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Transaxillary upper thoracic sympathectomy for primary palmar hyperhidrosis in children and adolescents.

Primary palmar hyperhidrosis is part of a triad of palmar, plantar, and axillary hyperhidrosis of unknown etiology, affecting children, adolescents, and young adults. Sixty-seven children and young adolescents were operated on during a 10-year period. A total of 103 transaxillary upper thoracic sympathectomies (36 bilateral) were performed, with no mortality. The immediate postoperative course was uneventful in 90%; the other 10% had mostly minor problems. The average hospitalization period was 3 to 4 days. Total abolition of palmar sweating was achieved in all but two patients in whom some residual moisture remained. Long-term extreme satisfaction was reported by 64 of 67 patients (94%). One was moderately satisfied, and two were not satisfied because of excessive "compensatory" sweating elsewhere. Compensatory sweating of some degree was reported by 45% of patients but did not alter satisfaction. By further limiting ganglionectomy to just one ganglion (T2 or T3), compensatory sweating possibly may be reduced further. Early surgery for severe palmar hyperhidrosis will save a child many years of agony and social discomfort because all types of conservative therapy are ineffective and cause unnecessary delay. A limited transaxillary upper thoracic sympathectomy is presently the authors' preferred approach, although ablation via thoracoscopy should not be excluded as further experience is gained with this modality.

Adolescent↗

Dopamine and norepinephrine in the alimentary tract changes after chemical sympathectomy and surgical vagotomy.

The aim of this study was to examine the distribution of dopamine and norepinephrine in the proximal alimentary tract of the rat and to assess the contributions of sympathetic and vagal fibers to the tissue concentrations of both catecholamines. Tissues were extracted in perchloric acid and the catecholamines were separated by high pressure liquid chromatography and detected electrochemically. In untreated rats (controls) both catecholamines were concentrated in the gastric muscle but norepinephrine levels were 6-8 times higher (corpus, dopamine 35 +/- 7 ng . g-1, norepinephrine 265 +/- 50 ng . g-1, mean +/- SE, n = 6). In the mucosa norepinephrine concentrations were 10-12 times higher (corpus, dopamine 12 +/- 3 ng . g-1, norepinephrine 140 +/- 26 ng . g-1). Chemical sympathectomy (6 hydroxydopamine, 100 mg . kg-1 ip 3 days) significantly reduced dopamine concentrations in muscle and norepinephrine in muscle, mucosa, pylorus and duodenum. In all tissues the effects on norepinephrine were greater. Surgical vagotomy significantly reduced dopamine concentrations in the gastric muscle, but not the mucosa. Norepinephrine concentrations in the stomach of vagotomized rats were significantly reduced only in the pylorus. Differences in the relative concentrations of dopamine and norepinephrine in gastric tissues of the normal rat and differences in the effects of sympathectomy and vagotomy suggest that dopamine and norepinephrine exist, to an extent, in separate populations of cells and that dopamine is not merely a precursor of norepinephrine. Gastric mucosal dopamine, which was mainly unaffected by either treatment, may exist in APUD cells.

Animals↗

Compensation between sympathetic nerves and adrenal medullary activity:effects of adrenodemedullation and chemical sympathectomy on catecholamine turnover.

To clarify functional compensation between the sympathetic nerves and the adrenal medulla, the effects of adrenodemedullation and chemical sympathectomy on norepinephrine (NE) turnover in some sympathetically innervated tissues and on NE and epinephrine (E) turnover in the adrenal gland were studied in rats. The rate of NE turnover was significantly accelerated by bilateral adrenodemedullation in the pancreas and in interscapular brown adipose tissue (IBAT). Chemical sympathectomy accelerated E turnover in the adrenal gland. These data indicate that some adrenergic nerves show functional compensation under conditions of depression of the adrenal medulla, and that compensatory acceleration of the adrenal medullary function occurs under conditions of adrenergic dysfunction.

Adipose Tissue, Brown↗

Chemical sympathectomy and utilization of coronary capillary reserve in rabbits.

