A computer model of denervation-reinnervation in skeletal muscle.

A computer model of the process of denervation and complete reinnervation of skeletal muscle has been developed for the purpose of exploring underlying mechanisms and for use in the development of new clinical and research tools for evaluating neuromuscular disease. Progressive motor neuron death and reinnervation in this model reproduces the fiber-type grouping, increased fiber density, and minimal increase of motor unit size seen in human chronic denervating diseases. Studies using the model suggest that (1) preferential involvement of motor units of one type could account for the abnormal fiber-type proportions observed in some diseases, (2) reinnervation by axons innervating adjacent fibers is compatible with single fiber multielectrode study results in that it does not produce a large increase in motor unit area, and (3) such reinnervation is sufficient to account for the increases in motor unit density that have been observed. The model has also been used in the development and testing of the Codispersion Index, a measure of the codistribution of two fiber types, which is useful in detecting fiber-type grouping.

The co-dispersion index for the measurement of fiber type distribution patterns.

There is a need for a practical and statistically manageable quantitative index of fiber type co-dispersion in skeletal muscle to allow investigation of the distribution of motor units in normal muscle and their rearrangement in pathological states. A new measure for this purpose, the Co-Dispersion Index (CDI), is introduced. This measure is based on contingency table analysis of nearest-neighbor relationships between muscle fibers. The CDI has a continuous range of values from -1 to +1, in which larger negative values indicate a greater tendency toward regular intermixing of fibers of different types, and larger positive values a greater segregation of fiber types. CDI evaluation overcomes the limitations of previously published quantitative methods for co-dispersion measurement and is well correlated with subjective human estimates of fiber type grouping.

Ultrastructural and capillary adaptation of gastrocnemius muscle to occlusive peripheral vascular disease.

The effect of chronic occlusive peripheral vascular disease (PVD) on the histochemistry and capillarity of the gastrocnemius muscle was studied in 129 biopsies taken from 93 subjects. Sixty-three patients underwent biopsy during surgical procedures, and data related to walking distance and ankle systolic pressure. Thirty biopsies taken from normal subjects post mortem served as a control group, and data were analyzed for fiber type distribution, fiber area, fiber type grouping, and fiber capillarity. Fiber type distribution did not alter significantly between the patients with PVD and the control group, but the mean fiber area of the type 1 fiber in male patients with intermittent claudication (IC) was reduced when compared to that in age-matched controls (4608 +/- 1181 mu 2, IC +/- 1 SD; 5795 +/- 1771 mu 2, controls +/- 1 SD) (P less than 0.05). When bilateral biopsies were taken from the gastrocnemii of patients with unilateral occlusions, the type 2 fibers in the diseased leg were significantly smaller than fibers of the control group (2821 +/- 953 mu 2, IC +/- 1 SD; 4318 +/- 1504 mu 2, controls +/- 1 SD) (P less than 0.02). Fiber type grouping, evidence of denervation and reinnervation of muscle, appeared to be more common in patients with more severe limb ischemia. Overall capillary numbers did not appear to alter with degree of ischemia, but fiber shrinkage appeared to compensate for any loss of capillaries in the more ischemic muscle. These data suggest that the limb of the untrained patient with IC does not adapt to ischemia by adjusting its exercise capacity but merely shows evidence of disuse. These adaptations suggest that there may be much to be gained by nonsurgical methods of treating IC.

Discrimination and consistency of five myosin ATPase stains in human normal and Duchenne dystrophic muscle.

Limitations in the ability of the human visual system to assess accurately the relative staining densities of individual fibers in muscle tissue stained for myosin. ATPase can complicate the objective evaluation of fiber type populations. In this study a novel approach is employed which utilizes human visual capabilities to provide accurate fiber classification. Using this approach, the ability of five ATPase staining techniques to discriminate fiber type categories in single samples of human normal and Duchenne dystrophic skeletal muscle is evaluated, as is the consistency of the fiber type classifications between stains. While no major discrepancies in fiber typing were observed in the sample of normal muscle, significant differences in classification, along with a decrease in the ability to discriminate fiber types were noted in the sample of Duchenne muscular dystrophy. For the most part, these discrepancies were resolved by a re-interpretation of the staining characteristics of fibers in one stain.