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[Quantitative analysis of particulate matter in infusion solutions, administration sets and additives (author's transl)].

There have been recevitly many comments on clinical and experimental reports which have demonstrated the safety problems associated with parenteral drugs contaminated with particles. Some countries have developed recommendations with a standard for counting of particles and their limits. Based on these limits, we have made a critical quantitative analysis of particulate matter in the most common commercially produced solutions, of particles added during manipulations in clinics and addition of drugs. Most authorities agree that particulate contamination should be kept to a minimum, above all in an intensive-care-unit where patients receive large quantities of solutions. As the risk to the patient is unacceptably high, many authors ask for filters to prevent the injection of particles in the bloodstream and their pathological consequences. A filter pore-size of 5 to 10 micron should be able to reduce this problem in a sufficient manner, without decreasing the infusion flow; whereas membrane-filters (0.22 micron), with their own problems, could also eliminate bacteria together with their microbiological hazards. Another source of particulate matter is represented by the injection of two or more drugs, administered at the same time, which may lead to chemical incompatibilities. This problem is not yet defined very well. To complete our quantitative analysis, we decided to start a prospective clinical study.

Critical Care↗

Gaseous pollutants in particulate matter epidemiology: confounders or surrogates?

Air pollution epidemiologic studies use ambient pollutant concentrations as surrogates of personal exposure. Strong correlations among numerous ambient pollutant concentrations, however, have made it difficult to determine the relative contribution of each pollutant to a given health outcome and have led to criticism that health effect estimates for particulate matter may be biased due to confounding. In the current study we used data collected from a multipollutant exposure study conducted in Baltimore, Maryland, during both the summer and winter to address the potential for confounding further. Twenty-four-hour personal exposures and corresponding ambient concentrations to fine particulate matter (PM(2.5)), ozone, nitrogen dioxide, sulfur dioxide, and carbon monoxide were measured for 56 subjects. Results from correlation and regression analyses showed that personal PM(2.5) and gaseous air pollutant exposures were generally not correlated, as only 9 of the 178 individual-specific pairwise correlations were significant. Similarly, ambient concentrations were not associated with their corresponding personal exposures for any of the pollutants, except for PM(2.5), which had significant associations during both seasons (p < 0.0001). Ambient gaseous concentrations were, however, strongly associated with personal PM(2.5) exposures. The strongest associations were shown between ambient O(3) and personal PM(2.5) (p < 0.0001 during both seasons). These results indicate that ambient PM(2.5) concentrations are suitable surrogates for personal PM(2.5) exposures and that ambient gaseous concentrations are surrogates, as opposed to confounders, of PM(2.5). These findings suggest that the use of multiple pollutant models in epidemiologic studies of PM(2.5) may not be suitable and that health effects attributed to the ambient gases may actually be a result of exposures to PM(2.5).

Adolescent↗

Tobacco smoke particulate matter chemistry by NMR.

The submicron liquid droplets constituting the particulate matter of mainstream tobacco smoke (PMMTS) are viscous and of a composition that is complex and poorly understood. PMMTS is often approximately 80% w/w 'tar' where 'tar'=total PMMTS- (nicotine+water). Many of the chemical agents in MTS responsible for smoking-related cancers are found at least partially in the PMMTS portion of MTS. The properties of PMMTS vary with brand and with puffing patterns. The chemical forms and total levels of nicotine, the identities/levels of other compositionally dominant compounds, and the identities/levels of carcinogens are of interest. Most studies of the composition of PMMTS have involved extraction then chromatography. Such methods allow the determination of low-level constituents, but alter the samples such that direct information regarding chemical conditions within the PMMTS cannot be obtained. Here, we utilize nuclear magnetic resonance spectroscopy (NMR) to examine native PMMTS in conventional cigarettes, including measurements of the brand-dependent fraction of PMMTS nicotine that is in the free-base form (increasing this fraction in inhaled tobacco smoke affects the rates of the processes governing nicotine deposition in the respiratory tract, and so has implications for smoking behavior and addiction). We also demonstrate the use of NMR for characterizing the composition of PMMTS (including the levels of selected cigarette additives) when the cosolvent DMSO-d6 is added to improve spectral resolution. The native and solvent-assisted results open the door to a range of future studies.