The effect of chemical sympathectomy with 6-hydroxydopamine (60 mg/kg, 5 days prior to the experiment) on coronary blood flow and the percentage of perfused myocardial arterioles and capillaries was investigated in anesthetized open-chest rabbits and compared to a control group. In half of the animals, coronary flow was determined using radioactive microspheres. The others were given fluorescein isothiocyanate-dextran to mark the perfused microvessels. Alkaline phosphatase stain was employed to locate the total microvasculature. A group of control and sympathectomized rabbits were administered 2 mg/kg of propranolol. Myocardial norepinephrine content was significantly decreased from 1108 +/- 161 (mean +/- SEM) in the control group to 162 +/- 31 ng/g wet weight in the denervated group as determined by HPLC technique and electrochemical analysis. However, the decrease in arterial blood pressure, heart rate, and coronary blood flow of the denervated group as compared to the control was not significant. Chemical sympathectomy significantly increased the number (Na) of the perfused capillaries from 57 +/- 3 to 66 +/- 3% and arterioles from 57 +/- 5 to 76 +/- 9%. A similar increase in the percentage of microvessels perfused with denervation was observed after propranolol. It is concluded that although denervation had no significant effect on the hemodynamic conditions or average coronary blood flow, it significantly increased the utilization of the myocardial microvessels. We suggest that the sympathetic nervous system and alpha adrenoceptors exert significant control of the utilization of coronary microvascular reserve.

Animals↗

Gastrointestinal neuropeptide concentrations following guanethidine sympathectomy.

In an effort to investigate the interaction of the adrenergic and enteric components of the autonomic nervous system, gut neuropeptide concentrations were examined following chemical sympathectomy. Adult male rats were treated with guanethidine (40 mg/kg i.p., 5 days/week for 5 weeks), which selectively destroys peripheral sympathetic neurons. Controls received equal volumes of saline vehicle. Tissues from fundic and pyloric stomach, duodenum, jejunum, jejuno-ileum, ileum, caecum and colon were extracted and concentrations of selected neuropeptides determined by radioimmunoassay. Dopamine-beta-hydroxylase (DBH) in peripheral nerve, measured as an index of degree of sympathectomy, was depleted 80-90%. One week after cessation of treatment, vasoactive intestinal peptide (VIP) was elevated in jejunum (52%), ileum (53%), caecum (41%) and colon (59%), as was neurotensin (NT) in caecum (117%) and colon (261%). Methionine-enkephalin (MET) was lowered in duodenum by 28%. With the exception of MET in duodenum and NT in caecum, these alterations normalized by 5 weeks post-treatment, although DBH remained depressed. Statistically non-significant increases in substance P content were observed in upper gut regions. An inhibitory sympathetic input to VIPergic and NTergic systems is postulated.

Animals↗

Effects of neonatal sympathectomy with 6-hydroxydopamine or guanethidine on survival of neurons in the intermediolateral cell column of rat spinal cord.

The effects of removing target cells on survival of, and inputs to, sympathetic preganglionic neurons were studied in rats that were sympathectomized with 6-hydroxydopamine (6-OHDA) or guanethidine sulfate. Separate groups of neonatal and 1-week male rats were given injections of 6-OHDA for 10 days and of guanethidine for 3 weeks (5 days/week), respectively. Histofluorescence results suggest that catecholaminergic neurons in most ganglia are destroyed with treatment except for adrenal medulla, which is unaffected [14], and the pelvic ganglion where only partial destruction occurs. Cells in the intermediolateral cell column from representative spinal cord segments of treated and control adult rats were counted. In 6-OHDA-treated rats, cells decreased in number in all segments compared to controls. In guanethidine-treated rats, cells were also decreased in number; in some segments the decrease was significantly greater than with 6-OHDA. Sympathectomy had no effect on neurons in the intermediate gray of L5 or in the ventral horn of T3. The results of this study demonstrate that peripheral sympathectomy causes loss of sympathetic preganglionic neurons and that guanethidine is slightly more effective than 6-OHDA.

