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PubMedDate not supplied

Progressive latissimus dorsi muscle denervation for free-flap dynamic cardiomyoplasty.

BACKGROUND: The creation of free muscle grafts for surgical myoplasty is limited by the dependence of muscle on its original nerve supply. The aim of this study was to develop a model of gradual denervation of a large skeletal muscle (latissimus dorsi) and evaluate the possibility that atrophic degeneration and loss of function would be reduced using progressive nerve compression instead of surgical division of the nerve. The effects of chronic stimulation prior to, and after, denervation were also evaluated. METHODS: Electrodes connected to a myostimulator were implanted on 24 latissimus dorsi muscles of 12 goats. Denervation of these muscles was achieved either by sectioning of the nerve by progressive compression using ameroid rings placed around the nerve. Electrostimulation of the muscle started either 5 weeks before (prestimulation), or immediately after the denervation. RESULTS: The model of gradual nerve compression was successfully created and did have less atrophy and loss of function at mid-term when compared with nerve division. Chronic electrostimulation of the muscle after nerve division had a beneficial effect on function and on the atrophic process. Chronic electrostimulation in our model of gradual nerve compression did not mirror these beneficial results. Detrimental results were observed in groups in which chronic electrostimulation was applied prior to nerve division or constriction.

Animals↗
PubMed1982

The effect of low-frequency electrical stimulation on the denervated extensor digitorum longus muscle of the rabbit.

Both extensores digitorum longi (EDL) muscles of rabbits were denervated by crushing the common peroneal nerves. The EDL muscle on one side was directly stimulated at 10-12 Hz via implanted electrodes. This treatment reduced the changes of twitch/tetanus ratios produced by denervation and prevented the slowing of contraction and relaxation that follows denervation. It is concluded that the stimulation reduced the duration of the active state of denervated muscles. These effects of stimulation were reduced after 5 weeks, probably because by that time the slowing effect of low-frequency activity on the fast muscles became apparent.

Animals↗
PubMed1999

Muscle fiber conduction velocity in situ (MFCV) in denervation, reinnervation and disuse atrophy.

OBJECTIVES: Muscle fiber conduction velocity (MFCV) was performed in disuse atrophy, in denervated muscle and during reinnervation as a possible index of muscle atrophy, and to clarify the evolution of the fiber size. MATERIAL AND METHODS: MFCV was performed in 12 patients with complete denervation of biceps brachii muscle and during various stages of reinnervation. Twenty-one patients with disuse quadriceps atrophy were also tested. Invasive MFCV was performed according to the method reported elsewhere (2). RESULTS: MFCV decreased significantly in denervated muscles. Reduction of MFCV was found during the first weeks and was progressive. Peak frequency in histograms decreased and the normal Gaussian distribution was lost. MFCV increased progressively after reinnervation with coexistence of slow and significant increase of faster MFCV. MFCV decreased significantly also during the first weeks after immobilization and improved by rehabilitation therapy. CONCLUSION: MFCV is a reliable method to test the muscle fiber size after denervation and immobilization, and its evolution by reinnervation and therapy.

Adolescent↗
PubMed1976

Responses of the denervated rat urinary bladder to alfa adrenoceptor stimulation.

The contractile responses of the rat detrusor muscle to noradrenaline were increased 2-3 weeks after partial denervation but had returned to control values 6-9 weeks after the denervation, probably because of reinnervation of denervated muscle cells. 6-9 weeks after partial denervation the excitatory alpha-adrenoceptor mediated response to stimulation of the remaining intact nerves was predominant, masking the subsequent inhibitory beta-receptor response, which at this time was seen only after alpha-receptor blockade. The possibility of an outgrowth of adrenergic fibres activating alpha-receptors in muscle cells normally not innervated by adrenergic nerves is discussed.

Animals↗
PubMed1977

Denervation stimulation of alpha-aminoisobutyric acid uptake by the diaphragm in developing rats.