Journal Article↗

The effects of ventilation and the dilution of smoke upon the clastogenic and aneugenic activity of tobacco particulate matter in cultured mammalian cells.

We demonstrate here that tobacco particulate matter (TPM) produced from both non-ventilated and ventilated cigarettes of varying tar contents induced structural and numerical aberrations in cultured Chinese hamster cells. Our data indicate that TPM from ventilated cigarettes is of lower potency in inducing both clastogenic and aneugenic effects compared with TPM from non-ventilated cigarettes. These observations provide support for the concept that the genotoxic activity (to cultured Chinese hamster cells) of cigarette smoke is reduced by increased ventilation to a greater extent than a 1:1 ratio between yield reduction and smoke dilution.

Aneuploidy↗

A study of the particulate matter PM10 composition in the atmosphere of Chillán, Chile.

Inhalable particulate matter (PM10) concentrations were measured over 24-h intervals at six different urban sites in the city of Chillán from September 2001 to April 2003. Sampling locations were selected to represent central city, commercial, residential, and industrial portions of the city. Chemical composition of PM10 was performed to samples of 47 mm diameter Teflon membranes within the city of Chillán. The spatial and temporal variability of the chemical composition of PM10 was evaluated taking into account additional data from meteorology and further air pollutants. The majority of PM mass was comprised of carbon, nitrate, sulfate, ammonium, and crustal components but in different proportion on different days and at different sites. The chemical analyses showed that carbonaceous substances and crustal material were the most abundant component of PM10 during the winter and summer, respectively. The concentrations of PM10 were higher during the cold season than during the warm season. The PM10 concentrations were higher in the downtown area of the city of Chillán, where also the chemical composition was more variable due to urban traffic and other anthropogenic sources.

Aerosols↗

Comparative studies on the concentration of rare earth elements and heavy metals in the atmospheric particulate matter in Beijing, China, and in Delft, The Netherlands.

Atmospheric particulate matter (APM) was collected at three sampling sites in Beijing, China, from February to June 1998. The concentrations of rare earth elements (REE) and cobalt (Co), zinc (Zn), copper (Cu), cadmium (Cd) and lead (Pb) in the APM were determined by inductively coupled plasma mass spectrometry (ICP-MS). The results obtained in Beijing, China, were compared to that obtained in Delft, the Netherlands, in 1997. The influence of coal combustion was considered. The results demonstrated that the content of APM, the concentrations of REE and Co, Zn, Cd, Pb in the APM in Beijing, China, were higher than that in Delft, the Netherlands. From the ratios of La to Ce, and La to Sm, which may be used as tracers for the origin of the REE, it is concluded that the origins of REE in China differ from those in the Netherlands.

Air Pollutants↗

Midpolarity and nonpolar wood smoke particulate matter fractions deplete glutathione in RAW 264.7 macrophages.

Wood smoke particulate matter (PM) is a complex mixture of components falling in a spectrum of highly polar to nonpolar species. Wood smoke PM is a likely factor in pulmonary disease and induces oxidative damage. Most toxicity studies focus upon nonpolar species such as polycyclic aromatic hydrocarbons (PAHs). However, the role of more polar PM constituents as toxicants is not clear. In this work, we evaluated the ability of multiple fractions of varying polarity to deplete glutathione (GSH) in RAW 264.7 macrophages and BEAS-2B bronchial epithelial cells. We utilized hot pressurized (subcritical) water to fractionate wood smoke PM into seven fractions of decreasing polarity. In contrast to polar fractions, midpolarity and nonpolar fractions exhibited greater GSH depletion (ED50 at PM concentrations of approximately 50 microg/mL). GSH depletion caused by nonpolar fractions (extracted at 250-300 degrees C) was associated with the presence of PAHs. In midpolarity fractions (extracted at 100-150 degrees C), oxy-PAHs, syringylguaiacyls, disyringyls, and lower molecular weight PAHs were found. Direct comparison of GSH depletion by individual oxy-PAHs and PAHs suggests that oxy-PAHs are contributors to oxidative stress caused by wood smoke PM. However, other unidentified PM constituents contribute to GSH depletion as well. The results indicate the toxicological importance of oxygenated organics found in midpolarity PM fractions.

