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At least 19 recordsLinked to original sources

Changes in cerebral morphology consequent to peripheral autonomic denervation.

Pure autonomic failure (PAF) is characterized by an acquired, selective, peripheral denervation of the autonomic nervous system. Patients with PAF fail to generate bodily states of arousal via the autonomic nervous system in response to physical or cognitive effort. We used voxel-based morphometry to test the hypothesis that changes in the morphology of brain regions involved in autonomic control would arise as a consequence to the longstanding absence of peripheral autonomic responses in PAF patients. Optimized voxel-based morphometry of structural magnetic resonance scans was used to test for regional differences in grey and white matter in 15 PAF patients and matched controls. There were no group differences observed in global measures of grey matter, white matter, or cerebrospinal fluid (CSF). We identified morphometric differences reflecting regional decreases in grey matter volume and concentration in anterior cingulate and insular cortices in PAF patients relative to controls. Morphometric differences in brainstem and subcortical regions did not reach statistical significance. Our findings suggest that peripheral autonomic denervation is associated with grey matter loss in cortical regions encompassing areas that we have previously shown are functionally involved in generation and representation of bodily states of autonomic arousal. The nature of these changes cannot be determined from morphometric analysis alone, but we suggest that they reflect experience-dependent change consequent upon loss of afferent input to brain regions involved in representation of autonomic states.

Adult↗

Pancreatic intraductal pressure: II. Effects of autonomic denervation.

The effects of autonomic denervation, local anaesthesia, and electrical stimulation on pancreatic intraductal pressure were studied in a group of dogs. Pressure studies were performed via a catheter placed in the distal pancreatic duct and by a transsphincteric route. Periampullary application of lidocain produced a decrease in the distal pancreatic duct pressure. Bilateral vagal section resulted in a significant pressure decrease while celiac ganglion plexus denervation produced additional pressure decreases. Electrical stimulation of the ampullary region resulted in a significant pressure increase. With transsphincteric pressure studies, bilateral vagotomy did not produce a significant pressure change, while celiac plexus denervation and pancreatic duct perfusion with lidocainin resulted in a moderate decrease in pressure. Electrical stimulation of the completely denervated perampullary region resulted in a significant pressure increase. These results suggest that the autonomic nervous system may affect the pancreatic ductal pressure, via its action on the sphincter mechanism of the main papilla, as well as on the ductal system. Local duodenopancreatic reflexes may play an additional role in controlling pancreatic duct pressure.

Animals↗

Experimental study of the pathogenesis of acute acalculous cholecystitis: role of autonomic denervation.

This study was undertaken to elucidate the role of autonomic denervation in the pathogenesis of acute acalculous cholecystitis. In Experiment I, the gallbladder was denervated by performing either celiac neurotomy (sympathetic denervation) or truncal vagotomy (parasympathetic denervation), or both, in dogs. In Experiment II, 45-min ischemia and 90-min reperfusion of the gallbladder with or without autonomic denervation were performed by simultaneously occluding the middle hepatic artery and superior mesenteric vein. Celiac neurotomy, and truncal vagotomy, or both, did not cause cholecystitis. Sympathetic denervation, however, decreased the amount of mucin in the gallbladder mucosa and parasympathetic denervation caused reduction of the tissue blood flow, as well as the accumulation of lipid peroxide and xanthine oxidase in the gallbladder mucosa. These changes were most remarkable 1-2 weeks after denervation and were alleviated 4 weeks after denervation. Ischemia-reperfusion 2 weeks after denervation caused more severe cholecystitis than ischemia-reperfusion alone. The most severe inflammation developed in animals that received both celiac neurotomy and truncal vagotomy. These results suggest that autonomic denervation alone does not induce acute cholecystitis, but that it plays an important role in the progression of the inflammatory process in ischemia-reperfusion injury.

Acute Disease↗

Acetylcholine sweatspot test for autonomic denervation.

