Stanley Salmons

Recovery of long-term denervated human muscles induced by electrical stimulation.

We investigated the restorative potential of intensive electrical stimulation in a patient with long‐standing quadriceps denervation. Stimulation started 18 months after injury. After 26 months, the thighs were visibly less wasted. Muscle cross‐sectional areas, measured by computerized tomography, increased from 36.0 cm2 to 57.9 cm2 (right) and from 36.1 cm2 to 52.4 cm2 (left). Knee torque had become sufficient to maintain standing without upper extremity support. Biopsies revealed evidence of both growth and regeneration of myofibers. The results suggest that electrical stimulation may offer a route to the future development of mobility aids in patients with lower motor neuron lesions. Muscle Nerve, 2004

Cardiac assistance from skeletal muscle : a critical appraisal of the various approaches

We review here various ways in which cardiac assistance might be derived from a patients own skeletal muscle. Calculations based on experimental data and optimistic estimates of the efficiency of the energy conversions involved suggest that the continuous assist available would be limited to about 2 litres a minute if a muscle were used to energise an electromechanical device. It would be more efficient to couple the energy mechanically or hydraulically, but these approaches still pose problems of anatomical placement, muscle attachment, fluid leakage, and cost. Unless these issues can be addressed, the use of skeletal muscle as an internal power source for mechanical circulatory assist devices will remain an unworkable concept. Configurations that couple skeletal muscle contraction directly to the circulation would be more efficient and less costly. In terms of the energy available, a skeletal muscle ventricle could be designed to provide a continuous partial assist of 1–21/min, with flows of up to 8 1/min sustainable for limited periods. Such an approach offers new possibilities for the surgical treatment of chronic cardiac failure.

Restoration of fast muscle characteristics following cessation of chronic stimulation

SummaryWhen fast-twitch skeletal muscles of the adult rabbit are subjected to continuous low-frequency activity by electrical stimulation of the corresponding motor nerves, the fibers undergo an ultrastructural transformation, so that after 6 weeks they have acquired an appearance typical of slow-twitch fibers. In the present study, stimulation was discontinued at this stage in order to follow the reverse transformation, in which the fibers recovered their original morphological characteristics under conditions of normal endogenous activity. Stereological techniques were used to assess the time course of this process over a period of 20 weeks in terms of fiber cross-sectional area, extent of T-system, thickness of the Z-band, and volume fraction of mitochondria in the fiber core. Fibers of transformed muscles were smaller than those of control muscles, but the differences were no longer evident after 9 weeks of recovery. After 2 weeks the T-system was still of limited extent, as is characteristic of slow-twitch fibers; it increased toward the amount typical of fast-twitch fibers between 2 and 4 weeks, and had reached its full extent by 12 weeks. The wide Z-bands characteristic of slow-twitch fibers were retained for 4 weeks, but the thickness had begun to decrease by 8 weeks and recovery was complete by 12 weeks. The mitochondrial volume did not increase during recovery, in contrast to the large increases which had been observed to take place between 2 and 6 weeks during the fast-to-slow transformation. Overall, the recovery of fast-twitch ultrastructural characteristics was complete, but followed a more extended time course, and involved less myofibrillar disruption at an intermediate stage, than the original fast-to-slow transformation.

Restoration of Fast Muscle Characteristics Following Cessation of Chronic Stimulation: Physiological, Histochemical and Metabolic Changes during Slow-To-Fast Transformation

Implantable electronic stimulators were used to subject fast-twitch tibialis anterior and extensor digitorum longus muscles of adult rabbits to a chronically increased level of use. Stimulation was discontinued after 6 weeks and physiological, histochemical and biochemical properties of the muscles were examined at intervals over the ensuing 20 weeks. Previous work had shown that 6 weeks of stimulation was sufficient to bring about a substantial transformation of type in fast-twitch muscles, which then exhibited much of the character of muscles of the slow-twitch type. The present experiments showed that these stimulation-induced changes were completely reversible. The time-course of reversion was such that the muscles had recovered their original fast properties by about 12 weeks after the cessation of stimulation. The contractile characteristics and post-tetanic potentiation typical of fast muscle returned rapidly, in only 3-4 weeks, and over the same period the proportion of histochemical type 1 fibres declined from about 70% to control levels. Changes in fatigue-resistance, capillary density and enzyme activity followed a more prolonged time-course; in particular, the decline in the activity of enzymes of oxidative metabolism corresponded closely to that already established for the mitochondrial volume fraction. Reacquisition of fast properties was not accompanied by any changes in specific force-generating capacity. Observations from these experiments and from a related morphological study fit into a ‘first-in, last-out’ pattern for the response to stimulation and recovery. The slow-to-fast reversion that takes place during the recovery period provides a further opportunity for testing causal associations within the events underlying type transformation. It has important consequences for therapeutic applications that make use of the fatigue-resistant character of chronically stimulated muscle.

