Sympathetic regulation of the cerebral circulation by the carotid chemoreceptor reflex

S. F. Vatner, L. L. Priano, J. D. Rutherford and W. T. Manders

The effects of carotid chemoreceptor reflex stimulation (intracarotid injection of nicotine 0.2 microgram/kg) were examined in conscious dogs on the cerebral circulation, using the radioactive microsphere technique to measure cerebral blood flow. In intact dogs (n = 18) with ventilation controlled, carotid chemoreceptor reflex stimulation increased (P less than 0.01) mean arterial pressure by 36 +/- 5% (SE) and calculated cerebral vascular resistance by 58 +/- 13%, whereas cerebral blood flow fell by 7 +/- 6% (NS). After bilateral cervical sympathectomy (n = 9), carotid chemoreceptor reflex stimulation induced significantly different (P less than 0.01) effects on cerebral blood flow, which rose by 42 +/- 8%, and cerebral vascular resistance, which did not change. To determine whether the difference in effect was due to the sympathectomy or merely to the repetition of the stimulus, another group of dogs (sham; n = 6) that had intact sympathetic nerves were studied a second time. In "sham" dogs, the repeat response to carotid chemoreceptor stimulation also induced significantly different effects from those in dogs with sympathectomy. Thus, in the conscious dog, stimulation of the carotid chemoreceptor reflex elicits significant sympathetically mediated vasoconstriction in cerebral vessels.
Am J Physiol Heart Circ Physiol 238: H594-H598, 1980;

study demonstrates that cerebral autoregulation is influenced by the autonomic innervation of cerebral vessels

Alpha adrenergic blockade improves impaired autoregulation when cerebral perfusion pressure (CPP) is lowered but worsens it when CPP is raised, indicating that PBZ impairs the ability of cerebral vessels to constrict during induced hypertension and improves their ability to dilate during induced hypotension.

JOHN STIRLING MEYER M.D.1; KUNIO SHIMAZU M.D.1; SHIGEMICHI OKAMOTO M.D.1; ATSUO KOTO M.D.1; TADAO OHUCHI M.D.1; ATSUO SARI M.D.1; ARTHUR DALE ERICSSON M.D.1

1 Department of Neurology, Baylor College of Medicine, and the Baylor-Methodist Center for Cerebrovascular Research, Houston, Texas 77025
© 1973 American Heart Association, Inc.

Changes of Catecholamines

1. The contents of norepinephrine, epinephrine, dopamine, and dopa of the heart were determined fluorimetrically in 24 dogs from 1 to 50 days following bilateral cervical sympathectomy. The results were compared with those obtained from intact dogs in the previous studies. 2. After bilateral cervical sympathectomy, the norepinephrine content show a rapid decrease from 4 days to 7 days and a slow decrease within the following 14 days. No tendency of recovery was apparent in the heart for 50 days following the operation, the norepinephrine content remaining almost at an equal level. The same operative procedure, however, had no significant effect on the concentrations of dopamine and dopa 3. It was postulated that norepinephrine could not be synthesized and/or accumulated in the heart following bilateral cervical sympathectomy, but that cardiac muscle might synthesize dopamine for itself.
Japanese circulation journal
Vol.29, No.1(19650120) pp. 11-15
KIMATA SHIN-ICHI 1
1The Third Department of Internal Medicine, Faculty of Medicine, University of Tokyo