A test for autonomic denervation based on the local sweat response to 0.1 ml 1% acetylcholine administered intradermally, which depends on an intact local sympathetic supply, is described. Diabetic autonomic neuropathy affects the longest fibres first and thus the test was applied to the feet. After painting a standard site on the dorsum of the foot with iodine and starch, acetylcholine was injected intradermally in the centre. The normal response, visible to the eye, is a uniform distribution of dark spots of iodine discolouration at the sites of sweat production. In diabetic autonomic neuropathy this pattern is lost to a varying degree. In a photographic image magnified x 10, the spots were counted in sixty 2.5 cm squares in a grid centred on the injection site. 50 normal volunteers aged 18-69 were tested. No effect of age or sex was found. Five or more squares with less than 6 spots was the definition of abnormal. 24 diabetic men who complained of impotence were investigated with the sweatspot test, a pupil test, and cardiovascular autonomic function tests. 13 had abnormal sweatspot tests with scores up to sixty squares with less than 6 spots. In keeping with the increased length of the sympathetic fibres to the feet compared with those to the iris, there was a 30% false-negative rate for the pupil test if the sweatspot test is taken as standard. Agreement between the cardiovascular tests and the sweatspot test was seen in only 17 patients. The sweatspot test appears to be a more sensitive indicator of autonomic neuropathy than the commonly used cardiovascular tests.

Acetylcholine↗

Autonomic denervation may be a prerequisite of diabetic neuropathic foot ulceration.

Studies using visceral (cardiovascular) autonomic function testing have left doubt as to the importance of autonomic neuropathy in the development of diabetic neuropathic foot ulceration. A test for peripheral autonomic denervation has been developed (acetylcholine sweatspot test), dependent on intradermal acetylcholine causing secretion by innervated sweat glands, detected by starch/iodine discoloration. The response is photographed and quantified using a grid (normal score = 0 or 1; abnormal = 5 to 60). The sweatspot test was applied to the feet of 19 diabetic patients with a history of foot ulceration, 17 with neuropathic pain, 8 complaining of numbness, and to 15 diabetic control patients. The sweatspot test score of the foot ulcer patients (median 54) was very much greater than that of the other groups (pain group, 4, p less than 0.005; numbness group, 2, p less than 0.01; diabetic control group, 2, p less than 0.0001). All the patients with neuropathic foot ulceration had peripheral autonomic denervation. The results suggest that autonomic denervation in the feet is always present in patients with diabetic neuropathic foot ulceration. Tests of peripheral autonomic denervation such as the acetylcholine sweatspot test may be useful to identify patients at risk of neuropathic foot ulceration.

Acetylcholine↗

Transcutaneous neuromuscular electrical stimulation effect on the degree of microvascular perfusion in autonomically denervated rat skeletal muscle.

OBJECTIVE: To determine the effect of transcutaneous neuromuscular electrical stimulation (TNMES) on the degree of microvascular perfusion in autonomically denervated skeletal muscle. DESIGN: A completely randomized experimental design was used to compare the effects of TNMES on the degree of microvascular perfusion in the tibialis anterior (TA) and extensor digitorum longus (EDL) muscles from autonomically denervated rats (Ch-TES) to the degree of microvascular perfusion in the same muscles of untreated controls, rats receiving only TNMES (TES), and rats receiving only autonomic denervation (shams). INTERVENTION: All electrical stimulation treatments were delivered via carbon silicone surface electrodes, and evoked sustained tetanic contraction of the TA and EDL muscles. Autonomic denervation was achieved by the application of chlorisondamine. MAIN OUTCOME MEASURES: The degree of microvascular perfusion was determined for the deep (DTA) and superficial (STA) region of the TA muscle and the EDL muscle by calculating their perfused microvessel/muscle fiber (PV/F) ratio. RESULTS: The PV/F ratio in the DTA from Ch-TES animals was greater (p < or = .05) than that in the same muscle from control and sham animals. The PV/F ratios in the STA and EDL from Ch-TES animals were not significantly (p > .05) different from the PV/F ratio in the respective muscles of shams. CONCLUSIONS: The response of the microvasculature in autonomically denervated skeletal muscle to TNMES that evokes muscle contraction is variable, and (2) mechanisms other than autonomic regulation may be involved in this hyperemic response.

