DETERMINANTS OF ISCHEMIC-INJURY TO SKELETAL-MUSCLE

Purpose: Ischemic injuries to the lower extremity are often graded in severity according to their duration. Other determinants may also infl uence the extent of an injury, however, and may be equally significant contributors to the final outcome. The purpose of this study was to c ompare 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 Metho ds: Animals' hindlimbs were rendered ischemic under differing conditio ns of each determinant and then reperfused for 48 hours. Necrosis in t he rectus femoris, semimembranosus, anterior tibial, and soleus muscle s was determined by nitroblue tetrazolium staining and computerized pl animetry. The severity of each animal's injury was quantified by calcu lating the cumulative percentage of necrosis by weight of all muscles excised from the ischemic limb. Results: Pour hours of ischemia at roo m temperature resulted in an average of 21% +/- 7% necrosis. Lengtheni ng the ischemic interval to 5 hours increased necrosis to 61% +/- 4% ( p < 0.01 vs 4 hours); however injuries were equally or more significan tly influenced by changes in ischemic temperature or small changes in ischemic limb residual (collateral) blood how. The most severe injurie s of any encountered were observed when limbs were maintained at body temperature during ischemia (92% +/- 9% necrosis after 5 hours of isch emia, p < 0.01 vs room temperature ischemia), whereas extremely small improvements in ischemic period residual how (by allowing pelvic colla teral cross-dow during ischemia) resulted in significant salvage in al l muscles studied. Muscles predominating in fast-twitch fibers had sig nificantly greater necrosis than did those richer in slow-twitch fiber s; 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 temp erature ischemia, where the distribution of necrosis was uniform. Conc lusionss: The results of this study indicate that muscle necrosis acco mpanying an ischemic event can be significantly influenced by numerous determinants in addition to ischemic time, each of which warrants car eful clinical scrutiny when appraising the extent of an injury.