.inist.fr/?aModele=afficheN&cpsidt=3017786

Sympathectomy mimicks SART stress-induced hyperalgesia

Frontiers in Bioscience 11, 2179-2192, September 1, 2006

Joint inflammation is reduced by dorsal rhizotomy and not by sympathectomy

Joint inflammation is reduced by dorsal rhizotomy and not by sympathectomy or spinal cord transection.

Annals of the Rheumatic Diseases 1994;53:309-314
http://ard.bmj.com/cgi/content/abstract/53/5/309

Sympathectomy alters bone architecture

Journal of Cellular Biochemistry

Volume 104 Issue 6, Pages 2155 - 2164

Allostasis - a state of imbalance responsible for Autoimmune disorders

In general, enhancing the sympathetic tone decreases both T0-cell and NK cell functions but not the proliferation of splenic B cells (Dowdell and Whitacre, 2000). In contrast, chemical sympathectomy, although having varying results, does seem to increase the severity of autoimmune disorders (Dowdell and Whitacre, 2000)
As far as metabolism, catecholamines promote mobilization of fuel stores at time of stress and act synergistically with glucocorticoids to increased glycogenolysis, gluconeogenesis, and lipolysis but exert opposing effects of protein catabolism, as noted earlier. One important aspect is regulation of body temperature (Goldsttein and Eisenhofer, 2000) Epinephrine levels are also positively related to serum levels of HDL cholesterol and negatively related to triglycerines. However, perturbing the balance of activity of various mediators or metabolism and body weight regulation can lead to well-known metabolic disorders such as type 2 diabetes and obesity.

At the same time, increased sympathetic activitation and nerephinephrine release is elevated in hypertensive individuals and also higher levels of insulin, and there are indications that insulin further increases sympathetic activity in a vicious cycle (Arauz-Pacheco et al.,1996)

As a result of either local production, cytokines often enter the the circultion and can be detected in plasma samples. Sleep deprivation and psychological stress, such as public speaking, are reported to elevate inflammatory cytokine level in blood (Altemus et al., 2001) Circulting levels of a number of inflammatory cytokines are elevated in relation to viral and other infections and contirbute to the feeling of being sick, as well as sleepiness, wiht both direct and indirect effects on the central nervous system (Arkins et al., 2000; Obal and Kueger, 2000)

Inflammatory autoimmune diseases, such as multiple sclerosis, rheumatoid arthritis, and type 1 diabetes, reflect an allostatic state that consists of at least three principal causes: genetic risk factors, (...) factors that contribute to the development of tolerance of self-antigens (...) and the hormonal mikieu that regulates adaptive immunes responses (Dowdell and Whitacre, 2000)

Allostasis, homeostasis and the costs of physiological adaptation

By Jay Schulkin
Cambridge University Press, 2004

Allostasis is the process of achieving stability, or homeostasis, through physiological or behavioral change. This can be carried out by means of alteration in HPA axis hormones, the autonomic nervous system, cytokines, or a number of other systems, and is generally adaptive in the