sympathectomy – its effect in the treatment of refractory angina pectoris

To document an improvement in the quality of life in a group of patients with refractory angina and videothoracoscopic sympathectomy (VTSY) during the early postoperative period and a six-month follow-up. Methods: Ten patients with angina CCS IV refractory to a conventional therapy underwent VTSY between the years 1998 and 2002 at our institution. All patients underwent a complex preoperative evaluation, including pain assessment using a visual analog scale (VAS). Proximal thoracic sympathetic blockage was performed in all patients as a diagnostic test. The resection of bilateral Th2-Th4 ganglions was performed under general anesthesia and selective lung ventilation. All patients were monitored 6 months after the VTSY. Results: No deaths occurred in our group of patients, with an average hospital stay of 4.1 days. Nine of the ten operated patients referred an important subjective relief of pain. There was a drop from 10 to 4 according to VAS (P<0.05), and from 4 to 2.4 according to CCS (P<0.05). Decreases in basal heart rate, norepinephrine level, and an occurrence of ventricular premature beats reached the level of statistical significance. Conclusions: The increasing number of patients with refractory angina prompted a search for an effective and safe therapy to improve the quality of their life. New evidence in the pathophysiology of an ischemic myocardium and investigation of the impact of thoracic sympathectomy suggests sympathetic denervation seems to be a possible alternative method for the treatment of refractory angina pectoris.

Martin Striteskya, Milos Dobiasa, Rudolf Demesb, Michal Semradc,*, Eva Poliachovaa, Tomas Cermaka, Jiri Charvatd and Ivan Maleke
Interact CardioVasc Thorac Surg 2006;5:464-468. doi:10.1510/icvts.2005.118976
© 2006 European Association of Cardio-Thoracic Surgery

Dopamine

Adrenalectomy, adrenal demedullation, denervation and chemical sympathectomy have been reported to decrease plasma dopamine levels.

Autonomic Pharmacology
By Kenneth J. Broadley
Published 1996
CRC PRESS

Sympathectomy alters acetylcholinesterase expression

Acetylcholinesterase was analysed after destruction of adrenergic nerves by 6-hydroxy-dopamine or bilateral stellate sympathectomy. Effectiveness of treatment was verified by determining noradrenaline concentrations in right ventricle. Acetylcholinesterase activity was assayed in homogenates of atria and portions of left ventricular free wall.

Sympathectomy caused a small decrease in acetylcholinesterase activity, due to a decrease in the activity of the tetrameric globular form of the enzyme. Choline acetylcholinesterase activity was not altered by sympathectomy, which is an indication that cholinergic nerves were not affected.

Conclusions – The contribution of adrenergic neurones to the cardiac pool of acetylcholinesterase is measurable and consists primarily of the tetrameric globular form of the enzyme.
Copyright © 1990, European Society of Cardiology
Cynthia Nyquist Battie and Nancy Moran

Serum Dopamine-beta-Hydroxylase: Decrease after Chemical Sympathectomy

Dopamine-{beta}-hydroxylase, the enzyme which converts dopamine to norepinephrine, is released into the perfusate upon stimulation of the isolated perfused adrenal gland and after stimulation of the nerves to the isolated perfused spleen. This study was undertaken to determine whether dopamine-{beta}-hydroxylase activity could be detected circulating in blood. By using a sensitive new enzymatic assay, a dopamine-{beta}-hydroxylase activity was found in the blood of both man and the rat. It is located in the serum and is not associated with the formed elements of blood. The serum activity is similar to that of purified bovine adrenal dopamine-{beta}-hydroxylase in that it requires the presence of ascorbic acid, catalase, fumarate and oxygen for full activity. Furthermore, as is also the case with the adrenal enzyme, serum activity is increased in the presence of cupric ions. The Km values for substrate in human and rat sera are similar, and both are close to values determined in rat adrenal glands and stellate ganglia. The mean activity ±SE in the serum of six rats was 2.27±.04 nmoles/ml serum/20 min, and that of four normal humans ranged from 96.2 to 284 nmoles/ml/20 min.
1 Laboratory of Clinical Science, National Institute of Mental Health, Bethesda, Maryland 20014
RICHARD WEINSHILBOUM 1 JULIUS AXELROD
(Circulation Research. 1971;28:307.)
© 1971 American Heart Association, Inc.

