The objectives of this study were (1) to determine whether short-term exposures to concentrated air particles (CAPs) cause pulmonary inflammation in normal rats and rats with chronic bronchitis (CB); (2) to identify the site within the lung parenchyma where CAPs-induced inflammation occurs; and (3) to characterize the component(s) of CAPs that is significantly associated with the development of the inflammatory reaction. Four groups of animals were studied: (1) air treated, filtered air exposed (air-sham); (2) sulfur dioxide treated (CB), filtered air exposed (CB-sham); (3) air treated, CAPs exposed (air-CAPs); and (4) sulfur dioxide treated, CAPs exposed (CB-CAPs). CB and normal rats were exposed by inhalation either to filtered air or CAPs during 3 consecutive days (5 hours/day). Pulmonary inflammation was assessed by bronchoalveolar lavage (BAL) and by measuring the numerical density of neutrophils (Nn) in the alveolar walls at the bronchoalveolar junction and in more peripheral alveoli. CAPs (as a binary exposure term) and CAPs mass (in regression correlations) induced a significant increase in BAL neutrophils and in normal and CB animals. Nn in the lung tissue significantly increased with CAPs in normal animals only. Greater Nn was observed in the central compared with peripheral regions of the lung. A significant dose-dependent association was found between many CAPs components and BAL neutrophils or lymphocytes, but only vanadium and bromine concentrations had significant associations with both BAL neutrophils and Nn in CAPs-exposed groups analyzed together. Results demonstrate that short-term exposures to CAPs from Boston induce a significant inflammatory reaction in rat lungs, with this reaction influenced by particle composition.

Airborne pathogens are associated with the spread of infectious diseases and increased morbidity and mortality. Herein we present an emerging chemical free, nanotechnology-based method for airborne pathogen inactivation. This technique is based on transforming atmospheric water vapor into Engineered Water Nano-Structures (EWNS) via electrospray. The generated EWNS possess a unique set of physical, chemical, morphological and biological properties. Their average size is 25 nm and they contain reactive oxygen species (ROS) such as hydroxyl and superoxide radicals. In addition, EWNS are highly electrically charged (10 electrons per particle on average). A link between their electric charge and the reduction of their evaporation rate was illustrated resulting in an extended lifetime (over an hour) at room conditions. Furthermore, it was clearly demonstrated that the EWNS have the ability to interact with and inactivate airborne bacteria. Finally, inhaled EWNS were found to have minimal toxicological effects, as illustrated in an acute in-vivo inhalation study using a mouse model. In conclusion, this novel, chemical free, nanotechnology-based method has the potential to be used in the battle against airborne infectious diseases.

BackgroundEpidemiologic studies suggest a positive association between fine particulate matter and arterial blood pressure, but the results have been inconsistent.ObjectivesWe investigated the effect of ambient particles on systemic hemodynamics during a 5-hr exposure to concentrated ambient air particles (CAPs) or filtered air (FA) in conscious canines.MethodsThirteen dogs were repeatedly exposed via permanent tracheostomy to CAPs (358.1 ± 306.7 μg/m3, mean ± SD) or FA in a crossover protocol (55 CAPs days, 63 FA days). Femoral artery blood pressure was monitored continuously via implanted telemetry devices. We measured baroreceptor reflex sensitivity before and after exposure in a subset of these experiments (n = 10 dogs, 19 CAPs days, 20 FA days). In additional experiments, we administered α-adrenergic blockade before exposure (n = 8 dogs, 16 CAPs days, 15 FA days). Blood pressure, heart rate, rate–pressure product, and baroreceptor reflex sensitivity responses were compared using linear mixed-effects models.ResultsCAPs exposure increased systolic blood pressure (2.7 ± 1.0 mmHg, p = 0.006), diastolic blood pressure (4.1 ± 0.8 mmHg; p < 0.001), mean arterial pressure (3.7 ± 0.8 mmHg; p < 0.001), heart rate (1.6 ± 0.5 bpm; p < 0.001), and rate–pressure product (539 ± 110 bpm × mmHg; p < 0.001), and decreased pulse pressure (−1.7 ± 0.7 mmHg, p = 0.02). These changes were accompanied by a 20 ± 6 msec/mmHg (p = 0.005) increase in baroreceptor reflex sensitivity after CAPs versus FA. After α-adrenergic blockade, responses to CAPs and FA no longer differed significantly.ConclusionsControlled exposure to ambient particles elevates arterial blood pressure. Increased peripheral vascular resistance may mediate these changes, whereas increased baroreceptor reflex sensitivity may compensate for particle-induced alterations in blood pressure.

