Surgical thoracic sympathectomy can result in functional changes in the intrathoracic organs

Surgical thoracic sympathectomy such as ESD (endoscopic thoracic sympathectic denervation) or heart transplantation can result in an imbalance between the sympathetic and parasympathetic activities and result in functional changes in the intrathoracic organs. Therefore, the procedures affecting sympathetic nerve functions, such as epidural anesthesia, ESD, and heart transplantation, may cause an imbalance between sympathetic and parasympathetic activities (1, 6, 16, 17). Recently, it has been reported that ESD results in functional changes of the intrathoracic organs. In conclusion, our study demonstrated that ESD adversely affected lung function early after surgery and the BHR was affected by an imbalance of autonomic activity created by bilateral ESD in patients with primary focal hyperhidrosis. Journal of Asthma, 46:276–279, 2009 http://informahealthcare.com/doi/abs/10.1080/02770900802660949

patients that has been treated with ETS need to be observed during high-level exercise

CARDIOVASCULAR EFFECTS OF BILATERAL ENDOSCOPIC TRANSTHORACIC SYMPATHICOTOMY AT REST AND DURING EXERCISE IN PATIENTS WITH PALMAR HYPERHIDROSIS

AUTHORS: Kazushi Takaishi, MD, Etsuo Tabo, MD, Kazuo Nakanishi, MD, Masao Soutani, MD,PhD, Kyoji Tsuno, MD, Tatsuru Arai, MDAFFILIATION: Ehime University, Shigenobu, Japan.
INTRODUCTION: Palmar hyperhidrosis is characterized by an overactivity of the sympathetic fibers passing through T2 and T3 ganglia. Although endoscopic transthoracic sympathicotomy (ETS) is an effective treatment for palmar hyperhidrosis, the partial cardiac denervation that follows may cause impairment of cardiovascular function at rest and during exercise. The purpose of this study was to compare the cardiovascular response to exercise between patients with palmar hyperhidrosis and a normal control population, and to examine the effects of ETS on cardiovascular response in patients with palmar hyperhidrosis.
METHODS: After institutional approval and informed consent, 16 patients with palmar hyperhidrosis undergoing bilateral T2- T4 ETS and 10 healthy volunteers were studied. First, before ETS administration, heart rate (HR), blood pressure (BP), and serum catecholamine (SC) at rest were measured in the patient group and in normal subjects. Then, changes in HR, BP and SC as a result of isometric handgrip exercise (IHE) were measured in both groups. Finally, HR and BP at rest, changes in HR and BP as a result of general exercise (GE), and changes in HR, BP and SC as a result of IHE were measured in the patient group both one day before and one day after ETS was administered.RESULTS: Although there was no significant difference in HR and BP at rest between the patient group before ETS and normal subjects, the value of serum adrenaline in the patient group (0.6 ng/ml) was significantly lower than that in normal subjects (2.6 ng/ml, p<0.01). Changes in HR, BP and SC to IHE were similar in both groups before ETS. HR and BP at rest, and changes in HR and BP as a result of GE and IHE were significantly decreased after ETS (p<0.05).

DISCUSSION: HR and BP at rest and cardiovascular response to exercise were similar in patients with palmar hyperhidrosis before ETS and in the normal control population. Therefore, we consider that patients with palmar hyperhidrosis have no overactivity of the sympathetic nerve. However, because bilateral ETS causes the suppression of cardiovascular response to exercise, patients that has been treated with ETS need to be observed during high-level exercise.

K Takaishi, E Tabo, K Nakanishi, M Soutani, K Tsuno, T Arai:
Cardiovascular effects of bilateral endoscopic transthoracic sympathicotomy at rest and during exercise in patients with palmar hyperhidrosis.
International Anesthesia Research Society
The 74th Clinical and Scientific Congress 2000 

Snipping the nerve may stop 'flight-or-fight' stress response

What do sweaty palms and abnormal heart rhythms have in common? Both can be initiated by the nervous system during an adrenaline-driven "flight-or-fight" stress reaction, when the body senses danger.

Hyperhidrosis, an abnormal flight-or-fight response of the sympathetic nervous system that causes excessively sweaty palms may also contribute to problems like dangerous irregular rhythms from the lower chambers of the heart, known as ventricular arrhythmias.

UCLA cardiologists have now found that surgery to snip nerves associated with the sympathetic nervous system on both the left and right sides of the chest may be helpful in stopping dangerous, incessant ventricular arrhythmias — known as an "electrical storm" — when other treatment methods have failed. This same type of surgery has been used for years to alleviate hyperhidrosis.

