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A study of the results of lumbar sympathectomy in the treatment of peripheral vascular occlusive disease has been presented. Results continue to be encouraging in properly selected patients, as they have been since 1947.
Temporary chemical sympathectomy was accomplished by daily injection of the catecholamine-depleting agent, reserpine, for the first six days of life. The rat pups were then allowed to mature, and their submandibular glands (SMG) sequentially examined by light and electron microscopy. Reserpine retarded SMG development by about two weeks when compared to saline-treated litter-mates. One day after the end of reserpine treatment, glands appeared rudimentary, similar to those of newborns. With age the glands matured, and seven weeks after treatment (eight weeks of age), there were few structural differences between glands from experimental or control animals. In a separate experiment, 12 newborn rats were treated with reserpine for six days and then allowed to mature to 12 weeks. Three developed an obstructive sialadenitis. Several experiments were run to see if this lesion could be replicated. Only three of 36 more animals developed sialadenitis, so its induction was neither consistent nor reproducible.
Adult rats received intraperitoneal injections of guanethidine or saline for 5 weeks. Six to 8 weeks following completion of treatment, concentrations of substance P and neuropeptide Y (NPY) were measured by radioimmunoassay in the superior cervical ganglion (SCG) and thoracic spinal cord. The SCG was also immunostained for NPY and substance P. No differences were observed in thoracic spinal cord content of either NPY or substance P. We observed depletion of NPY immunoreactive neurons and NPY levels in the SCG, and pharmacologic evidence of postganglionic denervation in guanethidine-treated rats. In guanethidine-treated rats, there was a marked increase of substance P levels in the SCG, where substance P was localized in fibers, but not cell bodies. Thus, sprouting of substance P-containing sensory fibers in the sympathetic ganglia occurs following postganglionic sympathectomy in adult rats.
In the present study we report on the levels of dihydroxyphenylalanine (DOPA), dopamine and their metabolites, 3-O-methyl-DOPA, homovanillic acid and dihydroxyphenylacetic acid, in the dorsal root ganglion (DRG) where dopaminergic sensory neurons have recently been identified. HPLC with electrochemical detection was used. Chemical sympathectomy, induced by daily injection of 30 mg/kg/sc of guanethidine over 4 days, did not modify these levels. DOPA, dopamine and their metabolites were also detected in the dorsal root in both intact and sympathectomized rats. The present results show that in the DRG, DOPA and dopamine do not derive from sympathetic nerves, and agree with previous reports suggesting that there is a peripheral dopaminergic sensory innervation. In addition the identification of 3-O-methylDOPA, the extraneuronal metabolite of DOPA is not only the precursor of dopamine in the DRG but may be released from DRG cells. The high 3-O-methyl-DOPA/DOPA ratio found in the DRG and the dorsal root suggests that DOPA could play a role as neurotransmitter or modulator in the peripheral sensory innervation, as it has been proposed for the central nervous system and the sympathetic system.
This study was carried out to examine the innervation of the nude fetal thymus during ontogeny and to see if lymphopoietic activity would occur within these thymic lobes in the absence of sympathetic neuronal input. Fetal thymic rudiments from nu/nu mice were removed and examined for galoxylic acid-induced histofluorescence to detect the catecholaminergic nerves. Some of these lobes were organ cultured for 5 to 7 days in the presence of deoxyguanosine to eliminate any existing lymphoid cells within the rudiments. Such "nonlymphoid" thymic rudiments were implanted into the anterior eye chambers of syngenic BALB/c mice (heterozygous) from which cervical sympathetic ganglia and part of the sympathetic chain had been surgically removed (right side) one week earlier. The left side was only sham operated. The thymic implants were allowed to grow for up to 21 days on both sides; they were then removed and examined by histofluorescence, immunofluorescence, and light microscopy. The results indicate for the first time that the nude fetal thymus is innervated by sympathetic nerves and that following sympathectomy the nude thymus is able to sustain lymphopoietic activity and generate lymphoid cells which have characteristics present on thymocytes during in vivo development in normal mice, such as binding to peanut agglutinin and expression of Thy-1 antigen. The relationship between the presence of sympathetic inhibitory influence and the thymic atrophy seen in the nude mice during ontogeny, is being investigated.
