Objective: We performed these studies to learn how iodine in the form of free iodide behaves during stress. Design: Prospective observational trial using samples obtained from human trauma patients and retrospective observational study using remnant samples from human sepsis patients and arctic ground squirrels. Preclinical interventional study using hind-limb ischemia and reperfusion injury in mice. Setting: Level I trauma center emergency room and ICU and animal research laboratories. Subjects: Adult human sepsis and trauma patients, wild-caught adult arctic ground squirrels, and sexually mature laboratory mice. Interventions: Ischemia and reperfusion injury was induced in mice by temporary application of tourniquet to one hind-limb. Iodide was administered IV just prior to reperfusion. Measurements and Main Results: Free iodide was measured using ion chromatography. Relative to iodide in plasma from normal donors, iodide was increased 17-fold in plasma from trauma patients and 26-fold in plasma from sepsis patients. In arctic ground squirrels, iodide increases over three-fold during hibernation. And during ischemia/reperfusion injury in mice, iodide accumulates in ischemic tissue and reduces both local and systemic tissue damage. Conclusions: Iodide redistributes during stress and improves outcome after injury. Essential functions of iodide may have contributed to its evolutionary selection and be useful as a therapeutic intervention for human patients.
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