Influence of Diisopropyl Fluorophosphate, an Irreversible Cholinesterase Inhibitor, on Autonomic Modulation

Abstract

After the Gulf War, approximately 25-32% of the 700,000 veterans deployed are still facing cardiovascular issues, joint pain and muscle pain, neurophysiological problems, and various symptoms that cannot be medically explained. These medical mysteries are commonly known as Gulf War Illness (GWI). It is important to know that understanding how these various symptoms are related allows for treatment as veterans return back to civilian life, preventing exposure to further diseases. In this study we used mice that were exposed to diisopropyl fluorophosphate (DFP), a cholinesterase inhibitor that can be used as a substitute for sarin gas, which was used during the Gulf War. Acutely, DFP can increase the parasympathetic modulation by inhibiting the enzyme acetylcholinesterase; however, the chronic effects are not known. Heart rate variability is a tool that allows us to indirectly measure the autonomic modulation. It is worth noting that diseases influence a higher sympathetic modulation than normal. In this study, the animals exposed to DFP showed a lower parasympathetic modulation (-33%) which in turn led to a higher sympathovagal balance when compared to the control group. This implies that DFP contributes to alterations in cardiac autonomic modulation. Further research is required, but at least some of the mechanisms were understood as to how sarin gas could have influenced the cardiac dysfunction associated with GWI.

Faculty Sponsors

Dr. Mariana Morris, Dr. Rodrigo Schmidt, Dr. Filipe Stoyell-Conti, Dr. Jacqueline Machi, Dr. Robert Speth

Project Type

Event

Location

Alvin Shermany Library

Start Date

4-5-2019 1:00 PM

End Date

4-5-2019 5:00 PM

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Apr 5th, 1:00 PM Apr 5th, 5:00 PM

Influence of Diisopropyl Fluorophosphate, an Irreversible Cholinesterase Inhibitor, on Autonomic Modulation

Alvin Shermany Library

After the Gulf War, approximately 25-32% of the 700,000 veterans deployed are still facing cardiovascular issues, joint pain and muscle pain, neurophysiological problems, and various symptoms that cannot be medically explained. These medical mysteries are commonly known as Gulf War Illness (GWI). It is important to know that understanding how these various symptoms are related allows for treatment as veterans return back to civilian life, preventing exposure to further diseases. In this study we used mice that were exposed to diisopropyl fluorophosphate (DFP), a cholinesterase inhibitor that can be used as a substitute for sarin gas, which was used during the Gulf War. Acutely, DFP can increase the parasympathetic modulation by inhibiting the enzyme acetylcholinesterase; however, the chronic effects are not known. Heart rate variability is a tool that allows us to indirectly measure the autonomic modulation. It is worth noting that diseases influence a higher sympathetic modulation than normal. In this study, the animals exposed to DFP showed a lower parasympathetic modulation (-33%) which in turn led to a higher sympathovagal balance when compared to the control group. This implies that DFP contributes to alterations in cardiac autonomic modulation. Further research is required, but at least some of the mechanisms were understood as to how sarin gas could have influenced the cardiac dysfunction associated with GWI.