September 06, 2005
Lindsay B. Wicher presents her Final Doctoral Dissertation Defense Tuesday, September 6, 2005 at 11:00am in 2005 Michael Hooker Research Center.Effects of Inhaled Combustion-Derived Particulate Matter on Indices of Cardiac, Pulmonary, and Thermoregulatory Function in Spontaneously Hypertensive Rats Using a Novel Exposure Method To Characterize Dose

(Under the direction of Dr. Louise M. Ball and Dr. William P. Watkinson)

It is well established that an association exists between elevated levels of ambient particulate matter (PM) and reported incidences of cardiopulmonary illness and death. Animal toxicological research has been conducted to elucidate the pathways and mechanism(s) by which these effects are mediated; however, concerns remain regarding the toxicity of surrogate PM species, as well as the high concentrations commonly employed in these studies. To address these issues, Spontaneously Hypertensive (SH) rats were exposed via inhalation to a combustion-derived PM (HP12), a particle with a more relevant metal profile than residual oil fly ashes used previously. Animals were divided into air and HP12 groups and exposed for 6 hr/day (0, 3, or 12 mg/m3) for either one or four days while maintained inside whole-body plethysmograph chambers. This methodology permitted continuous acquisition of noninvasive pulmonary functional parameters during exposure and the system was found to be reliable and consistent over these exposure protocols. Rats were surgically implanted with radiotelemeters that continuously monitored electrocardiogram (ECG), heart rate (HR), systemic arterial blood pressure (BP), and core temperature (Tco) throughout the study; all rats were sacrificed at six days post-exposure to obtain blood and bronchoalveolar lavage fluid (BALF). Following a 4-day exposure, there were no changes in HR, BP, or Tco, but ECG abnormalities were observed in .50% of the rats exposed to 12 mg/m3 HP12. There were slight increases in a few blood and BALF indices, while there were only minor effects on respiratory parameters. In a subsequent study, SH rats were exposed to 13 mg/m3 of HP12 and sacrificed at the cessation of exposure to assess particle deposition in tracheas and lung lobes. Total deposition was 20-60

Committee Members:

Louise M. Ball, Ph.D.

William P. Watkinson, Ph.D.

David Leith, Ph.D.

Daniel L. Costa, Ph.D.

John J. Vandenberg, Ph.D.

For further information please contact Rebecca Riggsbee Lloyd by email at Rebecca_Lloyd@unc.edu

 

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