Inhaled ambient-level traffic-derived particulates decrease cardiac vagal influence and baroreflexes and increase arrhythmia in a rat model of metabolic syndrome.

BACKGROUND: Epidemiological studies have linked exposures to ambient fine particulate matter (PM2.5) and traffic with autonomic nervous system imbalance (ANS) and cardiac pathophysiology, especially in individuals with preexisting disease. It is unclear whether metabolic syndrome (MetS) increases susceptibility to the effects of PM2.5. We hypothesized that exposure to traffic-derived primary and secondary organic aerosols (P + SOA) at ambient levels would cause autonomic and cardiovascular dysfunction in rats exhibiting features of MetS. Male Sprague Dawley (SD) rats were fed a high-fructose diet (HFrD) to induce MetS, and exposed to P + SOA (20.4 ± 0.9 µg/m3) for 12 days with time-matched comparison to filtered-air (FA) exposed MetS rats; normal diet (ND) SD rats were separately exposed to FA or P + SOA (56.3 ± 1.2 µg/m3). RESULTS: In MetS rats, P + SOA exposure decreased HRV, QTc, PR, and expiratory time overall (mean effect across the entirety of exposure), increased breathing rate overall, decreased baroreflex sensitivity (BRS) on three exposure days, and increased spontaneous atrioventricular (AV) block Mobitz Type II arrhythmia on exposure day 4 relative to FA-exposed animals receiving the same diet. Among ND rats, P + SOA decreased HRV only on day 1 and did not significantly alter BRS despite overall hypertensive responses relative to FA. Correlations between HRV, ECG, BRS, and breathing parameters suggested a role for autonomic imbalance in the pathophysiologic effects of P + SOA among MetS rats. Autonomic cardiovascular responses to P + SOA at ambient PM2.5 levels were pronounced among MetS rats and indicated blunted vagal influence over cardiovascular physiology. CONCLUSIONS: Results support epidemiologic findings that MetS increases susceptibility to the adverse cardiac effects of ambient-level PM2.5, potentially through ANS imbalance.

Scaling and sustaining COVID-19 vaccination through meaningful community engagement and care coordination for underserved communities: hybrid type 3 effectiveness-implementation sequential multiple assignment randomized trial.

BACKGROUND: COVID-19 inequities are abundant in low-income communities of color. Addressing COVID-19 vaccine hesitancy to promote equitable and sustained vaccination for underserved communities requires a multi-level, scalable, and sustainable approach. It is also essential that efforts acknowledge the broader healthcare needs of these communities including engagement in preventive services. METHODS: This is a hybrid type 3 effectiveness-implementation study that will include a multi-level, longitudinal, mixed-methods data collection approach designed to assess the sustained impact of a co-created multicomponent strategy relying on bidirectional learning, shared decision-making, and expertise by all team members. The study capitalizes on a combination of implementation strategies including mHealth outreach with culturally appropriate messaging, care coordination to increase engagement in high priority preventive services, and the co-design of these strategies using community advisory boards led by Community Weavers. Community Weavers are individuals with lived experience as members of an underserved community serving as cultural brokers between communities, public health systems, and researchers to co-create community-driven, culturally sensitive public health solutions. The study will use an adaptive implementation approach operationalized in a sequential multiple assignment randomized trial design of 300 participants from three sites in a Federally Qualified Health Center in Southern California. This design will allow examining the impact of various implementation strategy components and deliver more intensive support to those who benefit from it most. The primary effectiveness outcomes are COVID-19 vaccine completion, engagement in preventive services, and vaccine confidence. The primary implementation outcomes are reach, adoption, implementation, and maintenance of the multicomponent strategy over a 12-month follow-up period. Mixed-effects logistic regression models will be used to examine program impacts and will be triangulated with qualitative data from participants and implementers. DISCUSSION: This study capitalizes on community engagement, implementation science, health equity and communication, infectious disease, and public health perspectives to co-create a multicomponent strategy to promote the uptake of COVID-19 vaccination and preventive services for underserved communities in San Diego. The study design emphasizes broad engagement of our community and clinic partners leading to culturally sensitive and acceptable strategies to produce lasting and sustainable increases in vaccine equity and preventive services engagement. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT05841810 May 3, 2023.

