CARDIOVASCULAR VULNERABILITY TO PARTICULATE EXPOSURE

已发现颗粒空气污染与心血管住院和死亡率之间存在流行病学关联，但对人类对颗粒暴露作出反应的生理机制知之甚少。犬对浓缩的飞灰和/或细颗粒物的反应是ECG复极异常，包括ST段异常、T波交替（猝死易感性的指标）以及肾上腺素能活动亢进和迷走神经介导效应的典型变化，具体取决于犬的基础状态。在易感的成年人中，我们建议检查颗粒暴露是否会导致类似的变化，特别是在自主神经功能，心肌电导，复极和易怒的措施。室外和室内PM2~5、PM10、CO、O3、NO2、502和温度将被视为暴露。将在两个为期3个月的夏季期间招募并评估50名60-90岁活跃成年人组成的波士顿社区小组;该小组研究将在随后的两个夏季在污染较高的社区重复进行。每周一次，持续12周，参与者将接受仰卧位和直立位血压、血氧测定和连续ECG霍尔特监测，持续25分钟（仰卧休息5分钟，直立站立5分钟，运动5分钟，恢复5分钟和缓慢呼吸5分钟）。电生理学结局将包括ECG复极异常、室性早搏、心率变异性测量; PR和QT间期。将考虑基础疾病和药物的改变或反应。第二项研究对800多名门诊患者进行了评估，将评估颗粒暴露与波士顿两个心肺康复单位在重复运动期间常规收集的心肺运动数据之间的关系。这些将使我们能够评估颗粒暴露是否与预测心血管脆弱性和猝死的生理变化相关，这些变化是基于年龄或疾病敏感的。

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.