Ion Chromatography and Mass Spectroscopy for Trauma Ions
Abstract
We recently showed that iodine redistribution is a conserved life process used by organisms to respond to stress and that iodide supplementation improves outcome. These observations are the result of our work with a group of redox active anions called Elemental Reducing Agents (ERAs). For the past several years we have described many important functions for ERAs in biology and human health; one, that ERAs can be intravenously administered to animals to reduce oxygen consumption in mammals, and two, that ERAs can be used to improve outcome in various military and civilian models of ischemia and reperfusion injury (IRI). We showed that a likely mechanism by which one ERA provides benefit is iodideÕs ability to catalytically destroy the hydrogen peroxide and thereby decrease excessive damaging inflammation, sometimes referred to as Ôcytokine storm.Õ ERAs are essential nutrients for the human body, elements we constantly replenish through food consumption, but the chemical basis for their essentiality had been largely unknown. We found that ERAs are held in various biological ÔcompartmentsÕ (blood, thyroid, etc.) under normal conditions, but then become mobilized during severe physiologic stress. For example, we found that selenide is rapidly redistributed from the blood to recently reperfused tissue in animal models of ischemia reperfusion injury (IRI) and recently discovered that blood iodide naturally increases in response to trauma and sepsis: an increase of 17-fold within 2 hours of severe blunt force trauma and a 26-fold increase in sepsis patients. While these increases in blood iodide are striking, they still may be insufficient to limit damage from more excessive inflammation; for instance, we found it required increasing blood iodide levels by 5000-fold to control inflammation caused by balloon angioplasty in animal models and in human heart attack patients. Because iodide at this dose has a high therapeutic index, it opens us to the possibilities of studying ERAs as possible treatments for many military relevant diseases resulting from excessive inflammation, including COVID-19. With our current equipment, we cannot complete the large number of projects that should be done. Our existing ion chromatograph does not work well with gradient elution methods. In addition, it has no mass spectrometer. As a result we require 10 times more sample because we collect fractions by hand and then carry each fraction 3 miles away to a borrowed facility where (when time is available) we have to individually run inductively coupled mass spectrometry to get essential mass information required for compound identification. This has decreased productivity both in the length of time required to do analysis and limits the number of samples we can run. It has taken us 2 years to get two studies done in which we analyzed about 300 samples and about 60 peaks by mass spectrometry. With an in-house mass spectrometer, we could have retrieved those same results in a month or two. As outlined below, we currently have reached out to physician scientists across the country and have planned or initiated more than 20 additional studies. With the ion chromatograph mass spectrometer system requested in this proposal, we will be able to vastly accelerate throughput to better understand the relationship between ERA redistribution during physiologic stress and hopefully come closer to harnessing the power of these essential nutrients for use therapeutically to improve outcomes in a host of military relevant physiological stress/injury conditions. This equipment will not only provide training experiences for people in my lab but also the many trainees working in the labs around the US whose samples we will be studying.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Jun 25, 2021
- Source ID
- W911NF2110199
Entities
People
- Mark Roth
Organizations
- Army Contracting Command
- Fred Hutchinson Cancer Center
- United States Army