The UCLA team's findings are reported in the Dec. 27–Jan. 3 issue of the Journal of the American College of Cardiology. The study is one of the first to assess the impact of bilateral cardiac sympathetic denervation (BCSD), surgery on both sides of the heart, to control arrhythmias. The research builds on previous work at UCLA in which a similar procedure was performed only on the left side. But for some patients to obtain relief, the researchers said, it must be done bilaterally. 

http://newsroom.ucla.edu/releases/snipping-key-nerves-may-help-life-220281 

Sympathectomy - a neurocardiologic disorder

Bilateral thoracic sympathectomies or sympathotomies are done for refractory palmar hyperhidrosis [85–87]. Iontophoresis, botulinum toxin injection, and glycopyrrolate cream are alternatives. Because sweating is mediated mainly by sympathetic cholinergic fibers, autonomic neurosurgery is usually effective; however, a variety of expected and unexpected consequences can result, including ectopic (e.g., plantar) hyperhidrosis, gustatory sweating, Horner syndrome, and decreased heart rate responses to exercise. The latter seems to be related to partial cardiac denervation [88]. Anecdotally, fatigue, altered mood, blunted emotion, and decreased ability to concentrate can develop after bilateral thoracic sympathectomies. 

β-Adrenoceptor blockers are a mainstay of treatment for CPVT. An automated defibrillator may have to be implanted. Treatment for CPVT also includes left sympathectomy. Such treatment leaves open the theoretical possibilities of denervation supersensitivity of cardiac adrenoceptors and compensatory activation of the adrenomedullary hormonal system; however, plasma levels of catecholamines have not been assessed in CPVT with or without therapeutic cardiac denervation.

Table 1. Neurocardiologic disorders that feature abnormal catecholaminergic function

Disorders where abnormal catecholaminergic function is etiologic Hypofunctional states without central neurodegeneration
Acute, primary
Neurocardiogenic syncope Spinal cord transection Acute pandysautonomia Sympathectomy
Acute, secondary
Drug-related (e.g., alcohol, tricyclic antidepressant, chemotherapy, opiate, barbiturates, benzodiazepines, sympatholytics, general anesthesia)
Seizures
Guillain–Barre syndrome Alcohol

Chronic, primary

Pure autonomic failure
Horner's syndrome
Familial dysautonomia
Carotid sinus syncope

Adie's syndrome Dopamine-β-hydroxylase deficiency
Sympathectomy 

http://onlinelibrary.wiley.com/doi/10.1111/j.1755-5922.2010.00244.x/full

https://archive.is/UMW1w

Patients may develop bradycardia after surgical procedure to treat sweaty hands and blushing

Upper-Thoracic Sympathectomy; Patients may develop bradycardia after surgical procedure

Heart Disease Weekly. Atlanta: Feb 23, 2003. pg. 71

direct injury to the anatomic structure of the autonomic nervous system in the thoracic cavity, and postthoracotomy pain may contribute independently or in association with each other to the development of these arrhythmias

Anesthesiol Res Pract. 2013;2013:413985. doi: 10.1155/2013/413985. Epub 2013 Oct 23.

Supraventricular arrhythmias after thoracotomy: is there a role for autonomic imbalance?

Vretzakis G1, Simeoforidou M, Stamoulis K, Bareka M.

Author information

Abstract

Supraventricular arrhythmias are common rhythm disturbances following pulmonary surgery. The overall incidence varies between 3.2% and 30% in the literature, while atrial fibrillation is the most common form. These arrhythmias usually have an uneventful clinical course and revert to normal sinus rhythm, usually before patent's discharge from hospital. Their importance lies in the immediate hemodynamic consequences, the potential for systemic embolization and the consequent long-term need for prophylactic drug administration, and the increased cost of hospitalization. Their incidence is probably related to the magnitude of the performed operative procedure, occurring more frequently after pneumonectomy than after lobectomy. Investigators believe that surgical factors (irritation of the atria per se or on the ground of chronic inflammation of aged atria), direct injury to the anatomic structure of the autonomic nervous system in the thoracic cavity, and postthoracotomy pain may contribute independently or in association with each other to the development of these arrhythmias. This review discusses currently available information about the potential mechanisms and risk factors for these rhythm disturbances. The discussion is in particular focused on the role of postoperative pain and its relation to the autonomic imbalance, in an attempt to avoid or minimize discomfort with proper analgesia utilisation.