Effects of fresh and aged vehicular exhaust emissions on breathing pattern and cellular responses--pilot single vehicle study.

The study presented here is a laboratory pilot study using diluted car exhaust from a single vehicle to assess differences in toxicological response between primary emissions and secondary products resulting from atmospheric photochemical reactions of gas phase compounds with O3, OH and other radicals. Sprague Dawley rats were exposed for 5 h to either filtered room air (sham) or one of two different atmospheres: (i) diluted car exhaust (P)+Mt. Saint Helens Ash (MSHA); (ii) P+MSHA+secondary organic aerosol (SOA, formed during simulated photochemical aging of diluted exhaust). Primary and secondary gases were removed using a nonselective diffusion denuder. Continuous respiratory data was collected during the exposure, and bronchoalveolar lavage (BAL) and complete blood counts (CBC) were performed 24 h after exposure. ANOVA models were used to assess the exposure effect and to compare those effects across different exposure types. Total average exposures were 363 ± 66 µg/m³ P+MSHA and 212 ± 95 µg/m³ P+MSHA+SOA. For both exposures, we observed decreases in breathing rate, tidal and minute volumes (TV, MV) and peak and median flows (PIF, PEF and EF50) along with increases in breathing cycle times (Ti, Te) compared to sham. These results indicate that the animals are changing their breathing pattern with these test atmospheres. Exposure to P+MSHA+SOA produced significant increases in total cells, macrophages and neutrophils in the BAL and in vivo chemiluminescence of the lung. There were no significant differences in CBC parameters. Our data suggest that simulated atmospheric photochemistry, producing SOA in the P+MSHA+SOA exposures, enhanced the toxicity of vehicular emissions.

Toxicological evaluation of realistic emission source aerosols (TERESA): introduction and overview.

Determining the health impacts of sources and components of fine particulate matter (PM(2.5)) is an important scientific goal. PM(2.5) is a complex mixture of inorganic and organic constituents that are likely to differ in their potential to cause adverse health outcomes. The Toxicological Evaluation of Realistic Emissions of Source Aerosols (TERESA) study focused on two PM sources--coal-fired power plants and mobile sources--and sought to investigate the toxicological effects of exposure to emissions from these sources. The set of papers published here document the power plant experiments. TERESA attempted to delineate health effects of primary particles, secondary (aged) particles, and mixtures of these with common atmospheric constituents. TERESA involved withdrawal of emissions from the stacks of three coal-fired power plants in the United States. The emissions were aged and atmospherically transformed in a mobile laboratory simulating downwind power plant plume processing. Toxicological evaluations were carried out in laboratory rats exposed to different emission scenarios with extensive exposure characterization. The approach employed in TERESA was ambitious and innovative. Technical challenges included the development of stack sampling technology that prevented condensation of water vapor from the power plant exhaust during sampling and transfer, while minimizing losses of primary particles; development and optimization of a photochemical chamber to provide an aged aerosol for animal exposures; development and evaluation of a denuder system to remove excess gaseous components; and development of a mobile toxicology laboratory. This paper provides an overview of the conceptual framework, design, and methods employed in the study.

Laboratory evaluation of a prototype photochemical chamber designed to investigate the health effects of fresh and aged vehicular exhaust emissions.

