Mechanisms underlying the protection from contraction -induced skeletal muscle injury provided by exercising with passive stretches.

Contraction-induced injury can occur during everyday activities when muscles are stretched while activated (lengthening contractions). Administration of passive stretches during which the muscle is lengthened without activation reduces the severity of injury following subsequent lengthening contractions. Contraction-induced injury is initiated by mechanical damage followed by an inflammatory response leading to a secondary injury and the degeneration of damaged muscle fibers. Conditioning with passive stretches may protect against injury by decreasing the initial mechanical damage, the secondary injury, or both. This thesis investigated potential mechanisms underlying protective adaptations induced by passive-stretch-conditioning in mice. Understanding these mechanisms is important for designing safe effective conditioning programs to reduce injury, particularly for populations susceptible to contraction-induced injury like the elderly. The best measure of the magnitude of initial mechanical damage is the deficit in force either immediately following a protocol of lengthening contractions that did not fatigue the muscle or immediately following recovery from fatigue. Shortly after lengthening contractions, the force deficits in the absence of fatigue were not different for conditioned and unconditioned muscles, supporting the conclusion that passive-stretch-conditioning does not reduce initial mechanical damage. The magnitude of the secondary injury was determined by measuring force deficits, numbers of fibers that showed morphological evidence of injury, and infiltration of muscles by inflammatory cells three days after lengthening contractions. Inhibiting nitric oxide production during passive-stretch-conditioning prevented the reduction in force deficit, number of injured fibers, and inflammation typically observed following lengthening contractions for conditioned muscles. Thus, nitric oxide produced during passive stretches appeared to have anti-inflammatory effects during subsequent lengthening contractions. Moreover, increased levels of substrate for nitric oxide production were sufficient to decrease lengthening contraction-induced force deficits, damage to fibers and inflammation, even in the absence of prior passive stretches. Passive stretches alone resulted in neutrophil infiltration of the muscle and prevention of this low level inflammatory response eliminated the protective effects of passive stretches. We conclude that passive-stretch-conditioning reduces injury following subsequent lengthening contractions not by decreasing initial mechanical damage, but through a reduction in the secondary injury, specifically by blunting inflammation.Ph.D.Animal PhysiologyBiological SciencesCellular biologyHealth and Environmental SciencesKinesiologyPhysical therapyUniversity of Michigan, Horace H. Rackham School of Graduate Studieshttp://deepblue.lib.umich.edu/bitstream/2027.42/125698/2/3208500.pd