NE synthesis was abolished by chronic sympathectomy

This study presents evidence that dopaminergic neurons innervate the cat carotid body. Immunocytochemical studies revealed many tyrosine hydroxylase (TH)-positive nerve fibers in the carotid body which establish extensive contacts with type I cells. All TH-positive intralobular profiles disappeared with chronic carotid sinus nerve (CSN) section, but survived sympathectomy following removal of the superior cervical ganglion. The level of endogenous dopamine (DA) in the CSN was higher than that for norepinephrine (NE). While both catecholamines were synthesized by the nerve at similar rates, NE synthesis was abolished by chronic sympathectomy, but DA synthesis remained largely unchanged following this procedure. Our data indicate that DA is not present in the CSN as a mere precursor of NE. Following a 3-hour incubation of carotid bodies with their attached nerves in media containing 20 µM3H-tyrosine, electrical stimulation of CSN C-fibers in chronically sympathectomized preparations provoked the release of 3H-DA, but not 3H-NE.

Copyright © 1993 S. Karger AG, Basel

Neurosignals 1993;2:16-26 (DOI: 10.1159/000109474)

L. Almaraz, Z.-Z. Wang, L.J. Stensaas, S.J. Fidone

sympathectomy on dopamine, noradrenaline and adrenaline content in some peripheral tissues

Dopamine, noradrenaline (NA) and adrenaline (Ad) depletion by 6-hydroxydopamine (6-OHDA) and pargyline plus 6-OHDA was investigated in the cat left ventricle, mesenteric and renal arteries, renal cortex, renal medulla and adrenal medulla. Catecholamine concentrations in plasma were also analyzed in these two experimental conditions. 6-OHDA alone or in combination with pargyline induced parallel decreases of NA and dopamine contents in the left ventricle. In the main trunk and proximal branches of the mesenteric artery and renal artery 6-OHDA selectively reduced NA without a parallel decrease in dopamine content. Previous treatment with pargyline abolished this selectivity. In the kidney of control animals, dopamine content was greater than could be attributed to its presence only in noradrenergic neurones. In the renal cortex 6-OHDA reduced significantly dopamine and NA contents, and in the renal medulla only NA levels were decreased by this drug. Pargyline plus 6-OHDA did not deplete the NA content either in the renal cortex or in the renal medulla, and only reduced significantly the dopamine content in the renal cortex. NA concentrations in plasma were increased by pargyline plus 6-OHDA whilst Ad remained unaffected. In the adrenal medulla only NA content was reduced either by 6-OHDA or pargyline plus 6-OHDA.
Br J Pharmacol. 1985 October; 86(2): 351–356.
M. M. Caramona and P. Soares-da-Silva

Sympathectomy also reduced the percent of DA (Dopamine)

The catecholamines (CAs), dopamine (DA) and norepinephrine (NE), are synthesized and stored in carotid body chemosensory type I cells. Previous studies in our laboratory demonstrated that low concentrations of nicotine preferentially evoke the release of NE from rabbit type I cells, whereas hypoxia mobilizes DA and NE in proportion to their stores in the tissue. The primary objective of the present study was to examine whether hypoxia, nicotine and elevated concentrations (30 mM) of K+ evoke the preferential release of DA vs. NE from cat carotid bodies superfused in vitro. In this species, where tissue stores of DA and NE are nearly equal, hypoxia evoked the preferential release of DA from normal carotid bodies. This pattern of release evoked by low O2 was also present following chronic removal of the superior cervical ganglion, which eliminated NE contained in the sympathetic innervation to the carotid body. In contrast, nicotine and high-K + preferentially mobilized NE in these sympathectomized animals. Sympathectomy also reduced the percent of DA (but not NE) content released from type I cells in response to any of the three stimuli. Our findings suggest that chemosensory type I cells possess stimulus-specific mechanisms for CA mobilization and that the sympathetic innervation modulates the metabolism and release of CAs in the cat carotid bodv.


