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Effect of orthotopic liver transplantation and chemical denervation of the liver on the activities of hepatic monoamine oxidase and catechol-O-methyltransferase.

The denervation of some tissue is associated with a fall in the activities of monoamine oxidase (MAO) and catechol-O-methyltransferase (COMT). Here we report on the effect of orthotopic liver transplantation and chemical denervation of the liver on the enzymes. Liver transplantation was performed on Lewis rats (n = 7). Denervation (n = 8) was by intraportal injection of 6-hydroxydopamine (75 mg/kg). A control group (n = 8) was also included. The norepinephrine content of the transplanted and denervated livers was reduced by greater than 99% (P < 0.001) and 95% (P < 0.001), respectively. The activity of hepatic COMT (substrate: catechol [5 mM] was not affected by transplantation or denervation. The activity of MAO with 0.1 mM 5-hydroxytryptamine (5-HT) (substrate for MAO-A) and with 0.01 mM 2-phenylethylamine (substrate for MAO-B) were not affected by denervation. In the transplanted liver, the activity of MAO with 5-HT and 2-phenylethylamine was increased by 26% (P < 0.05) and by 53% (P < 0.001), respectively. The ratios of the activities of the A to B forms of MAO (approximately 70% A to 30% B) was not affected by either procedure. Enzyme sensitivity for MAO inhibitors clorgyline and deprenyl were not significantly altered by transplantation. The concentration of plasma norepinephrine in the transplantation group was significantly lower than either the control (P < 0.001) or denervation groups (P < 0.05). We conclude from our results that the metabolism of circulating catecholamines by the liver is unlikely to be impaired after liver transplantation.

Animals↗

Impact of liver transplantation on cardiac autonomic denervation in familial amyloid polyneuropathy.

Familial amyloid polyneuropathy (FAP) is a rare and severe hereditary form of amyloidosis, due to the deposition of a genetic variant transthyretin essentially produced by the liver, and characterized by both sensorimotor and autonomic neuropathy. Liver transplantation (LT) is the most effective treatment to stop the progression of the disease. Cardiac amyloid infiltration is usually associated with cardiac denervation, restrictive cardiomyopathy, conduction disturbances, and sometimes sudden death. Whether the cardiac involvement related to amyloid deposition may be altered after LT remains unclear. We conducted the present study to define the outcome of cardiac involvement after LT in 31 patients with FAP (age, 39 +/- 12 yr). Patients were evaluated before and after LT (24 +/- 15 mo). Cardiac sympathetic denervation was assessed by both iodine-123 metaiodobenzylguanidine (MIBG) scintigraphy and heart rate variability (HRV) analysis. The scintigraphic importance of sympathetic denervation was evaluated globally on planar imaging using heart-to-mediastinum activity ratio (H/M) measured 4 hours after injection, and regionally using single-photon emission tomography (SPET) imaging. Amyloid myocardial infiltration was assessed by echocardiography. Diffuse sympathetic denervation was found when using cardiac MIBG planar imaging in patients evaluated before LT and compared with 12 control subjects (H/M: 1.45 +/- 0.29 vs. 1.98 +/- 0.35, p < 0.001). On SPET images, defects were diffuse in 12 patients and focal in 19 patients, with predominance at the inferior and apical segments. No change in sympathetic innervation was found in patients after LT as assessed either with planar imaging (H/M after LT: 1.46 +/- 0.28, p = not significant vs. H/M before LT) or with SPET imaging. HRV nonspectral indexes showed that the standard deviation of all cycles was significantly lower in patients compared with control subjects, and remained unchanged after LT. Conduction disturbances and ventricular arrhythmias were associated with low cardiac MIBG uptake, and progressed after LT. The left ventricular wall was slightly thickened in patients, and a further increase was observed after LT (posterior wall from 9.2 +/- 1.8 to 10.1 +/- 2.3 mm, p = 0.02; septal wall from 10.6 +/- 2.7 to 12.1 +/- 4, p = 0.046). Neurologic status stabilized in 26 patients, but worsened in the 5 patients who had the most severe cardiac sympathetic denervation before LT as measured by MIBG imaging. The magnitude of the cardiac sympathetic denervation remained stable 2 years after LT in patients with FAP, whereas the cardiac amyloid infiltration progressed. The importance of cardiac sympathetic denervation found in FAP patients before LT was associated with a neurologic worsening after LT.

