Cardiac function in a chemical toxin (organophosphate) induced model of gulf war Illness: benefit of exercise training

Abstract

BackgroundGulf War Illness (GWI) is a debilitating disease characterized by a cadre of neural, immunological and autonomic symptoms. We show that exposure to a sub‐lethal dose of Sarin lead to autonomic imbalance, cardiomyopathy and central nervous system changes. Diisopropyl fluorophosphate (DFP), an analogue of Sarin (GB), can be used as surrogate agent to produce neurotoxicity and neuro‐inflammation. There is limited information on the use of DFP to produce model of GWI with emphasis on the study of cardiovascular‐autonomic dysfunctions. Consideration was given to the inclusion of exercise training (ET) as part of the treatment of cardiac dysfunction induced by organophosphate exposure.ObjectiveThe aim was to determine the effect of chronic exercise training to the response to DFP on autonomic and cardiovascular function.MethodsMale C57BL/6J mice were divided into two groups (n=8/group): Sedentary (S) and trained (T) before and after DFP exposure. ET was performed on an electronic wheel at low intensity for 1 h/day, 5 days/wk. GWI model was induced by corticosterone (CORT) administered for 7 days (200 mg/l) followed by DFP (1.5 mg/kg, s.c). Cardiac function and ECG were assessed by transthoracic echocardiography (echo) under isoflurane anesthesia (2 – 2.5% on 0.8 l/min of O2).ResultsThe low dose of DFP produced left ventricular dilation on sedentary group, specifically, LV dilation of end systolic area (ESA) (S: 10.34±0.86 vs S+DFP: 6.69 ±0.41 cm2). The ET ameliorated DFP induced toxicity (T: 7.99 ±0.40 vs T+DFP 7.66±0.96cm2). Cardiac Output (CO) was reduced in sedentary group after DFP (S: 20.61±2.63 vs S+DFP: 14.78±0.85 ml/min), not change was observed in the ET group, revealing the efficacy of exercise protocol (T: 16.99±1.69 vs T+DFP: 17.90±1.42 ml/min). Myocardial performance index (MPI) and E/A ratio were significantly increased in S group after DFP exposure (MPI: S: 0.52±0.03 vs S+DFP: 0.60±0.02; E/A: S: 1.29±0.09 vs S+DFP: 1.64±0.07) changes that were not observed on T group (MPI: T: 0.50±0.04 vs T+DFP: 0.48±0.03; E/A: S: 1.35±0.09 vs S+DFP: 1.56±0.10) suggesting protection against DFP. Finally sympathetic modulation (LF) was increased in S group compared initial values and T group, as well as LF/HF ratio. Vagal modulation was similar between both groups.ConclusionIn conclusion, results demonstrate that DFP exerts a negative impact on cardiac/autonomic function. Our critical finding is that chronic exercise prevented most of the cardiovascular dysfunctions elicited by DFP, documenting the positive effects of exercise. This treatment protocol maybe equally applicable to other animal models or even humans.Support or Funding InformationThis work was funded under U.S. Department of Defense grant W81XWH‐13‐2‐0085This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.