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Electrical
Stimulation And Denervated Muscle
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Updated November 22, 2002
Adams L., Carlson B.M.,
Henderson L., and Goldman D. (1995) Adaptation of nicotinic acetylcholine
receptor, myogenin, and MRF4 gene expression to long-term muscle denervation. J.
Cell Biol. 131, 1341-1349.
Abstract: Muscle activity alters the expression of functionally distinct
nicotinic acetylcholine receptors (nAChR) via regulation of subunit gene
expression. Denervation increases the expression of all subunit genes and
promotes the expression of embryonic-type (alpha 2 beta delta gamma) nAChRs,
while electrical stimulation of denervated muscle prevents this induction. We
have discovered that the denervation- induced increases in alpha, beta, gamma,
and delta subunit gene expression do not persist in muscles that have been
denervated for periods extending beyond a couple of months. However, expression
of RNA encoding the epsilon-subunit remains elevated suggesting a return to
expression of predominantly adult-type (alpha 2 beta delta epsilon) nAChR in
long-term denervated muscles; a finding confirmed by single channel patch-clamp
analysis. Since the nAChR subunit genes are regulated by the MyoD family of
muscle regulatory factors, and the genes encoding these factors are also induced
following short-term muscle denervation, we determined their level of expression
in long- term denervated muscle. Although MyoD and myf-5 RNA levels remained
elevated, myogenin and MRF4 RNAs were induced only transiently by muscle
denervation. Surprisingly, Id-1, a negative regulator of transcription, was
gradually induced in denervated muscle with RNA levels peaking about two months
after denervation. It is likely that this maintained level of increased Id
expression, in conjunction with the returning levels of myogenin and MRF4
expression, account for the reduced level of embryonic receptors in long-term
denervated muscle. These changing patterns of gene expression may have important
consequences for the ability of muscle to recover function after denervation
Akeson W.H., Woo S.L.Y.,
Amiel D., et al (1974) Biomechanical and Biochemical Changes in the
Periarticular Connective Tissue During Contracture in the Immobilized Rabbit
Knee. Conn Tiss Res 2, 315-323.
al Amood W.S., Lewis D.M.,
and Schmalbruch H. (1991) Effects of chronic electrical stimulation on
contractile properties of long-term denervated rat skeletal muscle. J. Physiol
441, 243-256.
Abstract: 1. The contractile properties of fast-twitch (extensor digitorum
longus or EDL) and slow-twitch (soleus) muscles in the rat were followed for
periods of between 4 and 10 months after denervation. The effects of chronic
electrical stimulation during the last 3-8 weeks of denervation were
investigated. 2. The fall in tetanic tension that follows axotomy ended after
about 4 months' denervation. The equilibrium tension was about 0.75% of control
tension in EDL and 0.2-0.3% in soleus. 3. The low tension in soleus was due
partly to the small diameter of the muscle fibres (atrophy) and partly to their
necrosis that resulted in an 8-fold fall in specific tension (the force per unit
cross-sectional area). Similar but less extreme changes occurred in EDL. 4. It
is speculated that the final level of tension reached by unstimulated denervated
muscles is an equilibrium between decrease in force due to atrophy and necrosis
and increase due to regeneration. Differences between the final tension levels
in soleus and EDL cannot be accounted for quantitatively by known differences in
atrophy alone. Therefore, the rate of necrosis in soleus and of regeneration in
EDL may be higher. 5. Chronic stimulation of long-term denervated muscle
increased force generation by about 7-fold in EDL and between 20 and 55 times in
soleus. The final tension reached was between 4 and 5% of normal in both
muscles. Specific tension of fibres was almost completely restored by
stimulation and the number of fibres was normal. The failure to recover full
tension was largely due to failure to reverse denervation atrophy completely. 6.
Twitch contraction and relaxation times were identical in denervated-stimulated
soleus and EDL. There was no evidence for dependence on duration of stimulation
or tension of the muscle. The normalized maximum rate of rise of tetanic tension
remained higher in EDL than soleus
Amiel D., Woo S.L.Y.,
Harwood F.L., et al (1982) The Effect of Immobilization on Collagen Turnover in
Connective Tissue: A Biochemical-Biomechanical Correlation. Acta Orthop Scand
53, 324-332.
Andreose J.S., Xu R., Lomo
T., Salpeter M.M., and Fumagalli G. (1993) Degradation of two AChR populations
at rat neuromuscular junctions: regulation in vivo by electrical stimulation. J.
Neurosci. 13, 3433-3438.
Abstract: The effect of electrical stimulation on the stability of junctional
ACh receptors (AChR) on soleus muscles of Wistar rats was compared to that of
denervation and reinnervation. Denervation causes the degradation rate of the
slowly degrading AChRs (Rs) at the neuromuscular junction to accelerate and be
replaced by rapidly degrading AChRs (Rr), while reinnervation restabilizes the
accelerated Rs. Electrical stimulation initiated at the time of denervation
prevented the acceleration of the Rs. It could not, however, reverse the effect
of denervation if initiated after the AChRs became destabilized, nor could it
slow the degradation rate of the Rr. We conclude that electrical stimulation of
denervated muscle downregulates the expression of the Rr and prevents the
destabilization of Rs
Askmark H. and Wistrand P.J.
(1992) Leakage of carbonic anhydrase III from normal and denervated rat skeletal
muscle following contractile activity. Muscle Nerve 15, 643-647.
Abstract: Skeletal muscle extracellular carbonic anhydrase III was investigated
in anesthetized rats by a microdialysis technique. A small dialysis probe was
inserted into the tibialis anterior (TA) muscle and perfused continuously.
Perfusates were collected before and during muscle contraction, induced by
electrical stimulation of the muscle or of the sciatic nerve. In the perfusate
of resting normal and denervated muscle, the concentration of CA III was 10 to
12 ng/mL, as measured by a radioimmunosorbent technique. During contractile
activity, the concentrations of CA III increased markedly in the normal and
denervated muscle. A TA muscle suspended in physiological saline behaved
similarly, even though the leakage before and during contraction was higher than
in vivo. The results show that skeletal muscle leaks CA III both in vivo and in
vitro, a leakage which was markedly increased by contractile activity. The
microdialysis technique should also be useful in humans to study the efflux of
various proteins from different kinds of diseased or fatigued muscles
Carpenter S., Karpati G.
(1982) Necrosis of Capillaries in Denervation Atrophy of Human Skeletal Muscle.
Muscle & Nerve 5, 250-254.
