Peat smoke inhalation alters blood pressure, baroreflex sensitivity, and cardiac arrhythmia risk in rats.

Wildland fires (WF) are linked to adverse health impacts related to poor air quality. The cardiovascular impacts of emissions from specific biomass sources are however unknown. The purpose of this study was to assess the cardiovascular impacts of a single exposure to peat smoke, a key regional WF air pollution source, and relate these to baroreceptor sensitivity and inflammation. Three-month-old male Wistar-Kyoto rats, implanted with radiotelemeters for continuous monitoring of heart rate (HR), blood pressure (BP), and spontaneous baroreflex sensitivity (BRS), were exposed once, for 1-hr, to filtered air or low (0.38 mg/m3 PM) or high (4.04 mg/m3) concentrations of peat smoke. Systemic markers of inflammation and sensitivity to aconitine-induced cardiac arrhythmias, a measure of latent myocardial vulnerability, were assessed in separate cohorts of rats 24 hr after exposure. PM size (low peat = 0.4-0.5 microns vs. high peat = 0.8-1.2 microns) and proportion of organic carbon (low peat = 77% vs. high peat = 65%) varied with exposure level. Exposure to high peat and to a lesser extent low peat increased systolic and diastolic BP relative to filtered air. In contrast, only exposure to low peat elevated BRS and aconitine-induced arrhythmogenesis relative to filtered air and increased circulating levels of low-density lipoprotein cholesterol, complement components C3 and C4, angiotensin-converting enzyme (ACE), and white blood cells. Taken together, exposure to peat smoke produced overt and latent cardiovascular consequences that were likely influenced by physicochemical characteristics of the smoke and associated adaptive homeostatic mechanisms.

A single exposure to eucalyptus smoke sensitizes rats to the postprandial cardiovascular effects of a high carbohydrate oral load.

OBJECTIVE: Previous studies have shown that air pollution exposure primes the body to heightened responses to everyday stressors of the cardiovascular system. The purpose of this study was to examine the utility of postprandial responses to a high carbohydrate oral load, a cardiometabolic stressor long used to predict cardiovascular risk, in assessing the impacts of exposure to eucalyptus smoke (ES), a contributor to wildland fire air pollution in the Western coast of the United States. MATERIALS AND METHODS: Three-month-old male Sprague Dawley rats were exposed once (1 h) to filtered air (FA) or ES (700 µg/m3 fine particulate matter), generated by burning eucalyptus in a tube furnace. Rats were then fasted for six hours the following morning, and subsequently administered an oral gavage of either water or a HC suspension (70 kcal% from carbohydrate), mimicking a HC meal. Two hours post gavage, cardiovascular ultrasound, cardiac pressure-volume (PV), and baroreceptor sensitivity assessments were made, and pulmonary and systemic markers assessed. RESULTS: ES inhalation alone increased serum interleukin (IL)-4 and nasal airway levels of gamma glutamyl transferase. HC gavage alone increased blood glucose, blood pressure, and serum IL-6 and IL-13 compared to water vehicle. By contrast, only ES-exposed and HC-challenged animals had increased PV loop measures of cardiac output, ejection fraction %, dP/dtmax, dP/dtmin, and stroke work compared to ES exposure alone and/or HC challenge alone. DISCUSSION AND CONCLUSIONS: Exposure to a model wildfire air pollution source modifies cardiovascular responses to HC challenge, suggesting air pollution sensitizes the body to systemic triggers.

Pulmonary exposure to peat smoke extracts in rats decreases expiratory time and increases left heart end systolic volume.

