Nadziejko Christine, Fang Kaijie, Chen Lung Chi, Cohen Beverly, Karpatkin Margaret, Nadas Arthur
Department of Environmental Medicine, New York University School of Medicine, 57 Old Forge Road, Tuxedo NY 10987, USA.
Res Rep Health Eff Inst. 2002 Oct(111):7-29; discussion 31-8.
Epidemiologic studies have shown that exposure to particulate air pollution is associated with short-term increases in cardiovascular morbidity and mortality. These adverse effects of inhaled particulate matter (PM*) may be the indirect result of a PM-induced increase in blood coagulability. This explanation is biologically plausible because prospective studies have shown that increases in blood coagulation parameters are significantly associated with risk of adverse cardiovascular events. We examined the hypothesis that acute exposure to elevated levels of PM causes prothrombotic changes in blood coagulation parameters. Rats with indwelling jugular vein catheters were exposed for 6 hours to filtered air or concentrated ambient PM in New York City air (n = 9 per group per experiment). PM less than 2.5 microm in mass median aerodynamic diameter (PM2.5) was concentrated for animal exposures using a centrifugal concentrator. Blood samples were taken at four time points: before and immediately after exposure and at 12 and 24 hours after the start of exposure. At each time point, six coagulation parameters (platelet count, fibrinogen level, factor VII activity, thrombin-antithrombin complex [TAT] level, tissue plasminogen activator [tPA] activity, and plasminogen activator inhibitor [PAI] activity) were measured as well as all standard blood count parameters. Five concentrated-PM exposure experiments were performed over a period of 8 weeks in the summer of 1999. PM exposure concentrations ranged from 95 to 341 microg/m3. Statistical significance was determined by two-way analysis of variance (ANOVA) on the postexposure data with time and exposure status as main effects. There were no consistent exposure-related effects on any of the end points across the five experiments and no indication of any dose-dependent effects. Most of the statistically significant differences that were observed do not represent adverse effects. Therefore, the results of this study do not indicate that exposure to concentrated ambient PM causes adverse effects on blood coagulation in healthy rats.
流行病学研究表明,暴露于空气中的颗粒物污染与心血管疾病发病率和死亡率的短期上升有关。吸入颗粒物(PM*)的这些不利影响可能是PM导致血液凝固性增加的间接结果。这种解释在生物学上是合理的,因为前瞻性研究表明,血液凝固参数的增加与不良心血管事件的风险显著相关。我们检验了以下假设:急性暴露于高水平的PM会导致血液凝固参数发生促血栓形成变化。将留置颈静脉导管的大鼠暴露于过滤空气或纽约市空气中浓缩的环境PM中6小时(每个实验每组n = 9)。使用离心浓缩器对质量中位空气动力学直径小于2.5微米的PM(PM2.5)进行浓缩,以供动物暴露使用。在四个时间点采集血样:暴露前、暴露后立即以及暴露开始后12小时和24小时。在每个时间点,测量六个凝血参数(血小板计数、纤维蛋白原水平、因子VII活性、凝血酶 - 抗凝血酶复合物 [TAT] 水平、组织纤溶酶原激活物 [tPA] 活性和纤溶酶原激活物抑制剂 [PAI] 活性)以及所有标准血常规参数。在1999年夏季的8周时间内进行了五次浓缩PM暴露实验。PM暴露浓度范围为95至341微克/立方米。通过对暴露后数据进行双向方差分析(ANOVA)来确定统计学显著性,以时间和暴露状态作为主要效应。在这五个实验中,没有观察到任何与暴露相关的对任何终点的一致影响,也没有任何剂量依赖性影响迹象。观察到的大多数统计学显著差异并不代表不利影响。因此,本研究结果并未表明暴露于浓缩的环境PM会对健康大鼠的血液凝固产生不利影响。