Carraro U., Libera L.D.,
Catani C., Danieli-Betto D. (1982) Chronic Denervation of Rat Diaphragm:
Selective Maintenance of Adult Fast Myosin Heavy Chains. Muscle & Nerve 5,
515-524.
Carraro U., Catani C.,
Saggin L., Zrunek M., Szabolcs M., Gruber H., Streinzer W., Mayr W., and Thoma
H. (1988) Isomyosin changes after functional electrostimulation of denervated
sheep muscle. Muscle Nerve 11, 1016-1028.
Abstract: Isomyosin analyses by biochemical, immunochemical, and histochemical
investigations have been carried out in five sheep following unilateral
recurrent laryngeal nerve paralysis and direct functional electrostimulation of
the denervated cricoarytenoid posterior muscle. Myosin light chains were
identified by two-dimensional gel electrophoresis. Myosin heavy chains were
analyzed by one-dimensional SDS-polyacrylamide gel electrophoresis. Slow myosin
heavy chain was identified by orthogonal peptide mapping and immunochemistry.
The stimulation effect at cellular level was determined using adenosine
triphosphatase (ATPase) histochemistry. A dramatic increase of the type 1 fiber
area (slow, fatigue-resistant fibers) could be seen after many weeks of an
increasing regime of low-frequency direct electrical stimulation. Biochemically,
the amount of slow myosin was always higher than in normal muscles. Some muscles
were transformed almost completely to the slow type. At the time they were
studied and with the methods employed, the expression of embryonic isomyosin was
not observed. In conclusion, after numerous weeks of maintained functional
activity, elicited by direct electrostimulation, the denervated muscle
regionally showed areas of hypertrophy or at least lack of atrophy of slow
myofibers without major signs of muscle damage
Cole B.G. and Gardiner P.F.
(1984) Does electrical stimulation of denervated muscle, continued after
reinnervation, influence recovery of contractile function? Exp. Neurol. 85,
52-62.
Abstract: The study was conducted to determine if daily electrical stimulation
of denervated muscle, initiated the day following crush denervation and
continued for 8 weeks (i.e., 5 weeks after presumptive reinnervation), would
influence denervation-associated alterations in muscle size and in situ
contractile properties of rat gastrocnemius. A stimulation protocol of brief,
strong, isometric contractions was designed to maximize the beneficial effects
as described by previous authors. By 8 weeks after crush, unstimulated muscles
were still significantly lighter in wet weight, were tetanically weaker, and
showed slower isometric contractile responses in situ than controls. Denervated
muscles which had been stimulated daily were heavier and tetanically stronger
(the latter not different from controls) than those in the nonstimulated group.
Muscle weights from groups of animals killed at 2 or 4 weeks after nerve crush
indicated the major benefit of stimulation occurred during this initial 4-week
period. In situ fatigue properties were unaffected by denervation or
stimulation. A protocol of electrical stimulation-evoked strong contractions,
initiated soon after denervation and continued after reinnervation, was
effective in attenuating the strength-related, but not speed-related, changes in
neuromuscular function resulting from denervation. These latter changes are
presumably the result of loss of "neurotrophic influence" and/or continuous
low-tension muscle activity lost as a result of denervation
Dasse K.A., Chase D., Burke
D., et al. (1981) Mechanical Properties of Tenotomized and
Denervated-tenotomized Muscles. Am J Physiol 241C, 150-153.
David E., Jayasree V.,
Ramakrishna O., Govindappa S., and Reddanna P. (1983) Effect of in vivo
electrical stimulation on the carbohydrate metabolism of control and denervation
atrophied muscle of dog, Canis domesticus. Indian J. Physiol Pharmacol. 27,
289-297.
Abstract: The standardized programme of electrical stimulation was applied to
the control and denervation atrophied muscle of dog, Canis domesticus and the
pattern of changes in the carbohydrate metabolism was analysed in the control
(C), denervated control (DC), control stimulated (CS) and denervated stimulated
(DS) gastrocnemius muscles. The programme of electrical stimulation of the
control muscle has elevated glycogenolysis, glycolysis and increased the level
of operation of TCA cycle with decreased mobilization of carbohydrates into
hexose monophosphate pathway, indicating the setting in of trained condition.
Sciatectomy, on the other hand, lowered the level of operation of glycogenolysis
and decreased the utilization of carbohydrates through hexose-mono and di-phosphate
pathways and TCA cycle. The programme of electrical stimulation applied to the
denervated muscle has restored the utilization of carbohydrates through hexose
mono and diphosphate pathways and oxidative metabolism indicating the
applicability of this programme of electrical stimulation in the treatment of
muscular atrophy
Davis H.L. (1983) Is
electrostimulation beneficial to denervated muscle? A review of results from
basic research. Physiother Can 35, 306-312.
Doupe J. (1943) Studies in
Denervation: The Effect of Electrical Stimulation on the Circulation and
Recovery of Denervated Muscle. J Neurol, Neurosurg and Psychiat 6, 136.
Eberstein A. and Pachter B.R.
(1986) The effect of electrical stimulation on reinnervation of rat muscle:
contractile properties and endplate morphometry. Brain Res. 384, 304-310.
Abstract: Denervated extensor digitorum longus muscles of Wistar rats were
electrically stimulated in vivo for 4 days (2h per day) after peroneal nerve
crush 1 cm from the muscle. Isometric contractile properties and endplate
ultrastructure were measured on days 11 and 18. On day 11, the time to peak
(116% of control) and 1/2-relaxation time (136% of control) for the twitch
tensions of stimulated muscles measured in vivo were significantly less than
those (127% and 157% of controls, respectively) of non-stimulated muscles. Peak
twitch and tetanic tensions were not significantly different. The postsynaptic
area of endplates for stimulated muscles were closer in size to controls than
those for the non-stimulated ones. On day 18, no difference was found in the
contractile responses between stimulated and non-stimulated groups. Similarly,
the postsynaptic areas were the same for both groups. These results demonstrate
that denervated muscle stimulated electrically for 4 days prior to reinnervation
can preserve the structure of the endplate as well as accelerate recovery of
normal function in reinnervated muscle fibers after 11 days of denervation
Eberstein A. and Eberstein
S. (1996) Electrical stimulation of denervated muscle: is it worthwhile? Med.
Sci. Sports Exerc. 28, 1463-1469.