Exposure to wildland fire-related particulate matter (PM) causes adverse health outcomes. However, the impacts of specific biomass sources remain unclear. The purpose of this study was to investigate cardiopulmonary responses in rats following exposure to PM extracts collected from peat fire smoke. We hypothesized that peat smoke PM would dose-dependently alter cardiopulmonary function. Male Sprague-Dawley rats (n = 8/group) were exposed to 35 µg (Lo PM) or 350 µg (Hi PM) of peat smoke PM extracts suspended in saline, or saline alone (Vehicle) via oropharyngeal aspiration (OA). Ventilatory expiration times, measured in whole-body plethysmographs immediately after OA, were the lowest in Hi PM exposed subjects at 6 min into recovery (p = .01 vs. Lo PM, p = .08 vs. Vehicle) and resolved shortly afterwards. The next day, we evaluated cardiovascular function in the same subjects via cardiac ultrasound under isoflurane anesthesia. Compared to Vehicle, Hi PM had 45% higher end systolic volume (p = .03) and 17% higher pulmonary artery blood flow acceleration/ejection time ratios, and both endpoints expressed significant increasing linear trends by dose (p = .01 and .02, respectively). In addition, linear trend analyses across doses detected an increase for end diastolic volume and decreases for ejection fraction and fractional shortening. These data suggest that exposure to peat smoke constituents modulates regulation of ventricular ejection and filling volumes, which could be related to altered blood flow in the pulmonary circulation. Moreover, early pulmonary responses to peat smoke PM point to irritant/autonomic mechanisms as potential drivers of later cardiovascular responses.

Mild allergic airways responses to an environmental mixture increase cardiovascular risk in rats.

Recent epidemiological findings link asthma to adverse cardiovascular responses. Yet, the precise cardiovascular impacts of asthma have been challenging to disentangle from the potential cardiovascular effects caused by asthma medication. The purpose of this study was to determine the impacts of allergic airways disease alone on cardiovascular function in an experimental model. Female Wistar rats were intranasally sensitized and then challenged once per week for 5 weeks with saline vehicle or a mixture of environmental allergens (ragweed, house dust mite, and Aspergillus fumigatus). Ventilatory and cardiovascular function, measured using double-chamber plethysmography and implantable blood pressure (BP) telemetry and cardiovascular ultrasound, respectively, were assessed before sensitization and after single and final allergen challenge. Responses to a single 0.5 ppm ozone exposure and to the cardiac arrhythmogenic agent aconitine were also assessed after final challenge. A single allergen challenge in sensitized rats increased tidal volume and specific airways resistance in response to provocation with methacholine and increased bronchoalveolar lavage fluid (BALF) eosinophils, neutrophils, lymphocytes, cytokines interleukin (IL)-4, IL-5, IL-10, IL-1ß, tumor necrosis factor-α, and keratinocyte chemoattract-growth-related oncogene characteristic of allergic airways responses. Lung responses after final allergen challenge in sensitized rats were diminished, although ozone exposure increased BALF IL-6, IL-13, IL-1 ß, and interferon-γ and modified ventilatory responses only in the allergen group. Final allergen challenge also increased systolic and mean arterial BP, stroke volume, cardiac output, end-diastolic volume, sensitivity to aconitine-induced cardiac arrhythmia, and cardiac gene expression with lesser effects after a single challenge. These findings demonstrate that allergic airways responses may increase cardiovascular risk in part by altering BP and myocardial function and by causing cardiac electrical instability.

Ambient Particulate Matter and Acrolein Co-Exposure Increases Myocardial Dyssynchrony in Mice via TRPA1.

Air pollution is a complex mixture of particulate matter and gases linked to adverse clinical outcomes. As such, studying responses to individual pollutants does not account for the potential biological responses resulting from the interaction of various constituents within an ambient air shed. We previously reported that exposure to high levels of the gaseous pollutant acrolein perturbs myocardial synchrony. Here, we examined the effects of repeated, intermittent co-exposure to low levels of concentrated ambient particulates (CAPs) and acrolein on myocardial synchrony and the role of transient receptor potential cation channel A1 (TRPA1), which we previously linked to air pollution-induced sensitization to triggered cardiac arrhythmia. Female B6129 and Trpa1-/- mice (n = 6/group) were exposed to filtered air (FA), CAPs (46 µg/m3 of PM2.5), Acrolein (0.42 ppm), or CAPs+Acrolein for 3 h/day, 2 days/week for 4 weeks. Cardiac ultrasound was conducted to assess cardiac synchronicity and function before and after the first exposure and after the final exposure. Heart rate variability (HRV), an indicator of autonomic tone, was assessed after the final exposure. Strain delay (time between peak strain in adjacent cardiac wall segments), an index of myocardial dyssynchrony, increased by 5-fold after the final CAPs+Acrolein exposure in B6129 mice compared with FA, CAPs, or Acrolein-exposed B6129 mice, and CAPs+Acrolein-exposed Trpa1-/- mice. Only exposure to acrolein alone increased the HRV high frequency domain (5-fold) in B6129 mice, but not in Trpa1-/- mice. Thus, repeated inhalation of pollutant mixtures may increase risk for cardiac responses compared with single or multiple exposures to individual pollutants through TRPA1 activation.