3-Iodobenzylguanidine↗

Effect of denervation on hindlimb regeneration in Xenopus laevis larvae.

Xenopus laevis larvae at stages 51-57, according to Nieuwkoop and Faber, were subjected to amputation of the right hindlimb or of both limbs at the thigh or the tarsal level, as well as to somatic denervation of the right limb. Larvae at the same stage having undergone amputation of the right limb or of both limbs and sham denervation of the right limb were used as controls. In experimental series I a single denervation of the right limb was performed at the time of amputation. In experimental series II repeated denervations were performed (before, during and after amputation). Results show that in larvae at stages 51-53 subjected to limb amputation at the proximal level (thigh) even repeated denervation of the right limb did not prevent regeneration, although giving rise to various degrees of hypotrophy. In stage-55 larvae partial inhibition of the regenerative process in the right limb was clearly visible only after repeated denervations and amputation at the proximal level. After amputation at the distal level (tarsalia) the regenerative process in the right limb underwent no significant delay with respect to the controls, although the regenerated right limb was hypotrophic. In stage-57 larvae even a single denervation at the time of amputation was enough to inhibit regeneration of the right limb after either proximal or distal amputation. Therefore, in Xenopus laevis larvae, nerve-dependence for hindlimb regeneration takes place proximodistally as the nerve fibers grow in the limb and it gradually undergoes a process of proximodistal differentiation.(ABSTRACT TRUNCATED AT 250 WORDS)

Amputation, Surgical↗

Effects of chronic nicotine administration on the denervated rat adrenal medulla.

1 The effects of chronic nicotine administration (1 or 10 mg/kg, s.c., twice daily) were studied in intact and denervated rat adrenal glands to determine the relative roles of central input and direct actions on catecholamines. 2 Catecholamine depletion was obtained in the intact glands from 1-7 days of treatment with 10 mg/kg, with recovery by 14 days of treatment; catecholamines were not decreased in denervated adrenal glands. 3 Catecholamine depletion was accompanied by a decline in functional storage vesicles (determined by [3H]-adrenaline uptake per gland) in the intact side, while no change was seen in the denervated side; the proportion of newly synthesized vesicles increased markedly during 1-7 days of treatment with 10 mg/kg in the intact side, while a much smaller increase of shorter duration was seen in the denervated adrenal gland. 4 Chronic nicotine administration at either dose level induced tyrosine hydroxylase in both intact and denervated glands, but the increase occurred more slowly in the denervated glands. 5 Dopamine beta-hydroxylase levels increased similarly in both sides during treatment with nicotine (10 mg/kg). 6 These studies suggest that although long-term adrenal denervation eliminates the catecholamine depletion caused by chronic administration of nicotine, the mechanisms for induction of catecholamine synthesizing enzymes are still capable of responding to the drug.

Adrenal Medulla↗

Lack of nicotinic supersensitivity in frog sympathetic neurones following denervation.