Fast-to-slow transformation in stimulated rat muscle.

Several previous studies have failed to demonstrate changes due to chronic stimulation in contractile speed of innervated fast rat muscles, and it has been suggested that the adaptive capacity of skeletal muscle in this species is limited. We have reassessed this contention. Fast muscles of the rat hind limb were stimulated continuously at 10 or 20 Hz for 55–61 days. The maximum shortening velocity of the extensor digitorum longus muscles was reduced to 50% of the control value. The proportion of type 1 fibers increased from 4% in control muscle to 34% in stimulated muscles and there was a corresponding reduction in type 2B/D fibers. The proportion of type 2A fibers after stimulation was similar to that in control muscles. These results, taken together with our published analyses of myosin isoform composition of these muscles, show that the mechanisms that control gene expression in response to activity are not exclusive to larger mammals.

The Nτ‐Methylhistidine content of myosin in stimulated and cross‐reinnervated skeletal muscles of the rabbit

It has been known that the characteristics of slowand fast-twitch muscles are not immutable and transformation from the slow to the fast type of muscle and vice versa can take place [l-7] . Recently we reported that fast muscle subjected to chronic lowfrequency stimulation acquired an electrophoretic pattern of light chains and a light meromyosin paracrystal staining pattern, identical to that of slow muscle [8,9] . We also reported a similar, but less complete, change in fast and slow muscles following crossreinnervation [ IO,1 1 ] . It was reported that N7-methylhistidine (NT-MeHis) is a normal component of the heavy chain of fasttwitch skeletal muscle myosin but it is absent from slow-twitch muscle myosin of adult rabbits [12-141. It was of considerable interest to examine the N7MeHis content of the myosin in stimulated and crossreinnervated experiments, since increases or decreases

The dose-related response of rabbit fast muscle to long-term low-frequency stimulation

Rabbit tibialis anterior muscles were stimulated continuously at 2.5 Hz, 5 Hz, or 10 Hz for 10 months. The resulting adaptive transformation was dose‐related for contractile speed, myosin isoform composition, and enzyme activities. The “fast‐oxidative” state produced by stimulation at 2.5 Hz was stable: even after 10 months, 84% of the fibers were of type 2A. Absence of a secondary decline in oxidative activity in these muscles provided strong evidence of a causal link between myosin transitions and metabolic adaptation. Significant fiber loss occurred only after prolonged stimulation at 10 Hz. The myosin isoform composition of individual muscles stimulated at 5 Hz resembled that of muscles stimulated at either the lower or the higher frequency, behavior consistent with a threshold for fiber type change. In clinical applications such as cardiomyoplasty, muscles could be used more effectively by engineering their properties to combine speed and power of contraction with the necessary resistance to fatigue.

Stimulation-induced expression of slow muscle myosin in a fast muscle of the rat Evidence of an unrestricted adaptive capacity

Fast muscles of the rat hind limb were stimulated continuously at 10 or 20 Hz for periods of 55–61 days by means of an implantable neuromuscular stimulator. Gel electrophoresis clearly demonstrated the presence in stimulated muscles of slow myosin light and heavy chains, although fast isoforms were still present in all cases. Thus, contrary to previous reports, induction of slow myosin isoforms does occur in this, as in other, mammalian species. The time course of the response to stimulation appears to be more extended than that seen in the rabbit.

Quantitative morphology of stimulation-induced damage in rabbit fast-twitch skeletal muscles

SummaryThe purpose of this study was to examine the contention that stimulation-induced damage, resulting in degeneration with subsequent regeneration, plays a major role in the transformation of fibre type brought about by chronic electrical stimulation. Data from histological and histochemical sections of 9-day-stimulated rabbit fast-twitch muscles were analysed with multivariate statistical techniques. Fibre degeneration and regeneration varied non-systematically between sample areas at any given cross-sectional level. In the extensor digitorum longus muscle, but not in the tibialis anterior, there was more degeneration in proximal than in distal portions of the muscle. The extensor digitorum longus muscle consistently showed more degeneration than the tibialis anterior muscle. Degeneration was less extensive for an intermittent pattern of stimulation that delivered half the aggregate number of impulses of continuous stimulation. Degeneration and regeneration varied markedly between individual rabbits in each of the groups. Sections that revealed the most degeneration and regeneration also had more fibres that reacted positively with an anti-neonatal antibody. Rigorous analysis of different sources of variation has helped to explain apparent conflicts in the literature. The incidence of muscle fibre damage in the stimulated tibialis anterior muscle is low, showing that the contribution of degenerative-regenerative phenomena to fibre type conversion in this muscle is insignificant.

The application and technology of implantable neuromuscular stimulators: an introduction and overview.

The design of an implantable neuromuscular stimulator represents a trade-off in which the desire to maximise functionality and operational life competes with the need for the implanted device to be small, reliable, safe, and easy to use. In this introduction and overview we consider the basic problems and the different approaches to their solution.