Animals↗

Chemical sympathectomy favours vimentin expression in arterial smooth muscle cells of young rats.

The aim of the present study was to determine whether sympathectomy could influence the relative expression of two intermediate filament proteins, desmin and vimentin, two markers of differentiation, in arterial smooth muscle cells of the young rat. Newborn rats were treated with either repeated guanethidine or saline injections. Sections of the abdominal aorta, the femoral artery, the basilar and the middle cerebral arteries were processed simultaneously for immunofluorescence with monoclonal antibodies against desmin and vimentin and were then examined under either a conventional or a confocal laser-scanning microscope. In both cases, the mean optical density of the muscle layer staining was estimated by computerized image analysis. All artery sections from guanethidine-treated animals showed a significantly higher vimentin expression (108-119% of control values). Desmin expression was not significantly different except in the femoral artery after sympathectomy, where it was decreased by 6%. The relative increase of vimentin expression in sympathectomized blood vessels observed in the present study directly confirms previous morphometric and ultrastructural studies indicating that the sympathetic innervation of cerebral and peripheral blood vessels influences the phenotypic features of smooth muscle cells during post-natal development.

Animals↗

Effect of chemical sympathectomy on serum levels of thyroid hormones and the biochemical profile of domestic pigeons.

Recent studies have stressed the importance of the cholinergic system on avian metabolism. However, the role of the sympathetic nervous system (SNS) remains unclear. The present study was, therefore, aimed to probe the mechanisms for modulation of avian metabolism by the sympathetic nervous system after inhibition of the adrenergic responses. Activities of serum thyroid hormones (tri-iodothyronine, T3, and thyroxine, T4), body weight, hepatic weight, as well as total lipid and water content in the liver and body temperature were some of the parameters examined after chemical sympathectomy with 6-hydroxydopamine (6-OHDA) and reserpine treatment in 24-h starved pigeons. In addition, glucose was administered to the pigeons to identify the regulatory role played by glucose after disruption of the SNS. A reduction in body weight of the pigeons and an enhancement in the lipogenic machinery along with a corresponding increase in water content were some of the obvious effects in 6-OHDA+reserpine treated, as well as glucose-loaded sympathectomized birds. The cloacal temperature (Tc) and both the thyroid hormones showed a drastic decrease while the T3/T4 ratio was augmented as a result of sympathectomy. However, serum T3 and T4 levels were restored to control values when glucose load was given, indicating that glucose might be reversing some of the detrimental effects of 6-OHDA treatment by activating intrinsic autoregulatory mechanisms of thyroid gland, thereby reviving the levels of thyroid hormones. Thus, the influence of SNS appears to be crucial in the maintenance of serum thyroid hormones and body temperature, as well as metabolic activities of hepatic cells.

Animals↗

Decreased vasoactive intestinal polypeptide-immunoreactivity of parasympathetic neurons and target innervation following long-term sympathectomy.

Following long-term sympathectomy, parasympathetic neurons show increased expression of some catecholaminergic traits. The objective of this study was to determine if, in addition, expression of vasoactive intestinal polypeptide immunoreactivity (VIP-ir) is suppressed in parasympathetic neurons and a glandular target of the rat. Studies were conducted on the rat pterygopalatine ganglion and meibomian gland; the meibomian gland contains dense innervation that is strongly VIP-ir, and 99% of the VIP-ir neurons projecting to this target reside within the pterygopalatine ganglion. Two months following unilateral superior cervical ganglionectomy on postnatal day 30, DBH-ir fibers normally present within the eyelid were absent and there was a marked reduction in number and staining intensity of VIP-ir fibers within the meibomian gland. The percentage of pterygopalatine ganglion neurons displaying DBH-ir was increased from 43 +/- 4 to 65 +/- 2%. However, the percentage of parasympathetic neurons expressing VIP-ir was decreased from 96 +/- 4% to 76 +/- 1%. We conclude that sympathectomy not only enhances expression of some catecholaminergic traits but also suppresses VIP-ir within pterygopalatine ganglion parasympathetic neurons and meibomian gland target.