The sensitivity of bull-frog sympathetic neurones to nicotinic, cholinergic agonists has been studied in both normal (control) and surgically denervated ganglia. Using gross extracellular recording, the sensitivity to acetylcholine (ACh) increased 18-fold following denervation, while that to carbachol (CCh) was unchanged. Normal ganglia showed a similar sensitivity increase after inhibition of cholinesterase. This suggests that the rise in ACh sensitivity is due to reduced cholinesterase activity, not to true supersensitivity. There was no significant difference in resting membrane potential or input resistance between normal and denervated neurones. Neurones denervated for 7-50 days showed no significant change in sensitivity to ACh or CCh applied iontophoretically at a distance of 10 micron from the cell surface. In control ganglia, localized iontophoretic application of ACh revealed an uneven distribution of sensitivity which is attributed to the localization of receptors to synaptic areas. Fourteen days after denervation, the geometric mean sensitivity to focally applied ACh was not significantly different from that found in control ganglia. The variation in sensitivity to focally applied ACh at randomly chosen sites on denervated neurones was as great as that found in control ganglia. It is concluded that denervation does not cause frog sympathetic neurones to become supersensitive to ACh. The apparent increase in nicotinic ACh sensitivity observed using extracellular recording from whole ganglia is due not to a change in the number or distribution of ACh receptors, but to a decrease in cholinesterase activity.

Acetylcholine↗

Denervated human skeletal muscle: MR imaging evaluation.

Because determination of neurologic integrity after severe limb trauma is crucial in patient care, the authors assessed magnetic resonance (MR) imaging as a tool to map denervated motor units of skeletal muscle in patients with traumatic peripheral neuropathy. Denervation was confirmed in 22 patients with use of electromyography, surgery, or both. MR imaging was performed with moderately T1- and T2-weighted spin-echo and short-tau inversion-recovery (STIR) sequences. MR imaging was unreliable in depicting acute denervation. Muscles of patients with subacute denervation had prolonged T1 and T2, which contributed to conspicuous hyperintensity on STIR images. Chronically denervated muscles showed marked atrophy, variable changes on STIR images, and conspicuous fatty infiltration on T1-weighted images. Normal variants in motor unit anatomy were seen in denervated muscle volumes outside the expected distribution of the injured nerve. MR imaging is promising for the noninvasive mapping and monitoring of denervated muscle in subacute and chronic phases of peripheral neuropathy.

Extremities↗

Sympathetic denervation of resistance arteries increases contraction and decreases relaxation to flow.

The effect of chronic sympathetic and possibly sensory denervation on flow-induced changes in smooth muscle tone was examined in a branch of the rabbit ear artery (200-400 microns ID). The superior cervical ganglion and 1-cm portions of the greater and anterior auricular nerves were removed from 4-wk-old rabbits while under general anesthesia, and arterial segments were studied 21 days later. Efficacy of denervation was assessed by catecholamine histochemistry and by absence of a constrictor response to transmural electrical field stimulation. Intraluminal flow of physiological saline solution was made through a pipette into matched-innervated and -denervated segments. Flow-induced contraction was increased in the denervated compared with the contralateral innervated segments. At the lowest flow rate studied (1 microliters/min), the contraction increased more than six times. This is consistent with the previously described nonspecific, nondeviational hypersensitivity of denervated vascular smooth muscle to constrictor influences. By contrast flow-related dilation at 10 and 20 microliters/min was significantly diminished. An intraluminal flow rate could be found that resulted in dilation in innervated but not the matched-denervated segments. Endothelial-mediated dilation to acetylcholine was also impaired. Chronic sympathetic denervation increased the magnitude of flow contraction and decreased that of flow relaxation.

Animals↗

Assessment of a newly recognized association. Carotid sinus hypersensitivity and denervation of sternocleidomastoid muscles.