Abstract: Research conducted over the past 25 years has demonstrated that muscle
activity, not neurotrophic substances, is the most important factor in the
regulation of specific physiological and biochemical properties of muscle
fibers. Application of this knowledge has led to considerable experimentation
with chronic electrical stimulation as a possible clinical tool for the
treatment of denervated muscles. Evidence accumulated from animal studies has
indicated that direct electrical stimulation of denervated muscles can to a
large extent substitute for innervation and preserve or restore the normal
properties of the muscles. Appropriate stimulation parameters were critical for
a successful intervention, and the best results were obtained when the
stimulation pattern resembled the firing pattern of the normal motoneuron. Thus,
fast muscles required intermittent, brief, high frequency stimulation and slow
muscles needed continuous, low frequency stimulation. For human denervated
muscles, critical questions still remain to be resolved before electrical
stimulation will yield the optimum benefit. Research must be performed in human
subjects to define the appropriate stimulation parameters the stimulation
current, and the type and placement of electrodes
Eken T., Gundersen K. (1988)
Electrical Stimulation Resembling Normal Motor-Unit Activity: Effects on
Denervated Fast and Slow Rat Muscles. J Physiol 402,651-669.
Elliott D.R., Thomson J.D.
(1963) Dynamic properties of denervated rat muscle treated with electrotherapy.
Am. J. Physiol. 205:173-176.
Etgen G.J., Jr., Farrar R.P.,
and Ivy J.L. (1993) Effect of chronic electrical stimulation on GLUT-4 protein
content in fast-twitch muscle. Am. J. Physiol 264, R816-R819.
Abstract: Ins
Finol H.J., Lewis D.M.,
Owens R. (1981) The Effects of Denervation on Contractile Properties of Rat
Skeletal Muscle. J Physiol 319, 81-92.
Fisher E., Guttmann L.
(1942) Effect of Electrotherapy on Denervated Muscle. Lancet 1, 169.
Goldberg A.L., Etlinger
J.D., Goldspink D.F., and Jablecki C. (1975) Mechanism of work-induced
hypertrophy of skeletal muscle. Med. Sci. Sports 7, 185-198.
Abstract: Skeletal muscle can undergo rapid growth in response to a sudden
increase in work load. For example, the rat soleus muscle increases in weight by
40% within six days after the tendon of the synergistic gastrocnemius is
sectioned. Such growth of the overworked muscle involves an enlargement of
muscle fibers and occasional longitudinal splitting. Hypertrophy leads to
greater maximal tension development, although decreased contraction time and
reduced contractility have also been reported. Unlike normal developmental
growth, work-induced hypertrophy can be induced in hypophysectomized or diabetic
animals. This process thus appears independent of growth hormone and insulin as
well as testosterone and thyroid hormones. Hypertrophy of the soleus can also be
induced in fasting animals, in which there is a generalized muscle wasting. Thus
muscular activity takes precedence over endocrine influences on muscle size. The
increase in muscle weight reflects an increase in protein, especially
sarcoplasmic protein, and results from greater protein synthesis and reduced
protein breakdown. Within several hours after operation, the hypertrophying
soleus shows more rapid uptake of certain amino acids and synthesis of
phosphatidyl-inositol. By 8 hours, protein synthesis is enhanced. RNA synthesis
also increases, and hypertrophy can be prevented with actinomycin D. Nuclear DNA
synthesis also increases on the second day after operation and leads to a
greater DNA content. The significance of the increased RNA and DNA synthesis is
not clear, since most of it occurs in interstitial and satellite cells. The
proliferation of the non-muscle cells seems linked to the growth of the muscle
fibers; in addition, factors causing muscle atrophy (e.g. denervation) decrease
DNA synthesis by such cells. In order to define more precisely the early events
in hypertrophy, the effects of contractile activity were studied in rat muscles
in vitro. Electrical stimulation enhanced active transport of certain amino
acids within an hour, and the magnitude of this effect depended on the amount of
contractile activity. Stimulation or passive stretch of the soleus or diaphragm
also retarded protein degradation. Presumably these effects of mechanical
activity contribute to the changes occuring during hypertrophy in vivo. However,
under the same conditions, or even after more prolonged stimulation, no change
in rates of protein synthesis was detected. These findings with passive tension
in vitro are particularly interesting, since passive stretch has been reported
to retard atrophy or to induce hypertrophy of denervated muscle in vivo. It is
suggested that increased tension development (either passive or active) is the
critical event in initiating compensatory growth
Gorza L., Gundersen K., Lomo
T., Schiaffino S., Westgaard R.H. (1988) Slow-to-Fast Transformation of
Denervated Soleus Muscles by Chronic High-Frequency Stimulation in the Rat.J
Physiol 402, 627-649.
Gurney M.E. (1984)
Suppression of sprouting at the neuromuscular junction by immune sera. Nature
307, 546-548.
Abstract: Injury of afferent motor axons or pathological loss of motoneurones
from the spinal cord causes the remaining axons within a muscle to sprout and to
reinnervate the denervated muscle fibres. Sprouting occurs at two sites along
intramuscular axons, at nodes of Ranvier (nodal sprouting) and at the
neuromuscular junction (terminal sprouting). Terminal sprouting is also produced
by treatment with botulinum toxin and by other agents that render muscle
inactive. The muscle probably provides a signal for terminal sprouting as
restoration of muscle activity by direct electrical stimulation prevents
sprouting. Such a signal might be a local change on the muscle fibre surface or
a 'soluble' sprouting factor, although the failure to induce terminal sprouting
in one muscle by denervating adjacent muscles argues against the latter
hypothesis. I now report that rabbit antisera against a 56,000 (56K)-molecular
weight protein secreted by denervated rat muscle suppress botulinum
toxin-induced terminal sprouting in the mouse gluteus muscle. An immune response
against this protein has also been detected in serum of patients with
amyotrophic lateral sclerosis (ALS), a disease in which loss of motoneurones
from the spinal cord is not accompanied by the degree of sprouting and
reinnervation seen in other motoneurone diseases
Gutmann E. [Ed] (1962) The
Denervated Muscle. Prague, Publishing House of Czechoslovak Academy of Sciences.
Gutmann E., Gutmann L.
(1945) The Effect of Galvanic Exercise on Denervated and Re-innervated Muscles
in the Rabbit. J Neurol, Neurosurg & Psychiat 7, 7.
Gutmann E., Jakoubek B.
(1963) Effect of increased motor activity on regeneration of the peripheral
nerve in young rats. Physiol. Bohem. 12:463-468.
Haggmark T., Eriksson E.,
Jansson E. (1986) Muscle fiber type changes in human skeletal muscle after
injuries and immobilization. Orthopaedics 9, 181-185.
