Hamade Ali K, Tankersley Clarke G
Department of Environmental Health Sciences, John Hopkins University, Baltimore, MD 21205, USA.
Am J Physiol Regul Integr Comp Physiol. 2009 Apr;296(4):R1202-15. doi: 10.1152/ajpregu.90808.2008. Epub 2009 Jan 21.
Increased ambient particulate matter (PM) is associated with adverse cardiovascular and respiratory outcomes, as demonstrated by epidemiology studies. Several studies have investigated the role of copollutants, such as ozone (O(3)), in this association. It is accepted that physiological adaptation involving the respiratory system occurs with repeated exposures to O(3). We hypothesize that adaptation to PM and O(3) varies among different inbred mouse strains, and cardiopulmonary adaptation to O(3) is a synchronized response between the cardiac and respiratory systems. Heart rate (HR), HR variability (HRV), and the magnitude and pattern of breathing were simultaneously measured by implanted telemeters and by plethysmography in three inbred mouse strains: C57Bl/6J (B6), C3H/HeJ (HeJ), and C3H/HeOuJ (OuJ). Physiological responses were assessed during dual exposures to filtered air (FA), O(3) (576 +/- 32 parts/billion), and/or carbon black (CB; 556 +/- 34 mug/m(3)). Exposures were repeated for 3 consecutive days. While each strain showed significant reductions in HR during CB with O(3) preexposure (O(3)CB) on day 1, prominent HRV responses were observed in only HeJ and OuJ mice. Each strain also differed in their adaptation profile in response to repeated O(3)CB exposures. Whereas B6 mice showed rapid adaptation in HR after day 1, HeJ mice generally showed more moderate HR and HRV adaptation after day 2 of exposure. Unlike either B6 or HeJ strains, OuJ mice showed little evidence of HR or HRV adaptation to repeated O(3)CB exposure. Adaptation profiles between HR regulation and breathing characteristics were strongly correlated, but these associations also varied significantly among strains. These findings suggest that genetic factors determine the responsivity and adaptation of the cardiac and respiratory systems to repeated copollutant exposures. During O(3)CB exposure, adaptation of cardiac and respiratory systems is markedly synchronized, which may explain a potential mechanism for adverse effects of PM on heart function.
流行病学研究表明,环境中颗粒物(PM)增加与心血管和呼吸系统不良后果相关。多项研究调查了臭氧(O₃)等共存污染物在这种关联中的作用。人们公认,呼吸系统的生理适应会随着对O₃的反复暴露而发生。我们假设,不同近交系小鼠品系对PM和O₃的适应存在差异,并且心脏和呼吸系统对O₃的心肺适应是一种同步反应。通过植入式遥测器和体积描记法,同时测量了三个近交系小鼠品系:C57Bl/6J(B6)、C3H/HeJ(HeJ)和C3H/HeOuJ(OuJ)的心率(HR)、心率变异性(HRV)以及呼吸的幅度和模式。在同时暴露于过滤空气(FA)、O₃(576±32 ppb)和/或炭黑(CB;556±34 μg/m³)的过程中评估生理反应。暴露连续重复3天。虽然在第1天,预先暴露于O₃(O₃CB)的情况下,每个品系在接触CB时HR均显著降低,但仅在HeJ和OuJ小鼠中观察到明显的HRV反应。每个品系对反复的O₃CB暴露的适应情况也有所不同。B6小鼠在第1天后HR迅速适应,而HeJ小鼠在暴露第2天后通常表现出更适度的HR和HRV适应。与B6或HeJ品系不同,OuJ小鼠几乎没有证据表明其对反复的O₃CB暴露有HR或HRV适应。HR调节与呼吸特征之间的适应情况密切相关,但这些关联在不同品系之间也存在显著差异。这些发现表明,遗传因素决定了心脏和呼吸系统对反复共存污染物暴露的反应性和适应性。在O₃CB暴露期间,心脏和呼吸系统的适应明显同步,这可能解释了PM对心脏功能产生不良影响的潜在机制。