http://www.ncbi.nlm.nih.gov/pubmed/24235971

Infra-stellate upper thoracic sympathectomy results in a relative bradycardia during exercise, irrespective of the operated side

European Journal of Cardio-Thoracic Surgery > 2001 > 20 > 6 > 1095-1100

chronic interference with β-adrenergic receptors (via either sympathectomy or β-blockade) on cardiac mast cell morphology/activation and on interstitial collagen deposition

In the present study we investigated the effects of chronic interference with β-adrenergic receptors (via either sympathectomy or β-blockade) on cardiac mast cell morphology/activation and on interstitial collagen deposition. In rats subjected to chemical sympathectomizy with the neuro- toxin 6-hydroxydopamine (6-OHDA) we observed a significant increase of mast cell density, and in particular of degranulat- ing mast cells, suggesting a close relationship between the cardiac catecholaminergicsystem and mast cell activation. In parallel, chronic 6-OHDA treatment was associated with increased collagen deposition. The influence of the β-adren- ergic receptor component was investigated in rats subjected to chronic propranolol administration, that caused a further significant increase in mast cell activation associated with a lower extent of collagen deposition when compared to chem- ical sympathectomy. These data are the first demonstration of a close relationship between rat cardiac mast cell activation and the catecholaminergic system, with a complex interplay with cardiac collagen deposition. Specifically, abrogation of the cardiac sympathetic efferent drive by chemical sympathectomy causes mast cell activation and interstitial fibrosis, possibly due to the local effects of the neurotoxin 6-hydroxy- dopamine. In contrast, β-adrenergic blockade is associated with enhanced mast cell degranulation and a lower extent of collagen deposition in the normal myocardium. In conclusion, cardiac mast cell activation is influenced by β-adrenergic influences. 

http://www.ejh.it/index.php/ejh/article/viewFile/985/1108

Correspondence: Rosanna Nano,

Department of Animal Biology, University of Pavia,

European Journal of Histochemistry

2006; vol. 50 issue 2 (Apr-Jun):133-140

Chronic bradycardia can cause fatigue, shortness of breath on exertion and dizziness

Bradycardia is defined as a heart rate below 60 beats per minute. However, slow heart rates are often found in normal people, especially at rest or if very fit. Sinus bradycardia, junctional escape rhythm and Wenckebach block can also be seen in normal people and are usually asymptomatic.

Patients with asymptomatic bradycardia usually need no treatment.

Intermittent severe bradycardia can cause syncope. Chronic bradycardia can cause fatigue, shortness of breath on exertion and dizziness. Severe bradycardia can cause haemodynamic consequences of hypotension, altered conscious state, poor perfusion, ischaemic chest pain and cardiac failure. However, in the presence of bradycardia and haemodynamic compromise it is important to look for other factors such as myocardial infarction or poor ventricular function.

Patients with syncope, other symptoms or haemodynamic compromise due to bradycardia should be referred urgently for consideration of pacemaker implantation.

Transcutaneous pacing may be required in the emergency setting for acute severe bradycardia causing severe haemodynamic compromise. Temporary transvenous pacing may be required in patients with acute, symptomatic bradycardia. Patients with chronic symptomatic bradycardia and some patients with asymptomatic but significant bradyarrhythmias require permanent pacemaker implantation.

Revised February 2012. ©Therapeutic Guidelines Ltd (etg43demo November 2014) 

http://www.tg.org.au/etg_demo/desktop/tgc/cvg6/2878.htm 

regional myocardial denervation creates autonomic and electrophysiological heterogeneity and the substrate for heterogeneous drug actions

These data show that regional myocardial denervation creates autonomic and electrophysiological heterogeneity and the substrate for heterogeneous drug actions. This drug-induced electrophysiological heterogeneity may be another mechanism for proarrhythmia. 

