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Development of a Single High Fat Meal Challenge to Unmask Latent Cardiopulmonary Effects of Air Pollution Exposure in Rats
Martin, B., S. Snow, L. Thompson, M. Schladweiler, U. Kodavanti, M. Hazari, AND A. Farraj. Development of a Single High Fat Meal Challenge to Unmask Latent Cardiopulmonary Effects of Air Pollution Exposure in Rats. Annual Meeting of the Society of Toxicology, Baltimore, Maryland, March 12 - 16, 2017.
These findings may help uncover latent effects of air pollutant exposure at ambient levels at which people are likely to be exposed. This is especially important given the desire of the Air Office to understand health effects of exposure to air pollutant levels at and below current standards. This approach may facilitate a shift away from a reliance on overt measures of injury, which are unlikely to take place at low exposure levels.
Stress tests are used clinically to determine the presence of underlying disease and predict future cardiovascular risk. In previous studies, we used treadmill exercise stress in rats to unmask the priming effects of air pollution inhalation. Other day-to-day activities stress the cardiovascular system, and when modeled experimentally, may be useful in identifying latent effects of air pollution exposure. For example, a single high fat (HF) meal can cause transient vascular endothelial dysfunction and increases in LDL cholesterol, triglycerides (TG), oxidative stress, and inflammation. Given the prevalence of HF meals in western diets, the goal of this study was to develop a HF meal challenge in rats to see if air pollution primes the body for a subsequent stress-induced adverse response. Healthy male Wistar Kyoto rats were fasted for six hours and then administered a single oral gavage of isocaloric lard-based HF or low fat (LF) suspensions, or a water vehicle control. We hypothesized that rats given a HF load would elicit postprandial changes in cardiopulmonary function that were distinct from LF and vehicle controls. One to four hours after gavage, rats underwent whole body plethysmography to assess breathing patterns, cardiovascular ultrasounds, blood draws for measurements of systemic lipids and hormones and a test for sensitivity to aconitine-induced arrhythmia. HF gavage caused an increase in circulating TG relative to LF and vehicle controls and an increase in LDL cholesterol relative to LF gavage. HF gavage also caused a near significant increase in peak diastolic strain rate (p = 0.06) relative to vehicle, indicating alteration in myocardial performance during diastole. Interestingly, LF gavage significantly reduced sensitivity to aconitine challenge and caused a significant increase in adrenaline levels relative to the HF gavage and vehicle. There were no significant changes in breathing parameters or other cardiac endpoints and no alterations in circulating glucose, noradrenaline or corticosterone. In summary, although the impacts of the single HF gavage on cardiopulmonary function were minimal, systemic responses were characteristic of postprandial responses in humans. This approach may be useful for modeling real world stressors (i.e. HF diet) and determining the acute effects of low level air pollution otherwise imperceptible without secondary stress. (This abstract does not reflect EPA policy).