Cardiovascular effects of multipollutant exposure : mechanisms and interactions

Epidemiological studies have associated higher levels of heart-related hospitalizations and deaths with exposures to elevated levels of fine particle (PM2.5). Ozone (O3) which is a PM2.5 copollutant has also been implicated in deaths from heart-related illnesses. Biologically, inhalation of either of these pollutants can result in formation of reactive oxygen species, oxidative stress, and inflammation, which are involved in the formation of atherosclerotic plaques, increases in blood pressure, changes in heart rate variability and increased frequencies of abnormal heart beats. An important question is whether these two pollutants acting in concert can produce worse outcomes than either acting alone. We addressed this question in two ways. Atherosclerosisprone mice were exposed to concentrated ambient PM2.5 (CAPs), CAPs + 0.2 ppm O3 and O3, alone to examine whether the joint effects of the pollutants were different from the effects of either pollutant alone. The second approach was to contrast the health outcomes of CAPs exposures to particles formed or aged during periods of relatively high photochemical activity (i.e. spring/summer), which increases ambient O3 concentrations, with outcomes of exposures to fall/winter particles which are associated with lower O3 concentrations. We also examined whether there were intrinsic, qualitative, differences in the chemical constituents of the particles that might explain possible health outcome differences in contrasts of the summer vs. winter or CAPs mixtures with 0.2 ppm O3 aerosols. The findings were: 1. Effects of concurrent exposures to CAPs + O3 were not worse than the effects of exposures to the individual pollutants. HRV and ECG changes related to reduced oxygen delivery to the heart were decreased compared to those in air-exposed mice after exposures to CAPs or O3, alone, but not after concurrent exposures to CAPs + O3. Chemical differences that were measured in the particle-associated organic components when 0.2 ppm O3 was added were consistent with oxidation from alcohols -> aldehydes or ketones -> organic acids. We observed that reductions in HRV were associated with increased concentrations of aldehydes while more oxidized aerosols with higher concentrations of organic acids had less effect. 2. CAPs generated in ambient air during periods of high photochemical activity (i.e. summer) may be more biologically active than CAPs generated in the lower photochemical period. Indicators of HRV were decreased after exposure to CAPs in the summer, but HRV in mice exposed to CAPs in the Fall were the same, or increased, compared HRV in the air-exposed group. Blood pressure was significantly increased after the summer CAPs exposures but were reduced after the fall CAPs exposures. There were chemical differences with respect to the organic composition in ambient particles between summer and fall aerosols. 3. We did not demonstrate that after removing the organic constituents from CAPs by thermal denuding, the effects of exposures to the mixture of denuded particles + O3 will be the same as for O3, alone. 4. We demonstrated that O3 and CAPs altered different phases of cardiac activity. CAPs affected the ventricular phase of contraction while O3 affected the atrial