BACKGROUND: Carotid sinus syndrome has been reported recently to be associated with chronic denervation of the sternocleidomastoid muscles. To further understand the relationship between carotid mechanoreceptors and sternocleidomastoid denervation, the present study investigated the relation between the results of carotid sinus massage and electromyographic activity of the sternocleidomastoid muscles in patients without syncope. METHODS AND RESULTS: Patients were selected prospectively if they fulfilled strict exclusion criteria, particularly the absence of a history of syncope, pacemaker implantation, or drugs known to modify the behavior of the autonomic nervous system. A right and left carotid massage was performed for 10 seconds in 30 patients (22 men; mean age, 67.3 +/- 6.5 years). The results (monitoring for heart rate and blood pressure) were classified as normal, doubtful, or hypersensitive carotid sinus. Sternocleidomastoid electromyography activity was recorded from the right and left sides, and the results were classified as normal, moderate denervation, and severe denervation. Carotid sinus massage was normal in 13 patients (43%), doubtful in 9 (30%), and abnormal in 8 (27%). Electromyographic activity of the sternocleidomastoids was normal in 13 patients (43%) and revealed moderate denervation in 7 (24%) and severe chronic denervation in 10 (33%). The results of carotid sinus massage and sternocleidomastoid electromyography were highly concordant in each patient (kappa = .592, P < .00001) and in each side (right, kappa = .381, P < .03; left, kappa = .390, P < .01). CONCLUSIONS: Carotid sinus hypersensitivity and chronic denervation is a common finding in individuals older than 50 years of age. These two entities are significantly related, suggesting a pathophysiological relation of one to the other.

Aged↗

Effects of peripheral sympathetic denervation induced by guanethidine administration on the mechanisms regulating puberty in the female guinea pig.

The effects of peripheral sympathetic denervation induced by guanethidine administration to newborn and 10-day-old female guinea pigs on puberty, ovulation and the follicular population were analysed. Peripheral sympathetic denervation beginning at birth resulted in the loss of ovarian norepinephrine content (0.95. +/- 0.1 ng/mg wet tissue in untreated control animals vs non detectable in treated animals). Guanethidine administration to newborn or 10-day-old guinea pigs advanced puberty (age of vaginal opening: 27 +/- 1.2 days (newborn), 26 +/- 1.7 (10-day-old) vs 37 +/- 0.7 (control), P < 0.001) and ovulation. The number of corpora lutea in control and denervated animals was similar (3.5 +/- 0.2 vs 3.3 +/- 0.3). The relative weight (mg/100 g body weight) of the ovaries and adrenals in the denervated animals autopsied during the late follicular phase (24-48 h after vaginal opening) increased (ovaries: 27.8 +/- 1.3, 28.9 +/- 3.0 vs 20.9 +/- 0.8, P < 0.05; adrenals 36.4 +/- 1.4, 37.0 +/- 0.8 vs 31.6 +/- 1.5, P < 0.05), while the uterine weight diminished (179 +/- 13, 149 +/- 28 vs 292 +/- 20). When the animals were killed during the late luteal phase (9-11 days after vaginal closure), the relative weight of the ovaries of newborn guanethidine-treated animals was higher than that of the control animals (21.4 +/- 1.7 vs 16.8 +/- 1.4, P < 0.05). The mean number of follicles counted in the ovaries of denervated animals was significantly higher than in control animals (1736 +/- 230 vs 969 +/- 147, P < 0.05). The mean diameter of the follicles in the untouched control ovary in animals killed in the late follicular phase was significantly larger than from animals killed in the late luteal phase (263 +/- 3.9 microns vs 248 +/- 3.0 microns, P < 0.01). The mean diameter of the follicles measured in the ovaries of denervated animals was significantly higher than in controls (animals treated from birth 274 +/- 2.0 microns vs 255 +/- 2.4, P < 0.05; animals treated from day 10, 286 +/- 2.3 microns vs 257 +/- 2.3, P < 0.05). When the mean diameter of the follicles in the left and right ovary of the untouched control was analysed, the follicular diameter in the left ovary was significantly larger than in the right ovary (309 +/- 6.0 microns vs 214 +/- 3.9, P < 0.01); the response of the left and right ovaries to sympathetic denervation was the opposite. The results obtained in the present study suggest that ovarian innervation plays a role in the regulation of follicular growth, maturation and atresia which is not related to changes in steroid secretion by the ovary, but to other regulatory mechanisms.

