Cardiovascular effects caused by increasing concentrations of diesel exhaust in middle-aged healthy GSTM1 null human volunteers

• Published in: Inhalation toxicology 2014-05, Vol.26 (6), p.319-326
• Main Authors: Tong, Haiyan, Rappold, Ana G., Caughey, Melissa, Hinderliter, Alan L., Graff, Donald W., Berntsen, Jon H., Cascio, Wayne E., Devlin, Robert B., Samet, James M.
• Format: Article
• Language: English
• Subjects: Aged; Blood Pressure; Brachial Artery - physiology; brachial artery ultrasound; diesel exhaust; Dose-Response Relationship, Drug; Female; Genotype; Glutathione Transferase - genetics; Glutathione Transferase - physiology; GSTM1 null; Healthy Volunteers; Heart Rate; heart rate variability; Hemodynamics - drug effects; Humans; Male; Middle Aged; middle-aged healthy human participants; Vasoconstriction; Vehicle Emissions - toxicity
• ISSN: 0895-8378; 1091-7691
• DOI: 10.3109/08958378.2014.889257

Abstract Context: Epidemiological studies have shown an association between the incidence of adverse cardiovascular effects and exposure to ambient particulate matter (PM). Diesel exhaust (DE) is a major contributor to ambient PM and gaseous emissions in urban areas. Objective: This was a pilot study designed to evaluate concentration-dependent effects of short-term exposure to whole DE on the cardiovascular system in order to identify a threshold concentration that can elicit biological responses in healthy human volunteers. Materials and methods: Six healthy middle-aged participants with glutathione-S-transferase-Mu 1 (GSTM1) null genotype underwent sequential exposures to 100 µg/m3, 200 µg/m3, and 300 µg/m3 whole DE generated in real time using an idling diesel truck engine. Exposures were separated by 14 d and each was 2 h in duration. Results: We report concentration-dependent effects of exposure to DE, with 100 µg/m3 concentration causing minimal cardiovascular effects, while exposure to 300 µg/m3 DE for 2 h resulted in a borderline significant reduction of baseline brachial artery diameter (3.34 ± 0.27 mm pre- versus 3.23 ± 0.25 mm post-exposure; p = 0.08). Exposure to the highest concentration of DE also resulted in increases of 5 mmHg in diastolic blood pressure as well as a decrease in indices of the frequency domain of heart rate variability (HRV). Discussion and conclusions: These findings demonstrate that acute exposure to relatively high concentrations of DE produces cardiovascular changes in middle-aged GSTM1 null individuals. This study therefore suggests that arterial vasoconstriction and changes in HRV are responses through which traffic-related air pollution increases the risk of adverse cardiovascular outcomes.