Laboratory experiments simulating atmospheric aging of motor vehicle exhaust emissions were conducted using a single vehicle and a photochemical chamber. A compact automobile was used as a source of emissions. The vehicle exhaust was diluted with ambient air to achieve carbon monoxide (CO) concentrations similar to those observed in an urban highway tunnel. With the car engine idling, it is expected that the CO concentration is a reasonable surrogate for volatile organic compounds (VOCs) emissions. Varying the amount of dilution of the exhaust gas to produce different CO concentrations, allowed adjustment of the concentrations of VOCs in the chamber to optimize production of secondary organic aerosol (SOA) needed for animal toxicological exposures. Photochemical reactions in the chamber resulted in nitric oxide (NO) depletion, nitrogen dioxide (NO2) formation, ozone (O3) accumulation, and SOA formation. A stable SOA concentration of approximately 40 µg m⁻³ at a chamber mean residence time of 30 min was achieved. This relatively short mean residence time provided adequate chamber flow output for both particle characterization and animal exposures. The chamber was operated as a continuous flow reactor for animal toxicological tests. SOA mass generated from the car exhaust diluted with ambient air was almost entirely in the ultrafine mode. Chamber performance was improved by using different types of seed aerosol to provide a surface for condensation of semivolatile reaction products, thus increasing the yield of SOA. Toxicological studies using Sprague-Dawley rats found significant increases of in vivo chemiluminescence in lungs following exposure to SOA.

Electrocardiographic and respiratory responses to coal-fired power plant emissions in a rat model of acute myocardial infarction: results from the Toxicological Evaluation of Realistic Emissions of Source Aerosols Study.

BACKGROUND: Ambient particulate matter (PM) derived from coal-fired power plants may have important cardiovascular effects, but existing toxicological studies are inadequate for understanding these effects. The Toxicological Evaluation of Realistic Emissions of Source Aerosols (TERESA) study aims to evaluate the toxicity of primary and secondary PM derived from coal-fired power plants. As a part of this effort, we evaluated in susceptible animals the effect of stack emissions on cardiac electrophysiology and respiratory function under exposure conditions intended to simulate an aged plume with unneutralized acidity and secondary organic aerosols (POS exposure scenario). METHODS: Rats with acute myocardial infarction were exposed to either stack emissions (n = 15) or filtered air (n = 14) for 5 h at a single power plant. Respiration and electrocardiograms were continuously monitored via telemetry and heart rate, heart rate variability (HRV), premature ventricular beat (PVB) frequency, electrocardiographic intervals, and respiratory intervals and volumes were evaluated. Similar experiments at another power plant were attempted but were unsuccessful. RESULTS: POS exposure (fine particle mass = 219.1 µg/m(3); total sulfate = 172.5 µg/m(3); acidic sulfate = 132.5 µg/m(3); organic carbon = 50.9 µg/m(3)) was associated with increased PVB frequency and decreased respiratory expiratory time and end-inspiratory pause, but not with changes in heart rate, HRV, or electrocardiographic intervals. RESULTS from a second power plant were uninterpretable. CONCLUSIONS: Short-term exposure to primary and unneutralized secondary PM formed from aged emissions from a coal-fired power plant, as simulated by the POS scenario, may be associated with increased risk of ventricular arrhythmias in susceptible animals.

Toxicological evaluation of realistic emission source aerosols (TERESA): summary and conclusions.

The toxicological evaluation of realistic emissions of source aerosols (TERESA) study seeks to delineate health effects of aerosols formed from emissions of particulate matter sources. This series of papers reports the findings of experiments using coal-fired power plants as the source of emissions and this paper summarizes the findings and knowledge acquired from these studies. Emissions were drawn directly from the stacks of three coal-fired power plants in the US, and photochemically aged in a mobile laboratory to simulate downwind power plant plume processing. The power plants used different sources of coal and had different emission controls. Exposure scenarios included primary particles, secondary particles and mixtures of these with common atmospheric constituents (α-pinene and ammonia). Extensive exposure characterization was carried out, and toxicological outcomes were evaluated in Sprague-Dawley rats exposed to different emission scenarios. Breathing pattern, pulmonary inflammatory responses, in vivo pulmonary and cardiac chemiluminescence and cardiac response in a model of acute myocardial infarction were assessed. The results showed no response or relatively mild responses to the inhaled aerosols studied; complex scenarios which included oxidized emissions and α-pinene to simulate biogenic secondary organic aerosol tended to induce more statistically significant responses than scenarios of oxidized and non-oxidized emissions alone. Relating adverse effects to specific components did not consistently identify a toxic constituent. These findings are consistent with most of the previously published studies using pure compounds to model secondary power plant emissions, but importantly add substantial complexity and thus have considerable merit in defining toxicological responses.