Adrenal Glands↗

Diaphragmatic denervation in intensive care unit patients.

The causes of prolonged requirement for mechanical ventilation in the intensive care unit (ICU) are currently a subject of investigation. Critical illness polyneuropathy (CIP), an axonal polyneuropathy that frequently occurs with prolonged sepsis and multi-organ failure, has been cited as a frequent cause of difficulty with weaning from a ventilator. The relative contribution of diaphragmatic denervation in ICU patients with and without CIP has not been definitively determined. We reviewed 102 ventilator dependent intensive care unit (ICU) patients. Critical illness polyneuropathy (CIP) was diagnosed based upon electrodiagnostic criteria. Electrodiagnostic studies included diaphragmatic needle electromyography (EMG) to evaluate for diaphragmatic denervation. The medical charts of the patients with diaphragmatic denervation were reviewed for etiologies other than CIP for the diaphragmatic denervation. Our results suggest: 1) Respiratory impairment in ICU patients may often be unrelated to either CIP or diaphragmatic denervation; 2) Only about half of ventilator dependent CIP patients have diaphragmatic denervation; 3) Diaphragmatic denervation in ICU patients frequently may be attributable to causes other than CIP.

Action Potentials↗

Altered balance of proteinase inhibitors in atrophic muscle after denervation.

Skeletal muscle denervation leads to an increase of proteolytic activity, which is also favoured by reduced levels of alpha1 antichymotrypsin and nexin II, two serine-proteinase inhibitors normally acting at the neuromuscular junction. In the present experiments we extended our investigation to other muscular proteinase inhibitors after denervation. In all muscles examined (soleus, plantaris, extensor digitorum longus) specific immunoreactivity for alpha2macroglobulin (alpha2M) and alpha1proteinase inhibitor (alpha-1-antitrypsin, ATI) was distributed in peri-endomysial structures as well as in small patches inside the fibres. By contrast, inter-alpha-trypsin inhibitor (ITI) was mainly localized in the extracellular matrix. These localization patterns did not change substantially in 15-days denervated muscles. Dot-blot analysis revealed a small decrease (about 15%) of alpha2M in 15-days denervated muscles, while ATI and ITI specific activities were substantially unchanged. RT-PCR allowed us to detect the above protease inhibitor mRNAs in normal muscle homogenates. Denervation atrophy induced by section of the sciatic nerve resulted in a remarkable reduction of (2macroglobulin mRNA (60%) and ITI (30%), but not ATI, as measured by computer-assisted semiquantitative densitometry of electrophoresed RT-PCR bands. The marked decrease of alpha2M we have detected in denervated muscle may be responsible, at least in part, for the proteolytic increase which is known to occur in skeletal muscle during denervation atrophy.

Alpha-Globulins↗

Radiofrequency lumbar zygapophysial (facet) joint denervation: a preliminary report of a new concept.

This is a preliminary report of a new concept of lumbar medial branch neurotomy by measurement of minimal sensory threshold. This technique is not recommended for routine clinical use until further controlled data are available. The lumbar zygapophysial joints (Z-joint) or facet joints, are a potential source of low back pain. In general, the principle innervation of the Z-joint is the medial branch of the posterior primary ramus of the same level as the target Z-joint as well as the level above. Denervation of the multifidus as evaluated by electromyography has become a measurement of successful Z-joint denervation. Two drawbacks to this method are that it takes one to several weeks for denervation potentials to develop and thus does not give the physician any sense of successful denervation intra-operatively. The other is that the Z-joint is innervated by the sensory fibers of the medial branches. As a result, the multifidus may be successfully denervated as demonstrated by electromyography but the Z-joints may be inadequately denervated. As a result, this technique describes measurement of minimal sensory threshold prior to lesioning and seeking to double that threshold as an additional, intra-operative measure of successful sensory denervation of the Z-joint.