Effect of denervation on accumulation of alpha-aminoisobutyric acid (AIB) by the the diaphragm was studied in 11-, 21-, 31-, and 51-day-old rats. In both innervated and denervated diphragms the accumulation steadily decreased with age. Denervation significantly enhanced accumulation at all ages, the relative increment being greater in older animals owing to the lower basal accumulation ratio for AIB. The denervation-induced stimulation was partially abolished by dactinomycin administration. The drug obviously inhibits the formation of new carrier sites at plasma membranes for AIB transport.

Age Factors↗
PubMed1984

Development of supersensitivity to methacholine in the rat detrusor following either parasympathetic denervation or decentralization.

The male rat urinary bladder belongs to those few structures where both the post- and preganglionic parasympathetic nerves are accessible for severance. In the present study the sensitivity to the parasympathomimetic drug methacholine of muscle strips of either denervated or decentralized bladders was examined in vitro. One week postoperatively denervated and decentralized bladders were sensitized to the same degree, the ED50 values being 4 times less than ED50 of unoperated control bladders. In contrast to the decentralized bladders the supersensitivity in the denervated ones was found to have increased further when tested four weeks postoperatively, the ED50 value being about 20 times less than that of controls. The present findings are in agreement with Cannon's "law of denervation". The results are discussed in relation to possible mechanisms behind the phenomenon of supersensitivity.

Animals↗
PubMed1986

Unilateral denervation of the rat urinary bladder and reinnervation: a predominance for ipsilateral changes.

Unilateral removal of the pelvic ganglion affected the bladder-half on the denervated side more profoundly than that on the non-denervated side. At an early stage (3-7 days) the former was heavier, had a lower choline acetyltransferase activity, developed less tension to nerve stimulation and, in course of time, became more sensitized to methacholine in vitro than the latter. At a late stage (30-60 days) the nerve-evoked contractile responses on the denervated side had increased, which was almost wholly attributed to the atropine-sensitive part of the contraction, but the recovery was not complete. On the non-denervated side the nerve-evoked responses were not significantly changed. It was calculated that in the normally innervated bladders 25-30% of the cholinergic nerves of each half were of contralateral origin. The figure was lower (18%) for the nerves mediating the atropine-resistant response.

Animals↗
PubMed1990

Effects of denervation on enzyme-histochemical and morphometrical properties of the rat soleus muscle in relation to age.

The soleus muscle of young adult (5 months), adult (10-11 months) and old (23 months) male Wistar rats was unilaterally denervated for a period of 3 weeks and studied with regard to enzyme-histochemical and morphometrical properties. Denervation caused a marked atrophy of all fibres, irrespective of age and enzyme-histochemical type. Fibres having myofibrillar ATPase staining characteristics intermediate to type I and type IIA fibres increased in number in all age groups and a reduction in the number/proportion of type I fibres was found in adult and old animals. These results indicate that a slow-to-fast shift in myofibrillar properties as a consequence of denervation, shown to occur in the soleus muscle of young animals, also takes place in old age. This supports the view that atrophic fibres with intermediate myofibrillar ATPase staining characteristics, and possibly also atrophic IIA fibres, seen in old soleus muscle could be type I fibres which have undergone a transformation in response to the age-related denervation process.

Adenosine Triphosphatases↗
PubMed1991

Blood pressure control in arterial- and cardiopulmonary receptor denervated dogs.

The mechanisms influencing arterial blood pressure and heart rate were studied in conscious foxhounds after chronic sino-aortic and cardiopulmonary denervation (N = 6). In previous investigations it was shown, that this denervation produces hypertension and tachycardia, which is confirmed by the present study: Mean arterial blood pressure increased from 101 +/- 3 to 123 +/- 6 mmHg (P less than 0.05), and heart rate rose from 85 +/- 6 to 124 +/- 5 beats min-1 (P less than 0.001). The variability of mean arterial blood pressure, but not that of heart rate increased (from 6 +/- 1 to 22 +/- 2 mmHg (P less than 0.001). The administration of the alpha-adrenergic blocker prazosin reduced both mean arterial blood pressure (-33 +/- 8 mmHg, P less than 0.01) and its variability (-12 +/- 1 mmHg, P less than 0.01), thus suggesting an alpha-adrenergic mediated hypertension. beta-blockade by propranolol blunted the heart rate increase (-24 +/- 5 beats min-1, P less than 0.05). Although plasma renin activity increased in the denervated dogs, converting enzyme inhibition had little effect on mean arterial blood pressure and heart rate. In conclusion, chronic sino-aortic and cardiopulmonary denervation enhances the alpha and beta-adrenergic component of cardiovascular control in a different fashion. While the alpha-adrenergic component induces fluctuations around an elevated arterial blood pressure level, the beta-adrenergic tone to the heart increases without any significant increase in variability.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1987

Comparison of the mode of action of succinylcholine and succinylmonocholine on rat skeletal muscle after denervation.