Circulation. 1991 Oct;;84(4):1709-14.
Modulation of drug effects by regional sympathetic denervation and supersensitivity.
Stanton MS, Zipes DP.
Krannert Institute of Cardiology, Department of Medicine, Indiana University School of Medicine, Indianapolis 46202. 

chronic interference with β-adrenergic receptors (via either sympathectomy or β-blockade) on cardiac mast cell morphology/activation and on interstitial collagen deposition

In the present study we investigated the effects of chronic interference with β-adrenergic receptors (via either sympathectomy or β-blockade) on cardiac mast cell morphology/activation and on interstitial collagen deposition. In rats subjected to chemical sympathectomizy with the neuro- toxin 6-hydroxydopamine (6-OHDA) we observed a significant increase of mast cell density, and in particular of degranulat- ing mast cells, suggesting a close relationship between the cardiac catecholaminergic system and mast cell activation. In parallel, chronic 6-OHDA treatment was associated with increased collagen deposition. The influence of the β-adren- ergic receptor component was investigated in rats subjected to chronic propranolol administration, that caused a further significant increase in mast cell activation associated with a lower extent of collagen deposition when compared to chem- ical sympathectomy. These data are the first demonstration of a close relationship between rat cardiac mast cell activation and the catecholaminergic system, with a complex interplay with cardiac collagen deposition. Specifically, abrogation of the cardiac sympathetic efferent drive by chemical sympathectomy causes mast cell activation and interstitial fibrosis, possibly due to the local effects of the neurotoxin 6-hydroxy- dopamine. In contrast, β-adrenergic blockade is associated with enhanced mast cell degranulation and a lower extent of collagen deposition in the normal myocardium. In conclusion, cardiac mast cell activation is influenced by β-adrenergic influences. 

http://www.ejh.it/index.php/ejh/article/viewFile/985/1108

Correspondence: Rosanna Nano,
Department of Animal Biology, University of Pavia,

European Journal of Histochemistry

2006; vol. 50 issue 2 (Apr-Jun):133-140

Anesthesiol Res Pract. 2013;2013:413985. doi: 10.1155/2013/413985. Epub 2013 Oct 23.

Supraventricular arrhythmias after thoracotomy: is there a role for autonomic imbalance?

Vretzakis G1, Simeoforidou M, Stamoulis K, Bareka M.

Author information

Abstract

Supraventricular arrhythmias are common rhythm disturbances following pulmonary surgery. The overall incidence varies between 3.2% and 30% in the literature, while atrial fibrillation is the most common form. These arrhythmias usually have an uneventful clinical course and revert to normal sinus rhythm, usually before patent's discharge from hospital. Their importance lies in the immediate hemodynamic consequences, the potential for systemic embolization and the consequent long-term need for prophylactic drug administration, and the increased cost of hospitalization. Their incidence is probably related to the magnitude of the performed operative procedure, occurring more frequently after pneumonectomy than after lobectomy. Investigators believe that surgical factors (irritation of the atria per se or on the ground of chronic inflammation of aged atria), direct injury to the anatomic structure of the autonomic nervous system in the thoracic cavity, and postthoracotomy pain may contribute independently or in association with each other to the development of these arrhythmias. This review discusses currently available information about the potential mechanisms and risk factors for these rhythm disturbances. The discussion is in particular focused on the role of postoperative pain and its relation to the autonomic imbalance, in an attempt to avoid or minimize discomfort with proper analgesia utilisation.

http://www.ncbi.nlm.nih.gov/pubmed/24235971

"Since changes in old age show some similarities with those following chronic sympathectomy"

"For the tracheobronchial tree. surgical (sympathectomy) and chemical (with 6-hydroxydopamine or reserpine) interventions lead to histological disappearance of the NA and NPY." (p.435)

" Prejunctional supersensitivity to norepinephrine after sympathectomy or cocaine treatment." (p. 410)

"Following chronic sympathectomy, substance P expression in presumptive sensory nerves....and NPY-expression in parasympathetic nerves ...to autonomically innervated tissues have both been shown to increase... Experiments using NGF and anti-NGF antibodies (Kessler et al., 1983) have suggested that competition between sympathetic and sensory fibers for target-derived growth factors could explain these apparently compensatory interactions,..." (p. 33)

"Since changes in old age show some similarities with those following chronic sympathectomy, it is tempting to consider whether alterations in one group of nerves in tissues with multiple innervations trigger reciprocal changes in other populations of nerves, perhaps through the mechanism of competition for common, target-produced growth factors. The nature of these changes is such that they could be nonadaptive and even destabilizing of cardiovascular homeostasis. (p. 34) 

