Determinants of ischemic injury to skeletal muscle.

Abstract

Ischemic injuries to the lower extremity are often graded in severity according to their duration. Other determinants may also influence the extent of an injury, however, and may be equally significant contributors to the final outcome. The purpose of this study was to compare the relative influences of ischemic time, temperature, residual blood flow, muscle location, and fiber type on postischemic necrosis in a rabbit model of skeletal muscle ischemia-reperfusion injury. Animals' hindlimbs were rendered ischemic under differing conditions of each determinant and then reperfused for 48 hours. Necrosis in the rectus femoris, semimembranosus, anterior tibial, and soleus muscles was determined by nitroblue tetrazolium staining and computerized planimetry. The severity of each animal's injury was quantified by calculating the cumulative percentage of necrosis by weight of all muscles excised from the ischemic limb. Four hours of ischemia at room temperature resulted in an average of 21% +/- 7% necrosis. Lengthening the ischemic interval to 5 hours increased necrosis to 61% +/- 4% (p < 0.01 vs 4 hours); however injuries were equally or more significantly influenced by changes in ischemic temperature or small changes in ischemic limb residual (collateral) blood flow. The most severe injuries of any encountered were observed when limbs were maintained at body temperature during ischemia (92% +/- 9% necrosis after 5 hours of ischemia, p < 0.01 vs room temperature ischemia), whereas extremely small improvements in ischemic period residual flow (by allowing pelvic collateral cross-flow during ischemia) resulted in significant salvage in all muscles studied. Muscles predominating in fast-twitch fibers had significantly greater necrosis than did those richer in slow-twitch fibers; this difference was apparent only after longer periods (5 hours) of ischemia. Thigh muscles sustained significantly greater injuries than did distal hindlimb muscles, except in animals subjected to body temperature ischemia, where the distribution of necrosis was uniform. The results of this study indicate that muscle necrosis accompanying an ischemic event can be significantly influenced by numerous determinants in addition to ischemic time, each of which warrants careful clinical scrutiny when appraising the extent of an injury.