Analysis of Variance↗

[Influence of upper abdominal autonomic denervation on pancreatic and gut hormone secretion].

The influence of the upper abdominal autonomic denervation on the secretions of insulin (IRI), vasoactive intestinal polypeptide (VIP), secretin, pancreatic glucagon (IRG) and gut glucagon-like immunoreactivity (Gut GLI) was studied. Adult mongrel dogs, which were divided into control, truncal vagotomy and upper abdominal autonomic denervation groups, were investigated by intraduodenal glucose infusion test under general anesthesia. The glucose level and the response of insulin, VIP, secretin, IRG and Gut GLI secretions in the truncal vagotomy group showed no significant difference compared with those in the control group. These findings suggested that the vagus nerve is not concerned largely in the glucose level and in response of insulin VIP, secretin, IRG, and Gut GLI induced by intraduodenal glucose loading. In the upper abdominal denervation group, severe diarrhea was manifested within 60 minutes after the intraduodenal glucose infusion test, and significantly increased responses were shown in secretions of insulin, VIP, secretin, IRG, and Gut GLI. These findings suggested that upper abdominal autonomic denervation acted acceleratory on the secretions of insulin, VIP, secretin, IRG and Gut GLI by intraduodenal glucose infusion test. In addition, it was suggested that dissection of upper abdominal autonomic plexus caused diarrhea after the intraduodenal glucose infusion test.

Abdomen↗

Autonomic denervation hypersensitivity in the primary glaucomas.

Autonomic denervation hypersensitivity of the iris was assessed in 44 patients with primary closed-angle glaucoma, 20 patients with primary open-angle glaucoma, and 40 age- and sex-matched control subjects. Significantly increased pupillary constriction in response to 2.5% methacholine chloride, indicating parasympathetic denervation hypersensitivity, was present in both closed-angle (p less than 0.02) and open-angle glaucoma patients (p less than 0.001), compared with the control group. Significantly increased pupillary dilatation in response to 0.5 per cent phenylephrine hydrochloride, indicating sympathetic denervation hypersensitivity of the iris, was also present in both closed-angle glaucoma (p less than 0.01) and open-angle glaucoma patients (p less than 0.05). The association between autonomic neuropathy and the primary glaucomas is discussed, with particular reference to the potential effects of autonomic dysfunction on aqueous dynamics.

Aged↗

Influence of autonomic denervation upon the kinetics of the ileal epithelium of the rat.

The effect of autonomic denervation upon the kinetics of the ileal epithelium of rats was studied by tracing 3H-thymidine labelled nuclei and counting mitotic figures and goblet cells. Counts of labelled nuclei and goblet cells provided information about cell migration along the intestinal epithelium. The mitotic index and turnover time of this population were calculated from the mitotic figures counts. Comparing denervated animals with sham operated controls, it was possible to conclude that autonomic denervation, either sympathectomy or parasympathectomy results in a decrease in mitotic activity. As a result of lower mitotic activity in the crypts, the turnover time increases and there is a delay in the migration of cells from the crypts towards the villi. Sympathectomy causes an early short-lived effect upon the kinetics of the crypt cell population, since after 27h there is a tendency to normality. Parasympathectomy produces a slower but continuous decline in mitotic activity.

Animals↗

Hemodynamic effects of dexmedetomidine, an alpha 2-adrenergic agonist, in autonomically denervated dogs.