Journal Article↗

Effects of sympathetic denervation and oxygen free radicals on neovascularization in skin flaps.

An island skin flap, with its sole blood supply based on the inferior epigastric vessels, in Sprague-Dawley rats (female, 220 to 250 gm) was used as a model for the investigation of neovascularization. Flap survival after pedicle ligation was considered an indicator of neovascularization. Vascular pedicles were ligated on days 2 to 5 after flap elevation, and the time course of neovascularization in the innervated and denervated flaps was determined by measurements of survival on day 7 after pedicle ligation (on days 9 to 12 postoperatively). Neovascularization sufficient to maintain viability was established at 4 and 5 days after flap elevation in the innervated and denervated flaps, respectively. The effects of various scavengers of oxygen free radicals on neovascularization were evaluated in the innervated and denervated flaps. The pedicles were ligated 3 days after flap elevation. Flap survival was assessed on day 7 after pedicle ligation (on day 10 postoperatively). Treatment with a single dose of deferoxamine (50 mg/kg) increased the viability from 48 to 69 percent of flap area in the denervated flaps (p < 0.01) but produced little effect on viability in the innervated flaps. In the denervated flaps, treatments with a single dose of superoxide dismutase, intravenously and intraarterially, also substantially increased the survival rates from 29 to 86 percent (marginally significant) and 100 percent (p < 0.05), respectively. Allopurinol improved the survival from 43 to 88 percent; the difference was not statistically significant. The results suggest that denervation resulted in a delay of neovascularization and that severe sympathetic denervation contributes to the production of oxygen free radicals, which may exert their inhibitory effects on neovascularization.

Allopurinol↗

Effects of denervation on cell cycle control in laryngeal muscle.

Denervation of skeletal muscle is thought to lead to an accelerated proliferation of myogenic stem cells known as satellite cells. The transition of these cells from a quiescent to a proliferative state is thought to require satellite cells to enter the cell cycle and replicate. Little is known about the expression of genes associated with cell cycle control, and so the objective of this study was to examine the effects of denervation and reinnervation of the posterior cricoarytenoid (PCA) muscle on key cell cycle genes. Female Sprague-Dawley rats were assigned to control, denervated, or reinnervated groups. Animals were killed at 7, 14, and 30 days after ligation of the recurrent laryngeal nerve. The PCA muscle was then analyzed for changes in the messenger RNA levels of key genes associated with cell cycle control, differentiation, and proliferation. Cyclin D1 is a key gene responsible for initiating progression of the cell cycle from G1 to S phase. Interestingly, neither denervation nor reinnervation affected the expression of this gene. In contrast, we found large increases in key cell cycle inhibitors (p21 and the growth arrest and DNA destruction 45 [GADD45] gene) in both the denervated and reinnervated groups. We interpret the increases in these cell cycle inhibitors to reflect (1) an inhibition of satellite cell proliferation and/or (2) a special form of apoptosis that results in the loss of myonuclei known to occur under atrophic conditions. To our knowledge, this is the first study to examine the effects of denervation on cell cycle regulation.

Analysis of Variance↗

The plasticity of denervated and reinnervated laryngeal muscle: focus on single-fiber myosin heavy-chain isoform expression.