Animals↗

Effects of partial sympathectomy of brown fat or of adrenomedullectomy on catecholamine metabolism in cold-reared rats.

1) The aim of this work was to study the effects of surgical denervation of the interscapular brown adipose tissue (IBAT) and of bilateral adrenal demedullation on cold adaptation of rats. 2) After sympathectomy in the 28 degree C rats, there were substantial decreases in the IBAT NE basal level and turnover rate but no modifications in the heart and adrenals. In the 16 degree C rats there were also decreases in the basal level and turnover rate of the IBAT NE but, in addition, significant increases in levels and turnover rates of NE in the heart and of epinephrine in the adrenals. 3) Bilateral adrenal demedullation led to increases in the NE basal level and turnover rate in the IBAT and the heart in the 16 degree C rats; no effects were observed in the 28 degree C rats. 4) It is concluded that in rats born and reared in a mild cold environment a compensatory stimulation of catecholamine production and turnover rate occurs in some organs after a partial sympathectomy of BAT or bilateral adrenal demedullation.

Adipose Tissue, Brown↗

Prevention of exercise-induced cardiac hypertrophy in rats by chemical sympathectomy (guanethidine treatment).

The effect of 'chemical sympathectomy', produced by daily intraperitoneal injections of guanethidine sulphate for six weeks, was studied in sedentary rats and in rats chronically exercised by swimming. The guanethidine-treatment itself caused the following changes. There was a reduction in the rate of weight gain resulting in a 7% lower final body weight. Organ content of noradrenaline was decreased by 90% in spleen and submandibular glands and by 83% in the heart. Urinary excretion of noradrenaline was also decreased, but to a lesser degree, both during rest (45% lower) and after acute exercise (46% lower), while the urinary excretion of adrenaline was no different from that of controls. There was a compensatory adrenal hypertrophy in the guanethidine-treated rats, with a significant increase in adrenal catecholamine levels that was more pronounced for noradrenaline (+45%) than for adrenaline (+11%). Chronic physical exercise produced the expected degree of cardiac hypertrophy in untreated rats, but this adaptive cardiac hypertrophy was completely absent in the exercised guanethidine-treated rats. The results indicate, firstly that a good degree of chemical sympathectomy was obtained and that the persistence of a considerable urinary excretion of catecholamines in the guanethidine-treated rats was due to a compensatory increase in the secretory activity of the adrenal medulla. Secondly, it is suggested that the adaptive cardiac hypertrophy produced by chronic exercise is not caused by a direct effect of the increased work load on the cardiac muscle cell, but is instead mediated by release of a trophic factor from cardiac sympathetic nerves, probably noradrenaline itself but possibly a secretory protein.

Adrenal Medulla↗

Neuropeptide Y in non-sympathetic nerves of the rat: changes during maturation but not after guanethidine sympathectomy.

Non-sympathetic neuropeptide Y-containing nerves were demonstrated by their persistence after destruction of sympathetic nerve terminals by acute 6-hydroxydopamine treatment for 48 h. In order to examine whether these neuropeptide Y-containing nerves reinnervate tissues following the loss of sympathetic nerves we administered guanethidine sulphate to one-week-old rat pups for three weeks to produce a complete and long-lasting sympathectomy and we monitored the innervation of the superior cervical ganglion, mesenteric vein, vas deferens and urinary bladder by noradrenaline- and neuropeptide Y-containing nerves two and 16 weeks later (assay and histochemical observations). By two weeks the reduction in neuropeptide Y content of tissues was similar to the reduction after acute sympathectomy with 6-hydroxydopamine treatment, indicating that there was no early reinnervation by non-sympathetic neuropeptide Y-containing nerve fibres at a time when sensory transmitters increase. Furthermore, there was no reinnervation by neuropeptide Y-containing nerve fibres by the time these sympathectomized animals had reached maturity, 16 weeks after cessation of treatment. Neuropeptide Y levels increased in the superior cervical ganglion with normal maturation but decreased in the prostatic end of the vas deferens. A non-sympathetic source of neuropeptide Y demonstrated in the immature rat vas deferens was no longer evident in the mature animal.