The hemodynamic effects of the alpha 2-adrenergic agonist, dexmedetomidine (DM), were studied in eight anesthetized, autonomically denervated dogs. Autonomic block decreased mean arterial pressure (MAP) and cardiac index (CI) by approximately 20% to 95 +/- 8 mm Hg and 4.1 +/- 0.1 L/min/m2, respectively (mean +/- SEM), and reduced norepinephrine (NE) and epinephrine plasma levels to almost undetectable levels. DM, administered intravenously (i.v.) either by bolus injection or by slow (20 min) infusion in doses between 1 and 30 micrograms/kg, had no effect on heart rate (HR), increased MAP significantly by 98%, decreased CI by 59%, and increased calculated systemic vascular resistance index (SVRI) significantly by 376%, maximally. The effect of the lowest dose was mediated mainly by arteriolar vasoconstriction, and that of higher doses was mediated by vasoconstriction and decreased CI. Left ventricular end-diastolic pressure (LVEDP) increased significantly from 6 +/- 2 to greater than 30 mm Hg. maximally. The effects were cumulative, and the first dose caused near maximal pressor effect; the resistance increase was as great with slow infusion as with bolus injection. Prazosin (1 mg/kg) did not affect the changes, but 0.3 mg/kg atipamezole, a selective alpha 2-antagonist, completely antagonized them. These observations demonstrate potent constriction of both arteriolar resistance and venous capacitance vasculature in dogs. The combination of decreased CI and increased filling pressure implies marked decrease in cardiac function which was, however, fully reversible by atipamezole.

Adrenergic beta-Agonists↗

Change in colonic motility after extrinsic autonomic denervation in dogs.

Changes in colonic motility were compared in dogs undergoing autonomic denervation of the paraaortic and presacral (group A), paraaortic (group B), or mesocolonic region (group C), and sham operation (group D). Five bipolar recording electrodes were placed into the seromuscular layer of the colon and rectum. The numbers of continuous electrical response activity and contractile electrical complex after an intragastric olive oil injection were smaller in group A than in the other groups (P < 0.05) from three weeks through six months after denervation. This difference was significant even in the proximal colon. These data suggest that the pelvic plexus may play an important role in colonic motility including the proximal colon. The damage to the plexus did not recover for at least six months after denevation. Pelvic plexus injury may thus be one of possible explanations for the prolonged change in bowel habit after anterior resection of the rectum.

Animals↗

Skin biopsy for assessment of autonomic denervation in Parkinson's disease.

Autonomic dysfunction in Parkinson's disease (PD) is considered a late complication of the disease or an adverse effect of anti-parkinsonian medications. Morphological changes are demonstrated only by postmortem examination. The study objective was to evaluate peripheral autonomic neural involvement in PD using punch skin biopsy. The study sample included 22 patients (mean age 50 +/- 7.7 years, mean disease duration 5.3 +/- 3.8 years) and 19 controls. Four-millimeter skin biopsies were immunohistochemically stained with anti-PGP 9.5 antibody. Autonomic innervation of the blood vessels, sweat glands, and erector pili muscles was assessed and rated from 0 (normal) to 2 (severe). Cutaneous autonomic innervation was decreased in patients compared to controls. Semi quantitative analysis demonstrated reduced autonomic innervation of the blood vessels (1.0 +/- 0.8 vs. 0.42 +/- 0.8 in controls; p < 0.02), of sweat glands (0.95 +/- 0.67 vs. 0.47 +/- 0.61; p < 0.02) and of the erector pili muscles (1.06 +/- 0.55 vs 0.21 +/- 0.42; p < 0.001). This method demonstrates that the peripheral autonomic system is affected in PD at early stage of the disease and that autonomic involvement in PD may be more prevalent than previously thought.

Adult↗

Autonomic denervation in jejunal mucosa of homosexual men infected with HIV.