Harada Y. (1983)
Experimental study of denervated rat muscle. Part II: The effects of electrical
stimulation on the denervated rat muscles. Nippon Seikeigeka Gakkai Zasshi 57,
859-867.
Abstract: Electrical stimulation has been widely employed for the treatment of
peripheral nerve lesion, however, its effects are not well known. Effects of
electrical stimulation on denervated muscles were studied by measuring the
weight of anterior crural muscles and the diameter of muscle fibers of the
extensor digitorum longus muscle of the rat. The muscle fibers were classified
by myofibrillar ATPase reaction. The denervated muscle showed loss of weight, a
marked decrease in diameter of type 1 fibers and a small increase in diameter of
type 2 fibers. Electrical stimulation suppressed weight loss of the denervated
muscles. Electrical stimulation with high frequency cycle, like phasic
motoneuron discharges, significantly suppressed the increase in diameter of type
2 muscle fibers. Electrical stimulation with low frequency cycle, like tonic
motoneuron discharge, significantly suppressed the decrease in diameter of type
1 muscle fibers
Heathcote R.D. (1989)
Acetylcholine-gated and chloride conductance channel expression in rat muscle
membrane. J. Physiol 414, 473-497.
Abstract: 1. During the differentiation of skeletal muscle, there is a
synchronized expression of a number of muscle-specific proteins including the
acetylcholine-gated ion channel (AChR). Another muscle- specific ion channel,
responsible for chloride conductance, was shown to be expressed in an
anticoordinate fashion to AChR. An organ culture system for rat lumbrical
muscles was developed to manipulate the expression of these two ion channels. 2.
Denervation induced a change in expression of both channels that was mimicked in
culture and reversed by direct electrical stimulation. 3. The time course of the
disappearance of both channels was similar and started immediately after
denervation (chloride conductance) or stimulation (AChR). The time course of the
appearance of AChR was delayed several days after denervation and culture but
chloride conductance increased immediately upon stimulation. 4. The loss of
chloride conductance in muscle cultured in cycloheximide exhibited first-order
kinetics, providing an estimate of the half-life (2.3 days) for the chloride
conductance channel. This resembled the disappearance of chloride conductance in
normal medium, suggesting that synthesis of this channel ceases following
denervation. The decrease in chloride conductance characteristic of denervated
muscle was not halted by cycloheximide. 5. Changes in chloride conductance
presumably alter the intracellular concentration of chloride. The possibility
that chloride might regulate the expression of AChRs in skeletal muscle was
tested by altering the intracellular concentration of chloride in muscles
maintained in organ culture. 6. Denervated muscles, whose intracellular
concentration of chloride is elevated, were cultured in medium containing 9 mM-chloride
(low-Cl- medium). AChR expression was reduced by either low-Cl- medium or
electrical stimulation. Together, low-Cl- medium and electrical stimulation
reduced expression more than either treatment alone. 7. The loss of AChRs in
low-Cl- medium was blocked when muscle fibrillation was halted by TTX. 8. When
chloride conductance was blocked by 9AC (9- anthracene carboxylic acid)
intracellular chloride was elevated to the levels seen in denervated muscle. The
elevated levels of chloride did not prevent the reduction in AChR expression
induced by electrical stimulation. 9. The uncoupling of AChR expression and the
intracellular concentration of chloride showed that they were not rigidly
linked. Chloride affects the expression of AChR indirectly, by altering the
activity of muscle cells
Herbison G.J., Teng C.,
Reyes T., and Reyes O. (1971) Effect of electrical stimulation on denervated
muscle of rat. Arch. Phys. Med. Rehabil. 52, 516-522.
Herbison G.J., Jaweed M.M.,
Ditunno J.F. (1979) Muscle Atrophy in Rats Following Denervation, Casting,
Inflammation and Tenotomy. Arch Phys Med & Rehabil 60, 401-404.
Herbison G.J., Jaweed M.M.,
and Ditunno J.F., Jr. (1983) Exercise therapies in peripheral neuropathies.
Arch. Phys. Med. Rehabil. 64, 201-205.
Abstract: The treatment of peripheral neuropathies should be aimed at
maintaining the range of motion of the joints, re-educating the patient in
skilled activities and optimizing the recovery of strength. Many techniques have
been described to substitute for, to strengthen and to improve the function of
residual innervated muscle; however, not all of these techniques are of
unquestioned value. Specifically, electrical stimulation does not appear to
enhance reinnervation of totally denervated muscle. Similarly, overstretching
weakened muscle may impair the use of paretic muscle. Because overwork may
damage partially denervated muscle, brief isometric or isotonic contractions may
be more beneficial for increasing strength than a program of habitual exhausting
activities
Herbison G.J., Jaweed M.M.,
Ditunno J.F. (1986) Electrical Stimulation of Sciatic Nerve in Rats After
Partial Denervation of Soleus Muscle. Arch Phys Med Rehabil 67, 79-83.
Hill M.A. and Bennett M.R.
(1986) Motoneurone survival activity in extracts of denervated muscle reduced by
prior stimulation of the muscle. Brain Res. 389, 305-308.
Abstract: Inactivation of skeletal muscle by denervation increases motoneurone
survival activity in extracts of skeletal muscle. The present investigation
shows that electrical stimulation of denervated muscle decreases motoneurone
survival activity in extracts of these muscles. The result suggests that
motoneurone survival is dependent on a factor(s) in muscle whose synthesis
and/or release is regulated by muscle contraction
Huizar P., Kuno M., Kudo N.,
Miyata Y. (1977) Reaction of Intact Spinal Motoneurones to Partial Denervation
of Muscle. J Physiol 265, 175-191.
Jeffe M. Savage N., Issacs
H. (1981) Biochemical Functioning of Mitochondria in Normal and Denervated
Mammalian Skeletal Muscle. Muscle & Nerve 4, 514-519.
Jones R., Vrbova G. (1970)
Effect of muscle activity on denervation hypersensitivity. J Physiol.
210:144-145.
Jones R., Vrbova G. (1974)
Two factors responsible for the development of denervation hypersensitivity. J
Physiol 236, 517-538.
Jozsa L., Kannus P., Thoring
J., Reffy A., Jarvinen M., Kvist M. (1990) The effect of tenotomy and
immobilization on intramuscular connective tissue: a morphometric and
microscopic study in rat calf muscles. J Bone and Joint Surg 72B:293-297.
