You are here:
MYOCARDIAL AND CARDIOVASCULAR EFFECTS FOLLOWING PULMONARY EXPOSURE TO ZINC
Citation:
Gilmour, P. S., C. F. Moyer, A. D. Ledbetter, M. Schladweiler, A. Nyska, AND U P. Kodavanti. MYOCARDIAL AND CARDIOVASCULAR EFFECTS FOLLOWING PULMONARY EXPOSURE TO ZINC. Presented at American Heart Association Meeting, Orlando, FL, November 9-12, 2003.
Description:
CARDIOVASCULAR INJURY FOLLOWING PULMONARY EXPOSURE TO ZINC
PS Gilmour, A Nyska, MC Schladweiler, AD Ledbetter, CF Moyer, JM Samet, and UP Kodavanti, CEMALB, UNC, Chapel Hill, NC; NIEHS, RTP, NC; US EPA/ORD/NHEERL/HSD, Chapel Hill, NC; Pathology Associates, Inc., Raleigh, NC; and US EPA/ORD/NHEERL/ETD, Research Triangle Park, NC.
Exposure to environmental particulate matter (PM) is associated with cardiovascular (CV) health effects. Although the mechanism(s) has yet to be determined, PM-associated metals are thought to play a role. Recent interest has focused on zinc, a major constituent of ambient and combustion PM; however, the role of pulmonary zinc exposure on coagulation factors and inflammation in the heart is unknown. We have recently shown that pulmonary exposure to zinc-containing PM causes myocardial lesions in rats. Therefore, we hypothesized that pulmonary exposure to zinc causes lung and heart thromboses, and cardiac inflammation and injury. Male Sprague-Dawley (SD) and Wistar-Kyoto (WKY) rats were intratracheally-instilled (IT) with 0, 1, or 2 mol/kg zinc sulfate (ZnSO4). Inflammation, blood parameter changes, and tissue plasminogen activator (tPA), thrombomodulin (TM), and tissue factor (TF) mRNA (PCR) in heart and lung tissues were analyzed 1 and/or 24 h post ZnSO4 IT. Lung and cardiac injury was evaluated 1, 4, 24, 48 and 96 h post IT. Myocardial lesions were characterized by immunohistochemical staining for troponin and apoptosis in cardiac sections. Significant increases in bronchoalveolar lavage fluid neutrophils, protein, and LDH occurred in the zinc-exposed SD rats, and not in controls. TF mRNA was significantly increased in the lungs of zinc-exposed SD rats. The expression of tPA and TM was significantly decreased in heart tissues of zinc-exposed SD rats. IT zinc took 24 h to clear from the lung during which time the liver levels increased, while there was only a modest increase in cardiac zinc. WKY rats exposed to zinc demonstrated cardiac lesions, which consisted of multi-focal myocardial degeneration, acute active inflammation, and myocardial necrosis. Control WKY rats did not demonstrate such cardiac lesions. These data suggest that pulmonary exposure to zinc has significant inflammatory and procoagulative effects in the lung and heart, and may play a critical role in PM-induced CV effects. This abstract does not reflect US EPA policy. Supported in part by #CR829522 between EPA and UNC.