The effects of equimolar concentrations (3.0 X 10(-5) M) of succinylcholine (SCh) and succinylmonocholine (SMC) were studied in-vitro at 20 degrees C in rat extensor digitorum longus muscle (EDL) 0-147 days after common peroneal nerve section. Analysis of simultaneous measurements of K+ efflux (mmolL-1 g-1) and contracture tension (mN) to SCh showed that there was a rapid increase in the mean values of both parameters up to 22-28 days after denervation (7.7 mmolL-1 g-1, 36 mN). At the end of the period studied, the contracture response declined to 4.0 mN whilst the capacity for K+ efflux remained relatively high (4.8 mmolL-1 g-1) in comparison with normal contralateral EDL muscle (n = 82) K+ efflux measurements (0.62 mmolL-1 g-1). A significant correlation (r = 0.86, P less than or equal to 0.001) was found between SCh-induced K+ efflux and contracture tension 1-56 days following nerve section which indicated that the development of the contracture response and K+ efflux were concomitant during the period specified. The ratios of maximum contracture tension/K+ efflux in response to SCh and SMC, 18-22 days after denervation were similar, 4.9 and 5.9, respectively. Results indicated that the mode of action of each agent was similar in denervated rat skeletal muscle, and that they were equally potent in their hyperkalaemic potential. Results of comparative measurements of membrane depolarization and contracture tension in response to SCh and SMC showed that both agents produced quantitatively similar responses at 7 and 14 days after denervation.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed2003

Nitric oxide-dependent in vitro secretion of amylase from innervated or chronically denervated parotid glands of the rat in response to isoprenaline and vasoactive intestinal peptide.

The basal in vitro release of amylase was similar from rat parotid lobules of innervated and chronically denervated glands and was unaffected by the inhibitors used in this study. The secretion of amylase induced by isoprenaline or vasoactive intestinal peptide (VIP) was reduced by one-third to one-half from the lobules of the innervated glands and even more so from the lobules of the denervated glands by ODQ, an inhibitor of soluble guanyl cyclase which is activated by nitric oxide (NO) and catalyses the cGMP production. The use of N (omega)-propyl-L-arginine (N-PLA) revealed that the evoked secretion of amylase in the denervated glands depended on the activity of neuronal type NO synthase to synthesize NO. Since the denervated gland is virtually devoid of NO synthase-containing nerve fibres, the neuronal type NO synthase was most probably of a non-neuronal source. NO-dependent amylase secretion was agonist related, since amylase secretion evoked by bethanechol and neuropeptide Y was not reduced by ODQ or N-PLA. Hence, under physiological conditions, activation of beta-adrenoceptors (sympathetic activity) and VIP receptors (parasympathetic activity) is likely to cause secretion of parotid amylase partly through a NO/cGMP-dependent intracellular pathway involving the activity of neuronal type NO synthase, possibly of acinar origin.

Adrenergic beta-Agonists↗
PubMed1984

Post-natal change in the effect of denervation on the rat vas deferens.

The vas deferens of 14-54 d old rats was denervated, isolated after 7 d, divided into prostatic and epididymal halves, and denervation supersensitivity to noradrenaline, acetylcholine, methacholine and tetramethylammonium (TMA) was examined. The supersensitivity to any of these agonists did not appear in rats younger than 21 d of age. Thereafter a leftward shift of the dose-response curve and an increase in the maximum contraction to noradrenaline were observed. The maximum contraction became progressively greater with development in the prostatic half but was approximately constant in the epididymal half. Supersensitivity to methacholine distinctly developed with age in the epididymal half. Only a subsensitivity to TMA was observed, suggesting that TMA acts on the nerve. The effect of denervation on the response to acetylcholine in the epididymal half resembled that to methacholine, and in the prostatic half resembled that to TMA. The developmental change in the effect of denervation on noradrenaline was discussed in relation to the full contractile ability of the vas halves, and that to cholinergic drugs was discussed in relation to nicotinic and muscarinic receptor population.