No studies have examined the effects of denervation on the single-fiber distribution of myosin heavy-chain (MyHC) isoforms in laryngeal muscle. The fast type IIB MyHC isoform represents the largest proportion of the myosin pool in the posterior cricoarytenoid (PCA) and the thyroarytenoid (TA) muscles. However, the fast type IIB MyHC isoform is distributed differently at the single-fiber level. Hence, we hypothesized that denervation would result in markedly different patterns of MyHC isoform expression at the single-fiber level. To test this hypothesis, we assigned animals to the following 3 groups: (1) control group; (2) denervation group; or (3) reinnervation group. Animals were killed 7, 14, 30, 90, and 180 days after denervation or reinnervation. Subsequently, the distribution of MyHC isoforms were electrophoretically determined in approximately 7200 single fibers. There were 4 key findings to emerge from this study: (1) The MyHC isoform profile of the PCA muscle, at both the whole-muscle and single-fiber level, is more malleable than that of the TA muscle. (2) In the PCA and TA muscles, denervation produced some similar changes, resulting in a large increase in the pool of fibers coexpressing fast type IIX and IIB MyHC isoforms. (3) Reinnervation of the TA muscle produced significant alterations in the single-fiber distribution of MyHC isoforms while having little effect on the whole-muscle MyHC isoform composition. (4) Since the transitions in MyHC isoform expression associated with denervation were limited primarily to fast type IIB to fast type IIX, we postulate that only minor reductions in muscle function would result (as defined by maximum shortening velocity and the force-velocity relationship).

Analysis of Variance↗

Tau expression in denervated rat muscles.

We studied whether denervation affects the expression of tau, in particular phosphorylated tau, and how it is degraded in rat soleus muscles. Immunoblot analysis showed a high molecular weight, approximately 110 kDa (big tau), in normal muscle. Tau levels increased significantly in denervated muscles treated with chloroquine (a lysosomotrophic agent) and in untreated ones, as compared to levels of similarly treated contralateral, innervated muscles. Most of the tau in the innervated and denervated muscles was phosphorylated. Immunohistochemically, tau and beta-tubulin colocated in the sarcoplasm of innervated, saline-treated (intact) muscle, but the staining intensities were very weak. Both proteins, however, were expressed extensively in these areas in the denervated muscles from saline-treated rats. In the denervated muscle of chloroquine-treated rats there were numerous autophagic vacuoles in the sarcoplasm, and phosphorylated-tau accumulation was marked within these vacuoles, indicative that tau first was taken into autophagic, vacuoles by nonselective autophagy then degraded via the lysosomal as well as the nonlysosomal calpain system. Our findings suggest that phosphorylated big tau accumulates with beta-tubulin in denervated muscular atrophy, possibly in order to maintain or preserve the integrity of the muscle fiber during progressive atrophy or regeneration.

Animals↗

Denervation enhances spontaneous inflammatory myopathy in SJL mice.

We studied the effect of denervation on the spontaneous inflammatory myopathy that occurs in SJL mice. Cryosections from innervated and denervated calf muscles were assessed for severity of inflammation, relative proportions of mononuclear cell subsets, and major histocompatibility complex (MHC) class I expression. A significant increase in mononuclear cell infiltrates occurred in the denervated muscle. Denervation also changed the composition of mononuclear cell infiltrates towards a higher percentage of CD8(+) T cells (19% versus 11%). MHC class I expression was enhanced in denervated muscle compared with innervated muscle. Our findings indicate that inflammation in muscle may be enhanced by denervation.

Animals↗

Dynamics of nuclei of muscle fibers and connective tissue cells in normal and denervated rat muscles.

The mitotic activity in muscles of growing rats and the effect of denervation were studied by means of continuous infusion of 5-bromo-2-deoxyuridine (BRDU). Denervated muscles after 10 weeks contained 20 to 60% fewer muscle nuclei than normal; BRDU labeled about 25% of the nuclei of normal soleus and extensor digitorum longus (EDL) and of denervated EDL muscles but only 5% in the denervated soleus muscle. Labeled nuclei persisted in denervated but not in normal muscles. After the main growth period, the turnover of myonuclei was at most 1 to 2% per week. The behavior of connective tissue nuclei was similar to that in muscle fibers. Infusion of BRDU had no effect on contractile properties. It is suggested that the exceptionally rapid atrophy of the denervated rat soleus associated with loss of satellite cells was due to loss of myonuclei and differentiation and fusion of satellite cells. The cause may possibly be that the phase of postdenervation fibrillation is shorter than in other muscles.

Animals↗