Animals↗

Bronchoconstriction provoked by exercise in a high-particulate-matter environment is attenuated by montelukast.

Airborne ultrafine and fine particulate matter (PM1 from fossil-fueled internal combustion engines may cause abnormal airway narrowing. Because of high PM1 exposure from ice resurfacing machines, the ice-rink athlete is especially vulnerable to PM1 toxicity. The purpose of this study was to evaluate protection by a single dose of montelukast in college ice hockey players following PM1 exposure exercise. Nine male ice hockey players (age 19.3+/-1.22 yr) performed 4 randomized, double-blinded, high-intensity, 6-min cycle ergometer trials in low [PM1] (2260+/-500 particles/cm3) and high [PM1] (348,600+/-121,600 particles/cm3) after placebo or montelukast. Pre- and postspirometry showed similar peak FEV1 (forced expiratory volume in 1 s) falls between placebo and montelukast after low [PM1] trials (14.5+/-18.06 vs. 9.5+/-11.75% of baseline, respectively). Peak FEV1 falls after high [PM1] trials were greater for placebo than for montelukast (17.3+/-9.79% vs. 1.7+/-5.77% of baseline; p<.0001). High [PM1] FEV1 fall after exercise following montelukast ingestion was less than after exercise following placebo ingestion under high and low [PM1] conditions and after exercise following montelukast ingestion under low [PM1] conditions at 5, 10, and 15 min postchallenge (p<.004, .0006, .009, respectively). Montelukast provided greater protection against bronchoconstriction after exercise during high [PM1] than low [PM1] exposure (approximately 90% vs. approximately 35%), suggesting that bronchoconstriction from PM1 exposure is predominately leukotriene mediated. The precise mechanism of airborne PM1-induced leukotriene-mediated airway narrowing remains unclear.

Acetates↗

Estimated hourly personal exposures to ambient and nonambient particulate matter among sensitive populations in Seattle, Washington.

Epidemiological studies of particulate matter (PM) routinely use concentrations measured with stationary outdoor monitors as surrogates for personal exposure. Despite the frequently reported poor correlations between ambient concentrations and total personal exposure, the epidemiologic associations between ambient concentrations and health effects depend on the correlation between ambient concentrations and personal exposure to ambient-generated PM. This paper separates personal PM exposure into ambient and nonambient components and estimates the outdoor contribution to personal PM exposures with continuous light scattering data collected from 38 subjects in Seattle, WA. Across all subjects, the average exposure encountered indoors at home was lower than in all other microenvironments. Cooking and being at school were associated with elevated levels of exposure. Previously published estimates of particle infiltration (Finf) were combined with time-location data to estimate an ambient contribution fraction (alpha, mean = 0.66+/-0.21) for each subject. The mean alpha was significantly lower for subjects monitored during the heating season (0.55+/-0.16) than for those monitored during the nonheating season (0.80+/-0.17). Our modeled alpha estimates agreed well with those estimated with the sulfur-tracer method (slope = 1.08; R2 = 0.67). We modeled exposure to ambient and nonambient PM with both continuous light scattering and 24-hr gravimetric data and found good agreement between the two methods. On average, ambient particles accounted for 48% of total personal exposure (range = 21-80%). The personal activity exposure was highly influenced by time spent away from monitored microenvironments. The median hourly longitudinal correlation between central site concentrations and personal exposures was 0.30. Although both alpha and the nonambient sources influence the personal-central relationship, the latter seems to dominate. Thus, total personal exposure may be poorly predicted by stationary outdoor monitors, particularly among persons whose PM exposure is dominated by nonambient exposures, for example, those living in tightly sealed homes, those who cook, and children.