Acetylcholine↗
PubMed1967

The action of tubocurarine and atropine on the normal and denervated rat diaphragm.

1. The potency with which tubocurarine chloride (TC) and atropine sulphate (AS) influence the amplitude of the end-plate potentials was measured in the rat diaphragm. This effect was compared with the action of these drugs on brief depolarizations evoked by iontophoretic application of ACh to end-plate-free spots of the chronically denervated fibre.2. TC and AS act similarly on e.p.p.s, but the concentrations necessary to cause the same effect are 2000-times higher for AS.3. The dose-response curves for both inhibitors are unchanged by prostigmine.4. Ten to twenty-five days after denervation the ACh-potentials of the sensitized end-plate-free parts of the membrane are less responsive to curare than the normal e.p.p.s are. AS is as effective in blocking ACh potentials of denervated muscles as it is in blocking normal e.p.p.s. The curare/atropine coefficient (dose ratio for equal effect) is 0.0005 for e.p.p.s and 0.003 for ACh potentials of the denervated membrane.5. Both blocking drugs reduce the amplitude of ACh-potentials evoked in the end-plate region of normally innervated rat diaphragm fibres as effectively as they reduce the amplitude of e.p.p.s.6. Neither TC nor AS have a presynaptic action in concentrations markedly reducing the e.p.p. amplitude.

Acetylcholine↗
PubMed1968

Renal sodium reabsorption after acute renal denervation in the rabbit.

1. Separate effects on the functions of left and right kidneys were examined after left-sided renal handling and acute denervation. Studies were done on pentobarbital-anaesthetized rabbits using clearance techniques to evaluate renal haemodynamics and water and electrolyte excretion.2. When compared with its counterpart, the handled kidney exhibited some decrease in function for at least 20 min. Recovery of most functions occurred in 40-60 min.3. The effects of denervation on renal functions were observed when the effects of handling had subsided. Renal plasma flow (R.P.F.) and glomerular filtration rate (G.F.R.) were not significantly changed, whereas the decrease in Na, K and water excretion, which was usually observed for no ascertained reason in the innervated kidney, was prevented.4. The magnitude of the denervation natriuresis was greater in these rabbits than in dogs studied previously; other functions studied were comparable in the two species.5. The results from thirty-five experiments are interpreted to indicate that denervation decreases Na reabsorption independently of G.F.R., perhaps by a direct effect on tubular transport, but more probably by a redistribution of filtration to nephrons of lesser reabsorptive capacity.

Animals↗
PubMed1972

Inhibition of denervation changes in skeletal muscle by blockers of protein synthesis.

1. A study was made of the effects of inhibitors of protein synthesis (actinomycin D, chloramphenicol and cycloheximide) on the in vivo development of extrajunctional cholinergic receptors, tetrodotoxin-resistant action potentials, slowing of the time course of the action potential, and on the fall in the resting membrane potential in denervated mouse skeletal muscle.2. Actinomycin D (0.5 mg/kg, I.P.) reduced the incorporation of uridine into skeletal muscle by 50-60% for 4-5 days. There was no simultaneous reduction in L-leucine incorporation.3. Actinomycin D (0.5 mg/kg I.P., 1 day after denervation) inhibited the development of extrajunctional cholinergic receptors, tetrodotoxin-resistant action potentials and the fall in resting membrane potential for approximately 4 days.4. The post-denervation fall in the maximum rate of rise and in the amplitude of the overshoot of the muscle fibre action potential was unaffected by actinomycin D treatment.5. Actinomycin D failed to inhibit the appearance of the membrane changes if given later than 2 days after denervation.6. Chloramphenicol (6 g/kg in divided doses) and cycloheximide (40 g/kg every 12 hr) were also able to inhibit the appearance of the membrane changes.7. It is concluded that some denervation induced changes in the muscle fibre membrane depend on the synthesis of new proteins. The results imply that the motor nerve cell normally exerts a regulatory influence on the genome of the muscle cell.

