Department of Pathology, University of Maryland, Baltimore, MD 21201, USA.
Lab Invest. 2012 Feb;92(2):224-35. doi: 10.1038/labinvest.2011.146. Epub 2011 Oct 3.
The contribution of chronic tobacco exposure in determining post-myocardial infarction (MI) left ventricular (LV) remodeling and possible therapeutic strategies has not been investigated systematically. In this small animal investigation, we demonstrate that chronic tobacco smoke exposure leading up to acute MI in rats is associated with greater histological extent of myocardial necrosis and consequent worse LV function. These findings are associated with increased transcriptomic expression of pro-inflammatory cytokines, tissue repair molecules and markers of oxidative stress in the myocardium. The results demonstrate that an N-acetyl cysteine (NAC) treatment significantly reduced tobacco-exposed induced infarct size and percent fractional shortening. A significantly increased LV end-systolic diameter was observed in tobacco-exposed sham compared to tobacco-naïve sham (4.92±0.41 vs 3.45±0.33; P<0.05), and tobacco-exposed MI compared to tobacco-naïve MI (8.24±0.3 vs 6.1±0.49; P<0.01) rats. Decreased intracardiac mRNA expression of the markers of inflammation, tissue repair and oxidative stress and circulating levels of pro-inflammatory cytokines accompanied these positive effects of NAC. The treatment of tobacco-exposed MI rats with NAC resulted in significantly increased levels of intracardiac mRNA expression of antioxidants, including superoxide dismutase, thioredoxin and nuclear factor-E2-related factor 2, as well as circulating levels of glutathione (7±0.12 vs 10±0.18; P≤0.001), where the levels were almost identical to the tobacco-naïve sham rats. These findings identify a novel post-infarction therapy for amelioration of the adverse effects of tobacco exposure on the infracted myocardium and advocate the use of dietary supplement antioxidants for habitual smokers to prevent and reverse cardiovascular adverse effects in the absence of successful achievement of cessation of smoking.
慢性烟草暴露在决定心肌梗死后（MI）左心室（LV）重构和可能的治疗策略中的作用尚未得到系统研究。在这项小动物研究中，我们证明了导致大鼠急性 MI 之前的慢性烟草烟雾暴露与更大的心肌坏死组织学范围和随之而来的更差的 LV 功能相关。这些发现与心肌中促炎细胞因子、组织修复分子和氧化应激标志物的转录组表达增加有关。结果表明，N-乙酰半胱氨酸（NAC）治疗显著减少了烟草暴露引起的梗死面积和百分比缩短。与烟草未暴露的假手术组相比，烟草暴露的假手术组的 LV 收缩末期直径明显增加（4.92±0.41 对 3.45±0.33；P<0.05），与烟草未暴露的 MI 组相比，烟草暴露的 MI 组的 LV 收缩末期直径也明显增加（8.24±0.3 对 6.1±0.49；P<0.01）。NAC 的这些积极作用伴随着炎症、组织修复和氧化应激标志物的心脏内 mRNA 表达减少和促炎细胞因子的循环水平降低。用 NAC 治疗烟草暴露的 MI 大鼠导致心脏内抗氧化剂的 mRNA 表达显著增加，包括超氧化物歧化酶、硫氧还蛋白和核因子-E2 相关因子 2，以及循环水平的谷胱甘肽（7±0.12 对 10±0.18；P≤0.001），其水平几乎与烟草未暴露的假手术大鼠相同。这些发现确定了一种新的梗死后治疗方法，可改善烟草暴露对梗死心肌的不利影响，并提倡习惯性吸烟者使用膳食补充抗氧化剂来预防和逆转心血管不良影响，而无需成功戒烟。