A novel method is presented which is suitable for assessing in-vivo the link between the physico-chemical properties of engineered nanomaterials (ENMs) and their biological outcomes. The ability of the technique to generate a variety of industry-relevant, property-controlled ENM exposure atmospheres for inhalation studies was systematically investigated. The primary particle size for Fe2O3, SiO2, Ag and Ag/SiO2 was controlled from 4 to 25 nm, while the corresponding agglomerate mobility diameter of the aerosol was also controlled and varied from 40 to 120 nm. The suitability of the technique to characterize the pulmonary and cardiovascular effects of inhaled ENMs in intact animal models is also demonstrated using in-vivo chemiluminescence (IVCL). The IVCL technique is a highly sensitive method for identifying cardiopulmonary responses to inhaled ENMs under relatively small doses and acute exposures. It is shown that moderate and acute exposures to inhaled nanostructured Fe2O3 can cause both pulmonary and cardiovascular effects.

BackgroundEpidemiologic evidence suggests that chronic stress may alter susceptibility to air pollution. However, persistent spatial confounding between these exposures may limit the utility of epidemiologic methods to disentangle these effects and cannot identify physiologic mechanisms for potential differential susceptibilities.ObjectivesUsing a rat model of social stress, we compared respiratory responses to fine concentrated ambient particles (CAPs) and examined biological markers of inflammation.MethodsTwenty-four 12-week-old male Sprague-Dawley rats were randomly assigned to four groups [stress/CAPs, stress/filtered air (FA), nonstress/CAPs, nonstress/FA]. Stress-group animals were individually introduced into the home cage of a dominant male twice weekly. Blood drawn at sacrifice was analyzed for immune and inflammatory markers. CAPs were generated using the Harvard ambient particle concentrator, which draws real-time urban ambient fine particles, enriching concentrations approximately 30 times. CAPs/FA exposures were delivered in single-animal plethysmographs, 5 hr/day for 10 days, and respiratory function was continuously monitored using a Buxco system.ResultsStressed animals displayed higher average C-reactive protein, tumor necrosis factor-α, and white blood cell counts than did nonstressed animals. Only among stressed animals were CAPs exposures associated with increased respiratory frequency, lower flows, and lower volumes, suggesting a rapid, shallow breathing pattern. Conversely, in animals with elevated CAPs exposures alone, we observed increased inspiratory flows and greater minute volumes (volume of air inhaled or exhaled per minute).ConclusionsCAPs effects on respiratory measures differed significantly, and substantively, by stress group. Higher CAPs exposures were associated with a rapid, shallow breathing pattern only under chronic stress. Blood measures provided evidence of inflammatory responses. Results support epidemiologic findings that chronic stress may alter respiratory response to air pollution and may help elucidate pathways for differential susceptibility.