Action Potentials↗
PubMed1973

Ionic properties of the neuromuscular junction of the frog: effects of denervation and pH.

1. The effects of denervation, reinnervation and pH on the ionic permeability changes mediated by junctional receptors have been studied in muscle fibres of the frog sartorius.2. The reversal potential of acetylcholine responses in denervated junctions was about 25 mV more negative than in normal junctions.3. The delay of the change in the ionic properties of junctional receptors was proportional to the nerve stump length: 10 and 14 days for lengths of 12 and 33 mm, respectively.4. When the motor nerve reinnervates the junction, the reversal potential of the acetylcholine responses comes back to the normal value before the neuromuscular transmission is restored.5. The Na/K conductance change decreases in high pH solutions. After denervation, the pH profile of this ratio is shifted to the acid values by about two pH units.6. These observations can be explained by assuming that the Na and K channels differ by the pK of their anionic groups and that the denervation induces an alteration of the sites that bear the charges.

Acetylcholine↗
PubMed1976

Noise analysis of drug induced voltage clamp currents in denervated frog muscle fibres.

1. Voltage clamp currents were recorded during iontophoretic application of steady doses of acetylcholine (ACh), carbachol or suberyldicholine to hyperpersensitive extrasynaptic regions of chronically denervated frog muscle fibers. Autocorrelation functions of drug induced current fluctuations were calculated and estimates of conductance gamma and average open time tau of the extrasynaptic ion channels were derived. 2. The average open time of an extrajunctional channel induced by acetylcholine is tauACh = 11 +/- 1-6 msec (+/- S.E.) at -80 mV and 8 degrees C. Carbachol and suberyldicholine open channels of tauCarb = 3-9 +/- 0-4 msec and tauSubCh = 19 +/- 2-5 msec (+/- S.E.) duration under the same conditions. The average open time of the extrasynaptic channel produced by each drug is three to five times longer than the value found for junctional channels in normal fibres. 3. The average open time of the extrajunctional channel is dependent on temperature and membrane potential. Lowering the temperature or increasing the membrane potential increases the average open time of the channels induced by any one of the drugs. 4. The conductance of a single extrajunctional channel opened by the action of acetylcholine is estimated to be gammaextra = 15 +/- 1-8 pmho (+/- S.E.). This is somewhat lower than the value of gammaep = 23 +/- 2 pmho (+/- S.E.) found for the conductance of a single open channel in the junctional membrane of normal fibres. The extrasynaptic channels opened by the action of carbachol and suberyldicholine have similar conductances to those produced by ACh. 5. The autocorrelation function of drug-induced current fluctuations, recorded at the former end-plate region of chronically denervated fibres often shows both a fast and a slow time constant. They correspond in value to the time constant of the autocorrelation function obtained from end-plate currents in normal fibres and from extrasynaptic currents in denervated fibres respectively. This could indicate that two populations of channels exist at the former end-plate region of denervated muscle fibres.

Acetylcholine↗
PubMed1977

Non-equivalence of impulse blockade and denervation in the production of membrane changes in rat skeletal muscle.

1. A complete and long lasting blockade of nerve impulses was established in the sciatic nerve of rats, by implanting silastic cuffs of critical internal diameters. Either marcaine-impregnated or plain cuffs were used. The contralateral sciatic nerve was sectioned. 2. At various days after the initial procedures, the extensor digitorum longus muscles of the two sides were examined with intracellular electrodes. 3. Decrease in resting membrane potential, fibrillatory activity and resistance of the action potential to tetrodotoxin developed not only in the denervated but also in the impulse-blocked muscles. In the latter, the fibres were normally innervated since they displayed miniature end-plate potentials and were excitable by nerve stimulation distal to the blocking cuff. 4. However, all of the above mentioned denervation-like changes were significantly less pronounced in the blocked muscles than in the denervated ones. 5. It is concluded that in addition to loss of nerve impulses, some other neural factor must be taken into account to explain the origin of muscle changes induced by denervation. The possible relation of this additional factor with nerve degeneration is discussed.

Action Potentials↗