Arjomandi Mehrdad, Wong Hofer, Donde Aneesh, Frelinger Jessica, Dalton Sarah, Ching Wendy, Power Karron, Balmes John R
Human Exposure Laboratory, Division of Occupational and Environmental Medicine, San Francisco General Hospital Medical Center, San Francisco, California; Division of Pulmonary and Critical Care Medicine, Department of Medicine, University of California San Francisco, San Francisco, California; Pulmonary Research Group, San Francisco Veterans Affairs Medical Center, San Francisco, California;
Human Exposure Laboratory, Division of Occupational and Environmental Medicine, San Francisco General Hospital Medical Center, San Francisco, California;
Am J Physiol Heart Circ Physiol. 2015 Jun 15;308(12):H1499-509. doi: 10.1152/ajpheart.00849.2014. Epub 2015 Apr 10.
Epidemiological evidence suggests that exposure to ozone increases cardiovascular morbidity. However, the specific biological mechanisms mediating ozone-associated cardiovascular effects are unknown. To determine whether short-term exposure to ambient levels of ozone causes changes in biomarkers of cardiovascular disease including heart rate variability (HRV), systemic inflammation, and coagulability, 26 subjects were exposed to 0, 100, and 200 ppb ozone in random order for 4 h with intermittent exercise. HRV was measured and blood samples were obtained immediately before (0 h), immediately after (4 h), and 20 h after (24 h) each exposure. Bronchoscopy with bronchoalveolar lavage (BAL) was performed 20 h after exposure. Regression modeling was used to examine dose-response trends between the endpoints and ozone exposure. Inhalation of ozone induced dose-dependent adverse changes in the frequency domains of HRV across exposures consistent with increased sympathetic tone [increase of (parameter estimate ± SE) 0.4 ± 0.2 and 0.3 ± 0.1 in low- to high-frequency domain HRV ratio per 100 ppb increase in ozone at 4 h and 24 h, respectively (P = 0.02 and P = 0.01)] and a dose-dependent increase in serum C-reactive protein (CRP) across exposures at 24 h [increase of 0.61 ± 0.24 mg/l in CRP per 100 ppb increase in ozone (P = 0.01)]. Changes in HRV and CRP did not correlate with ozone-induced local lung inflammatory responses (BAL granulocytes, IL-6, or IL-8), but changes in HRV and CRP were associated with each other after adjustment for age and ozone level. Inhalation of ozone causes adverse systemic inflammatory and cardiac autonomic effects that may contribute to the cardiovascular mortality associated with short-term exposure.
流行病学证据表明，接触臭氧会增加心血管疾病的发病率。然而，介导臭氧相关心血管效应的具体生物学机制尚不清楚。为了确定短期接触环境水平的臭氧是否会导致心血管疾病生物标志物的变化，包括心率变异性（HRV）、全身炎症和凝血功能，26名受试者以随机顺序分别接触0、100和200 ppb的臭氧4小时，并进行间歇性运动。在每次接触前（0小时）、接触后立即（4小时）和接触后20小时（24小时）测量HRV并采集血样。接触后20小时进行支气管镜检查及支气管肺泡灌洗（BAL）。采用回归模型检查各终点与臭氧暴露之间的剂量反应趋势。吸入臭氧会在各次暴露中导致HRV频域出现剂量依赖性的不良变化，这与交感神经张力增加一致[在4小时和24小时时，臭氧每增加100 ppb，低频到高频域HRV比值分别增加（参数估计值±标准误）0.4±0.2和0.3±0.1（P = 0.02和P = 0.01）]，并且在24小时时血清C反应蛋白（CRP）在各次暴露中出现剂量依赖性增加[臭氧每增加100 ppb，CRP增加0.61±0.24 mg/l（P = 0.01）]。HRV和CRP的变化与臭氧诱导的局部肺部炎症反应（BAL粒细胞、IL-6或IL-8）无关，但在调整年龄和臭氧水平后，HRV和CRP的变化相互关联。吸入臭氧会导致不良的全身炎症和心脏自主神经效应，这可能导致与短期接触相关的心血管死亡率增加。
