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

空气污染是全球第13大死亡原因，主要是由于心血管疾病死亡率过高。交感神经激活与暴露后心血管风险增加的快速发作和心率变异性的变化有关。因此，我们将验证超细颗粒暴露会增加人类受试者交感神经系统活动以及臭氧诱导的气道炎症会增加自主神经失调的假设。参与者将以随机、双盲、交叉的方式暴露于清洁空气、超细颗粒或超细颗粒和臭氧中。我们将测量血压，心率，呼吸，心输出量并使用微神经造影直接记录交感血管舒缩张力。为了阐明颗粒和臭氧影响自主神经系统的潜在机制，我们将评估局部和全身炎症反应以及痰和血液中神经营养因子的变化。交感神经活动的变化将与气道炎症和氧化应激的程度相关，在诱导痰以及血液和尿液中进行评估。我们的研究将深入了解空气污染，特别是超细颗粒暴露，增加人类受试者心血管风险的机制，并为机制和治疗研究提供人体模型。

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.