Autonomic nerves in jejunal mucosa of HIV-infected patients show severe structural damage on electron microscopic examination. The aim of this study was to quantify loss of autonomic axons from the lamina propria of HIV-infected patients in different clinical stages of disease. Jejunal biopsies were taken from 19 HIV-antibody-positive homosexual men and from 10 control patients. Autonomic fibres in the mucosa were stained with a neurone-specific polyclonal antibody, PGP 9.5. The density of axons was quantified by a point-counting technique using a Lennox eyepiece graticule under light microscopic examination. There was significant reduction in axonal density in the villi of HIV-infected patients [mean, 9.0; standard deviation (s.d.), 4.7] compared with controls (mean, 15.3; s.d., 5.2; P = 0.003), and in the pericryptal lamina propria of HIV-infected patients (mean, 17.8; s.d., 5.4) compared with controls (mean, 27.3; s.d., 6.2; P = 0.0002). Although autonomic denervation occurs throughout the jejunal mucosa of HIV-infected patients, there was no correlation between the clinical stage of HIV disease and the degree of denervation. The denervation was greatest in patients with the most severe diarrhoea, but this difference was not significant. This study provides the first quantitative morphological evidence for depletion of autonomic nerves in the jejunum of patients infected with HIV. Autonomic neuropathy may contribute to chronic diarrhoea in HIV disease.

AIDS-Related Complex↗

Baroreceptor-related dysrhythmias in piglets with selective autonomic denervation of the heart.

This study was carried out to determine whether selective cardiac autonomic denervation performed on neonatal swine would evoke dysrhythmias later in development. Piglets (n = 27; 5-10 days old) underwent unilateral stellate ganglion ablation, or right cardiac vagotomy, or sham surgery. Fifty to sixty days after denervation, acute experiments were performed to evaluate responses to baroreceptor activation. Of all animals who exhibited prolonged R-R intervals, only those with right stellate ganglion ablation had prolonged corrected QT intervals. Despite findings suggesting an arrhythmogenic state (predominance of left-sided cardiac innervation), dysrhythmias occurred in all animals with stellate ganglion ablation, regardless of laterality, but in few vagotomized or control animals. Our results suggest that partial sympathetic innervation may alter cardiac function so that dysrhythmias are more likely to occur during baroreceptor activation.

Animals↗

Effects of autonomic denervation on canine exocrine pancreatic secretion and blood flow.

The effect of autonomic denervation on the exocrine pancreatic secretion and blood flow was studied in a group of dogs. Pancreatic secretion was collected and analyzed for volume and bicarbonate by direct cannulation of the main papilla through a duodenotomy prior to and following truncal vagotomy and celiac plexus denervation. Pancreatic blood flow was determined by the radioisotope distribution method (141Ce). Truncal vagotomy causes a reduction in pancreatic secretion of volume and bicarbonate by 25-30%, while celiac denervation caused a reduction of 70% in the secretion. The mean baseline pancreatic blood flow was 0.5 ml/g pancreas/min. Truncal vagotomy did not cause any significant flow changes, while celiac denervation caused a significant increase in blood flow of 350% (to 1.75 ml/g/min). These results suggest that both the parasympathetic and the sympathetic system affect pancreatic secretion independently of their effect upon pancreatic blood flow.

Animals↗

[Vagal effects on inducibility of atrial fibrillation at different sites of pulmonary veins after autonomic denervation].

OBJECTIVE: To investigate the vagal effects on the inducibility of atrial fibrillation (AF) at different sites of pulmonary vein after autonomic denervation. METHODS: The bilateral cervical vagal trunks of 10 male mongrel dogs were isolated and decentralized. The ansae subclaviae were exposed, ligated, and cut. Needle electrodes were inserted into the subcutaneous tissue of the 4 extremities to record the myocardiogram. Right ventricle electrode was introduced via femoral vein and an electrode with 4 poles was sutured with the right appendage (RAA), left appendage (LAA), left atrium (LA), left superior pulmonary vein (LSPV), right superior pulmonary vein (RSPV), left inferior pulmonary vein (LIPV), and right inferior pulmonary vein (RIPV) respectively. Local burst stimulation (S1S1 = 80 ms, impulse duration = 0.5 ms) was performed on these sites to record the baseline AF inducibility. When sinus cardiac arrest for 2 s or complete atrio-ventricular block occurred programmed bilateral vagal nerves stimulation (VNS) was performed with the frequency of 12.5 Hz, impulse duration of 0.5 ms, and voltage of 5-8 V. Atropine 0.04 mg/kg was dripped intravenously. The changes of AV inducibility were observed. RESULTS: In the baseline state, S1S1 programmed stimulation on all the sites evoked single or multiple atrial premature beats and short runs of atrial tachycardia, only a few sites induced AF. However, S1S1 programmed stimulation combined with VNS significantly increased the frequencies of induced AV at the sites of 4 PVs (P < 0.05, P < 0.01). When atropine was dripped the AV induction rates at all sites did not changed significantly (all P > 0.05). CONCLUSION: Vagal nerve may play an important role in the initiation of AF originating from pulmonary veins.