CHEN J. (1) ; GOMEZ-NINO A. (2) ; GONZALEZ C. (2) ; DINGER B. (1) ; FIDONE S. (1) ;
Journal of the autonomic nervous system ISSN 0165-1838 CODEN JASYDS
Source / Source
1997, vol. 67, no1-2, pp. 109-113 (17 ref.)

Dopamine-beta-Hydroxylase: Decrease after Chemical Sympathectomy

Serum Dopamine-beta-Hydroxylase: Decrease after Chemical Sympathectomy
Richard Weinshilboum 1 and Julius Axelrod 2

1 Pharmacology-Toxicology Program, National Institute of General Medical Sciences, Bethesda, Maryland 20014
2 Laboratory of Clinical Science, National Institute of Mental Health, Bethesda, Maryland 20014

Dopamine-beta- hydroxylase is an enzyme that is localized to catecholamine-containing vesicles in sympathetic nerves and the adrenal medulla, and is also found in the serum. Treatment of rats with 6-hydroxydopamine, a drug which destroys sympathetic nerve terminals, leads to a decrease in serum dopamine-beta-hydroxylase activity. The decrease is not due to an effect on the adrenal medulla or to an increase in circulating inhibitor or inhibitors of enzyme. These data represent evidence that at least a portion of the circulating dopamine-beta-hydroxylase activity arises from sympathetic nerve terminals.

structural damage to the peripheral arteries

Longterm sympathetic denervation has been shown to
cause structural damage to the peripheral arteries.
The effects of long-term sympathectomy include
smooth muscle atrophy in the vessels, leading to
ultimate structural changes in the arterial tree. This in-
crease in blood flow has been implicated as an impor-
tant factor in the development of Charcot joint and
pedal ulceration. Ward et al.16 postulated that, flow in
the small distal vessels is inadequate as a result of
faster flow from ateriovenous shunting. Abnormally
high blood flow, vasodilation, and arteriovenous
shunting that result from sympathetic denervation
lead to abnormal venous pooling.

Richard M. Stess
Marilyn J. Waller

Hemodynamic responses were abolished after bilateral sympathectomy

Hemodynamic responses were diminished after bilateral vagotomy and abolished after bilateral
sympathectomy.
Conclusion Since activation of cardiac afferent nerves and reflex responses remained intact after
TMLR, but changed after vagotomy or sympathectomy, TMLR does not denervate the heart sufficiently
to be the cause of improved angina after TMLR (Transmyocardial laser revascularization)


Chemoreflexes
An Experimental Study
Benjamin B. Y. Chiang, MD; Andrew M. Roberts, PhD; Abul M. Kashem, MD, PhD;
William P. Santamore, PhD; Sufan Chien, MD; Laman Gray, Jr, MD;
Robert Dowling, MD

Vol. 135 No. 5, May 2000 Archives
Arch Surg.

ipsilateral ptosis, miosis, facial anhydrosis, vasomotor rhinitis

In contrast, cosmetic complications from ETS include Horner syndrome (ipsilateral ptosis, miosis, facial anhydrosis, vasomotor rhinitis) and, most importantly from a patient-satisfaction perspective, an increase in sweating elsewhere on the body (CH). To minimize these complications, much attention has been focused on how, and how much, sympathetic nerve innervation should be interrupted.

With traditional sympathectomies or ganglionectomies (Figure 3), severe CH may occur in 10% to 40% of postoperative patients.37 It is interesting that the sites affected with CH are generally the thermoregulatory, nonglabrous skin regions of the trunk/back, buttocks, groin, and thighs that sweat normally before ETS.

This may lead ultimately to long-term debilitating CH with few treatment options, and at least 5% of patients may regret undergoing the operation.

Mayo Clin Proc. 2005;80:824-828
Hyperhidrosis: Evolving Therapies for a Well-Established Phenomenon
JOHN H. EISENACH, MD; JOHN L. D. ATKINSON, MD; ROBERT D. FEALEY, MD