B57-18 Acute Silica Exposure Causes Persistent Cardiopulmonary Dysfunction

Introduction / Rationale to the study

Silica exposure poses risks in occupational settings – stone manufacturing, quarrying, construction, firefighting, and deployed military service veterans. Exposure to crystalline silica causes silicosis and pulmonary hypertension and increases the risk of lung cancer, COPD, and ischemic heart disease. Animal models of silicosis have focused on fibrosis and pulmonary inflammation while overlooking the cardiovascular consequences, leaving a major gap in our understanding of how silica-induced lung injury affects the cardiopulmonary system.

Methods

Silica (34 mg/kg, 0.2 µm diameter) in saline was instilled via endotracheal intubation in 13-15-week-old C57BL/6J mice (n = 3 silica, n = 3 sham). Mice were allowed 28 days recovery. Cardiopulmonary structure and function were assessed using multiple scales one month after exposure. Structural analyses included bronchoalveolar lavage (BAL) and histological analysis of the heart, lungs, and pulmonary arteries (proximal and distal). Functional testing included exercise testing, echocardiography of the right ventricle, pulmonary function testing (PFT),and biaxial mechanical testing of the proximal pulmonary artery (PA).

Results

Silica-exposed mice had increased mortality (33% versus 0%, p = 0.31). BAL showed an increase in cell count that persisted after exposure to silica. Histology revealed lungs from silica-exposed mice had increased mononuclear cell infiltrates and proteinaceous material in the alveolar space and fibrosis. While surviving mice appeared healthy, exercise testing revealed a decrease in daily running distance by silica-exposed mice (1,716 versus 2,217 m, p = 0.21). Echocardiography revealed impaired right ventricular function in the silica group: decreasedcontractility (TAPSE, 1.3 silica versus 1.7 mm sham, p = 0.06), increased free wall thickening (0.63 versus 0.29 mm, p = 0.07). Stiffness of PAs from mice exposed to silica was significantly greater (0.29 versus 0.13 kPa, p = 0.018) with less distensibility (p = 0.13), resulting in greater pulse wave velocity in the pulmonary circulation (19.5 versus 14.8 mm/s, p = 0.10). PFT revealed parenchymal stiffening (24.9 versus 22.7 cmH2O/mL, p = 0.09) and decreased compliance (0.068 vs. 0.072 µL/cmH2O, p = 0.10).

Conclusions

Recent legislative debate over the safety of engineered stones and dust inhalation in US service zones has highlighted the need to further investigate the health effects of silica exposure. The persistent cardiopulmonary effects remain under-explored. These findings suggest that despite subjective recovery from toxic inhalation exposures, persistent cardiopulmonary injury may be present. Efforts to increase the sample size, evaluate sex as a biological variable, and to measure the DLCO are currently in progress.

This abstract is funded by: NIH