Temporal association between pulmonary and systemic effects of particulate matter in healthy and cardiovascular compromised rats.
Exposure to particulate matter (PM) has been associated with increased morbidity and mortality among individuals with cardiovascular disease. It is hypothesized that systemic alterations occur concurrent to pulmonary injury/inflammation, and contribute to cardiac events in compromised hosts. We explored this hypothesis using a rat model for human hypertension and cardiovascular disease (spontaneously hypertensive, SH), and normotensive Wistar Kyoto (WKY) rats. SH and WKY rats (12-13 wk old) were exposed either intratracheally (IT; 0.0, 1.0, or 5.0 mg/kg in saline) or nose-only (15 mg/m(3) x 6 h/d x 3 d/wk x 1, 2 or 4 wk) to combustion source residual oil fly ash (ROFA) with low metal content, and examined 1, 2 or 4 d later. Bronchoalveolar lavage fluid (BALF) albumin and neutrophils increased (SH approximately equal WKY) at d 1 following ROFA IT. With inhalation exposure, both strains experienced progressive histological lung damage and increases in BALF albumin and neutrophils during 1 to 4 wk (SH > WKY). Acute lung injury from ROFA IT was temporally associated with increases in plasma fibrinogen in both strains, but only the SH rats responded to the acute 1-wk ROFA inhalation. Longer term (2 or 4 wk) ROFA caused progressive lung injury (SH > WKY), but did not sustain the increase in fibrinogen. BALF glutathione increased in a temporal fashion similar to fibrinogen; however, only WKY rats demonstrated this response. There was a small but consistent decrease in blood lymphocytes and an increase in blood neutrophils in SH rats exposed to ROFA acutely. In conclusion, acute PM exposure can provoke an acute systemic thrombogenic response associated with pulmonary injury/inflammation and oxidative stress in cardiovascular compromised rats. This evidence is consistent with greater cardiovascular events during acute PM episodes in compromised humans.
Kodavanti
Urmila P
UP
Experimental Toxicology Division, National Health and Environmental Effects Research Laboratory, Office of Research and Development, U.S. Environmental Protection Agency, Research Triangle Park, North Carolina 27711, USA. kodavanti.urmila@epa.gov
Schladweiler
Mette C
MC
Ledbetter
Allen D
AD
Hauser
Russ
R
Christiani
David C
DC
McGee
John
J
Richards
Judy R
JR
Costa
Daniel L
DL
D000280:Administration, Inhalation; D000336:Aerosols; D000418:Albumins / Q000378:metabolism; D000704:Analysis of Variance; D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry; D002244:Carbon / Q000008:administration & dosage / Q000633:toxicity*; D002318:Cardiovascular Diseases / Q000473:pathology*; D060729:Coal Ash; D004195:Disease Models, Animal; D006973:Hypertension / Q000473:pathology*; D007249:Inflammation; D008168:Lung / Q000378:metabolism* / Q000473:pathology*; D008297:Male; D009504:Neutrophils / Q000166:cytology; D009929:Organ Size; D010316:Particle Size; D052638:Particulate Matter; D051381:Rats; D011921:Rats, Inbred WKY; D013997:Time Factors
D000336:Aerosols; D000418:Albumins; D060729:Coal Ash; D052638:Particulate Matter; D002244:Carbon