Impairment of sympathetic and neural function has been claimed in cholesterol-fed animals (Panek et al., 1985). It has also been suggested that surgical sympathectomy may be useful in controlling atherosclerosis in certain arterial beds (Lichter et al., 1987). Defective cholinergic arteriolar vasodilation has been claimed in atherosclerotic rabbits (Yamamoto et al., 1988) and, in our laboratory, we have recently shown impairment of response to perivascular nerves supplying the mesenteric, hepatic, and ear arteries of Watanabe heritable hyperlipidemic rabbits (Burnstock et al., 1991). 
   Loss of adrenergic innervation has been reported in alcoholism (Low et al., 1975), amyloidosis (Rubenstein et al., 1983), orthostatic hypotension (Bannister et al., 1981), and subarachnoid haemorrhage (Hara and Kobayashi, 1988). Recent evidence shows that there is also a loss of noradrenergic innervation of blood vessels supplying malignant, as compared to benign, human intracranial tumours (Crockard et al., 1987). (p. 14)  

Vascular Innervation and Receptor Mechanisms: New    Perspectives 

Rolf Uddman

Academic Press, 2 Dec 2012 - Medical - 498 pages

Our data confirmed that sympathectomy in patients with EPH results in a disturbance of bronchomotor tone and cardiac function

Our study was composed of patients affected by EH, and

thus having a dysfunction of sympathetic activity. The

observed respiratory and clinical effects would probably not

be observed in healthy individuals.

(ii) The cardio-respiratory effects were observed 6 months after

operation. However, a longer postoperative period would

be required to determine if they are long-term effects.

(iii) The number of patients was too limited, thus our results

should be corroborated by larger studies.

CONCLUSION

Our data confirmed that sympathectomy in patients with

EPH results in a disturbance of bronchomotor tone and

cardiac function.

1. 
   
   

   Eur J Cardiothorac Surg (2012)

   doi: 10.1093/ejcts/ezs071

dennervation sensitization increases the arrhythmia susceptibility - Baker Medical Research Institute

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;

bradycardia and other cardiac complications are common following surgery to treat palmar hyperhidrosis and blushing

The most common side effects of sympathectomy are compensatory sweating, gustatory sweating and cardiac changes including decreasing heart rate, systolic-diastolic and mean arterial pressure. The mechanism of bradycardia and other cardiac complications that develop after thoracic sympathectomy are still unclear. (2009)

http://tipbilimleri.turkiyeklinikleri.com/abstract_54802.html

"decrease in cardiac output causing a decrease in cerebral perfusion"

Orthostatic syncope can occur after a spinal cord injury or sympathectomy

Neurocardiogenic syncope is also referred to as vasovagal, vasodepressor, neurally mediated, and reflex syncope. As the name implies, neurocardiogenic syncope involves the interaction of various autonomic nervous system reflexes, the central nervous system, and the cardiovascular system..sup.1,4,12-14 The Bezold-Harisch reflex is cited as the mechanism responsible for vasovagal syncope and has two components. There is "cardio-inhibitory syncope" due to a vagal (parasympathetic) mediated reflex causing bradycardia or even asystole, plus "vasodepressor syncope" from withdrawal of sympathetic input leading to a drop in PVR with venous pooling in the periphery leading to hypotension.

Vasovagal syncope can occur in heart transplant patients, suggesting that the Bezold-Harisch reflex or vagal stimulation plus sympathetic withdrawal as the only factor may be a somewhat simplistic explanation, and that other variables may also play a role.

Although there are many causes of cardiovascular syncope, the final common mechanism is a decrease in cardiac output causing a decrease in cerebral perfusion.
Orthostatic syncope can occur after a spinal cord injury or sympathectomy, which eliminates
the vasopressor reflexes, and in patients on certain medications, commonly antihypertensive and
vasodilator drugs.
http://www.thefreelibrary.com/Syncope+in+Pediatric+Patients-a0217945432

"Similar low values are observed in patients with sympathectomy and in patients with tetraplegia"

"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"

Low HRV is a risk factor for pathophysiology and psychopathology

http://www.ncbi.nlm.nih.gov/pubmed/18771686

lower HRV and elevated norepinephrine have been associated with a number of adverse health outcomes

	Fagundes, Christopher P.1 Murray, David M.2 Hwang, Beom Seuk1,3 Gouin, Jean-Philippe1,4 Thayer, Julian F.4,5 Sollers, John J.6 Shapiro, Charles L.7 Malarkey, William B.1,7,8,9 Kiecolt-Glaser, Janice K.1,9,10 kiecolt-glaser.1@osu.edu
	Psychoneuroendocrinology. Sep2011, Vol. 36 Issue 8, p1137-1147. 11p.