Abstract P2027: Short-term Ambient Particulate Exposure And Social Defeat Cause Reductions In Heart And Pulmonary Function

Abstract

Deployed service members and first responders are exposed to environments containing high levels of air pollution and psychological distress. Thus, we sought to investigate the interaction of these factors and whether the combination of PM and stress exposures exacerbate cardiac and lung dysfunction in a mouse model. Male C57BL/6 mice were exposed to filtered air (FA) or PM (≤2.5 μm) at concentrations of 137.7 ± 70.76 μg/m 3 (daily mean ± standard deviation) for five days/week for three weeks. A subset of each group was stressed via exposure to a retired male aggressor for two hours/day, 3-5 nights/week (FA-stress and PM-stress groups). Echocardiography revealed no changes in left ventricle (LV) systolic or diastolic indices, but a significant reduction in right ventricle (RV) stroke volume and cardiac output in the PM, FA-stress and PM-stress groups compared to the FA group (P<0.05 via two-way ANOVA). Pressure-volume loops displayed significantly reduced end-systolic elastance for the PM and PM-stress groups, but not for the FA-stress group when compared to FA controls, indicating reduced contractility (Ees, P<0.05 via two-way ANOVA). Data on respiratory mechanics was acquired using the flexiVent FX2 (SCIREQ Inc.) system. PM exposure caused an increase in lung resistance (Rrs), central airway resistance (Rn), and tissue damping (G) compared to FA (P<0.05 via two-way ANOVA at individual doses of methacholine). Also, the FA-stress and PM-stress groups experienced increased lung elastance (Ers), Rrs, Rn, and G compared to FA mice (P<0.05 via two-way ANOVA at individual doses). Tail-vein blood pressure measurements showed an increased diastolic pressure induced by PM exposure, but not by stress (P<0.05 via two-way ANOVA). RT-qPCR data revealed a significant decrease in RV NPPB gene expression and an increased RV Col1A1 expression for PM-exposed mice compared to FA (via two-way ANOVA). Additionally, RT-qPCR demonstrated that PM decreased the expression of many inflammatory markers (TNF-α, CCL2, IL6, and IL-1β) in the LV and RV relative to FA (P<0.05 via two-way ANOVA). Differences in NPPB and Col1A1 expression suggest increased fibrosis in the RV. Calculating capillary to myocyte ratio from a wheat germ agglutinin stain, there was an increase in capillary density of PM-exposed mice compared to FA (P<0.05 via t-test). Taken together, short-term exposure to PM with/without psychological distress impairs respiratory mechanics and RV function. Molecular analyses indicated changes in inflammation in both the LV and RV between the FA and PM groups, with additional changes in RV fibrosis. These results suggest that even short-term exposure to PM, including in occupational settings such as military burn pits, can cause notable cardiopulmonary dysfunction. This work was supported by the Department of Veterans Affairs Airborne Hazards and Burn Pits Center of Excellence