Kallo J.R. and Steinhardt
R.A. (1983) The regulation of extrajunctional acetylcholine receptors in the
denervated rat diaphragm muscle in culture. J. Physiol 344, 433-452.
Abstract: The regulation of the number of extrajunctional acetylcholine (ACh)
receptors was assayed by 125I-labelled alpha-bungarotoxin binding sites in
denervated rat diaphragm muscle in culture. Sustained K depolarization does not
eliminate extrajunctional ACh receptors. In fact, muscle cultured in high-K
medium (normal Cl) for 3 days exhibits a greater binding capacity than controls.
Under conditions in which the intracellular Cl concentration is unaltered
(high-K-low-Cl medium) this effect of high-K medium on the number of extra-junctional
ACh receptors is blocked. The number of extrajunctional receptors increases
24-48 h after exposure to high-K-normal Cl medium, similar to the time course of
the initial appearance of extrajunctional receptors in the denervated diaphragm
muscle in vivo or in organ culture in normal media. High-K-normal Cl medium did
not alter the rate of receptor degradation. Electrical stimulation of denervated
muscle strips cultured in low-Ca medium containing D-600 eliminated
extrajunctional receptors as efficiently as stimulation of muscles in control
medium. Electrical stimulation did not reduce the extrajunctional ACh receptor
population in glycerol-treated uncoupled muscles to the same extent as in
untreated muscles. The extrajunctional ACh receptor content of denervated muscle
cultured for 3 days in 2 and 5 mM-caffeine was reduced by about half
respectively. Denervated muscle cultured in 0.3 mM-caffeine did not differ from
control denervated muscle. Other agents which may alter intracellular cyclic
nucleotide levels: dibutyryl cyclic GMP, dibutyryl cyclic AMP, papaverine, and
sodium nitroprusside, did not mimic the effect of caffeine or electrical
stimulation in lowering the levels of extrajunctional ACh receptors. We conclude
that intracellular Ca release from the sarcoplasmic reticulum is necessary for
the elimination of extrajunctional ACh receptors in denervated muscle. The
levels of intracellular Cl also influence the population of extrajunctional
receptors. Conditions which lead to higher levels of intracellular Cl result in
greater rates of synthesis of ACh receptors
Karpati G., Engel W.K.
(1968) Correlative histochemical study of skeletal muscle after suprasegmental
denervation, peripheral nerve section and skeletal fixation. Neurology 18,
681-692.
Kern H., Hofer C.,
Strohhofer M., Mayr W., Richter W., and Stohr H. (1999) Standing up with
denervated muscles in humans using functional electrical stimulation. Artif.
Organs 23, 447-452.
Abstract: The use of electrical stimulation for denervated muscles is still
considered to be a controversial issue by many rehabilitation facilities and
medical professionals because prior clinical experience has shown that treating
denervated muscle tissue using exponential current over a long time period
constitutes an impossible task. Despite this fact, we managed to evoke tetanic
contractions in denervated muscle using a long duration stimulation with
anatomically shaped electrodes and sufficiently high amplitudes. The pulse
amplitudes, which were being used for this purpose, exceeded by far the MED-GV
and EC regulations (300 mJ/impulse). For this reason, an application has
recently been submitted to have the EC regulations changed accordingly. It takes
a tetanic contraction to achieve the desired muscle fiber tension, constituting
a hypertrophic stimulus. It is also an appropriate means of exercise, which is
capable of creating the metabolic and structural conditions needed (e.g,
increased mitochondrial volume and capillary density) to obtain satisfactory
muscle performance. With patients suffering from a complete spinal cord injury
at level D12/L1, having motor and sensory loss in both lower extremities, we
were able to train denervated muscle using long- duration stimulation, evoking
single muscle contractions at first, soon followed by tetanic contractions
against gravity. To increase the efficacy of this functional electrical
stimulation (FES) strengthening program, we used ankle weights. With daily FES
training over a period of 1-2 years, denervated muscle was exercised until it
produced torques between 16 and 38 Nm in the m. quadriceps. With that muscle
force, it is possible to stand up from a sitting position in parallel bars. Our
results show that denervated muscle in humans is indeed trainable and can
perform functional activities with FES. Furthermore, this method of stimulation
can assist in decubitus prevention and significantly improve the mobility of
paraplegics
Kraus W.E., Torgan C.E.,
Taylor D.A. (1994) Skeletal Muscle Adaptation to Chronic Low-Frequency Motor
Nerve Stimulation. Ex & Sport Sci Rev 22, 313-360.
Lieber R.L. (1992) Skeletal
Muscle Structure and Function. Baltimore, Williams & Wilkins.
Lieber RL (2002) Skeletal
Muscle Structure, Function & Plasticity. Philadelphia, Lippincott Williams &
Wilkins, pp 173-287.
Lomo T., Westgaard R.H.,
Engelbretsen L. (1980) Different stimulation patterns affect contractile
properties of denervated rat soleus muscles. In D. Pette [Ed], The Plasticity of
Muscle, New York, Walter de Gruyter, pp 297-309.
Lundborg G. (1988) Nerve
injury and repair. New York, Churchill Livingstone, 1988.
Melichna J., Gutmann E.
(1974) Stimulation and Immobilization Effects on Contractile and Histochemical
Properties of Denervated Muscle. Pflugers Arch 352, 165-178.
Mihelin M., Trontelj J.V.,
and Stalberg E. (1991) Muscle fiber recovery functions studied with double pulse
stimulation. Muscle Nerve 14, 739-747.
Abstract: Direct electrical stimulation with paired pulses at varied intervals
was used to study the propagation velocity and action potential amplitude
recovery functions (VRF and ARF) of single muscle fibers. Following a subnormal
period with slowed conduction, most of the muscle fibers tested in healthy
subjects showed a period of supernormal propagation velocity starting at 3 to 12
ms, with a peak between about 5 and 15 ms, a mean increase of 7%, and an
approximately logarithmic decay toward 1 second. The onset of supernormality was
earlier in muscle fibers from patients with muscular dystrophy and significantly
delayed in those from denervated muscles. Denervated muscle fibers also had a
significantly longer refractory period
Mokrusch T., Engelhardt A.,
Eichhorn K.F., Prischenk G., Prischenk H., Sack G., and Neundorfer B. (1990)
Effects of long-impulse electrical stimulation on atrophy and fibre type
composition of chronically denervated fast rabbit muscle. J. Neurol. 237, 29-34.