The autonomic receptors in the rat kidney were characterized using the radioligands [3H]prazosin, [3H]clonidine, [3H]dihydroalprenolol (DHA) and [3H]quinuclidinyl benzilate (QNB). The specific binding of [3H]prazosin, [3H]clonidine, [3H]DHA and [3H]QNB to rat kidney membranes was saturable and of high affinity, and showed a pharmacological specificity as well as stereospecificity which characterized renal alpha 1-, alpha 2- and beta-adrenoceptors and muscarinic cholinoceptors, respectively. There was a relatively greater density of alpha-adrenoceptors than beta-adrenoceptors or muscarinic cholinoceptors in the rat kidney. Chemical sympathectomy of rats with 6-hydroxydopamine X HBr (6-OHDA, 50 X 2 mg/kg i.v., 24 h interval) caused a significant increase (21-56%) in the Bmax values for renal [3H]prazosin, [3H]clonidine and [3H]DHA binding at 1 and 2 weeks following the treatment, without a change in the Kd values. 6-OHDA treatment had no significant effect on the Kd and Bmax values for [3H]QNB binding at 1-3 weeks after the treatment. The norepinephrine (NE) concentration was reduced (68-76%) in the 6-OHDA-treated rat kidney. In conclusion, the present study provides biochemical evidence for the possible localization of postsynaptic alpha 1-, alpha 2- and beta-adrenoceptors and muscarinic cholinoceptors in the rat kidney and also for the regulation of these adrenoceptors by the sympathetic nervous system.
The present study was designed to provide further evidence that high doses of systemically administered epinephrine can result in a post-ganglionic chemical sympathectomy and to look for evidence of regeneration of nerve terminals. Three days following the systemic administration of a high dose of epinephrine a prolapse of the cat nictitating membrane was observed. Examination of the inferior smooth muscle associated with the membrane revealed ultrastructural evidence of nerve terminal destruction which was associated with a marked depletion of endogenous norepinephrine as measured with a catecholamine radioenzyme assay. Three weeks following treatment, appearance of nerve terminals and endogenous norepinephrine levels in the contralateral nictitating membrane were indistinguishable from untreated controls. High doses of epinephrine appear to result in nerve terminal degeneration, followed by regeneration, similar to that reported following 6-hydroxydopamine.
Substance P (SP)-immunoreactive fibres have been found in the rat and guinea-pig irides. They are distributed parallel to the pupillary margin in the sphincter muscle, and in an irregular plexus in the dilator muscle of both species. Neuropeptide Y (NPY)-immunoreactive fibres have also been demonstrated in the anterior uvea, displaying a pattern similar to that of the adrenergic nerves. One month after sympathectomy, there was an increase both in the density and possibly in the number of SP-immunoreactive fibres in the denervated irides of both rodent species. In the sympathectomized iris, there was a very notable decrease in the density of NPY-immunoreactive fibres indicating that the NPY peptide most likely coexists with the classical sympathetic neurotransmitter, noradrenaline, in the sympathetic nerve supply derived from the superior cervical ganglion. The disappearance of dopamine beta-hydroxylase (DBH) immunostaining fibres confirmed the success of the sympathetic denervation.
After 20 years of experience with the "open" transaxillary approach, the authors are presently performing the thoracoscopic technique for upper thoracic sympathectomy in severe primary hyperhidrosis. During a period of 14 months, 23 operations were performed and 22 patients had immediate and permanent relief of palmar sweating. The immediate postoperative course was uneventful in all cases. Hospitalization was short, and all patients returned to school and full activity 3 to 5 days after operation. These initial results compare favorably to the "open" method and, pending further experience, are actually better in terms of less pain, early discharge, quicker return to normal activity, and a smaller, less conspicuous scar.