Cardiac and pulmonary oxidative stress in rats exposed to realistic emissions of source aerosols.

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.

Toxicological evaluation of realistic emission source aerosols (TERESA)-power plant studies: assessment of cellular responses.

The Toxicological Evaluation of Realistic Emission Source Aerosols (TERESA) project assessed primary and secondary particulate by simulating the chemical reactions that a plume from a source might undergo during atmospheric transport and added other atmospheric constituents that might interact with it. Three coal-fired power plants with different coal and different emission controls were used. Male Sprague-Dawley rats were exposed for 6 h to either filtered air or aged aerosol from the power plant. Four exposure scenarios were studied: primary particles (P); primary + secondary (oxidized) particles (PO); primary + secondary (oxidized) particles + SOA (POS); and primary + secondary (oxidized) particles neutralized + SOA (PONS). Exposure concentrations varied by scenario to a maximum concentration of 257.1 ± 10.0 µg/m(3). Twenty-four hours after exposure, pulmonary cellular responses were assessed by bronchoalveolar lavage (BAL), complete blood count (CBC), and histopathology. Exposure to the PONS and POS scenarios produced significant increases in BAL total cells and macrophage numbers at two plants. The PONS and P scenarios were associated with significant increases in BAL neutrophils and the presence of occasional neutrophils and increased macrophages in the airways and alveoli of exposed animals. Univariate analyses and random forest analyses showed that increases in total cell count and macrophage cell count were significantly associated with neutralized sulfate and several correlated measurements. Increases in neutrophils in BAL were associated with zinc. There were no significant differences in CBC parameters or blood vessel wall thickness by histopathology. The association between neutrophils increases and zinc raises the possibility that metals play a role in this response.

Toxicological evaluation of realistic emission source aerosols (TERESA)--power plant studies: assessment of breathing pattern.

Our approach to study multi-pollutant aerosols isolates a single emissions source, evaluates the toxicity of primary and secondary particles derived from this source, and simulates chemical reactions that occur in the atmosphere after emission. Three U.S. coal-fired power plants utilizing different coals and with different emission controls were evaluated. Secondary organic aerosol (SOA) derived from α-pinene and/or ammonia was added in some experiments. Male Sprague-Dawley rats were exposed for 6 h to filtered air or different atmospheric mixtures. Scenarios studied at each plant included the following: primary particles (P); secondary (oxidized) particles (PO); oxidized particles + SOA (POS); and oxidized and neutralized particles + SOA (PONS); additional control scenarios were also studied. Continuous respiratory data were obtained during exposures using whole body plethysmography chambers. Of the 12 respiratory outcomes assessed, each had statistically significant changes at some plant and with some of the 4 scenarios. The most robust outcomes were found with exposure to the PO scenario (increased respiratory frequency with decreases in inspiratory and expiratory time); and the PONS scenario (decreased peak expiratory flow and expiratory flow at 50%). PONS findings were most strongly associated with ammonium, neutralized sulfate, and elemental carbon (EC) in univariate analyses, but only with EC in multivariate analyses. Control scenario O (oxidized without primary particles) had similar changes to PO. Adjusted R(2) analyses showed that scenario was a better predictor of respiratory responses than individual components, suggesting that the complex atmospheric mixture was responsible for respiratory effects.

Effects of ambient particles and carbon monoxide on supraventricular arrhythmias in a rat model of myocardial infarction.

