Airborne Ultrafine and Fine Particulate Matter: A Cause for Endothelial Dysfunction in Man?

Airway Inflammation

particulate air pollution, leukotriene, asthma, montelukast, vascular endothelial dysfunction, nitric oxide(NO)endothelin (ET) system

The purpose of this study is to examine biological pathways of altered blood vessel function resulting from breathing airborne particulate. Blood artery function in healthy men will be measured after particulate exposure either on placebo or on an asthma medication that stops production of an inflammatory biological agent. Lung and blood profiles will be obtained before and after exposure to exhaust fumes. We believe that the inflammatory agent produced by the lungs from breathing these particles causes abnormal artery function.

Hourly ice resurfacing by gas and propane fueled machines creates high levels of ultrafine and fine particulate matter (PM1) in indoor ice rinks. PM1 exposure may disrupt the normal nitric oxide (NO)/endothelin (ET)-1 vasodilation system and promote atherosclerosis, and/or increase the risk of an acute cardiac event. Our specific aims are 1) to determine whether impaired endothelial-mediated vasodilation and forearm muscle tissue reoxygenation rate and blood volume change (to reactive hyperemia following artery occlusion) is associated with combustion-derived PM1 exposure, and 2) To characterize a PM1 induced mechanism of endothelial dysfunction which occurs via a leukotriene (LT)-associated, airway generated tumor necrosis factor-alpha (TNF-a) mediated pathway. Healthy low PM1 exposed males will be evaluated for endothelial dysfunction before and after artery occlusion using high resolution ultrasound and near-infrared spectroscopy (NIRS), before and after moderate exercise in blinded high and low \[PM1\]. Endothelial dysfunction among chronically PM¬1 exposed ice rink athletes will be determined to evaluate the feasibility of using this population as a model in future studies. TNF-a, IL-8, LTB4, LTC4, LTD4, LTE4, ET-1, NO, and differential cell counts will be measured in sputum and serum. \[PM1\] will be monitored and exposure levels will be typical of indoor ice rinks. LT involvement will be assessed in vivo by double-blind pharmacological manipulation during PM1 exposure during light exercise. Results will demonstrate whether endothelial-mediated vasodilation and muscle hemodynamics are influenced by PM1 exposure, and will elucidate an LT initiated TNF-a mediated pathway in ET-1 upregulation. Our results should provide information for understanding the effects of PM1 exposure on the atherosclerotic process and cardiovascular risk, and give insight to novel treatment and diagnostic modalities.

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