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PubMed1998

The denervated stomach as an esophageal substitute is a contractile organ.

OBJECTIVE: To determine whether the denervated stomach as an esophageal substitute is an inert conduit or a contractile organ. SUMMARY BACKGROUND DATA: The motor response of gastric transplants to deglutition suggests that the stomach pulled up to the neck acts as an inert organ. METHODS: The gastric motility of 11 healthy volunteers and 33 patients having either a gastric tube (GT) (n = 10) or their whole stomach (WS) (n = 23) as esophageal replacement was studied with perfused catheters during the fasting state, after a meal, and after intravenous administration of erythromycin lactobionate. A motility index was established for each period of recording by dividing the sum of the areas under the curves of all contractions of >9 mmHg by the time of recording. RESULTS: Over years, the denervated stomach recovers more and more motor activity, even displaying a real phase 3 motor pattern in 6 of the 10 WS patients and 1 of the 7 GT patients with >3 years of follow-up. Erythromycin lactobionate generates a phase 3-like motor pattern regardless of the length of follow-up. Extrinsic denervation of the whole stomach does not significantly modify the fasting motility index established >3 years after surgery (+17% on average, p > 0.05), but it reduces that in the fed period by an average of 62% (p = 0.0016). Tubulization of the denervated whole stomach lowers the fasting motility index by an average of 60% (p = 0.0248) and further impairs that in the fed period by an average of 67% (p = 0.0388). CONCLUSIONS: The denervated stomach as an esophageal substitute is a contractile organ that may even generate complete migrating motor complexes. Motor recovery is better in the fasting than in the fed period, and it is more marked in WS patients than in GT patients.

Adolescent↗
PubMedDate not supplied

Electron microscopic-cytochemical and biochemical studies of acetylcholinesterase activity in denervated muscle of rabbits.

Acetylcholinesterase (AChE) activity has been studied in normal, control and denervated muscle of rabbits by electron microscopic-cytochemistry and radiometric assay. A small amount of butyrylcholinesterase (BuChE) activity is also found in biochemical assay of unfixed muscle, but it is not demonstrable cytochemically in fixed specimens by the method used in this study. Both a soluble and particulate AChE activity are present in all specimens examined. The particulate activity is probably due to enzyme localized in the sarcotubular system and at the motor end-plate. Soluble AChE activity may represent those sites exhibiting random cytochemical end product, such as some areas of normal and denervated muscle and muscle nuclei, Schwann cells, and AChE-containing mononuclear cells in the connective tissue. There is a greater proportion of particulate than soluble AChE activity in normal and control muscle, a finding which is compatible with the well localized cytochemical sites. Four to six weeks post-denervation, there is a marked increase in extrajunctional AChE activity to peak values 15 to 30 fold above control values. The increase is accompanied by a reversal in the proportion of particulate to soluble enzyme, so that there is almost twice as much soluble as particulate AChE. There are also numerous "spots" of random cytochemical end product throughout extrajunctional muscle. The increase in levels of AChE activity, the change to predominantly soluble form, and the large numbers of new cytochemically active sites indicate that synthesis of new enzyme has taken place. Changes in AChE activity in denervated rabbit have been compared to those occurring in dystrophic mouse muscle. It has been suggested that there might be a relationship between the formation of new extrajunctional sarcoplasmic sites of AChE activity and the spread of alpha-bungarotoxin binding sites and chemosensitivity in developing and denervated muscle.

Acetylcholinesterase↗
PubMed1997

Expression of different isoforms of nitric oxide synthase in experimentally denervated and reinnervated skeletal muscle.

Denervated muscle fibers express enhanced levels of stress and apoptosis-associated proteins and undergo apoptosis. In experimentally denervated and reinnervated rat facial muscle, we now evaluate changes in the expression patterns of different isoforms of nitric oxide synthase (NOS)-generating nitric oxide (NO), which mediates oxidative stress and apoptosis. Physiological expression of NOS corresponds to a constant sarcolemmal staining pattern for neuronal NOS (nNOS) and a patchy sarcolemmal and weak sarcoplasmic labeling for the endothelial NOS-isoform, with no expression for inducible NOS (iNOS). Denervated muscle displayed distinct downregulation of nNOS with preserved expression of dystrophin. Also, denervated and immediately reinnervated muscle fibers showed decreased expression of nNOS. However, muscle fibers reinnervated for 10 weeks revealed a restored physiological expression of nNOS. There were no changes in the expression of endothelial and inducible NOS. As NO is known to induce growth arrest and collapse of neuronal growth cones, downregulation of NOS may contribute to promotion of axonal regeneration by aiding formation of new endplates. NO is upregulated in reinnervated muscle fibers and thus prevents polyneural hyperinnervation by extrajunctional synapses. Furthermore, downregulation of NOS during denervation is compatible with the finding that low levels of NO contribute to apoptosis instead of necrosis in disease states of oxidative stress.

