Mills Nicholas L, Törnqvist Håkan, Gonzalez Manuel C, Vink Elen, Robinson Simon D, Söderberg Stefan, Boon Nicholas A, Donaldson Ken, Sandström Thomas, Blomberg Anders, Newby David E
Centre for Cardiovascular Science, Edinburgh University, Edinburgh, Sweden.
N Engl J Med. 2007 Sep 13;357(11):1075-82. doi: 10.1056/NEJMoa066314.
Exposure to air pollution from traffic is associated with adverse cardiovascular events. The mechanisms for this association are unknown. We conducted a controlled exposure to dilute diesel exhaust in patients with stable coronary heart disease to determine the direct effect of air pollution on myocardial, vascular, and fibrinolytic function.
In a double-blind, randomized, crossover study, 20 men with prior myocardial infarction were exposed, in two separate sessions, to dilute diesel exhaust (300 mug per cubic meter) or filtered air for 1 hour during periods of rest and moderate exercise in a controlled-exposure facility. During the exposure, myocardial ischemia was quantified by ST-segment analysis using continuous 12-lead electrocardiography. Six hours after exposure, vasomotor and fibrinolytic function were assessed by means of intraarterial agonist infusions.
During both exposure sessions, the heart rate increased with exercise (P<0.001); the increase was similar during exposure to diesel exhaust and exposure to filtered air (P=0.67). Exercise-induced ST-segment depression was present in all patients, but there was a greater increase in the ischemic burden during exposure to diesel exhaust (-22+/-4 vs. -8+/-6 millivolt seconds, P<0.001). Exposure to diesel exhaust did not aggravate preexisting vasomotor dysfunction, but it did reduce the acute release of endothelial tissue plasminogen activator (P=0.009; 35% decrease in the area under the curve).
Brief exposure to dilute diesel exhaust promotes myocardial ischemia and inhibits endogenous fibrinolytic capacity in men with stable coronary heart disease. Our findings point to ischemic and thrombotic mechanisms that may explain in part the observation that exposure to combustion-derived air pollution is associated with adverse cardiovascular events. (ClinicalTrials.gov number, NCT00437138 [ClinicalTrials.gov].).
暴露于交通产生的空气污染与不良心血管事件相关。这种关联的机制尚不清楚。我们对稳定型冠心病患者进行了稀释柴油废气的控制性暴露试验，以确定空气污染对心肌、血管和纤溶功能的直接影响。
在一项双盲、随机、交叉研究中，20名曾有心肌梗死的男性在一个控制性暴露设施中，于休息和适度运动期间，分两个单独时段，分别暴露于稀释柴油废气（每立方米300微克）或过滤空气中1小时。在暴露期间，使用连续12导联心电图通过ST段分析对心肌缺血进行量化。暴露6小时后，通过动脉内注入激动剂评估血管舒缩和纤溶功能。
在两个暴露时段，心率均随运动增加（P<0.001）；在暴露于柴油废气和暴露于过滤空气期间，心率增加相似（P=0.67）。所有患者均出现运动诱发的ST段压低，但在暴露于柴油废气期间，缺血负担增加更明显（-22±4对-8±6毫伏秒，P<0.001）。暴露于柴油废气并未加重已有的血管舒缩功能障碍，但确实降低了内皮组织纤溶酶原激活物的急性释放（P=0.009；曲线下面积减少35%）。
短暂暴露于稀释柴油废气可促进稳定型冠心病男性的心肌缺血并抑制内源性纤溶能力。我们的研究结果指出了缺血和血栓形成机制，这可能部分解释了暴露于燃烧源空气污染与不良心血管事件相关这一观察结果。（临床试验注册号，NCT00437138 [ClinicalTrials.gov]。）
