Mechanisms involved in the development of contraction-induced injury to single muscle fibres of rats.

Abstract

The initial mechanism responsible for contraction-induced injury was investigated in single permeabilized muscle fibres from fast extensor digitorum longus (EDL) and slow soleus muscles of rats. Three hypotheses were tested: (1) following single stretches of fibres from EDL muscles, the magnitude of the injury, assessed by the deficit in Ca$\sp{2+}$ activated maximum isometric force, is dependent on the magnitude of strain and average force developed; (2) fast muscle fibres are more susceptible to injury than slow muscle fibres; and (3) the regions of a fibre with the longest sarcomere lengths during a maximum isometric contraction are the same regions that contain damaged sarcomeres when the fibre is returned to initial length after a single stretch that results in a force deficit. At the beginning of each experiment, fibre length was set at optimum length for force development (L$\sb{\rm f}$). Single isovelocity stretches (0.5 L$\sb{\rm f}$/s) of varying strains were imposed on passive, submaximally activated, or maximally activated fibres. Following a stretch, evidence of damage was confirmed by electron micrographs. Following single stretches of maximally activated fibres, the force deficit was predicted equally well, R$\sp2$ = 0.80, by the strain, the work done, and the simultaneous, but independent effects of strain and average force. When the force deficit data for the three conditions of activation were analyzed together, the best predictor of the force deficit was the simultaneous effect of strain and average force, R$\sp2$ = 0.52. For a given strain, the force deficits produced in passive and maximally activated fast fibres were two-fold and five-fold greater respectively than the force deficits for slow fibres. Despite differences in the susceptibility to injury, the mechanism responsible for the injury and the type of damage sustained were similar for fast and slow fibres. Following single stretches of 5% strain or greater, maximally activated fibres were damaged severely, but damage was localized to the ultrastructure of small groups of sarcomeres. In contrast, for passive fibres the damage to individual sarcomeres was less severe, but the damage was distributed uniformly throughout the fibre. Analysis of diffraction patterns and light micrographs of soleus fibres indicated that the region of a fibre with the longest average sarcomere lengths during an isometric contraction contained the majority of the damaged sarcomeres after a stretch that produced a force deficit of 10%. The results of the present study support the hypothesis that the development of contraction-induced injury is a mechanical event which is initiated when longer sarcomeres in series with shorter sarcomeres are stretched excessively and upon return to initial length some of the sarcomeres at longer lengths are damaged and lose their ability to develop force.