REDUCTION OF SKELETAL-MUSCLE INJURY THROUGH STRESS CONDITIONING USING THE HEAT-SHOCK RESPONSE

The heat-shock response refers to specific reversible changes in cellular metabolism that impart a protective effect on individual cells, as well as entire organisms, against subsequent noxious stimuli. Our objective was to quantify skeletal muscle injury following an ischemic event in a rat model by measuring levels of adenosine triphosphate and creatine phosphate. The animals were divided into two experimental groups. Animals in group 1 (n = 15) were subjected to limb ischemia alone, and animals in group 2 (n = 15) were treated with heat-shock conditioning prior to the onset of ischemia. Skeletal muscle specimens also were examined ultrastructurally by electron microscopy. Levels of creatine phosphate were higher in skeletal muscle obtained from animals in group 2. Mean levels of creatine phosphate +/- SEM for groups 1 and 2 were 1.12 +/- 0.06 mu mol/gm and 1.95 +/- 0.11 mu mol/gm, respectively (p < 0.0001). This represents 18.4 and 31.9 percent of baseline nonischemic levels for groups 1 and 2, respectively (p < 0.0001). Adenosine triphosphate levels were measured in skeletal muscle samples from a subset of animals in each experimental group, group 1 (n = 6) and group 2 (n = 5), and were not significantly different. Electron microscopy demonstrated mitochondrial changes consistent with ischemic injury in group 1, but only nonspecific changes were noted in specimens from group 2. The presence of the primary 72-kDa heat-shock protein (HSP 72) was confirmed only in those animals treated by heat-shock conditioning. We conclude that prior stress conditioning using the heat-shock response confers significant biochemical and ultrastructural protection against ischemic injury in rat skeletal muscle.