Backgound: Frostbite injury results in serious skeletal muscle damage. Potentially the inflammatory response due to frostbite causes local muscle degeneration. Previous studies have shown that the heat shock proteins (hsp) are able to protect against oxidative stress and inflammation. Results: In the present study we examined the effects of the heat shock protein inducer, 17‐Dimethylaminoethylamino‐17‐demethoxygeldanamycin (17‐DMAG) which was administered within 45 minutes following frostbite injury. Our results show that rat hind‐limb muscles injected with 17‐DMAG following frostbite injury exhibit less inflammatory cell infiltration as compared to control rat hind‐limb muscles. In agreement with this observation, we found that the increased heat shock protein expression results in a decrease in inflammatory cytokine expression. We also found that administration of 17‐DMAG after frostbite injury is able to preserve muscle function. Our results therefore suggest that 17‐DMAG protects skeletal muscle if administered shortly after frostbite injury. Conclusion: We conclude that compounds such as 17‐DMAG that induce heat shock proteins are able to preserve skeletal muscle function and structure if injected within 45 minutes after frostbite injury. Our studies provide the basis for the development of a potential therapeutic strategy to treat injury caused by frostbite. Grant Funding Source: This research was supported by an award from the USAMRMC.

BackgroundSkeletal muscle damage due to frostbite represents a serious medical problem. Oxidative stress and inflammatory response cause muscle degeneration following skeletal muscle injury. Studies have shown that the heat shock proteins (hsp) are able to protect against oxidative stress and inflammation.ResultsIn the present study we used rat hindlimbs to examine the effects of several heat shock protein inducers, such as radicicol, 17‐AAG and 17‐DMAG following frostbite injury. Our results show that rat hindlimb muscles injected with these hsp inducers following frostbite injury exhibit less damage, less hypercontracted muscle fibers and less inflammatory cell infiltration as compared to control rat hindlimb muscles. We also find that these heat shock protein inducing compounds are able to conserve muscle function even when administered after frostbite injury has occurred. These results suggest that hsp inducing compounds are able to protect skeletal muscle if administered in the early stages following frostbite injury.ConclusionWe conclude that compounds that induce heat shock proteins are able to preserve skeletal muscle function and structure if injected shortly after frostbite injury. Our studies provide the basis for the development of therapeutic strategies to treat injury caused by frostbite involving severe muscle damage.This research was supported by an award from the USAMRMC.

Background: Frostbite injury results in serious skeletal muscle damage. The inflammatory response due to frostbite causes local muscle degeneration. Previous studies have shown that the heat shock proteins (hsps) are able to protect against inflammation. In addition, our previous studies showed that increased expression of hsp70 is able to protect skeletal muscle against cryolesion. Therefore, our aim was to determine if the induction of the heat shock proteins are able to minimize inflammation and protect skeletal muscle against frostbite injury. Results: In the present study we used the hsp90 inhibitor, 17-dimethylaminoethylamino-17- demethoxygeldanamycin (17-DMAG) which was administered within 30 minutes following frostbite injury. Rat hind-limb muscles injected with 17-DMAG following frostbite injury exhibited less inflammatory cell infiltration as compared to control rat hind-limb muscles. In agreement with this observation, we found that increased hsp expression resulted in decreased inflammatory cytokine expression. Additionally, we found that administration of 17-DMAG after frostbite injury is able to preserve muscle tissue structure as well as function. Conclusion: We conclude that compounds such as 17-DMAG that induce the heat shock proteins are able to preserve skeletal muscle function and structure if injected within 30 minutes after frostbite injury. Our studies provide the basis for the development of a potential therapeutic strategy to treat injury caused by frostbite.

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