Implantable device for long-term electrical stimulation of denervated muscles in rabbits

Lanmüller, Hermann; Ashley, Zoe; Unger, Ewald; Sutherland, Hazel; Reichel, Martin; Russold, Michael Friedrich; Jarvis, Jonathan C.; Mayr, Winfried; Salmons, Stanley

doi:10.1007/bf02344737

Cited by 25 publications

(20 citation statements)

References 16 publications

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“…2 To achieve reliable direct muscle activation for periods up to 3 months, we used implanted programmable stimulators developed specifically for the project. 23 Stimulation was initiated 10 weeks after nerve section; by this time, muscle mass is about 40% of normal. 2 This experimental design reflects clinical reality: stimulation would not normally be initiated until some months post-injury, so the requirement is for a technique that will reverse established denervation atrophy.…”

Section: Methodsmentioning

confidence: 99%

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Therapeutic stimulation of denervated muscles: The influence of pattern

et al. 2008

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Muscular atrophy due to denervation can be substantially reversed by direct electrical stimulation. Some muscle properties are, however, resistant to change. Using a rabbit model of established denervation atrophy, we investigated whether the extent of restoration would vary with the stimulation protocol. Five patterns, delivering 24,000-480,000 impulses/day, were applied for 6 or 10 weeks. The wet weight, cross-sectional area, tetanic tension, shortening velocity, and power of denervated muscles subjected to stimulation all increased significantly. The fibers were larger and more closely packed and there was no evidence of necrosis. There was a small increase in excitability. Isometric twitch kinetics remained slow and fatigue resistance did not improve. The actual pattern of stimulation had no influence on any of these findings. The results, interpreted in the context of ultrastructural changes and an ongoing clinical study, reaffirm the clinical value of introducing stimulation during the initial non-degenerative phase. They indicate that there would be little therapeutic benefit in adopting regimes more energetically demanding than those in current use, and that the focus should now shift to protocols that represent the least intrusion into activities of daily living.

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Section: Methodsmentioning

confidence: 99%

“…This selective motor denervation left sensation to the limb intact and avoided problems of selfmutilation. The implantable stimulator 23 was then introduced into the peritoneal cavity and anchored with sutures to the abdominal wall. The two leads and electrodes were conducted subcutaneously from the abdomen to the denervated hindlimb.…”

Section: Methodsmentioning

confidence: 99%

Therapeutic stimulation of denervated muscles: The influence of pattern

et al. 2008

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“…Implantable electrical stimulators (29) were inserted into the peritoneal cavity and secured in place. The wires and electrodes were routed subcutaneously from the abdomen to the left hindlimb.…”

Section: Methodsmentioning

confidence: 99%

Atrophy, but not necrosis, in rabbit skeletal muscle denervated for periods up to one year

Ashley¹,

Sutherland²,

Lanmüller³

et al. 2007

American Journal of Physiology-Cell Physiology

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JC. Atrophy, but not necrosis, in rabbit skeletal muscle denervated for periods up to one year. Am J Physiol Cell Physiol 292: C440 -C451, 2007; doi:10.1152/ajpcell.00085.2006.-Our understanding of the effects of long-term denervation on skeletal muscle is heavily influenced by an extensive literature based on the rat. We have studied physiological and morphological changes in an alternative model, the rabbit. In adult rabbits, tibialis anterior muscles were denervated unilaterally by selective section of motor branches of the common peroneal nerve and examined after 10, 36, or 51 wk. Denervation reduced muscle mass and cross-sectional area by 50 -60% and tetanic force by 75%, with no apparent reduction in specific force (force per cross-sectional area of muscle fibers). The loss of mass was associated with atrophy of fast fibers and an increase in fibrous and adipose connective tissue; the diameter of slow fibers was preserved. Within fibers, electron microscopy revealed signs of ultrastructural disorganization of sarcomeres and tubular systems. This, rather than the observed transformation of fiber type from IIx to IIa, was probably responsible for the slow contractile speed of the muscles. The muscle groups denervated for 10, 36, or 51 wk showed no significant differences. At no stage was there any evidence of necrosis or regeneration, and the total number of fibers remained constant. These changes are in marked contrast to the necrotic degeneration and progressive decline in mass and force that have previously been found in long-term denervated rat muscles. The rabbit may be a better choice for a model of the effects of denervation in humans, at least up to 1 yr after lesion.force; shortening velocity; electron microscopy; histochemistry MUCH OF OUR KNOWLEDGE of the effects of long-term denervation of mammalian skeletal muscle comes from experimental studies of total sciatic section in the rat (7,32,54). The mass of the affected muscles falls rapidly within 5-7 days of axotomy (11,18,22,25,55,57,58) and declines further to 30 -50% of control weight in succeeding weeks (1,5,11,14,23,41,60). After several months, muscle weight stabilizes at ϳ5-20% of control (1,13,45).Within the muscles, individual fibers show a reduction of ϳ70% in cross-sectional area (CSA) over a period of months (5,14,21,37), and over 90% (1,21,45) in the longer term. Initially, fast (type II) fibers are more susceptible to atrophy than slow (type I) fibers (5,7,32,38,48,54,59), but over more prolonged periods the fiber types atrophy to a similar extent (6, 54). Corresponding to this reduction in fiber CSA, there is a striking and progressive increase in interstitial collagen and fat (32). At the ultrastructural level, atrophic muscle fibers show evidence of disorganization, including loss or misalignment of sarcomeres, dissociation of the T system and sarcoplasmic reticulum (SR), and changes in the sarcomeric location of mitochondria (32, 51, 52).The major physiological correlate of these morphological changes is a loss of force-generati...

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“…The influence of electrical stimulation on further myogenic differentiation has been analyzed in vitro www.intechopen.com (Donnelly et al, Stern-Straeter et al 2005) and in vivo (Fujita et al 2007). For clinical applications, devices for electrical stimulation have to be implantable and suitable for longterm stimulation (Jarvis & Salmons 2001, Lanmuller et al 2005. The in vivo experiments of Dennis and co-workers using implantable stimulation devices in the rat demonstrated that muscle mass as well as the maximum force of a denervated muscle can be maintained by electrical stimulation (Dennis et al 2003).…”

Section: Electrical Stimulation and Neurotizationmentioning

confidence: 99%