Animals↗
PubMed1991

Mr 40,000 and Mr 39,000 pertussis toxin substrates are increased in surgically denervated dog ventricular myocardium.

To test the general hypothesis that cardiac innervation may participate in myocardial G protein regulation, we examined the effects of complete intrapericardial surgical denervation or sham operation in dogs. In particulate fractions of dog left ventricular (LV) myocardium harvested 28-33 days after denervation or sham operation, Mr 40,000 and Mr 39,000 pertussis toxin-sensitive substrates (G proteins) were increased by 31% (1.31 +/- 0.084 vs 1.00 +/- 0.058 OD, arbitrary units, p less than 0.01) and 40% (1.40 +/- 0.117 vs. 1.000 +/- 0.084 OD, arbitrary units, p less than 0.02), respectively, as compared with sham-operated controls. The Mr 40,000 pertussis toxin-sensitive band comigrated with a pertussis toxin-sensitive substrate in human erythrocyte membranes known to contain an alpha Gi species. In these same preparations basal, GTP and GppNHp stimulated adenylate cyclase activities were decreased in denervated heart by 20, 26, and 19%, respectively, consistent with increased activity of an inhibitory G protein. In contrast, Gs function was not altered, because cyc(-) membranes reconstituted with membrane extracts and fluoride and beta-receptor-stimulated adenylate cyclase activity were not different between groups. Furthermore, adenylate cyclase catalytic subunit function as assessed with forskolin and manganese stimulation was not different between preparations of control and denervated heart. We conclude that in preparations of surgically denervated dog myocardium Mr 40,000 and Mr 39,000 pertussis toxin-sensitive G proteins are increased by 31 and 40%, respectively, and that functional alterations in adenylate cyclase activity exist, consistent with increased inhibitory G-protein function.

5'-Nucleotidase↗
PubMed1989

Analysis of fibrogenic processes in denervated tissues of spinal cord injury patients.

To test the hypothesis that altered collagen metabolism is a contributing factor in the apparent delayed wound healing in denervated regions of spinal cord injury (SCI) patients, a tissue implant (PVA) was used to directly measure collagen deposition. Sterile PVA implants were placed subcutaneously in the inner aspect of the upper arm above the cord injury (innervated) and in the inner aspect of the upper leg below the cord injury (denervated) of 20 spinal cord injury patients and compared to eight healthy volunteers. On day 14, the implants were removed and analyzed histologically by trichrome stain and biochemically for hydroxyproline as a measure of collagen deposition. No remarkable histologic differences were observed in the sponge material removed from the upper regions compared to the lower denervated regions of the spinal cord injury patients. Sponges from both areas were infiltrated with fibroblasts containing well-developed rough endoplasmic reticulum and large quantities of trichrome-positive collagen. Likewise, upper and lower histology of controls was identical and nondistinguishable from the corresponding sections obtained from the spinal cord injury patients. Quantitation of the hydroxyproline in the arms of the spinal cord injury patients (n = 20) showed 4.3 +/- 0.7 nmol hydroxyproline per milligram of sponge compared to 4.1 +/- 0.4 nmol/mg in the denervated regions of the lower limb. The hydroxyproline content in the arms of control volunteers was 5.2 +/- 0.7 nmol/mg compared to 3.9 +/- 0.8 nmol/mg in the leg (n = 8). These observations suggest that fibrogenic processes in denervated regions are not reduced significantly compared to innervated regions.

Adult↗
PubMed1992

Effect of total extrinsic denervation and atropine on HCl-stimulated pancreatic exocrine secretion and CCK release in conscious dogs.

