Lord Kevin, Moll David, Lindsey John K, Mahne Sarah, Raman Girija, Dugas Tammy, Cormier Stephania, Troxlair Dana, Lomnicki Slawo, Dellinger Barry, Varner Kurt
Department of Cardiopulmonary Sciences, LSU Health Sciences Center, New Orleans, LA 70112, USA.
J Recept Signal Transduct Res. 2011 Apr;31(2):157-67. doi: 10.3109/10799893.2011.555767.
Exposure to airborne particles is associated with increased cardiovascular morbidity and mortality. During the combustion of chlorine-containing hazardous materials and fuels, chlorinated hydrocarbons chemisorb to the surface of transition metal-oxide-containing particles, reduce the metal, and form an organic free radical. These radical-particle systems can survive in the environment for days and are called environmentally persistent free radicals (EPFRs). This study determined whether EPFRs could decrease left ventricular function before and after ischemia and reperfusion (I/R) in vivo. Male Brown-Norway rats were dosed (8 mg/kg, intratracheal) 24 h prior to testing with particles containing the EPFR of 1, 2-dichlorobenzene (DCB230). DCB230 treatment decreased systolic and diastolic function. DCB230 also produced pulmonary and cardiac inflammation. After ischemia, systolic, but not diastolic function was significantly decreased in DCB230-treated rats. Ventricular function was not affected by I/R in control rats. There was greater oxidative stress in the heart and increased 8-isoprostane (biomarker of oxidative stress) in the plasma of treated vs. control rats after I/R. These data demonstrate for the first time that DCB230 can produce inflammation and significantly decrease cardiac function at baseline and after I/R in vivo. Furthermore, these data suggest that EPFRs may be a risk factor for cardiac toxicity in healthy individuals and individuals with ischemic heart disease. Potential mechanisms involving cytokines/chemokines and/or oxidative stress are discussed.
暴露于空气中的颗粒物与心血管疾病发病率和死亡率的增加有关。在含氯有害物质和燃料燃烧过程中，氯代烃化学吸附到含过渡金属氧化物颗粒的表面，使金属还原，并形成有机自由基。这些自由基 - 颗粒系统可在环境中存活数天，被称为环境持久性自由基（EPFRs）。本研究确定了EPFRs是否会在体内缺血再灌注（I/R）前后降低左心室功能。在测试前24小时，给雄性棕色挪威大鼠气管内注射含1,2 - 二氯苯（DCB230）的EPFR颗粒（8毫克/千克）。DCB230处理降低了收缩和舒张功能。DCB230还引发了肺部和心脏炎症。缺血后，DCB230处理的大鼠收缩功能显著降低，但舒张功能未受影响。对照组大鼠的心室功能未受I/R影响。I/R后，处理组大鼠心脏中的氧化应激更大，血浆中8 - 异前列腺素（氧化应激生物标志物）增加。这些数据首次证明，DCB230可在体内基线和I/R后引发炎症并显著降低心脏功能。此外，这些数据表明，EPFRs可能是健康个体和缺血性心脏病患者心脏毒性的一个危险因素。文中讨论了涉及细胞因子/趋化因子和/或氧化应激的潜在机制。
