Effects of fiber type on ischemia-reperfusion injury in mouse skeletal muscle.

Abstract

Tourniquets frequently used during surgery involve tissue ischemia followed by postoperative reperfusion. However, little information is available on the functional consequences of this procedure in skeletal muscle. The goal of this study was to use skeletal muscles of C57BL/6 adult male mice to assess functional, structural, and biochemical characteristics after hindlimb vessel occlusion. Experimental manipulation involved application of a tourniquet to the hindlimb for a 3-hour period (n = 65). Muscles were then excised after various periods of reperfusion. Soleus and extensor digitorum longus muscles were chosen as representative of slow oxidative and fast glycolytic muscle fiber types, respectively. The most striking functional change found after ischemia-reperfusion injury was markedly improved endurance of extensor digitorum longus muscles. These fast-twitch glycolytic muscle fibers became much more resistant to fatigue during recovery from ischemia-reperfusion injury. There was a progressive increase in force generation in both muscles during recovery; however, soleus muscles recovered function more quickly after ischemia-reperfusion than extensor digitorum longus muscles. Also, extensor digitorum longus muscles recovered mass more slowly than soleus muscles at 7 and 14 days after ischemia. Structurally, extensor digitorum longus muscles had more severely damaged mitochondria, sarcoplasmic reticulum, and myofibrils. Surprisingly, no differences in oxidative enzyme activity (citrate synthase) and oxidative damage (in protein and lipids) were found after ischemia-reperfusion. The results indicate that muscle fiber type has a significant impact on the nature of ischemia-reperfusion injury in skeletal muscle. Thus, muscle fiber composition would be expected to affect recovery from the clinical use of tourniquets and other ischemic procedures. Furthermore, the results suggest that damage to structures involved in energy transduction and excitation-contraction coupling may play a role in the effects.