In 10 dogs with pancreatic fistulas, we studied the effect of extrinsic pancreatic innervation and atropine on protein and bicarbonate secretion and cholecystokinin (CCK) release after intraduodenal perfusion with HCl. Before and after extrinsic denervation of the pancreas, the dogs were given 0.05 M HCl in increasing doses (1.5-48 mmol/h). Tests were repeated with atropine. Increasing doses of HCl resulted in a dose-dependent release of protein and bicarbonate output in both the intact and the denervated pancreas. However, pancreatic denervation significantly decreased pancreatic secretion in response to low loads but not to high loads of HCl. HCl-stimulated CCK release was not altered by pancreatic denervation. In the intact pancreas, atropine significantly reduced bicarbonate and protein response to low loads but not to high doses of HCl. In the denervated gland, atropine had no further inhibitory effect on exocrine pancreatic secretion. Furthermore, atropine showed no influence on HCl-stimulated CCK release under either condition.

Animals↗
PubMed2001

Radiofrequency facet joint denervation in the treatment of low back pain: a placebo-controlled clinical trial to assess efficacy.

STUDY DESIGN: A prospective double-blind randomized controlled trial was performed. OBJECTIVE: To assess the efficacy of percutaneous radiofrequency articular facet denervation for low back pain. SUMMARY OF BACKGROUND DATA: Uncontrolled observational studies in patients with low back pain have reported some benefits from the use of facet joint radiofrequency denervation. Because the efficacy of percutaneous radiofrequency had not been clearly shown in previous studies, a randomized controlled trial was conducted to assess the efficacy of the technique for improving functional disabilities and reduce pain. METHODS: For this study, 70 patients with low back pain lasting of more than 3 months duration and a good response after intraarticular facet injections under fluoroscopy were assigned randomly to receive percutaneous radiofrequency articular facet denervation under fluoroscopic guidance or the same procedure without effective denervation (sham therapy). The primary outcomes were functional disabilities, as assessed by the Oswestry and Roland-Morris scales, and pain indicated on a visual analog scale. Secondary outcomes included spinal mobility and strength. RESULTS: At 4 weeks, the Roland-Morris score had improved by a mean of 8.4% in the neurotomy group and 2.2% in the placebo group, showing a treatment effect of 6.2% (P = 0.05). At 4 weeks, no significant treatment effect was reflected in the Oswestry score (0.6% change) or the visual analog pain score (4.2% change). At 12 weeks, neither functional disability, as assessed by the Roland-Morris scale (2.6% change) and Oswestry scale (1.9% change), nor the pain level, as assessed by the visual analog scale (-7.6% change), showed any treatment effect. CONCLUSIONS: Although radiofrequency facet joint denervation may provide some short-term improvement in functional disability among patients with chronic low back pain, the efficacy of this treatment has not been established.

Adult↗
PubMed1976

Natriuresis and renin release by the denervated dog kidney during furosemide administration.

Renal excretion of sodium and water, renal venous plasma renin activity and renin secretion rate were measured during the administration of furosemide (5 mg/kg) to 10 anesthetized dogs, previously subjected to unilateral splanchnicotomy ("renal denervation"). Denervation diuresis and natriuresis, observed during control periods, did not occur when the diuretic was given and there were no significant changes in glomerular filtration rate or renal plasma flow in either the intact or denervated kidneys. Despite the abolition of denervation natriuresis with furosemide, plasma renin activity and renin secretion rate were depressed by splanchnicotomy. Thus, changes in the sodium load to the macula densa do not seem to play a decisive role in decreasing renin release following renal denervation.

Animals↗
PubMed1980

Influence of renal denervation on urine concentration in awake and anaesthetized dogs.

The role of renal nerves in urine concentration was studied in clearance experiments with unilaterally renal-denervated dogs prepared by surgical bladder division. Urine concentration was assessed under conditions of: (1) stimulation of ADH release by dehydration or barbiturate anaesthesia; (2) mannitol diuresis, and (3) isotonic saline diuresis. Differences in TcH2O/GFR between the intact and denervated kidney were not significant in any of the experimental groups. However, in dehydrated conscious dogs Uosm of the intact kidney (939 +/- 58 mmol/kg H2O) was significantly higher (P less than 0.05) than that of the denervated organ (806 +/- 51 mmol/kg H2O). In the intact kidney the medullary content of total solutes and sodium per kg wet tissue was 684 +/- 26 mmol and 208 +/- 12 mmol, respectively. This was significantly higher (P less than 0.005) than corresponding values of 581 +/- 23 mmol and 171 +/- 14 mmol per kg wet tissue measured in the denervated organ. We suggest that a slight impairment of urine concentration (lower Uosm) in the denervated kidney of conscious dogs may depend on decreased medullary hypertonicity.