Air Pollutants↗

Retained nitrate, hydrated sulfates, and carbonaceous mass in federal reference method fine particulate matter for six eastern U.S. cities.

Material balance of fine particulate matter (PM2.5) measured with the Federal Reference Method (FRM) is developed for one rural and five urban locations in the eastern half of the United States using routine Speciation Trends Network (STN) and FRM chemical measurements and thermodynamic models. The Aerosol Inorganics Model is used to estimate retained particle bound water, and an ammonium nitrate evaporation model is used to estimate nitrate concentrations retained on the Teflon-membrane filter of the FRM. To address large uncertainties in carbonaceous mass calculated from STN carbon measurements, retained carbonaceous mass is derived by material balance between PM2.5 FRM mass and estimates of its non-carbon constituents. The resulting sulfate, adjusted nitrate, derived water, inferred carbonaceous material balance approach (SANDWICH) is compared with reconstructed fine mass (RCFM) using the Interagency Monitoring of Protected Visual Environments monitoring program equation. For this study, the SANDWICH method resulted in approximately 21-27% higher sulfate mass and approximately 24-85% lower nitrate mass. The combined mass associated with sulfates and nitrates, however, are well within +/- 10% of the proportion derived using the more traditional RCFM method. The discrepancies between SANDWICH and measurement-derived carbonaceous mass vary from -21% to +56% on an annual basis and are attributed in part to urban-rural source influences and uncertainties in estimating FRM-retained carbonaceous mass.

Air Pollutants↗

Statistical comparison of diesel particulate matter measurement methods.

Four methods are used to quantify diesel particulate matter (DPM) in the mine environment: respirable combustible dust sampling (RCD), size selective sampling with gravimetric analysis (SSG), respirable dust sampling with elemental carbon (EC) analysis, and respirable dust sampling with total carbon (TC) analysis. The authors assembled data from three underground mine studies to statistically compare these methods. The sampling protocol used in each study was similar. For all the four methods, samples were collected in triplicate at three locations-upwind and downwind of the diesel scoop and on the scoop. The methods were compared with respect to their precision, selectivity, sensitivity, and LOD, as well as their limitations in measuring DPM concentrations. This constitutes a meta-analysis of the available data and provides information over a broader range of mining conditions and DPM concentrations than any of the individual studies. The weighing imprecision for the SSG method is almost twice that for the RCD technique. The imprecision of the EC and TC methods are a function of the mass loading, and EC has a lower imprecision than TC. The EC method was used as the reference "gold standard" against which the other methods were evaluated. The RCD, SSG, and TC methods exhibited substantial levels of interference, leading to much higher minimum concentrations that can be measured by these methods. Of the three, the SSG method has the highest level of interference, primarily from nondiesel material that is collected in the <0.8 microm size range.

Air Pollutants, Occupational↗

Toxicologic and epidemiologic clues from the characterization of the 1952 London smog fine particulate matter in archival autopsy lung tissues.

Exposure to atmospheric fine particulate matter (PM), even at low ambient concentrations, has clearly been linked to increases in mortality and morbidity. A 10- micro g m(-3) increase in PM10 (PM < 10 micro m) has been found to produce a 0.5% increase in daily mortality. The mechanism of action is a source of debate, although recent attention has focused on the cardiac effects of PM exposures. Likewise, several possible etiologic agents have been implicated, including ultrafine PM (PM <or= 100 nm), metals, and the acid components, yet the responsible constituent remains undetermined. During the catastrophic PM exposure episode in London in December 1952, some 4,000 excess deaths occurred at the height of the event. The extreme mortality during that episode and the preservation of archival autopsy tissues allow us the unique opportunity to report on the form and composition of December 1952 London PM in situ in tissues from persons known to have died from the smog exposure. Because absolute increases in mortality with current levels of PM in Western Europe and North America are low, analogous tissues are unlikely to be contemporaneously available. Taking a lung compartment (airway, airspace, interstitium, and lymph node) approach, we differentiated exposures contemporary with death from those of earlier origin. Electron microscopic analyses revealed the dominance of retained soot and a surfeit of other particle types. A variety of metal-bearing particle types were found in all compartments, but Pb, Zn, and SnZn types appeared the least biopersistent. The results support the acute toxicologic importance of ultrafine carbonaceous and metal PM.