Animals↗

Effect of local autonomic denervation on in vitro responsiveness of lymphocytes from rat submaxillary lymph nodes.

The local autonomic denervation of rat submaxillary lymph nodes was achieved by a unilateral sympathetic superior cervical ganglionectomy and/or the unilateral section of chorda tympani (that resulted in ipsilateral parasympathetic decentralization of the submandibular territory). This study was performed to determine: (1) whether local sympathetic and/or parasympathetic denervation of rat submaxillary lymph nodes brought about changes in lymph node cellularity, natural killer activity and lipopolysaaccharide (LPS)- and concanavalin A (Con A)-induced cell proliferation in Freund's adjuvant-injected rats; (2) whether the effect of the immunosuppressive drug cyclosporine in rat submaxillary lymph nodes was affected by a single or combined unilateral ganglionectomy plus decentralization. A unilateral ganglionectomy, or the combination of ganglionectomy plus decentralization, performed 7 days earlier, decreased significantly cellularity in ipsilateral submaxillary lymph nodes, while a unilateral decentralization failed to affect it. Natural killer activity increased ipsilaterally after ganglionectomy or decentralization, and decreased after the combined surgical procedure. LPS-induced cell proliferation augmented significantly after ganglionectomy or decentralization, while Con A-induced T lymphocyte proliferation remained unaffected. In the sham-operated side, cyclosporine decreased submaxillary lymph node cell number and natural killer activity, while it increased the proliferative response to LPS. The depressive effect of cyclosporine on lymph node cellularity was no longer observed in ganglionectomized or decentralized lymph nodes, but was found after the combined surgical denervation. Decentralization, or decentralization plus ganglionectomy, blunted the depressive effect of cyclosporine on natural killer activity. The stimulatory effect of cyclosporine on lymphocyte proliferation induced by LPS was reversed both by ganglionectomy or by decentralization and was suppressed by the combined surgical procedure. Neither treatment affected Con A-induced proliferation of T lymphocytes. The results further indicate that an appropriate sympathetic and parasympathetic local environment may be needed for immunomodulation, as well as for cyclosporine activity in lymphoid tissue.

Animals↗

Motor activity and transit in the autonomically denervated jejunum.

The role of extrinsic (autonomic) innervation in postprandial contractile activity of the small intestine is unknown. Using a canine model, we investigated the effects of complete extrinsic denervation on the parameters of fasting and postprandial jejunal contractions and their relationship to intestinal transit. Individual contractions were recorded using strain gauge transducers. Spatial and temporal parameters of contractions were analyzed by computer methods. Bolus injection of 14C-polyethylene glycol was used to calculate intestinal transit rates. Statistical comparisons of control and denervated animals were made by nonparametric tests. Extrinsic denervation did not abolish fasting or fed motor activity, but the following effects were observed: (1) the frequency of migrating motor complexes (MMCs) increased; (2) the onset of fed motor activity was delayed, and the duration of fed activity was shortened; (3) frequency, mean amplitude, and mean area of postprandial contractions were decreased; (4) fewer contractions propagated distally, and mean propagation distance was shortened; and (5) intestinal transit was slower for solids, but not for liquids. In the small intestine, extrinsic nerves modulate motor activity, which is under primary control of the intrinsic (enteric) nervous system.

Animals↗