Aging↗

Guanethidine sympathectomy of mature rats leads to increases in calcitonin gene-related peptide and vasoactive intestinal polypeptide-containing nerves.

Changes in the innervation of the heart (right atrium), mesenteric blood vessels, vas deferens and superior cervical ganglia have been examined following long-term sympathectomy of the mature rat. Patterns of innervation were investigated by histochemical and immunohistochemical techniques, while levels of noradrenaline and neuropeptides were measured by neurochemical assays. Large doses of guanethidine (80 mg/kg) were given daily for four weeks to 12-14 week-old male rats which were killed at 18-20 weeks of age. Catecholamine-containing nerves were severely depleted or absent in all tissues, together with a reduction in noradrenaline content. Neuropeptide Y levels were depleted by 97% in vas deferens, 78% in mesenteric vein and 50% in right atrium and superior cervical ganglion. Increases in levels of calcitonin gene-related peptide were seen in the mesenteric vein (up seven-fold), superior cervical ganglia (up 11-fold) and vas deferens (prostatic portion up three-fold), which were also evident by assessment of immunolabelling of nerve fibres. Calcitonin gene-related peptide levels were not increased in the right atrium. In addition, an increase in vasoactive intestinal polypeptide-immunoreactive nerve fibre density was seen in the mesenteric artery and vas deferens, although no significant differences were observed in assays of vasoactive intestinal peptide levels in any tissue. No changes were seen in the innervation of any of the tissues by substance P-immunoreactive nerve fibres either by immunohistochemical or immunochemical assay assessment. This study indicates that there are selective changes in the mature nervous system in response to the loss of sympathetic nerves. Differences between these changes and the response of the developing nervous system to long-term sympathectomy are discussed.

Animals↗

The effect of bilateral sympathectomy on noise induced temporary threshold shift.

The cochlea is innervated by sympathetic nerves originating or passing the superior cervical ganglion. The termination of one type (the vascular independent) is in the habenular region close to the auditory nerve fibers, and the other, the perivascular type, is associated with blood vessels, particularly in the spiral vessel of the tympanic lip. Suggested functions have so far received partial evidence in the literature. Borg (1982) suggested the protective value of sympathectomy of the ear in noise. Our experiments further elaborate this protective value, as it was seen that bilateral cervical sympathectomy diminished the temporary threshold shift in awake, sound exposed GP.

Acoustic Stimulation↗

Plasticity of autonomic nerves: differential effects of long-term guanethidine sympathectomy on the sensory innervation of the rat uterus during maturation.

The sensory nerves, containing substance P and calcitonin gene-related peptide, and noradrenaline-containing sympathetic nerves of the rat uterus were analyzed following long-term sympathectomy with guanethidine in prepubertal (four weeks), young adult (eight weeks) and fully adult animals (18 weeks). Immunohistochemical and histochemical methods were used in association with nerve density measurements and biochemical assays. The main findings were as follows: (1) long-term guanethidine treatment completely abolished the noradrenergic innervation of the uterine horn and parametrial tissue and markedly reduced the tissue levels of noradrenaline in both regions at the three ages analysed; (2) in the uterine horn guanethidine treatment had no effect on the tissue levels of either calcitonin gene-related peptide or substance P or on the density of calcitonin gene-related peptide-containing nerves, at any of the three ages studied; (3) in the parametrial tissue increased levels of calcitonin gene-related peptide were observed at 8 and 18 weeks of age, together with a significant increase in the density of calcitonin gene-related peptide-containing nerves. Substance P levels showed a transient increase in this tissue at eight weeks. In conclusion, long-term sympathectomy with guanethidine resulted in an increase in calcitonin gene-related peptide and substance P in sensory nerves in the parametrial tissue, but not in the uterine horn. The changes in the parametrial tissue only occurred after puberty. It is suggested that sensory nerves in the uterine horn may be less responsive to sympathetic denervation since loss of sympathetic nerves occurs as part of a normal physiological process during pregnancy in this region.