Adult↗

Correlations between mutagenic activity of organic extracts of airborne particulate matter, NOx and sulphur dioxide in southern Germany: results of a two-year study.

GOALS, SCOPE AND BACKGROUND: Among other substances, sulphur dioxide (SO2), nitric oxide (NO) and nitrogen dioxide (NO2) are parameters which are routinely measured to describe basic air quality. Organic extracts of airborne particulate matter contain mutagenic chemical compounds of different origins. The aim of the study was to find correlations between routine monitoring data and mutagenic activity of organic extracts of simultaneously drawn samples. METHODS: Specimens were collected over a period of two years at 8 sampling sites in south-west Germany. Simultaneously, concentrations of NO, NO2, and SO2 were measured on-line within the framework of the official air monitoring network of Baden-Württemberg, Germany. Dust samples were collected for biotesting using high volume air samplers equipped with glass fibre filters. After sampling was completed, filters were extracted and samples were prepared for biological testing. Mutagenic activity was tested by means of the plate incorporation assay (Ames test) using S. typhimurium TA98 and TA100 tester strains. During the first year of the study, all tests have been performed with and without metabolic activation. Additionally, a series of tests has been performed in parallel with TA98 and TA98NR. RESULTS AND DISCUSSION: Comparison of Ames test data obtained with and without metabolic activation indicates no statistically significant difference between both methods. Therefore, during the second year of the study, all tests have been performed without metabolic activation. Average yearly activities at the sampling sites were between 1 and 27 Revertants per m3 (Rev/m3). High activities were preferably found at congested sites (Karlsruhe, up to 95 Rev/m3). However, peak values of over 100 Rev/m3 were found in other places where pollution by traffic is significantly lower. The reason for these high level values is not evident. Tests performed using TA98NR tester strain indicate a significant share (average 31%) of compounds requiring activation by nitroreductase for mutagenic activity. Average mutagenic activity can be correlated to routine monitoring parameters. Comparison of averaged data for particular sampling sites indicates significant correlation between nitric oxide and mutagenic activity in TA98 (r2=0.90), while correlation between nitrogen dioxide (0.84) or sulphur dioxide (0.52) and mutagenic activity is weaker. For TA100, correlations are generally weaker than for TA98. Comparison of data for mutagenic activity and routine monitoring data of distant sites being sampled simultaneously shows parallel behaviour. CONCLUSIONS: Results from this study show that mutagenic activity can be compared to seasonal and local variations of gaseous indicator air pollutants. Tester strain TA98 generally shows the best correlations. Although pollution by particle-bound mutagenic substances is significantly higher during the cold season than during summer on average, mutagenic activity of airborne dust is not a continuous effect. During winter, peak levels as well as low pollution periods can occur. Even during winter time mutagenic activity can reach very low levels typical for summertime. Comparison of results for distant sampling sites where samples have been collected simultaneously indicate that 'classical' indicators of air pollution and bacterial mutagenicity of organic extracts from airborne particulate matter are influenced by connected effects. Seasonal trend of mutagenic activity, in particular, is similar to the concentrations of nitrogen oxide. NO is a strong indicator for vehicle exhaust gases. It is concluded that the average mutagenic activity at particular sites can be estimated using NO concentrations as an indicator.