Abstract: The efficacy of electrical stimulation on a chronically denervated
muscle depends on stimulus parameters, which have an important influence on the
development of atrophy. Stimulus frequency and/or total activity are
particularly responsible for the development of some histological, biochemical
and contractile features. The present study in 18 rabbits deals with a recently
developed electrical stimulus, which had proved effective in maintaining muscle
force following denervation. This current has (1) unusual long bidirectional
rectangular impulses (20 ms) and (2) a frequency of 25 Hz, which is between the
frequencies of
Moruzzi E.V., Bergamini E.
(1983) Effect of Denervation on Glycogen Metabolism in Fast and Slow Muscle of
Rat. Muscle & Nerve 6, 356-366.
Nemeth P.M. (1982)
Electrical stimulation of denervated muscle prevents decreases in oxidative
enzymes. Muscle Nerve 5, 134-139.
Abstract: The influence of muscular contraction on the oxidative enzymes and the
diameters of muscle fibers was investigated. Soleus muscles of guinea pigs were
denervated for four weeks. The denervated fibers showed a reduction in the
intensity of staining for beta-hydroxybutyrate dehydrogenase, cytochrome oxidase,
succinate dehydrogenase, and NADH- dependent tetrazolium reductase. Denervation
also resulted in a decrease in fiber diameter. Denervated soleus muscles were
electrically stimulated to contract over a four-week period at a frequency
normally received by slow contracting muscles. Electrical stimulation caused the
stain intensity of histochemical reactions for oxidative enzymes to appear to be
normal or greater than normal in 90% of the denervated fibers. Stimulation also
caused 69% of the denervated fibers to be of normal or greater than normal size.
The results demonstrate that contraction of denervated muscle by electrical
stimulation prevents the loss of oxidative enzymes and the atrophy associated
with denervation
Nemoto K., Williams H.B.,
Nemoto K., Lough J., and Chiu R.C. (1988) The effects of electrical stimulation
on denervated muscle using implantable electrodes. J. Reconstr. Microsurg. 4,
251-5, 257.
Abstract: This experimental study investigated the effects of continuous
electrical stimulation on denervated muscle. The canine peroneal nerve was
severed and repaired microsurgically, and the denervated extensor muscle group
of the leg was stimulated continuously with an implantable electrode and pulse
generator. EMG study, muscle force measurement, muscle weight measurement,
histology, and histochemistry were performed to study the effect at eight weeks
after the operation. Continuous electrical stimulation (pulse frequency 130 pps,
burst rate approximately 1 train/min) was effective in decreasing muscle atrophy
and in improving muscle force. These findings may have broader clinical
applications
Nix W.A. (1985) Effect of
Electrical Stimulation on Denervated Muscle. In: Nix W.A., Vrbova G., Electrical
Stimulation and Neuromuscular Disorders. New York, Springer-Verlag, 114-131.
Nix W.A., Reichmann H., and
Schroder M.J. (1985) Influence of direct low frequency stimulation on
contractile properties of denervated fast-twitch rabbit muscle. Pflugers Arch.
405, 141-147.
Abstract: A continuous electrical 8 Hz impulse pattern imposed directly via
implanted electrodes on denervated fast twitch muscle induced changes in its
contractile characteristics. Compared with non-stimulated denervated muscle,
stimulated muscle showed slowing of contraction time and improved fatigue
resistance. The reaction for succinic dehydrogenase was more intense in the
denervated stimulated muscle, indicating an increased capacity of oxidative
enzymes. The rate of atrophy was not influenced by stimulation. The 8 Hz
frequency pattern is the mediator for these changes in the characteristics of
denervated muscles. It demonstrates a comparable effect on innervated muscle.
The contralateral normal innervated muscle was also influenced by the electrical
stimulation. Contraction time as well as twitch tension were increased. This
finding is important when using the normal muscle as intraindividual control
Nix W.A., Vrbova G. (1986)
Electrical Stimulation and Neuromuscular Disorders. Berlin, Springer-Verlag.
Nix W.A. and Dahm M. (1987)
The effect of isometric short-term electrical stimulation on denervated muscle.
Muscle Nerve 10, 136-143.
Abstract: Electrical stimulation was applied daily for 20 minutes to denervated
rabbit extensor digitorum longus muscle. One group was stimulated with short
tetani, another with 1-Hz frequency, using isometric contractions for both.
Tetanic stimulation induced severe fibrosis and is harmful to denervated muscle.
One Hertz stimulation retarded denervation-induced fatigue and atrophy, as well
as slowing of contraction time
Nix W.A. (1989) [The
plasticity of motor units in change of the activity pattern by electric
stimulation--electrostimulation and its possible clinical applications].
Fortschr. Neurol. Psychiatr. 57, 94-106.
Abstract: Motoneuron and muscle fibers interact on the motor unit level, whereby
discharge characteristics from the neuron imposed on the muscle seem to play a
major role. Within the unit all muscle fibers are biochemically homogeneous and
display a high degree of plasticity under different functional demands. To
distinguish the existing different units rationals are listed that classify the
units by physiological and histochemical parameters. Furthermore the review
summarizes the available knowledge on the importance of activity patterns--as a
biological principle--involved in the control of phenotypic expression of
innervated and denervated muscle. The sequelae are shown of electrical
stimulation on innervated and denervated animal muscles. In extent to these
findings the consequences are discussed for stimulation procedures that can be
imposed on normal and diseased human muscles as a therapeutic tool
Osborne S.L. (1951) The
Retardation of Atrophy in Man by Electrical Stimulation of Muscles. Arch Phys
Med Rehabil 32, 523.
Pachter B.R., Eberstein A.,
Goodgold J. (1982) Electrical Stimulation Effect on Denervated Skeletal
Myofibers in Rats. Arch Phys Med Rehabil 63, 427-430.
Pette D. (1990) The Dynamic
State of Muscle Fibers. Berlin, Walater de Gruyter.
Poo M.M. (1982) Rapid
lateral diffusionof functional Ach receptors in embryonic muscle cell membrane.
Nature 295:333-334.
Reichmann H. and Nix W.A.
(1985) Changes of energy metabolism, myosin light chain composition, lactate
dehydrogenase isozyme pattern and fibre type distribution of denervated
fast-twitch muscle from rabbit after low frequency stimulation. Pflugers Arch.
405, 244-249.
Abstract: The influence of low frequency (8-10 Hz) electrical stimulation on
denervated fast-twitch muscle from rabbit was investigated. Prolonged direct
stimulation of denervated muscle resulted in higher oxidative enzyme activities.
