Recent epidemiological studies suggest that long-term exposure to particulate matter (PM) causes chronic effects on the cardiovascular system that result in cumulative increases cardiovascular morbidity and mortality. Since atherosclerosis is a progressive irreversible condition and an underlying cause of many cardiovascular diseases, we hypothesized that long-term exposure to PM causes adverse cardiovascular effects by exacerbating atherosclerosis. In this study, we exposed C57- and ApoE-deficient (ApoE-/-) and ApoE, LDLr (DK)-deficient mice to concentrated ambient PM2.5 for 6 h/5 days/wk, for up to 5 mo. The overall mean exposure concentration for these groups of animals was 110 microg/m3. The cross-sectional area of the aorta root of DK mice was examined morphologically using confocal microscopy for the severity of lesion, extent of cellularity, and lipid contents. Aortas from the arch to the iliac bifurcations were also sectioned longitudinally and lesion areas were stained with Sudan IV. All DK mice regardless of exposure had developed extensive lesions in the aortic sinus regions, with lesion areas that covered more than 79% of the total area. In male DK mice, the lesion areas in the aortic sinus regions appeared to be enhanced by concentrated ambient particles (CAPs), with changes approaching statistical significance (p = .06). In addition, plaque cellularity was increased by 28% (p = .014, combined), whereas there were no CAPs-associated changes in the lipid content in these mice. When examining the entire aorta opened longitudinally, both the ApoE-/- and DK mice had prominent areas of severe atherosclerosis covering 40% or more of the lumenal surface. Visual examination of all images suggested that plaques tend to form in clusters concentrating near the aortic arch and and the iliac bifurcations. Quantitative measurements showed that CAPs exposure increased the percentage of aortic intimal surface covered by grossly discernible atherosclerotic lesion by 57% in the ApoE-/- mice (p = .03). Changes produced by CAPs in male (10% increase) or female DK mice (8% increase) were not statistically significant. In this study, we have demonstrated that subchronic exposure to CAPs in mice prone to develop atherosclerotic lesions had a significant impact on the size, severity, and composition of aortic plaque.

No abstract

Respiratory-tract infection, specifically pneumonia, contributes substantially to the increased morbidity and mortality among elderly individuals exposed to airborne particulate matter of <10 microm diameter (PM(10)). These epidemiological findings suggest that PM(10) may act as an immunosuppressive factor that can undermine normal pulmonary antimicrobial defense mechanisms. To investigate whether, and how, compromised pulmonary immunocompetence might contribute to increased mortality, two sets of laboratory studies were performed. The first examined the effects of a single inhalation exposure to concentrated ambient PM(2.5) (CAPS) from New York City air on pulmonary/systemic immunity and on the susceptibility of exposed aged rats to subsequent infection with Streptococcus pneumoniae. The second set of studies determined whether CAPS exposure, at a concentration approximating or somewhat greater than the promulgated 24-h NAAQS of 65 microg/m(3), could exacerbate an ongoing infection. Taken together, results demonstrated that a single exposure of healthy animals to CAPS had little effect on pulmonary immune function or bacterial clearance during subsequent challenge with S. pneumoniae. Alternatively, CAPS exposure of previously infected rats significantly increased bacterial burdens and decreased percentages of lavageable neutrophils and proinflammatory cytokine levels compared to those in infected filtered-air-exposed controls. These studies demonstrate that a single exposure to ambient PM(2.5) compromises a host's ability to handle ongoing pneumococcal infections and support the epidemiological findings of increased pneumonia-related deaths in ambient PM-exposed elderly individuals.

We modified, assembled, tested, and validated the versatile aerosol concentration enrichment system (VACES) developed by Sioutas et al. (1999) for use in a subchronic experiment that involved exposure of mice in vivo and of respiratory epithelial cells in vitro to concentrated ambient particles (CAPs). Since the labor-intensive nose-only exposure regimen is not an option in a long-term experiment, a whole-body exposure mouse chamber was designed specifically for use with the VACES. The exposure system concsists of a stainless-steel (SS) tub with 32 cubicles (1 mouse per cubicle) separated by perforated SS sheets. The tops of these cubicles are covered with perforated plastic sheets to allow telemetry monitoring during the exposure. In each exposure chamber, perforated aluminum tubes are used to distribute CAPs evenly (within 2% difference) throughout the exposure chamber. The exhaust consists of perforated aluminum tubes covered with a urine shield. The modification to the original design of the VACES facilitated the operation of the system in a subchronic study. Mass flow controllers maintain a constant flow rate into the exposure chambers. For a sham control exposure, the identical system is used, except that a HEPA filter at the inlet to the VACES removes 98% of ambient particles. The entire system allow for simultaneous exposure of 64 mice to CAPs, with an equal number of sham-expose mice as controls. Telemetry receives have been modified so that 16 mice per group with electrocardiograph (EKG) transmitters can be monitored during exposure. Furthermore, a BioSampler is used to collect CAPs (one sample per day) for the in vitro exposures. In this article, the assessments of flow and particle distribution of the exposure chamber as well as the performance of the system during the subchronic exposure experiment are described.

The mechanism of gastric mucosal protection by an antiulcer agent, geranylgeranylacetone (GGA), against ethanol-induced injury was investigated. The experiments were conducted with groups of rats with and without intraperitoneal indomethacin pretreatment. Animals received intragastrically either a dose of GGA (200 mg/kg) or a vehicle, followed 30 min later by 1 ml of absolute ethanol. The rats were sacrificed after 30 min and the gastric mucosa was subjected to macroscopic and histologic assessment and the measurements of adherent mucus, its dimension and chemical composition. In the absence of GGA, ethanol produced advanced macroscopic necrosis ( > 38%) and the extensive necrotic lesions were visible upon histologic examination. Pretreatment with GGA significantly reduced (p < 0.001) the extent and depth of mucosal necrotic lesions caused by ethanol, and this protection was not thwarted by indomethacin. Evaluation of the adherent mucus and its dimension by Alcian blue uptake and inverted microscope technique revealed that GGA was also capable of preventing the untoward effect of indomethacin on the adherent gastric mucus gel and its thickness. Results of chemical analyses established that in the absence of GGA indomethacin caused an increase in mucus protein (15%) and a decrease in its covalently bound fatty acids (67%) and lipids (36%). The decrease in lipids was particularly reflected in the content of phospholipids. Indomethacin, however, had no apparent effect on the composition of gastric mucus elaborated in the presence of GGA. The results suggest that gastric mucosal protective action of GGA is not mediated by endogenous prostaglandins but rather appears to involve the metabolism of mucosal lipids.