Anesthesia↗
PubMed1996

The effect of succinylcholine on energy metabolism studied by 31P-NMR spectroscopy in rat denervated skeletal muscle.

BACKGROUND: The goals of this study were: (1) to demonstrate the differences of metabolic changes induced by succinylcholine (SCh) administration between normal and denervated muscle by 31P-NMR spectroscopy: (2) to determine whether three kinds of drugs (vecuronium, midazolam and magnesium sulfate) could prevent these metabolic changes. METHODS: Following unilateral sciatic nerve section, 20 male Wistar rats were studied at three-week intervals. After SCh 1 mg.kg-1 was administered intravenously, the changes of the inorganic phosphate/phosphocreatine (Pi/PCr) ratio, the beta ATP/(PCr+Pi) ratio, and intracellular pH were measured by 31P-NMR both in normal and denervated hind limb muscles of 5 rats. The other 15 rats were allocated to the pretreatment groups by the following drugs: vecuronium 0.02 mg.kg-1, midazolam 0.1 mg.kg-1 and magnesium sulfate 60 mg.kg-1. After pretreatment 3 min before SCh administration, we measured the same parameters by 31P-NMR. RESULTS: SCh administration did not change the Pi/PCr ratio in normal muscle, but significantly increased that in denervated muscle (P < 0.05). This increase of the Pi/PCr ratio was also observed in all pretreated groups but was minimal as compared with that in non-pretreatment denervated muscle. CONCLUSION: These data suggested that SCh administration decreased the level of "energy reserve" in denervated muscle, and that this metabolic change was not totally inhibited by vecuronium, midazolam, or magnesium sulfate.

Adenosine Triphosphate↗
PubMed1998

Succinylcholine-induced fasciculations in denervated rat muscles as measured using 31P-NMR spectroscopy: the effect of pretreatment with dantrolene or vecuronium.

BACKGROUND: We have previously demonstrated by 31P nuclear magnetic resonance (NMR) that succinylcholine (SCh) induces metabolic changes in denervated muscle. To specify those changes, we attempted to inhibit them using two different kinds of drugs, dantrolene and vecuronium. METHODS: Three weeks after unilateral sciatic nerve section, 75 male Wistar rats were randomly assigned to one of the following 5 groups: (1) non-pretreated normal muscle group; (2) non-pretreated denervated muscle group; (3) denervated muscle group pretreated with a low dose of vecuronium (0.02 mg.kg(-1)); (4) denervated muscle group pretreated with a high dose of vecuronium (0.2 mg.kg(-1)); (5) denervated muscle group pretreated with dantrolene (2 mg.kg(-1)). The change of the inorganic phosphate/phosphocreatine (Pi/PCr) ratio of each muscle was measured by 31P-NMR before and after SCh (1 mg.kg(-1)) administration and the corresponding peak amplitude of the electromyograms (EMG) was determined. RESULTS: The high dose of vecuronium totally inhibited SCh-induced fasciculation on EMG (100%-->2%). In this group, though the Pi/PCr ratio significantly increased 10 min after SCh, the peak after 5 min disappeared. The inhibition with dantrolene was about the same order of magnitude as with the low dose of vecuronium (35%:21%). However, the increase in the Pi/PCr only lasted about 10 min, in contrast to the other drugs. CONCLUSION: Our findings indicate that the Pi/PCr increases 5 and 10 min after SCh, respectively, as a result of two different processes. The first peak is caused by an excessive energy consumption in response to excessive muscle contraction. This in turn triggers the second peak, caused by breakdown of glycogen, initiated by an increased Ca2+ concentration.

Animals↗
PubMed1988

Posthatching changes in levels and molecular forms of acetylcholinesterase in slow and fast muscles of the chicken: effects of denervation and direct electrical stimulation.

