Results of this study clearly demonstrate that the EC and EC subfractions drive the acute changes in HR, HRV and BP in hypertensive rats exposed to an urban-industrial aerosol. These findings are consistent with our previous report of EC’s relation with HR in the same rat model , but we now extend these observations to identify EC-associated effects on BP as well, suggesting a more profound overall impact on cardiovascular health. Furthermore, we detected associations between EC subfractions and cardiac function, especially between EC1 and EC2 with HR and HRV. By comparison to EC, OC was associated with only modest and sometimes opposing cardiovascular effects in PM2.5-exposed rats. To our knowledge, our current findings are the first to describe associations of cardiovascular health effects with inhaled PM2.5 carbon subfractions using thermal/optical analytical methods.
Although not all source apportionment studies include EC and OC in their factor resolution, those that do typically find that these PM components load onto mobile source emissions factors [24, 25]. Furthermore, the separation of carbonaceous fractions derived from progressive oxidation temperatures suggest that the subfraction EC1 is generally linked to diesel engine sources, whereas OC fractions (OC1-4) are normally associated with gasoline emissions [17, 26]. It is notable, therefore, that the adverse cardiovascular responses we describe for EC and its subfractions are consistent with HR, HRV and BP responses reported during controlled exposures to whole diesel engine exhaust in the same SH strain of rats we used in the current study [27, 28]. While major components of laboratory-generated diesel exhaust are gaseous inorganic compounds (nitrogen oxides, sulfur dioxide, and carbon monoxide), the minor components of particulate EC and of volatile and semivolatile organic compounds (OC) have been linked to stimulation of both sympathetic and parasympathetic cardiovascular effects in SH rats where exposures compared whole versus filtered exhaust [29, 30]. A major difference in our field studies compared to laboratory-generated diesel engine exhaust is the atmospheric transformation of EC core particulates that might result in surface adherence of volatile organic hydrocarbons such as carbonyls, or in oxidative modifications that alter the particle’s toxicity [31, 32]. OC was a major component of PM2.5 mass at our urban site, and though not strongly associated with health effects in our study, it may contribute to cardiovascular effects as a surface component of diesel soot particles.
Our study location in Dearborn, MI is located near automotive production industries with heavy vehicle and diesel traffic in the surrounding community. Of note are several active trucking facilities within a mile of the site, with several hundred trucks loading and unloading cargo daily, as well as a railyard within 250 m of the site. We recently compared cardiometabolic responses in twenty-five volunteers before, during and after ambient exposures at this same industrial site, relative to their residences in rural upwind areas of Dexter, MI . After five daily exposures, decreases in HRV and insulin resistance were associated with increased PM2.5. Further analyses of source:health effect relationships found that changes in HR, BP and trends for impaired endothelial function were associated with the diesel source factor that impacted this site . Fewer health effects were associated with other PM source factors, with motor vehicle sources being linked to changes in BP, and iron/steel and secondary aerosol source factors being associated with changes in HR. We recently reported dramatic drops in BP and HR in fructose-fed rats with cardiometabolic syndrome exposed to PM2.5 at this same site in Dearborn; however, analyses to attribute specific sources with CV responses have not been completed . Our findings with EC and subfractions in the current study adds to our previous work with PM2.5-exposed SH rats where EC and traffic sources had robust associations with changes in HR and HRV in urban Detroit, MI and Steubenville, OH [20, 21].
To date, carbon subfraction analysis has been employed in air pollution studies primarily to incorporate fractions into source apportionment analyses and, ideally, to improve source factor resolution [36, 37]. For the most part, such studies have also been able to differentiate gasoline from diesel emissions, as discussed above. In addition, some work has investigated indoor and non-indoor sources of carbon fractions in residential homes . We were able to identify one in vitro study including carbon subfractionation in which human lung epithelial cells were exposed to dust from soil and road surfaces in the western United States . Release of inflammatory mediators was most highly correlated with the EC1 fraction, while lesser correlation coefficients were observed for OC fractions and pyrolized carbon. Compared to other EC fractions, compounds that comprise EC1 and EC2 would be more volatile, of smaller molecular weight, and a less complex structure. Less clear are the molecular targets, receptors or proteins with which different subfractions may preferentially interact to elicit biological responses. In addition to the greater responses induced in airway cells, smaller sized EC1 compounds would theoretically be better able to translocate and influence extarpulmonary responses. However, epidemiological or clinical evidence for EC subfraction-associated health effects is lacking, and we speculate that EC and EC1may be markers for other pollutants or pollutant mixtures that underlie the health effects we describe in exposed rats.
In similar PM2.5 field exposures in urban areas we have previously identified associations of health effects with a number of trace elements that are linked to industrial activities in the Midwest [21, 40]. In the current analyses, several elements had statistically significant associations with HR, HRV and BP, but we interpret the effect sizes as having questionable biological relevance (e.g., < 0.1 bpm HR). Interestingly the greatest and most consistent effects were found with uranium, which had a considerable effect estimate for its association with increases in diastolic BP (13 mmHg). Using x-ray diffraction analysis to assess Detroit PM constituents, our colleagues showed that uranium is colocalized with EC in graphene structures . Its source in the urban industrial airshed in southwest Michigan is unknown although it has been associated with coal combustion . In our study, despite health effects associated with this element, other elements and components typically associated with coal-fired power plant emissions such as sulfate, selenium, and arsenic, yielded no adverse health effects findings.
Compared to most of our community-based animal studies, the current investigation is limited by the use of 8 h-integrated PM2.5 samples to estimate effects on daily changes in cardiovascular responses. Our group is unique in that we have used 30-minute sampling periods for both particle collection and cardiotelemetry recording; however, the necessary instrumentation was not available for all studies in this project. A second limitation is the lack of normotensive control subjects with which to compare our responses in the SH rats. We have previously used Wistar Kyoto rats as our healthy controls, but because of space limitations in the exposure chamber they were omitted to allow for a larger group number of hypertensive rats. As such any translation of our findings to understand potential susceptibility is limited.
In summary, this is the first report of cardiovascular health effects linked to inhalation exposure to ambient PM2.5 carbon subfractions. Increased BP and HR and decreases in HRV showed robust associations with EC, and our initial findings using thermal optical approaches yielded strong relationships of EC1 and EC2 with changes in HR and HRV. Interestingly, we found relatively fewer and weaker responses with OC fractions or trace elements. Black carbon has been proposed as an important indicator of PM-induced health effects , and our results with EC add to this evidence, specifically for adverse cardiovascular responses. Future research efforts that include the analyses of carbon subfractions are needed to confirm our observations, and will help to further characterize the contribution of EC to the health risk of PM2.5 exposures.