Morrison Michael L, Iwata Akiko, Wick Merry L, VandenEkart Emily, Insko Michael A, Henning Daniel J, Frare Carla, Rice Sarah A, Drew Kelly L, Maier Ronald V, Roth Mark B
Division of Basic Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA.
Laboratory and Clinical Research, Faraday Pharmaceuticals, Seattle, WA.
Crit Care Explor. 2020 Sep 30;2(10):e0215. doi: 10.1097/CCE.0000000000000215. eCollection 2020 Oct.
We performed these studies to learn how iodine in the form of free iodide behaves during stress.
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.
Level I trauma center emergency room and ICU and animal research laboratories.
Adult human sepsis and trauma patients, wild-caught adult arctic ground squirrels, and sexually mature laboratory mice.
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.
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.
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.
我们开展这些研究以了解游离碘形式的碘在应激期间的行为表现。
对从人类创伤患者获取的样本进行前瞻性观察试验,对人类脓毒症患者和北极地松鼠的剩余样本进行回顾性观察研究。对小鼠进行后肢缺血再灌注损伤的临床前干预研究。
一级创伤中心急诊室和重症监护病房以及动物研究实验室。
成年人类脓毒症和创伤患者、野生捕获的成年北极地松鼠以及性成熟的实验室小鼠。
通过对小鼠一侧后肢临时应用止血带来诱导缺血再灌注损伤。在再灌注前静脉注射碘化物。
使用离子色谱法测量游离碘。与正常供体血浆中的碘相比,创伤患者血浆中的碘增加了17倍,脓毒症患者血浆中的碘增加了26倍。在北极地松鼠中,冬眠期间碘增加了三倍多。并且在小鼠缺血/再灌注损伤期间,碘在缺血组织中蓄积并减少局部和全身组织损伤。
碘在应激期间重新分布,并改善损伤后的结局。碘的基本功能可能促成了其进化选择,并且作为对人类患者的治疗干预可能有用。