Different inflammatory responses in the remote organs during tourniquet-induced hindlimb ischemia-reperfusion

Tourniquets are a tool used to stop life threatening hemorrhages and create bloodless surgical fields. The military also uses this tool and currently all deployed personnel are trained and carry tourniquets with them. Despite the tourniquet's usefulness, it causes skeletal muscle injuries and is associated with secondary organ damage. Previous studies on skeletal muscle tourniquet-induced ischemia-reperfusion (IR) showed the involvement of inflammatory cytokines in tissue damage. Objective: This study is to investigate the inflammatory responses of various organs after the induction of hindlimb IR. We hypothesize that protein expression of interleukin 1-beta (IL-1β) and TNF-alpha (TNF-α) (two proinflammatory cytokines) would increase in remote organs after skeletal muscle tourniquet-induced IR. Methods: For hindlimb IR induction, a tourniquet was applied to the unilateral hindlimb of male C57BL/6 mice and was on hindlimb at the greater trochanter for 3hrs. After 3hrs of the tourniquet treatment, reperfusion was allowed to occur for 1, 3, 7, 14, or 28 days. Finally, mice were euthanized, and tissues were collected for Western blot analysis. Results: In the lungs, the expression of IL-1β and TNF-α increased on 3-day, 7-day, 14-day and 28-day IR, compared to control levels. In the liver, IL-1β expression increased at 7, 14, and 28 days as compared to control levels, whereas TNF-α in the liver increased at 3 and 7 days before returning to control levels. In the heart, there were no changes in the expression of TNF-α and IL-1β. Conclusion: Based on the data, it is suggested that the protein levels of IL1-β and TNF-α after tourniquet-induced hindlimb IR varies depending on the different organs and IR time-points. Seeing how proinflammatory cytokines vary in the different organs can provide novel therapeutic approaches to prevent secondary organ damage during tourniquet-induced hindlimb IR. This research is supported by the NIH/NIGMS 1R01GM145736 to Y-L Li. This abstract was presented at the American Physiology Summit 2025 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board was not involved in the peer review process.