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ToxSci Advance Access published online on March 16, 2005
Toxicological Sciences, doi:10.1093/toxsci/kfi142
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Toxicological Sciences © The Author 2005. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved. For Permissions, please email: journals.permissions@oupjournals.org
Received December 24, 2004
Accepted February 20, 2005

Respiratory Toxicology

THE RAT EAR VEIN MODEL FOR INVESTIGATING IN VIVO THROMBOGENICITY OF ULTRAFINE PARTICLES (UFP)

Vanessa M Silva 1*, Nancy Corson 1, Alison Elder 1, and Günter Oberdörster 1

1 University of Rochester, Department of Environmental Medicine, Rochester, NY

* To whom correspondence should be addressed.
Vanessa M Silva, E-mail: gunter_oberdorster{at}urmc.rochester.edu


  Abstract

Recent studies in rodents indicate that intravenous or intratracheal administration of ultrafine particles (UFP) increases thrombogenesis in a surgically-exposed peripheral vein after photodynamic excitation of intravenously-injected rose bengal (RB). We sought to adapt the invasive peripheral vein RB model to a non-invasive monitoring of ear veins under an inverted microscope. Animals received either intraperitoneal, intravenous bolus, or intravenously-infused doses of RB. An ear vein was illuminated by a green laser and formation of a thrombus was captured with a digital camera. In contrast to intravenous or intraperitoneal administration, only continuous intravenous infusion produced a steady state RB plasma level and reproducible thrombus responses in different ear veins of the same rat. This system was then used to study the thrombogenic effects of intravenously-administered positively or negatively charged 60 nm ultrafine polystyrene particles (PSP). Significant dose-dependent enhancement of thrombus formation was found, as indicated by decreased laser illumination time to 33% of baseline values at 0.5 mg/kg. Negatively-charged PSP of the same size failed to affect thrombus formation. We also studied the thrombogenic effect of PSP without the use of RB. Findings were the same as in the presence of RB, albeit illumination time had to be increased. When 0.5 mg/kg was instilled intratracheally, the laser illumination time to form a thrombus was decreased to 42% of baseline value. These results are consistent with previous findings using the invasive model and validate the use of this non-invasive ear vein model to evaluate thrombogenic effects of UFP depositing in the respiratory tract.


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