Oil Fly Ash-Induced Elevation of Plasma Fibrinogen Levels in Rats

Abstract

Particulate matter air pollution (PM) has been associated with morbidity and mortality from ischemic heart disease and stroke in humans. It has been hypothesized that alveolar inflammation, resulting from exposure to PM, may induce a state of blood hypercoagulability, triggering cardiovascular events in susceptible individuals. Previous studies in our laboratory have demonstrated acute lung injury with alveolar inflammation in rats following exposure to residual oil fly ash (ROFA), an emission source particulate. In addition, increased mortality has been documented following exposure to ROFA in rats with preexistent cardiopulmonary disease. ROFA's toxicity derives from its soluble metal content, which appears also to drive the toxicity of ambient PM. The present study was conducted to test the hypothesis that exposure of rats to a toxic PM, like ROFA, would adversely alter hemostatic parameters and cardiovascular risk factors thought to be involved in human epidemiologic findings. Sixty-day-old male Sprague-Dawley rats were exposed by intratracheal instillation (IT) to varying doses (0.3, 1. 7, or 8.3 mg/kg) of ROFA, 8.3 mg/kg Mt. Saint Helen's volcanic ash (MSH, control particle), or 0.3 ml saline (SAL, control). At 24 h post-IT, activated partial thromboplastin time (APTT), prothrombin time (PT), plasma fibrinogen (PF), plasma viscosity (PV), and complete blood count (CBC) were performed on venous blood samples. No differences from control were detected in APTT and PT in ROFA-exposed rats; however, ROFA exposure did result in elevated PF, at 8.3 mg/kg only. In addition, PV values were elevated in both ROFA and MSH-exposed rats relative to SAL-control rats, but not significantly. Although no changes were detected in APTT and PT, alteration of important hematologic parameters (notably fibrinogen) through PM induction of an inflammatory response may serve as biomarkers of cardiovascular risk in susceptible individuals.

Air pollution and blood markers of cardiovascular risk.

“…However, they are consistent with the results of a controlled human exposure Environmental Health Perspectives • VOLUME 109 | SUPPLEMENT 3 | June 2001 study that reported increases in plasma fibrinogen (35), as well as with the animal study (22). While further results will be necessary to sort out the conflicting reports in epidemiologic studies, the weight of the evidence suggests that airborne particles are associated with increases in fibrinogen.…”

“…Recently, Peters and co-workers reported an air pollution episode and daily variations in air pollution were associated with increased plasma viscosity (21). Gardner and colleagues reported increases in fibrinogen in animals exposed to urban particles (22). Human volunteers exposed to concentrated air particles also have increased levels of plasma fibrinogen (23).…”

Biologic effects of oil fly ash.

“…A related extrapulmonary impact of ROFA is an elevation in plasma concentrations of fibrinogen in exposed rats (42). …”

Thrombogenicity and cardiovascular effects of ambient air pollution

“…12 After PM inhalation, the lung releases locally and into the systemic circulation pro-oxidative (ie, reactive oxygen species) or proinflammatory (ie, cytokines such as IL-6 and TNF-␣) mediators or both and vasoactive hormones such as endothelins. [13][14][15][16][17][18][19][20] Acute-phase reactions take place and lead to the increase in plasma of such reactants as C-reactive protein and fibrinogen. In the lung the secretion of adhesion molecules by inflamed endothelial cells results in binding and activation of leukocytes and platelets, formation of platelet-leukocyte conjugates, and generation of hemostatically active, tissue factor-bearing microparticles.…”