High-Throughput Video Processing of Heart Rate Responses in Multiple Wild-type Embryonic Zebrafish per Imaging Field.

Heart rate assays in wild-type zebrafish embryos have been limited to analysis of one embryo per video/imaging field. Here we present for the first time a platform for high-throughput derivation of heart rate from multiple zebrafish (Danio rerio) embryos per imaging field, which is capable of quickly processing thousands of videos and ideal for multi-well platforms with multiple fish/well. This approach relies on use of 2-day post fertilization wild-type embryos, and uses only bright-field imaging, circumventing requirement for anesthesia or restraint, costly software/hardware, or fluorescently-labeled animals. Our original scripts (1) locate the heart and record pixel intensity fluctuations generated by each cardiac cycle using a robust image processing routine, and (2) process intensity data to derive heart rate. To demonstrate assay utility, we exposed embryos to the drugs epinephrine and clonidine, which increased or decreased heart rate, respectively. Exposure to organic extracts of air pollution-derived particulate matter, including diesel or biodiesel exhausts, or wood smoke, all complex environmental mixtures, decreased heart rate to varying degrees. Comparison against an established lower-throughput method indicated robust assay fidelity. As all code and executable files are publicly available, this approach may expedite cardiotoxicity screening of compounds as diverse as small molecule drugs and complex chemical mixtures.

Acute peat smoke inhalation sensitizes rats to the postprandial cardiometabolic effects of a high fat oral load.

Wildland fire emissions cause adverse cardiopulmonary outcomes, yet controlled exposure studies to characterize health impacts of specific biomass sources have been complicated by the often latent effects of air pollution. The aim of this study was to determine if postprandial responses after a high fat challenge, long used clinically to predict cardiovascular risk, would unmask latent cardiometabolic responses in rats exposed to peat smoke, a key wildland fire air pollution source. Male Wistar Kyoto rats were exposed once (1 h) to filtered air (FA), or low (0.36 mg/m3 particulate matter) or high concentrations (3.30 mg/m3) of peat smoke, generated by burning peat from an Irish bog. Rats were then fasted overnight, and then administered an oral gavage of a HF suspension (60 kcal% from fat), mimicking a HF meal, 24 h post-exposure. In one cohort, cardiac and superior mesenteric artery function were assessed using high frequency ultrasound 2 h post gavage. In a second cohort, circulating lipids and hormones, pulmonary and systemic inflammatory markers, and circulating monocyte phenotype using flow cytometry were assessed before or 2 or 6 h after gavage. HF gavage alone elicited increases in circulating lipids characteristic of postprandial responses to a HF meal. Few effects were evident after peat exposure in un-gavaged rats. By contrast, exposure to low or high peat caused several changes relative to FA-exposed rats 2 and 6 h post HF gavage including increased heart isovolumic relaxation time, decreased serum glucose and insulin, increased CD11 b/c-expressing blood monocytes, increased serum total cholesterol, alpha-1 acid glycoprotein, and alpha-2 macroglobulin (p = 0.063), decreased serum corticosterone, and increased lung gamma-glutamyl transferase. In summary, these findings demonstrate that a HF challenge reveals effects of air pollution that may otherwise be imperceptible, particularly at low exposure levels, and suggest exposure may sensitize the body to mild inflammatory triggers.