Furthermore, single fibre analyses for succinate dehydrogenase showed a more
uniform distribution of activity in stimulated-denervated muscle when compared
to normal muscle. As was also the case following stimulation of innervated
muscle, glycolytic enzymes were decreased in activity and the LDH-isozyme
pattern was also shifted towards heart type. No change of the myosin light chain
pattern could be observed after 56 days of stimulation
Rothstein J. and Berlinger
N.T. (1986) Electronic reanimation of facial paralysis--a feasibility study.
Otolaryngol. Head Neck Surg. 94, 82-85.
Abstract: We set out to adapt the concept of functional electrical stimulation
to the reanimation of the paralyzed face. In the New Zealand white rabbit model
we studied the strength-duration curves of both innervated and denervated facial
muscles. We next studied the electromyographic signals corresponding to
different strengths of contraction of innervated facial muscles. With
Teflon-coated stainless steel electrodes implanted at opposite ends of the
denervated muscle groups under study, bipolar stimulation yielded useful mimetic
function that was modifiable by varying the voltage output and the rate of pulse
generation. We demonstrated that an electronic circuit can indeed respond to the
voltage generated within a functioning facial muscle, and then reproducibly
trigger a corresponding graphic signal in synchrony with the mimetic function.
The next step will be to adapt an electronic circuit that will deliver a
predetermined electrical current to a denervated facial muscle in response to a
determined generated voltage in the contralateral corresponding innervated
facial muscle
Salerno G.M., Bleicher J.N.,
and McBride D.M. (1991) Restoration of paralyzed orbicularis oculi muscle
function by controlled electrical current. J. Invest Surg. 4, 445-456.
Abstract: A canine model of facial nerve paralysis was studied to apply
controlled electrical current to the peripherally denervated orbicularis oculi
muscle, in the attempt to effectively restore the absent function of this
denervated muscle. After unilateral facial nerve neurotmesis was performed in
eight dogs, the denervated orbicularis oculi muscles of four dogs were
electrically stimulated for 75 postoperative days (40 min/day). Denervated and
normal orbicularis oculi muscles were electrophysiologically studied and
compared with the Student t test. During the study period, minimum closure of
denervated treated orbicularis oculi muscles was evoked with average stimulus
strength (80-ms duration) of 1.61 +/- 0.22 log mA x ms, not significantly
different from that of denervated nontreated or normal orbicularis oculi
muscles. From days 10 through 30 only, maximum closure of denervated treated
orbicularis oculi muscles was achieved with mean pulse strength (80-ms duration)
of 2.37 +/- 0.09 log mA x ms, significantly lower (P less than .01) than that
evoking the same type of contraction from denervated nontreated muscles (80-ms
duration, mean 2.83 +/- 0.10 log mA x ms). In addition, denervated treated
muscle pulse strength eliciting maximum contraction was not significantly
different from that of normal orbicularis oculi muscles during the same period.
This finding was not observed, however, from day 40 through the end of the
study. This investigation demonstrates (1) the transient reversal of denervation
changes of paralyzed orbicularis oculi muscle by daily electrical stimulation,
and (2) the feasibility of restoring orbicularis oculi muscle function by
controlled electrical current
Schimrigk K., McLaughlin J.,
Gruninger W. (1977) The Effect of Electrical Stimulation on the Experimentally
Denervated Rat Muscle. Scand J Rehabil Med 9, 55-60.
Sebille A., Fontanges P.,
Legagneux J., Mira J.C., and Pecot-Dechavassine M. (1988) Portable stimulator
for direct electrical stimulation of denervated muscles in laboratory animals.
J. Biomed. Eng 10, 371-372.
Abstract: A portable lightweight stimulator for small animals is described. It
delivers pulse trains of high intensity and is convenient for denervated muscle
studies. It does not cause discomfort and does not restrict activity
Shaffer D.V., Branes G.K.,
Watkin K.G., et al. (1954) The Influence of Electrical Stimulation on the Course
of Denervation Atrophy. Arch Phys Med Rehabil 35, 491-499.
Stanco A.M. and Werle M.J.
(1998) Agrin and acetylcholine receptor distribution following electrical
stimulation. Muscle Nerve 21, 407-409.
Abstract: Electrical stimulation is a therapeutic modality available for the
preservation of muscle function following peripheral nerve injury. Agrin, a
synaptic basal lamina protein, induces accumulation of acetylcholine receptors (AChRs)
and other molecules at the neuromuscular junction. Electrical stimulation of
denervated muscle does not alter agrin and AChR distribution at abandoned
synaptic sites, supporting the hypothesis that the existing aggregation of
synaptic molecules, which may be necessary for successful reinnervation, is
unaltered by electrical stimulation of denervated muscle
Stolov W.C., Weilepp T.G.
(1966) Passive Length-Tension Relationship of Intact Muscle, Epimysium and
Tendon in Normal and Denervated Gastrocnemius of the Rat. Arch Phys Med &
Rehabil 47, 612-620.
Stolov W.C., Weilepp T.G.,
Riddell W.M. (1970) Passive Length-Tension Relationship and Hydroxyproline
Content of Chronically Denervated Skeletal Muscle. Arch Phys Med & Rehabil 51,
517-525.
Stolov W.C., Fry L.R.,
Riddell W.M., et al. (1973) Adhesive forces between muscle fibers and connective
tissue in normal and denervated rat skeletal muscle. Arch Phys Med & Rehabil 54,
208-213.
Thomson J.D. (1955)
Mechanical Characteristics of Skeletal Muscle Undergoing Atrophy of Denervation.
Arch Phys Med & Rehabil 34, 606-611.
Thomson J.D. (1957) Effect
of Electrotherapy on Some Mechanical Properties of Denervated Muscle. Am J Phys
Med 36, 16-20.
Trontelj J. and Stalberg E.
(1983) Responses to electrical stimulation of denervated human muscle fibres
recorded with single fibre EMG. J. Neurol. Neurosurg. Psychiatry 46, 305-309.
Abstract: Denervated muscle fibres were stimulated electrically with needle
electrodes introduced close to a recording single fibre electrode. The
denervated muscle fibre could be driven with rates up to 100 Hz. The jitter was
large at threshold but low at suprathreshold stimulus strength. There was
evidence of discrete low threshold sites along the denervated muscle fibre, seen
as stepwise latency change on smoothly changing stimulus strength, hepatic
activation from other fibres and also as extra-discharges originating from such
sites
Venkatarami R.K., Dhananjaya
R.Y., Govindappa S., and Reddanna P. (1983) Induced muscular work overload and
disuse on the serum carbohydrate metabolism of dog, Canis domesticus. Arch. Int.