The evolution of acetylcholinesterase (AChE) activity and AChE molecular form distribution were studied in slow-tonic anterior latissimus dorsi (ALD) and in fast-twitch posterior latissimus dorsi (PLD) muscles of chickens 2-18 days of age. In ALD as well as in PLD muscles, the AChE-specific activity increased transiently from day 2 to day 4; the activity then decreased more rapidly in PLD muscle. During this period asymmetric AChE forms decreased dramatically in ALD muscle and the globular forms increased. In PLD muscle, the most striking change was the decline in A8 form between days 2 and 18 of development. Denervation performed at day 2 delayed the normal decrease in AChE-specific activity in PLD muscle, whereas little change was observed in ALD muscle. Moreover, A forms in these two muscles were virtually absent 8 days after denervation. Direct electrical stimulation depressed the rise in AChE-specific activity in denervated PLD muscle and prevented the loss of the A forms. Furthermore, the different molecular forms varied according to the stimulus pattern. In ALD muscle, electrical stimulation failed to prevent the effect of denervation. This study emphasizes the differential response of denervated slow and fast muscles to electrical stimulation and stresses the importance of the frequency of stimulation in the regulation of AChE molecular forms in PLD muscle during development.

Acetylcholinesterase↗
PubMedDate not supplied

Increased renal prostanoid synthesis after unclipping the one-kidney, one-clip hypertensive rat: effect of renal denervation.

Renal denervation of hypertensive one-kidney, one-clip (1K, 1C) rats resulted in a minor fall in blood pressure (216, s.e.m. = 4, to 182, s.e.m. = 4, mmHg) 24 h later, which returned to predenervation levels with 1 week. Subsequent unclipping led to a similar fall in blood pressure in denervated (202, s.e.m. = 4 to 142, s.e.m. = 3) and sham-denervated (211, s.e.m. = 5 to 147, s.e.m. = 4) rats. Unclipping also resulted in a marked rise in urinary PGE2 and 6-keto PFG1 alpha in both denervated and sham-denervated animals. It appears that 1K, 1C hypertension, 8 weeks after clipping, is only slightly dependent on renal nerves. Unclipping results in increased renal synthesis of PGE2 and PGI2 which is not dependent on intact renal innervation.

Animals↗
PubMed1995

Effect of renal nerve denervation on tissue catecholamine content in spontaneously hypertensive rats.

1. To clarify the possible role of tissue catecholamines in the development of hypertension, we investigated the effect of bilateral renal denervation on the catecholamine contents of central and peripheral tissues in spontaneously hypertensive rats (SHR). 2. Norepinephrine (NE) content in renal cortex, renal medulla, and adrenal gland was higher in 7 week old SHR than age-matched Wistar-Kyoto rats (WKY). Dopamine (DA) content in the brainstem and hypothalamus was also higher in SHR, but NE and epinephrine (EPI) content in these areas were not different between strains. Similar differences in catecholamines were observed in 9 week old rats in which a sham operation of bilateral renal denervation was performed 2 weeks previously. 3. Bilateral renal denervation produced an almost complete reduction of NE content in the kidney in both strains and prevented the development of hypertension. DA content in the brainstem was also decreased by renal denervation in SHR but not in WKY. NE and EPI content in central tissues were not affected by renal denervation. 4. These results suggest that DA content in brainstem area, as well as NE content in the kidney, have a relationship in the development of hypertension in SHR.

Animals↗
PubMed2001

Adaptive changes in locomotor control after partial denervation of triceps surae muscles in the cat.

This report concerns a test of the hypothesis that gain in the stretch reflex pathway of cat medial gastrocnemius (MG) muscle during locomotion increases after denervation of its synergists, lateral gastrocnemius (LG), soleus (SOL) and plantaris (PL) muscles. In four cats, MG, tibialis anterior (TA) and vastus lateralis (VL) muscles were implanted with electromyogram (EMG) electrodes. The cats walked on a row of elevated pegs, some of which were spring-loaded and could be triggered to pop up at the moment of foot touchdown, rapidly dorsiflexing the foot. Pre-stretch EMG activity in MG as well as short-, medium- and long-latency responses to the dorsiflexions were compared before and after unilateral denervation of synergists. Short- and medium-latency responses of MG to perturbations increased in proportion to the increase in pre-stretch EMG in the days and weeks after partial denervation. This argues against an adaptive increase in stretch reflex gain independent of centrally generated extensor drive. Local anaesthesia of the skin of the paw did not significantly change the sizes of the stretch responses of MG before or after partial denervation. We conclude that pre-stretch EMG activity as well as stretch reflexes in MG muscle increased substantially after denervation of synergistic muscles. The data were consistent with an adaptive increase in central locomotor drive, causing more motoneuronal activity, which in turn resulted in an increase in the size of stretch reflexes.

