Abstract 411: In Utero Exposure to PM2.5 Causes Adult Cardiovascular Dysfunction and Reduced Exercise Capacity

Abstract

Objective: Exposure to particulate matter 2.5 μm (PM2.5) during intrauterine development is associated with adverse cardiovascular outcomes at adulthood. Deteriorations in cardiac function are observed with increased myocardial demand in PM2.5-exposed individuals. The goal of this study was to determine the effects of in utero PM2.5exposure on exercise training capacity and cardiac function in adult mice. Methods: Female FVB mice were exposed either to filtered air (FA) or PM2.5at an average concentration of 73.61μg/m 3 for 6h/day, 7days/wk throughout pregnancy. 12wk old male offspring from exposed dams were assigned to in utero FA (n=5) or PM2.5 (n=5) exposed groups which underwent exercise training for 3 weeks (housed with running wheels for 3 weeks). We measured total distance travelled and performed echocardiography at baseline, 1, 2 and 3 weeks. Results: There was a progressive decrease in total distance travelled each week in the in utero PM2.5 exposed mice (Week 1: 12.2±3.46 Km FA, 5.32±2.06 Km PM2.5; Week 2: 41.4±9.62 Km FA, 17.28±6.60 Km PM2.5; Week 3: 61.8±16.59 Km FA, 25.92.±8.62 Km PM2.5) compared to the in utero FA exposed mice. When comparing to their respective sedentary counterparts, the FA exercise group showed increased fractional shortening (%FS), left ventricular end systolic (LVESd) and diastolic (LVEDd) diameters, suggesting eccentric hypertrophy. There was a modest decrease in %FS and marked increase in posterior wall thickness during diastole (PWTd) in the PM2.5 exercise group suggesting concentric hypertrophy. Comparison of in utero FA vs PM2.5 exercise groups after 3 weeks of exercise training showed reduced %FS and marked decrease in LVEDd in the PM2.5 exercise group compared to the FA exercise group. Furthermore, a decrease in PWTs and increased PWTd was also observed in the PM2.5 group compared to FA controls. Conclusions: In utero PM2.5exposure reduced exercise capacity at adulthood and the development of both systolic and diastolic dysfunction. Thus, our study showed that individuals residing in high pollution areas are predisposed to develop cardiac dysfunction under conditions of increased myocardial demand.