Animals↗

Sympathetic neural modulation of the immune system. I. Depression of T cell immunity in vivo and vitro following chemical sympathectomy.

Chemical sympathectomy of adult mice with 6-hydroxydopamine (6-OHDA) either prior to or following epicutaneous sensitization with the trinitrophenyl (TNP) hapten decreased the delayed hypersensitivity (DH) response to ear challenge. To determine if uptake of 6-OHDA into sympathetic nerve terminals, and their subsequent destruction, was required for suppression of DH, the catecholamine uptake blocker, desipramine, was employed to block 6-OHDA-induced sympathetic denervation. Pretreatment with desipramine prevented the depression of DH. In vivo treatment with the beta blocker, propranolol, did not alter the 6-OHDA effect, eliminating the potential contribution of released catecholamines, acting on beta-adrenoceptors, to DH reduction. Sympathectomy before sensitization also diminished hapten-specific T cell reactivity of sensitized lymph node (LN) cells, as measured in vitro by IL-2 production and CTL generation. In vivo DNA synthesis in draining LN in response to immunization was modestly decreased following 6-OHDA. Thus, sympathetic denervation appears to impair T cell activity in vivo and in vitro. Overall, these results indicate the SNS plays a role in generation of cell-mediated immunity.

Animals↗

Sensory but not parasympathetic nerves are required for ocular vascular remodeling following chronic sympathectomy in rat.

Choroidal vascularity increases following chronic sympathetic denervation in rats. The mechanisms of this remodeling are unclear. Since both nitric oxide and substance P/CGRP have been suggested as angiogenic factors in other targets, we hypothesized that sensory or parasympathetic nerves may also participate in ocular vascular remodeling. To test this hypothesis, sympathetic denervation was accomplished by superior cervical ganglionectomy. Sensory denervation was induced by subcutaneous injections of capsaicin on postnatal days 2 and 9, and ocular parasympathetic innervation was ablated by pterygopalatine ganglion excision on postnatal day 60. Eyes were processed and sectioned for light microscopic histomorphometry. Sympathetic denervation for 6 weeks resulted in increased choroidal thickness, vascular luminal area, numbers of large venules and large arterioles, and capillaries in the outer nuclear layer. Capsaicin pretreatment prevented sympathectomy-induced increases in choroidal thickness, vascular luminal area and large venules and large arterioles, whereas pterygopalatine ganglionectomy was without effect. Both sensory and parasympathetic denervation attenuated increases in outer nuclear layer capillaries. These studies indicate that increased choroidal vascularity noted after chronic sympathectomy requires intact sensory innervation.

Animals↗

Cervical sympathectomy causes photoreceptor-specific cell death in the rat retina.

Changes in the regulation of the vasculature of the eye may be related to some age-related ocular diseases. We have previously shown that loss of sympathetic innervation, as can normally occur with age, resulted in substantial vascular growth of the choroid. The current study was designed to determine whether changes induced by sympathetic denervation causes significant loss of photoreceptors and increased glial cell reactivity in the retina. Sympathetic denervation was performed followed by immunohistochemistry, TUNEL staining, and protein expression analysis to investigate photoreceptor loss. There was a significant reduction (30%) in photoreceptor numbers in the sympathectomized eye. This loss was due to apoptosis, as there was over a doubling in apoptotic cell numbers after sympathectomy. This loss of photoreceptors in the sympathectomized eye resulted in a significantly reduced width of the outer nuclear layer of the retina when compared to the contralateral eye. Increased glial fibrillary acidic protein (GFAP) staining was also noted after sympathectomy in the ganglion cell layer with streaking toward the bipolar cell layer. These results suggest that loss of sympathetic innervation may cause significant changes to the physiology of the choroid.

Animals↗