Adaptation, Physiological↗
PubMed1997

The effect of carotid sinus denervation on fetal heart rate variation in normoxia, hypoxia and post-hypoxia in fetal sheep.

OBJECTIVE: To investigate whether carotid sinus nerve reflexes are linked to the increase in heart rate variation in acute (one hour) hypoxia in late gestation fetal sheep DESIGN: Comparison of short term variation between intact and carotid sinus denervated fetuses in normoxia, hypoxia and post-hypoxia. SUBJECTS: Sixteen chronically catheterised pregnant sheep in late gestation. RESULTS: There was no significant difference in short term variation between intact and denervated fetuses in normoxia. In intact fetuses short term variation increased significantly in hypoxia. In denervated fetuses it tended to increase in hypoxia, but this was not statistically significant. During the post-hypoxia period, short term variation increased significantly in denervated fetuses, although at this time it was decreasing in intact fetuses. When the decrease in pH was small intact fetuses showed a significantly greater increase in short term variation than denervated fetuses in hypoxia. In contrast, short term variation increased similarly in both groups when the pH decrease was greater (> 0.03 in early hypoxia and > 0.05 in late hypoxia). CONCLUSIONS: Carotid sinus nerve reflexes have an important influence on heart rate variation in hypoxia and post-hypoxia. It appears that other mechanisms (e.g. a rise in circulating catecholamines) are linked to an increase in heart rate variation when mild acidemia occurs in hypoxia.

Animals↗
PubMed1980

Protease inhibitors reduce effects of denervation on muscle end-plate acetylcholinesterase.

The effects of certain protease inhibitors on end-plate acetylcholinesterase (AChE) activity, as well as on wet weight and total protein, were studied in vivo in intact and denervated anterior gracilis muscles from the rat. A combination of leupeptin, pepstatin, and aprotinin, administered intraarterially, partly prevented the early (24 h) denervation-induced decrease in muscle weight and protein content. In turn, leupeptin and aprotinin, either alone or in combination, markedly reduced the decay of AChE activity in the denervated muscles, whereas pepstatin alone was ineffective. Such effects were additive in that the inhibitors in combination were more effective than when they were used separately. Additional experiments indicated that none of the inhibitors, at the concentrations used, affected AChE activity directly, nor did they have a significant effect during processing of the muscle samples. These findings indicate that the initial decay of AChE activity with denervation was effectively reduced by the inhibitors, probably through inactivation of proteolytic enzymes which, otherwise, would be increase in denervated muscle.

Acetylcholinesterase↗
PubMed1984

Effect of denervation on a cholinergic-specific ganglioside antigen (Chol-1) present in Torpedo electromotor presynaptic plasma membranes.

The presence of Chol-1, an antigen identified in the plasma membrane of cholinergic electromotor nerve terminals of Torpedo marmorata, was investigated in Torpedo electric organ after 3, 6, and 9 weeks' denervation. Denervation was monitored by the cessation of stimulus-evoked discharge potentials, by the reduction in nerve terminals seen morphologically, and by the decrease in ACh and ChAT contents. The content of ganglioside-bound sialic acid did not show any appreciable change with time. Some modification of ganglioside pattern on TLC was observed after 9 weeks' denervation. The presence of Chol-1 after denervation was assayed by its activity in inhibiting the selective complement-induced lysis of the cholinergic subpopulation of guinea pig cortical synaptosome which is mediated by the anti-Chol-1 antiserum. Denervation did not affect Chol-1 immunoreactivity although it did alter the distribution of the immunoreactivity among gangliosides. The possible significance of the results is discussed.

Acetylcholine↗