Inflammatory Responses of the Remote Organs After Tourniquet-Induced Ischemia-Reperfusion in Mouse Hindlimb

Abstract

Tourniquet use is the most effective tool for controlling life-threatening extremity hemorrhage before other treatments and for creating bloodless operating fields in surgical procedures. However, tourniquet-induced ischemia-reperfusion (IR) also causes skeletal muscle injury and associated secondary end-organ damage. Our previous studies have demonstrated that there are involvements of inflammatory cytokines in tourniquet-induced skeletal muscle IR injuries. The objective of this study is to investigate the inflammatory responses of end-organs after tourniquet-induced mouse hindlimb IR. We hypothesized that tourniquet use would result in an inflammatory response in the remote organs. The unilateral hindlimbs of mice were subjected to 3 hours of tourniquet application by placing a rubber band at the hip joint. Then the rubber bands were released for reperfusion over different periods of time (1, 3, 7, and 14 days). The mRNA levels of IL-1β and TNFα (two inflammatory cytokines) in the lungs, liver, kidneys, and heart were measured using real-time RT-PCR analysis. In the lungs, the levels of IL-1β and TNFα mRNA were significantly elevated at day 1 after tourniquet-induced IR, then decreased at days 3 and 7, and returned to a high level at day 14. In the liver, the levels of IL-1β and TNFα mRNA were increased at day 1 and remained at a high level until day 14. However, tourniquet-induced hindlimb IR did not change the levels of IL-1β or TNFα mRNA in the kidneys or heart during the whole period of tourniquet-induced IR. In conclusion, these results suggest that the inflammatory response to tourniquet-induced hindlimb IR is different among distant organs, which will help to develop therapeutic strategies for different end-organs after tourniquet-induced hindlimb IR. NIH/NIGMS 1R01GM145736 to Y-LL. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.