Air Pollutants↗

Endotoxin and particulate matter on surgical gloves.

Because of the continual need to protect of health care workers, gloves are increasingly used. Most gloves purchased are powdered. Besides having deleterious effects on wound healing, glove powder can act as a vehicle for latex allergens, endotoxin, and possibly bacteria. Few tested gloves had undetectable levels of endotoxin, and only one was free from particulate matter. Since powder particles can become airborne and are thus easily spread, concerns for health care professionals and patients arise. To reduce risks for exposure, glove-selection criteria must include low or undetectable levels of latex allergens, endotoxin, and particulate matter.

Endotoxins↗

Physico-chemical characterization of indoor/outdoor particulate matter in two residential houses in Oslo, Norway: measurements overview and physical properties--URBAN-AEROSOL Project.

Indoor/outdoor measurements have been performed in the Oslo metropolitan area during summer and winter periods (2002-2003) at two different residential houses. The objective of the measurement study was to characterize, physically and chemically, the particulate matter (PM) and gaseous pollutants associated with actual human exposure in the selected places, and their indoor/outdoor relationship. In this paper, we focus on the PM measurements and examine the relationship between the indoor and outdoor PM concentrations taking into account the ventilation rate, indoor sources and meteorological conditions. The indoor/outdoor measurements indicate the important contribution of the outdoor air to the indoor air quality and the influence of specific indoor sources such as smoking and cooking to the concentration of PM inside houses. However, no specific correlation was found between the indoor/outdoor concentration ratio and the meteorological parameters. This study provides information on the physical characteristics and the relationship of indoor to outdoor concentration of particulate matter in residential houses. Moreover, the parameters that influence this relationship are discussed. The results presented here are specific to the sampled houses and conditions used and provide data on the actual human exposure characteristics which occur in the spatial and temporal scales of the present study.

Aerosols↗

Speciation of nickel in airborne particulate matter by means of sequential extraction in a micro flow system and determination by graphite furnace atomic absorption spectrometry and inductively coupled plasma mass spectrometry.

A four-stage sequential extraction procedure for the speciation of nickel has been applied to ambient aerosol samples. The determination of the soluble, sulfidic, metallic and oxidic Ni fractions in particulate matter was carried out by graphite furnace (electrothermal) atomic absorption spectrometry (ETAAS) and inductively coupled plasma mass spectrometry (ICP-MS). An EDTA solution, a mixture of diammonium citrate and hydrogen peroxide, and a KCuCl3 solution were used as leaching agents for the determination of the soluble, sulfidic and metallic species, respectively, and nitric acid was used for the determination of oxidic compounds after microwave digestion of particulate matter sampled on filters. A new micro scale filter holder placed in a closed flow injection analysis (FIA) system for use in nickel speciation by means of sequential extraction, and the results of the optimisation of the extraction conditions are described. The temperature program for ETAAS was optimised for all extraction solutions with the aid of temperature curves. Pyrolysis temperatures of 900. 600 and 1,000 degrees C were found to be optimum for EDTA, hydrogen peroxide plus ammonium citrate and KCuCl3-containing solutions, respectively. Airborne dust was sampled on lilters at two locations near to a metallurgical plant in Dortmund, Germany. Concentrations in the low ng m(-3) range down to the detections limits (0.1-0.3 ng m(-3)) and various nickel species were found to be present in the collected dust. The mean fractions of total nickel (sampling period of one month) were found to contain 36+20% of soluble, 6 +/- 4% of sulfidic, 11 +/- 15% of metallic and 48 +/- 18% of oxidic nickel.

Air Pollutants↗

Ultrafine but not fine particulate matter causes airway inflammation and allergic airway sensitization to co-administered antigen in mice.

