Effects of chronic electrical stimulation on long-term denervated muscles of the rabbit hind limb

Abstract

We investigated the extent to which activity induced by chronic electrical stimulation could restore the mass and contractile function of rabbit tibialis anterior (TA) muscles that had undergone atrophy as a result of prolonged denervation. Denervation was carried out by selectively interrupting the motor nerve branches to the ankle dorsiflexors in one hind limb. Stimulators were implanted, with electrodes on the superficial and deep surfaces of the denervated TA muscle. Ten weeks later, the mass and mid-belly cross-sectional area (CSA) of TA muscles subjected to denervation alone had fallen to approximately 40% of normal. At this stage, stimulators in the other rabbits were activated for 1 h/day to deliver 20-ms rectangular bipolar constant-current pulses of 4 mA amplitude at 20 Hz with a duty cycle of 1s ON/2s OFF, a total of 24,000 impulses/day. The animals were examined after a further 2, 6 or 10 weeks. Stimulation restored the wet weight of the denervated muscles to values not significantly different to those of normal, innervated controls. It increased CSA from 39% to 66% of normal, and there was a commensurate increase in maximum isometric tetanic force from 27% to 50% of normal. Light and electron microscopic examination revealed a marked improvement in the size, packing, and internal organization of the stimulated-denervated muscle fibres, suggestive of an ongoing process of restoration. Excitability, contractile speed, power, and fatigue resistance had not, however, been restored to normal levels after 10 weeks of stimulation. Similar results were found for muscles that had been denervated for 39 weeks and then stimulated for 12 weeks. The study demonstrates worthwhile benefits of long-term electrical stimulation in the treatment of established denervation atrophy.

VEGF Improves Skeletal Muscle Regeneration After Acute Trauma and Reconstruction of the Limb in a Rabbit Model

“…Another study showed that intramuscular administration of a plasmid engineered to induce VEGF expression enhanced preserved grip strength in a rat model of amyotrophic lateral sclerosis which suggests that VEGF administration might be neuroprotective and a practical approach for treating motor disorders [16]. Although data on muscle force restoration after musculoskeletal injury for this type of model were not available at the time we conducted our study, recently published studies [2,4] confirm the restoration of muscle force we observed.…”

“…We assumed a 25% difference would be clinically important. The expected effect size greater than 20% for calculation was estimated from data on the use of longterm electrical stimulation to improve muscle force and muscle atrophy [2]. The calculation revealed that 11 animals would be required per group.…”

“…The calculation revealed that 11 animals would be required per group. Although muscle force restoration data of this type of model were not available at the time, one study showed a difference of 23% to be beneficial in the treatment of denervation atrophy [2].…”

Excitation-contraction coupling and mechano-sensitivity in denervated skeletal muscles

“…Altogether, these findings support the hypothesis that electrical stimulation-induced changes in intracellular [Ca 2+ ] may mimic the lost nerve influence and may play a key role in modifying denervated muscle gene expression. Hence, these observations provide a potential molecular explanation of the muscle recovery that occurs in response to the rehabilitation strategy of FES in mammals and humans [3,5,38], which was developed as a result of empirical clinical observations [37,38]. In SCI patients after months of twitch training [37], and thus of intracellular [Ca 2+ ] transients, the restored muscle morphology and tetanic contractility agree with improvements of the synthesis/degradation balance of sarcolemmal, ECC, cytoskeleton and myofibrillar proteins.…”

Experimental studies on post-transectional facial nerve regrowth and functional recovery of paralyzed muscles of the face in rats and mice

“…[167][168][169][170][171] However, evidence has yet to be presented as to whether, and to what degree, preservation of a larger muscle mass and better functional properties of denervated muscles would promote functional recovery after reinnervation.…”