The association between short-term increases in particulate air pollution and increased cardiovascular morbidity and mortality is well documented. Recent studies suggest an association between particulate matter with aerodynamic diameter < 2.5 microm (PM2.5) and supraventricular arrhythmias (SVA), but the results have been inconsistent. We evaluated this hypothesis in a rat model of acute myocardial infarction (AMI). Diazepam-sedated Sprague-Dawley rats with AMI were exposed (1 h) to either filtered air (n = 16), concentrated ambient fine particles (CAPS; mean = 645.7 microg/m3; n = 23), carbon monoxide (CO; 35 ppm; n = 19), or CAPs and CO (n = 24). Each exposure was immediately preceded and followed by a 1-h exposure to filtered air (baseline and postexposure periods, respectively). Surface electrocardiograms were recorded and the frequency of supraventricular premature beats was quantified. Among rats in the CAPS group, the probability of observing any SVA decreased from baseline to the exposure and postexposure periods. This pattern was significantly different than that observed for the filtered air group during the exposure period (p = .048) only. In the subset of rats with one or more SVA during the baseline period, the change in SVA rate from baseline to exposure period was significantly lower in the CAPS (p = .04) and CO (p = .007) groups only, as compared to the filtered air group. No significant effects were observed in the group simultaneously exposed to CAPS and CO. Thus, the results of this study do not support the hypothesis that exposure to ambient air pollution increases the risk or frequency of supraventricular arrhythmias.

Cardiac effects of carbon monoxide and ambient particles in a rat model of myocardial infarction.

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.

Chronic social stress and susceptibility to concentrated ambient fine particles in rats.

BACKGROUND: Epidemiologic 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. OBJECTIVES: Using a rat model of social stress, we compared respiratory responses to fine concentrated ambient particles (CAPs) and examined biological markers of inflammation. METHODS: Twenty-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. RESULTS: Stressed animals displayed higher average C-reactive protein, tumor necrosis factor-alpha, 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). CONCLUSIONS: CAPs 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.

Concentrated ambient particles alter myocardial blood flow during acute ischemia in conscious canines.

BACKGROUND: Experimental and observational studies have demonstrated that short-term exposure to ambient particulate matter (PM) exacerbates myocardial ischemia. OBJECTIVES: We conducted this study to investigate the effects of concentrated ambient particles (CAPs) on myocardial blood flow during myocardial ischemia in chronically instrumented conscious canines. METHODS: Eleven 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 microg/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. RESULTS: CAPs 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). CONCLUSIONS: These 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.

Mechanisms of inhaled fine particulate air pollution-induced arterial blood pressure changes.

BACKGROUND: Epidemiologic studies suggest a positive association between fine particulate matter and arterial blood pressure, but the results have been inconsistent. OBJECTIVES: We 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. METHODS: Thirteen dogs were repeatedly exposed via permanent tracheostomy to CAPs (358.1+/-306.7 microg/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 alpha-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. RESULTS: CAPs 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 x 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 alpha-adrenergic blockade, responses to CAPs and FA no longer differed significantly. CONCLUSIONS: Controlled 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.

Permanent tracheostomy for long-term respiratory studies.

BACKGROUND: We describe a modified surgical technique for permanent, anterior tracheal-wall stoma for chronic, repeat respiratory studies in trained, conscious dogs. These cannula-free tracheostomies require minimal daily maintenance, permit repeat intubation with endotracheal tubes modified for airflow respiratory measurement, and facilitate up to 6 h continuous administration of aerosol agents during long-term or repeat respiratory studies. METHODS: In 20 dogs, during a 30 to 40 min procedure, portions of tracheal rings 2-4 were removed to create an oval stoma, approximately 2 x 1 cm. The dermis was secured to the transected cartilage and tracheal mucosa in such a manner that skin covered the sternohyoid muscles and grew-in flush with the tracheal mucosa at the stomal opening. Stomas were cleaned daily, and fur was clipped weekly around the stomal site. No other maintenance procedures or environmental modifications were needed. Animals breathed through both the stoma and the upper airway and barked normally. RESULTS: Stomas remained viable in long-term animals (n = 4) ongoing for 70.3 +/- 32.2 mo (mean +/- SEM), with an ongoing maximum of 126 mo. Postmortem examinations were performed on shorter-term animals (n = 16) sacrificed at 16.7 +/- 7.3 mo. Thirteen showed no appreciable tracheal stenosis and three showed <10% stenosis at the level of the stoma. Histopathological examination of the stomal opening and surrounding tissue revealed minimal chronic inflammation and no evidence of necrosis or infection. CONCLUSIONS: During long-term respiratory studies, this practical and dependable tracheal stoma provides a means for examining acute and chronic effects of environmental and pathophysiological influences on the respiratory system of conscious dogs.