CARDIOVASCULAR VULNERABILITY TO PARTICULATE EXPOSURE

颗粒空气污染与心血管住院和死亡率之间的流行病学关联已被发现，但对人类对颗粒暴露作出反应的生理机制知之甚少。犬对高浓度粉煤灰和/或细颗粒的反应伴有ECG复极异常，包括ST段异常、t波交替（对猝死的易感指标），以及典型的肾上腺素能活性和迷走神经介导效应的变化，这取决于犬的潜在状态。在易感成人中，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、心肌传导、复极和易怒方面。室外和室内的PM2~5， PM10， CO, O3, NO2, 502和温度将被视为暴露。波士顿社区小组将招募50名60-90岁的活跃成年人，并在两个3个月的夏季期间进行评估；该小组研究将在随后的两个夏季在污染程度较高的社区重复进行。受试者每周接受一次仰卧位和直立位血压、血氧仪和连续心电图动态心电图监测，持续25分钟（仰卧休息5分钟，直立休息5分钟，运动5分钟，恢复5分钟，慢呼吸5分钟），共12周。电生理结果包括心电图复极异常、室性早搏、心率变异性测量；PR和QT间期。将考虑潜在疾病和药物的改变或反应。第二项研究将评估波士顿两家心肺康复单位在重复运动中常规收集的颗粒物暴露与心肺运动数据之间的关系。这将使我们能够评估颗粒暴露是否与可预测心血管易感性和因年龄或疾病而易受影响的活动者猝死的生理变化有关。

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.