Experimental Exposure to Air Pollutants and Sympathetic Nerve Activity in Human Subjects

点击翻译按钮获取中文摘要

Air pollution is the 13th leading cause of mortality worldwide largely through excess cardiovascular mortality. Sympathetic activation is implicated by the rapid onset of the cardiovascular risk increase after exposure and changes in heart rate variability. Therefore, we will test the hypothesis that ultrafine particle exposure increases sympathetic nervous system activity in human subjects and that ozone-induced airway inflammation augments autonomic dysregulation. Participants will be exposed to clean air, ultrafine particles, or ultrafine particles and ozone in a randomized, double-blind, and cross-over fashion. We will determine blood pressure, heart rate, respiration, cardiac output and directly record sympathetic vasomotor tone using microneurography. To elucidate the underlying mechanisms through which particles and ozone affect the autonomic nervous system, we will assess the local and systemic inflammatory response as well as the changes in neurotrophic factors in sputum and blood. Changes in sympathetic activity will be correlated with the degree of airway inflammation and oxidative stress assessed in induced sputum as well as in blood and urine. Our study will provide insight in the mechanisms through which air pollution, particularly ultrafine particle exposure, increases cardiovascular risk in human subjects and generate a human model for mechanistic and therapeutic studies.