BACKGROUND: Airborne particulate matter (PM) is an important factor associated with the enhanced prevalence of respiratory allergy. The PM adjuvant activity on allergic sensitization is a possible mechanism of action involved, and the induction of airway inflammation is suggested to be of importance in PM-induced adjuvant activity. OBJECTIVE: Because differently sized PM have different toxic potentials, we studied the role of particle size in the induction of airway inflammation and allergic sensitization. This was done using fine (0.250 and 0.260 micro m) and ultrafine (0.029 and 0.014 micro m) titanium dioxide (TiO(2)) and carbon black particles (CBP) with known differences in airway toxicity. METHODS: Mice were intranasally exposed to ovalbumin (OVA) alone or in combination with one of the different particles. The induction of airway inflammation and the immune adjuvant activity were studied in the lungs and lung-draining peribronchial lymph nodes (PBLN) at day 8. OVA-specific antibodies were measured at day 21, and the development of allergic airway inflammation was studied after OVA challenges (day 28). RESULTS: When administered at the same total particle mass (200 micro g), exposure to ultrafine TiO(2) and CBP-induced airway inflammation, and had immune adjuvant activity. The latter was shown by increasing both the PBLN cell numbers and the production of OVA-specific T-helper type 2 (Th2) cytokines (IL-4, IL-5, IL-10 and IL-13). Whereas OVA-specific IgE and IgG1 levels in serum were only increased in animals exposed to the ultrafine TiO(2), allergic airway inflammation could be detected in both ultrafine TiO(2)-and CBP-treated groups after challenges with OVA. CONCLUSION: Our data show that only the ultrafine particles, with a small diameter and a large total surface area/mass, cause airway inflammation and have immune adjuvant activity in the current model supporting the hypothesis that particle toxicity is site-dependent and related to adjuvant activity.

Animals↗

Particulate matter exposure impairs systemic microvascular endothelium-dependent dilation.

Acute exposure to airborne pollutants, such as solid particulate matter (PM), increases the risk of cardiovascular dysfunction, but the mechanisms by which PM evokes systemic effects remain to be identified. The purpose of this study was to determine if pulmonary exposure to a PM surrogate, such as residual oil fly ash (ROFA), affects endothelium-dependent dilation in the systemic microcirculation. Rats were intratracheally instilled with ROFA at 0.1, 0.25, 1 or 2 mg/rat 24 hr before experimental measurements. Rats intratracheally instilled with saline or titanium dioxide (0.25 mg/rat) served as vehicle or particle control groups, respectively. In vivo microscopy of the spinotrapezius muscle was used to study systemic arteriolar dilator responses to the Ca2+ ionophore A23187, administered by ejection via pressurized micropipette into the arteriolar lumen. We used analysis of bronchoalveolar lavage (BAL) samples to monitor identified pulmonary inflammation and damage. To determine if ROFA exposure affected arteriolar nitric oxide sensitivity, sodium nitroprusside was iontophoretically applied to arterioles of rats exposed to ROFA. In saline-treated rats, A23187 dilated arterioles up to 72 +/- 7% of maximum. In ROFA- and TiO2-exposed rats, A23187-induced dilation was significantly attenuated. BAL fluid analysis revealed measurable pulmonary inflammation and damage after exposure to 1 and 2 mg ROFA (but not TiO2 or < 1 mg ROFA), as evidenced by significantly higher polymorphonuclear leukocyte cell counts, enhanced BAL albumin levels, and increased lactate dehydrogenase activity in BAL fluid. The sensitivity of arteriolar smooth muscle to NO was similar in saline-treated and ROFA-exposed rats, suggesting that pulmonary exposure to ROFA affected endothelial rather than smooth muscle function. A significant increase in venular leukocyte adhesion and rolling was observed in ROFA-exposed rats, suggesting local inflammation at the systemic microvascular level. These results indicate that pulmonary PM exposure impairs systemic endothelium-dependent arteriolar dilation. Moreover, because rats exposed to < 1 mg ROFA or TiO2 did not exhibit BAL signs of pulmonary damage or inflammation, it appears that PM exposure can impair systemic microvascular function independently of detectable pulmonary inflammation.

Air Pollutants↗