Postischemic conditioning does not reduce muscle injury after tourniquet-induced ischemia-reperfusion injury in rats

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Abstract

Background:

The widespread application of tourniquets has reduced battlefield mortality related to extremity exsanguinations. Tourniquet-induced ischemia-reperfusion injury (I/R) can contribute to muscle loss. Postischemic conditioning (PostC) confers protection against I/R in cardiac muscle and skeletal muscle flaps. The objective of this study was to determine the effect of PostC on extremity muscle viability in an established rat hindlimb tourniquet model.

Methods:

Rats were randomly assigned to PostC-1, PostC-2, or no conditioning ischemic groups (n = 10 per group). Postischemic conditioning, performed immediately after tourniquet release, consisted of four 15-second cycles (PostC-1) or eight 15-second cycles (PostC-2) of alternating occlusion and perfusion of hindlimbs. Twenty-four hours later, muscles were excised. The primary end points were muscle edema and viability; secondary end points were histologic and markers of oxidative stress.

Results:

Ischemia-reperfusion injury decreased viability in all tourniquet limbs, but viability was not improved in either PostC group. Likewise, I/R resulted in substantial muscle edema that was not reduced by PostC. The predominant histologic feature was necrosis, but no significant differences were found among groups. Markers of oxidative stress were increased similarly among groups after I/R, although myeloperoxidase activity was significantly increased only in the no conditioning ischemic group. A protective effect from PostC was not observed in our model suggesting that PostC was not effective in reducing I/R skeletal muscle injury or any benefits of PostC were not sustained for 24 hours when tissues were assessed.

Conclusion:

These negative findings are pertinent as the military investigates different strategies to extend the safe time for tourniquet application.

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