Muscle impairment occurs rapidly and precedes inflammatory cell accumulation after mechanical loading

Abstract

Modified muscle use can result in muscle atrophy and impairment. We tested whether inflammatory cell concentrations correlate temporally with muscle impairment during modified loading periods. Rat hindlimbs were unloaded for 10 days followed by reloading. The density of neutrophils and ED1+ macrophages was significantly increased by 16.5- and 9.8-fold, respectively, after 1 day of reloading. ED2+ macrophage concentration was not significantly increased until 3 days of reloading. Maximal isometric tetanic tension (P(o); N/cm2) decreased during hindlimb suspension (HS), which was followed by a second drop in P(o) after 2 h of reloading. This latter loss in muscle force was uncoupled with the significant elevation in muscle inflammatory cell concentrations. Experiments where HS soleus muscles were incubated with caffeine revealed that at least 40% of the P(o) decrement at 2 h could be associated with a loss of efficiency of the excitation-contraction (E-C) coupling process. These data suggest that an important mechanism for the early loss in force is the inability to activate the contractile machinery likely caused by a failure in the E-C coupling process during the reloading period.

Nonsteroidal Anti-Inflammatory Drug Reduces Neutrophil and Macrophage Accumulation but Does Not Improve Tendon Regeneration

“…1, E to H). The sequence of inflammatory cell accumulation was similar to previous observations in tendons and skeletal muscles (Frenette et al, 2002;Marsolais et al, 2001). Immunolabeling with the PECAM antibody showed that blood vessels are highly concentrated in the paratenon (Fig.…”

Macrophages Protect against Muscle Atrophy and Promote Muscle Recovery in Vivo and in Vitro

“…15,32 The effect of etoposide on circulating leukocytes that we reported is in agreement with the observations of Van't Wout et al in 1989, 18 who described an 82% decrease in circulating monocytes and a small but nonsignificant decrease in blood granulocytes after 3 days of etoposide injections. Daily etoposide injections induced a similar reduction in macrophages in reloaded soleus muscles at day 3.…”

Adaptations of the Motor System in Animal Models of Spinal Cord Injury and Disuse

“…Evidence from other models of inactivity and immobilization suggests that some of these changes, in fact, are induced very early after inactivity and reduced muscular activity and loading. For example, a 10% loss of body weight (Pierotti et al, 1990) accompanied by a 40-50% decrease of SOL mass, TPT and 1/2 RT (Frenette et al, 2002) and a rapid reduction in slow myofibril proteins (Thomason et al, 1987) have been reported after 1-2 weeks of hindlimb suspension in rats. Comparable results have been found within less than 2 weeks in rats after spinal cord isolation (i.e., de-afferented and spinalized, Grossman et al, 1998) or in microgravity (Fitts et al, 2001).…”