The characteristics of [3H]Ro 5-4864 binding to "peripheral" benzodiazepine receptors (PBR) in the central nervous system and peripheral tissues were examined after chemical sympathectomy with 6-hydroxydopamine (6-OHDA). One week after the intracisternal administration of 6-OHDA, the number of [3H]Ro 5-4864 binding sites (Bmax) in the hypothalamus and striatum increased 41 and 50%, respectively, concurrent with significant reductions in catecholamine content. An increase (34%) in the Bmax of [3H]Ro 5-4864 to cardiac ventricle was observed one week after parenteral 6-OHDA administration. In contrast, the Bmax of [3H]Ro 5-4864 to pineal gland decreased 48% after 6-OHDA induced reduction in norepinephrine content. The Bmax values for [3H]Ro 5-4864 binding to other tissues (including lung, kidney, spleen, cerebral cortex, cerebellum, hippocampus and olfactory bulbs) were unaffected by 6-OHDA administration. The density of pineal, but not cardiac PBR was also reduced after reserpine treatment, an effect reversed by isoproterenol administration. These findings demonstrate that alterations in sympathetic input may regulate the density of PBR in both the central nervous system and periphery in a tissue specific fashion.
The mydriatic response to alpha 1-adrenergic agonists was used as a functional index of postsynaptic alpha 1-adrenoceptors in mouse iris dilator muscle. Topical ocular application of methoxamine or phenylephrine caused dose-related mydriasis which was inhibited by pretreatment with prazosin or phentolamine. Chemical sympathectomy with topical 6-hydroxydopamine (6-OHDA) produced supersensitivity to phenylephrine but not methoxamine. Daily antidepressant treatment for 14 days with desipramine (10 mg/kg, i.p.), amitriptyline (10 mg/kg, i.p.), fluoxetine (2 mg/kg, i.p.), or moclobemide (40 mg/kg, i.p.) did not alter the response to methoxamine. Central alpha 1-adrenoceptors labelled with [3H]prazosin were similarly unaffected except for a modest downregulation produced by fluoxetine. These results demonstrate that postsynaptic alpha 1-adrenoceptors in mouse CNS and iris dilator muscle are refractory to manipulations known to alter their sensitivity in other tissues.
Rats that were neonatally sympathectomized with guanethidine (GUA) and given access to a four-component supermarket diet (SD) when either adolescent or adult gained weight at the same rate as controls. Adrenodemedullation (MDL) of adults, either alone or in combination with GUA treatment, also failed to influence the development of dietary obesity. Neonatal sympathectomy induced small changes in caloric consumption and diet preferences. These results question the notion that the sympathetic nervous system (SNS) is an essential contributor to the control of body weight and the development of dietary obesity.
Adult female rats that underwent sympathectomy induced by guanethidine treatment (10, 20 or 40 mg/kg) exhibited markedly increased water intake, but did not display significant alterations of either food intake, body weight, or the Lee Index of obesity. Guanethidine treatment did not attenuate amphetamine anorexia as evidenced by comparable dose-dependent reductions in food intake to d-amphetamine sulfate (0.25, 0.50, 1.0, and 2.0 mg/kg) in sympathectomized and control rats. These data are not consistent with the hypothesis that amphetamine anorexia is partially mediated via enhanced BAT thermogenesis.
The course of 2 patients with posttraumatic reflex sympathetic dystrophy is presented and discussed. The importance of determining the exact level of sensory blockade in order to know the necessary level of the sympathectomy is emphasized. It is suggested that in patients with reflex sympathetic dystrophy, the diagnosis should include the exact upper anatomical level of sympathetic truncus involvement, which can be easily achieved with sensory epidural blockade.
To investigate the routes of neural spread of pseudorabies (Aujeszky's disease) virus (PRV), the effects of chemical sympathectomy by 6-hydroxydopamine (6-OHDA) on clinical signs and viral spread in mice inoculated intraocularly with PRV were examined. Similar to non-treated mice, the treated mice developed pruritus as a major clinical sign, followed by peracute death, but the time of death tended to be slightly delayed in about half of the treated mice. On immunohistological examination, viral antigens in treated mice were found to be markedly reduced in all the ipsilateral retinae; they were detected diffusely in the forebrain area with a localization in the mammillary area. In the treated mice, viral antigens were also reduced in the ipsilateral trigeminal nerve ganglia as well as in its central nuclei. These findings indicate that both the sympathetic nervous system and the trigeminal nervous system play an important role in the neural spread of PRV. Possible involvement of the dopaminergic nervous system, particularly in the eye, as the main site of viral growth was discussed.
