CARDIOVASCULAR VULNERABILITY TO PARTICULATE EXPOSURE

已发现颗粒物空气污染与心血管住院和死亡率之间的流行病学联系，但对人类对颗粒物暴露做出反应的生理机制知之甚少。犬只对浓缩的飞灰和/或细小颗粒的心电图复极异常有反应，包括ST段异常、T波交替(猝死的易感性指标)，以及典型的肾上腺素能亢进和迷走神经调节效应的变化，这取决于狗的潜在状态。在易感人群中，我们建议检查接触颗粒物是否会导致类似的变化，特别是在自主神经功能、心肌电导、复极和应激性方面的测量。室外和室内PM2~5、PM10、CO、O3、NO2、502和温度将被视为暴露量。波士顿社区的一个由50名60-90岁的活跃成年人组成的小组将在两个为期3个月的夏季期间被招募和评估；这一小组研究将在随后的两个夏天在污染较高的社区重复进行。参与者将在12周内每周接受一次仰卧位和直立位的血压、血氧仪和连续的动态心电图监测，持续25分钟(仰卧位休息5分钟，直立站立5分钟，锻炼5分钟，恢复5分钟，缓慢呼吸5分钟)。电生理结果将包括心电复极异常、室性早搏、心率变异性的测量、PR和QT间期。将考虑潜在疾病和药物的修饰或反应。另一项针对800名门诊患者的研究将评估颗粒物暴露与波士顿两家心肺康复病房重复锻炼期间常规收集的心肺运动数据之间的关联。这将使我们能够评估颗粒物暴露是否与预测心血管脆弱性和因年龄或疾病而易受影响的活跃人群的生理变化有关。

Epidemiologic associations between particulate air pollution and cardiovascular hospitalization and mortality have been found, but little is understood about the physiologic mechanisms by which humans respond to particulate exposure. Canines respond to concentrated fly-ash and/or fine particles with ECG repolarization abnormalities including ST segment abnormalities, T-wave alternans (an index of susceptibility to sudden death), and changes typical of both hyperadrenergic activity and vagally mediated effects, depending on the underlying status of the dogs. In susceptible adults we propose to examine whether particle exposure results in similar changes, particularly in measures of autonomic function, myocardial conductance, repolarization, and irritability. Outdoor and indoor PM2~5, PM10, CO, O3, NO2, 502 and temperature will be considered as exposures. A Boston community-based panel of 50 active adults 60-90 yr of age will be recruited and evaluated over two 3-month summer periods; this panel study will be repeated in a higher pollution community in two subsequent summers. Once per week for l2 weeks the participants will receive supine and upright blood pressure, oximetry and continuous ECG Holter monitoring for a 25 minute period (5 minutes of rest supine, 5 minutes of standing upright, 5 minutes of exercise, 5 minutes of recovery and 5 minutes of slow breathing.) Electrophysiologic outcomes will include ECG repolarization abnormalities, ventricular premature beats, measures of heart rate variability; PR and QT intervals. Modification or response by underlying disease and medication will be considered. A second study of >800 outpatients will assess the associations between particulate exposure and cardiopulmonary exercise data routinely collected during repeated exercise in two Boston cardiac and pulmonary rehabilitation units. These will enable us to assess whether particulate exposure is associated with physiologic changes predictive of cardiovascular vulnerability and sudden death in active humans who are susceptible on the basis of age or disease.