Physiol Biochim. 91, 411-416.
Abstract: Serum carbohydrate metabolism was analysed in control, control
stimulated, denervation atrophied and denervation stimulated dogs, Canis
domesticus. The muscular training has resulted in the hypoglycemia through the
mobilization of glucose into both hexose mono- and diphosphate pathways. The
denervation atrophy, on the contrary, resulted in hyperglycemia because of
exactly opposite changes in the carbohydrate metabolism in the serum and also
possibly due to the lack of uptake by the muscle. The training programme of
electrical stimulation applied to this denervated muscle has wiped off the
hyperglycemia. The importance of muscular work in modulating the serum
carbohydrate metabolism was indicated
Vodovnik L., Valencic V.,
Strojnik P., Klun B., Stefancic M., and Jelnikar T. (1982) Improvement of some
abnormal motor functions by electrical stimulation. Med. Prog. Technol. 9,
141-147.
Abstract: Clinical results obtained from electrical stimulation of muscle,
nerve, spinal cord, cerebellum, and cerebrum are surveyed. Some more data are
presented from our own experience with stimulating denervated muscle and
cerebellum. Mechanisms which might be responsible for its clinical effects on
the muscle, synapse, or nervous system are discussed
Vrbova G., Gordon T., Jones
R. (1978) Nerve-Muscle Interaction. London, Chapman and Hall.
Westgaard R.H. (1975)
Influence of activity on the passive electrical properties of denervated soleus
muscle fibres in the rat. J. Physiol 251, 683-697.
Abstract: The technique of direct electrical stimulation of denervated muscle
was used to study the role of muscle activity per se in controlling the passive
electrical properties of muscle fibres. 2. Specific membrane resistance and
capacitance of the denervated and the denervated- stimulated muscle fibres were
measured by a sinewave technique at frequencies between 5 and 240 Hz. The
parameter values were constant at low frequencies up to a variable transition
frequency and declined rapidly at higher frequencies. 3. Following denervation
the low- frequency value of specific membrane resistance increased (2291 omega
cm2 for 19-day denervated fibres vs. 766 omega cm2 for innervated fibres), the
specific membrane capacitance declined (2-7 muF/cm2 vs. 3- 6 muF/cm2) and the
transition frequency shifted towards lower frequencies. The specific internal
resistance was higher in denervated fibres (301 omega cm for 19-day denervated
fibres vs. 240 omega cm in innervated fibres) apart from a transient decline
after 5 days of denervation (164 omega cm). 4. Direct electrical stimulation for
2 weeks beginning on the 5th day after denervation restored all parameters
listed above to their original values before denervation. 5. Stimulation
arrested in most cases further atrophy from the time of stimulation but did not
restore normal fibre size
Williams H.B. (1996) The
value of continuous electrical muscle stimulation using a completely implantable
system in the preservation of muscle function following motor nerve injury and
repair: an experimental study. Microsurgery 17, 589-596.
Abstract: Functional recovery following motor nerve injury and repair is
directly related to the degree of muscle atrophy that takes place during the
period of nerve regeneration. The extent of this muscle atrophy is related to a
number of factors including the accuracy of nerve repair; the distance through
which the nerve must regenerate; the age of the patient; and the type of nerve
injury and other associated tendon and soft tissue and bony damage. Atrophy of
muscle that is always associated with nerve injury is a combination of disuse
and degeneration. Our hypothesis proposed the following question: "Would
continuous electrical stimulation of the denervated muscle during the period of
nerve regeneration maintain the integrity of the muscle fibers and hence their
potential functional capacity?" We have completed a series of animal studies
(rabbit and canine models) in our laboratory using a completely implantable
system to provide continuous muscle stimulation following nerve injury and
microsurgical repair. In several different experiments, the nerves under study
were cut and repaired at 4 and 12 cm from the muscles to study the effects of
short- and long-term recovery. In all experiments, a beneficial effect was
demonstrated with improved morphology and functional capacity of the
reinnervated stimulated muscles when compared with nonstimulated controls. In
addition, electrical stimulation using this implantable system could be applied
for extended periods without evidence of discomfort in the experimental animals
Willison R.G. (1978)
Preservation of Bulk and Strength in Muscles Affected by Neurogenic Lesions.
Muscle & Nerve 1, 404-406.
Woodcock A.H., Taylor P.N.,
and Ewins D.J. (1999) Long pulse biphasic electrical stimulation of denervated
muscle. Artif. Organs 23, 457-459.
Abstract: In recent years a number of studies have employed long pulse biphasic
stimulation as a treatment for denervated muscle to improve tissue quality and
in some cases to improve contractile capability sufficient to restore function.
However, in the U.K., this treatment is yet to be widely adopted clinically. A 5
subject, case based pilot study of long pulse biphasic direct stimulation of
peripheral limb denervated muscle is being conducted and its effect on the
tissue evaluated by measurement of muscle bulk, limb blood flow, and skin
temperature. In cases of partial denervation. trapezoidal shaped pulses are used
to minimize sensory and motor nerve fiber recruitment
Zealear D.L., Rainey C.L.,
Jerles M.L., Tanabe T., and Herzon G.D. (1994) Technical approach for
reanimation of the chronically denervated larynx by means of functional
electrical stimulation. Ann. Otol. Rhinol. Laryngol. 103, 705-712.
Abstract: Functional electrical stimulation (FES) of the posterior
cricoarytenoid (PCA) muscle to produce vocal fold abduction offers an
alternative approach to current surgical therapies for bilateral vocal fold
paralysis. The purpose of this study was to characterize the application of FES
to chronically denervated PCA muscles. Specific goals were to develop a stimulus
delivery system for the PCA muscle, determine a practical means of implantation,
and identify stimulus parameters effective in activating chronically denervated
muscle. Seventeen dogs were implanted with planar electrode arrays 3 months
after unilateral recurrent laryngeal nerve resection. A nail-bed electrode array
allowed discrete activation of the PCA muscle and gave the greatest abductions,
with minimal charge dissipation. Muscle mapping revealed hot-spot regions on the
PCA muscle surface, in which stimulation produced maximum abduction. A
conservative stimulus paradigm effective in activating chronically denervated
muscle was a 1- second pulse train of 2-millisecond-duration pulses, delivered
at a tetanizing frequency of 30 Hz and an amplitude of 4 to 14 mA
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