Ambient air pollution is a complex mixture of particulate matter (PM) and gaseous pollutants such as carbon monoxide (CO). The effect of exposure to CO, alone or in combination with ambient PM, on arrhythmia incidence is unclear. To evaluate these effects, left-ventricular myocardial infarction was induced in Sprague-Dawley rats by thermocoagulation. Diazepam-sedated rats were exposed (1 h) to either filtered air (n = 40), CO (35 ppm, n = 19), concentrated air particles (CAPs, median concentration = 350.5 microg/m(3), n = 53), or CAPs and CO (CAPs median concentration = 318.2 microg/m(3), n = 23), 12-18 h after surgery. Each exposure was immediately preceded and followed by a 1 h exposure to filtered air (pre-exposure and post-exposure periods, respectively). The CO target dose of 35 ppm is related to the 1 h U.S. National Ambient Air Quality Standard. Surface electrocardiograms were recorded and heart rate and arrhythmia incidence were quantified. CO exposure reduced ventricular premature beat (VPB) frequency by 60.4% (p = 0.012) during the exposure period compared to controls. This effect was modified by both infarct type and the number of pre-exposure VPBs, and was not mediated through changes in heart rate. Overall, CAPs exposure increased VPB frequency during the exposure period, but this effect did not reach statistical significance. This effect was modified by the number of pre-exposure VPBs. Overall, neither CAPs nor CO had any effect on heart rate, but CAPs increased heart rate in specific subgroups. No significant interactions were observed between the effects of CO and CAPs. In this animal model, the responses to CO and CAPs are distinctly different.

In vivo chemiluminescence (CL) is a measure of reactive oxygen species in tissues. CL was used to assess pulmonary and cardiac responses to inhaled aerosols derived from aged emissions of three coal-fired power plants in the USA. Sprague–Dawley rats were exposed to either filtered air or: (1) primary emissions (P); (2) ozone oxidized emissions (PO); (3) oxidized emissions + secondary organic aerosol (SOA) (POS); (4) neutralized oxidized emissions + SOA (PONS); and (5) control scenarios: oxidized emissions + SOA in the absence of primary particles (OS), oxidized emissions alone (O), and SOA alone (S). Immediately after 6 hours of exposure, CL in the lung and heart was measured. Tissues were also assayed for thiobarbituric acid reactive substances (TBARS). Exposure to P or PO aerosols led to no changes compared to filtered air in lung or heart CL at any individual plant or when all data were combined. POS caused significant increases in lung CL and TBARS at only one plant, and not in combined data from all plants; PONS resulted in increased lung CL only when data from all plants were combined. Heart CL was also significantly increased with exposure to POS only when data from all plants were combined. PONS increased heart CL significantly in one plant with TBARS accumulation, but not in combined data. Exposure to O, OS, and S had no CL effects. Univariate analyses of individual measured components of the exposure atmospheres did not identify any component associated with increased CL. These data suggest that coal-fired power plant emissions combined with other atmospheric constituents produce limited pulmonary and cardiac oxidative stress.

BackgroundExperimental and observational studies have demonstrated that short-term exposure to ambient particulate matter (PM) exacerbates myocardial ischemia.ObjectivesWe conducted this study to investigate the effects of concentrated ambient particles (CAPs) on myocardial blood flow during myocardial ischemia in chronically instrumented conscious canines.MethodsEleven canines were instrumented with a balloon occluder around the left anterior descending coronary artery and catheters for determination of myocardial blood flow using fluorescent microspheres. Telemetric electrocardiographic and blood pressure monitoring was available for four of these animals. After recovery, we exposed animals by inhalation to 5 hr of either filtered air or CAPs (mean concentration ± SD, 349.0 ± 282.6 μg/m3) in a crossover protocol. We determined myocardial blood flow during a 5-min coronary artery occlusion immediately after each exposure. Data were analyzed using mixed models for repeated measures. The primary analysis was based on four canines that completed the protocol.ResultsCAPs exposure decreased total myocardial blood flow during coronary artery occlusion by 0.12 mL/min/g (p < 0.001) and was accompanied by a 13% (p < 0.001) increase in coronary vascular resistance. Rate–pressure product, an index of myocardial oxygen demand, did not differ by exposure (p = 0.90). CAPs effects on myocardial blood flow were significantly more pronounced in myocardium within or near the ischemic zone versus more remote myocardium (p interaction < 0.001).ConclusionsThese results suggest that PM exacerbates myocardial ischemia by increased coronary vascular resistance and decreased myocardial perfusion. Further studies are needed to elucidate the mechanism of these effects.