The effects of 6-hydroxydopamine (6-OHDA), N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine (DSP-4) and anti-nerve growth factor (anti-NGF) on the development and growth of a tumor of non-neuronal origin were studied in mice. Murine LPC-1 plasmacytoma cells were grown either subcutaneously (s.c.) as solid tumors in the hindleg or intraperitoneally (i.p.) in ascitic form. Growth of s.c. tumors was monitored by caliper measurements of the hindleg at the site of tumor cell inoculation; growth of ascitic tumors was followed by electrophoretic determination in plasma of the tumor associated protein IgG2a kappa, M component. Adult mice were treated with 6-OHDA or DSP-4 six hours prior to tumor cell implantation; newborn mice were treated with anti-NGF and tumor cells were given 9 weeks later. Both chemical- and immunosympathectomy significantly altered the growth pattern of solid and ascitic tumors (P less than 0.0001). The effect of sympathectomy on the growth of solid tumors was most pronounced during the early phase of tumor growth. The data document that the effect of each drug treatment on tumor growth was not due to direct cytotoxic actions of the agents employed on tumor cells but the result of impairment of sympathetic functions. The findings of this study suggest a role of the sympathetic nervous system in tumor growth.
Swimming-stress is known to inhibit glucose-stimulated insulin secretion and stimulate glucagon secretion. In the present study, in mice, we investigated the relative contribution of sympathetic nerves and the adrenals to these effects. Mice were pretreated either with adrenalectomy or chemical sympathectomy induced by i.v. injection of 6-hydroxydopamine (6-OHDA), which destroys sympathetic nerve terminals. Two days later, the mice were injected i.v. with either glucose (5.6 mmol/kg) or saline, immediately before being subjected to 2 min swimming-stress or 2 min resting. Directly thereafter, blood was sampled. In normal controls, swimming inhibited glucose-stimulated insulin secretion and elevated plasma glucagon levels (P less than 0.01). Both these responses were absent both in adrenalectomized and in chemically sympathectomized mice. We also found that in resting animals, adrenalectomy reduced plasma levels of glucagon (P less than 0.05) and glucose (P less than 0.01), and that in adrenalectomized mice, swimming lowered basal plasma insulin levels (P less than 0.05). Furthermore, 6-OHDA-treatment elevated basal plasma glucagon levels (P less than 0.01). Thus, we show that, in the mouse, the inhibition of glucose-stimulated insulin secretion and the stimulation of glucagon secretion that occur during swimming-stress are both dependent on mechanisms requiring both the adrenals and intact sympathetic nerve terminals.
Our aims were to measure gastric and small bowel transit of radiolabeled chow or liquids in rats and to assess the effect of pharmacologically induced chronic sympathectomy of at least 5 weeks duration. Three series of experiments were performed. In series I, four rats in each group underwent i.p. chloral hydrate anesthesia, tracheostomy with intubation and mechanical ventilation: they received by gavage 1.0 g rat chow dissolved in 1.5 ml saline labeled with 1.0 mCi 99mTc-DTPA In series II, four rats in each group were anesthetized with only i.p. chloral hydrate and received 1.5 ml labeled saline. Rats were placed on a gamma camera for dynamic acquisition of 1-min images for 7 h in series I, and 4 h in series II. Activity was quantitated in stomach and cecum; gastric emptying was analyzed by the power exponential model. In series III, four rats in each group were studied for 1 h on gamma camera and sacrificed after 5 h. At the end of each study, the stomach, small bowel, cecum and colon were removed and radioactivity counted in each organ in a dose calibrator. Quantitation of radioactivity by gamma camera was highly accurate: labeled chow in the stomach at 7 h was identical by external camera and counting of the excised organ (linear regression slope = 1.01, r = 0.97, P less than 0.0001). Similar precision was observed with labeled liquids (slope = 0.93, r = 0.93, P = 0.001). Chow emptied slower than liquid in both groups (P = 0.048). Ileocecal movement of isotope occurred by bolus transfers.(ABSTRACT TRUNCATED AT 250 WORDS)