Ecstasy produces left ventricular dysfunction and oxidative stress in rats.
Ecstasy produces left ventricular dysfunction and oxidative stress in rats.
复制标题
摇头丸会导致大鼠左心室功能障碍和氧化应激。
DOI：
10.1093/cvr/cvn129
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发表时间：
2008
影响因子：
10.8
通讯作者：
Varner,KurtJ
中科院分区：
文献类型：
--
作者：
Shenouda,SylviaK;Lord,KevinC;McIlwain,Elizabeth;Lucchesi,PamelaA;Varner,KurtJ
我们的目的是确定是否重复，狂欢管理的3，4-亚甲二氧基甲基苯丙胺（摇头丸;方法和结果应用超声心动图和压力-容积电导导管对4次摇头丸狂欢大鼠左心室结构和功能进行了研究（9 mg/kg i. v.给药4天，中间间隔10天停药期）。处理组和对照组大鼠的心脏用于生化和蛋白质组学分析或成年LV肌细胞的分离。在第四次狂饮后，治疗的心脏表现出离心性LV扩张和舒张功能障碍。在体内，收缩功能没有改变，但是，与对照组大鼠的肌细胞相比，在体内用摇头丸治疗的大鼠的肌细胞对电刺激的收缩反应的幅度明显较小。与对照组大鼠相比，迷魂药治疗组大鼠的肌细胞中细胞内钙（Fura-2测定）峰值增加幅度也显著较小。从迷魂药治疗的大鼠心肌细胞的细胞内钙瞬变的松弛动力学显着较长。兴奋能显著增加左心室硝基酪氨酸含量。蛋白质组学分析显示，增加硝化的收缩蛋白（肌钙蛋白-T，原肌球蛋白α-1链，肌球蛋白轻多肽，肌球蛋白调节轻链），线粒体蛋白（Ub-细胞色素-C还原酶和ATP合成酶），和肌浆网钙ATPase.ConclusionThe反复狂欢管理摇头丸产生偏心左心室扩张和功能障碍，伴随着氧化应激。这些功能反应可能是由参与兴奋-收缩偶联和/或线粒体能量产生的蛋白质的氧化还原修饰引起的。总之，这些结果表明摇头丸有可能产生严重的心脏毒性和心室功能障碍。
AimsOur aim was to determine whether the repeated, binge administration of 3,4-methylenedioxymethamphetamine (ecstasy; MDMA) produces structural and/or functional changes in the myocardium that are associated with oxidative stress.Methods and resultsEchocardiography and pressure–volume conductance catheters were used to assess left ventricular (LV) structure and function in rats subjected to four ecstasy binges (9 mg/kg i.v. for 4 days, separated by a 10 day drug-free period). Hearts from treated and control rats were used for either biochemical and proteomic analysis or the isolation of adult LV myocytes. After the fourth binge, treated hearts showed eccentric LV dilation and diastolic dysfunction. Systolic function was not alteredin vivo; however, the magnitude of the contractile responses to electrical stimulation was significantly smaller in myocytes from rats treatedin vivowith ecstasy compared with myocytes from control rats. The magnitude of the peak increase in intracellular calcium (measured by Fura-2) was also significantly smaller in myocytes from ecstasy-treated vs. control rats. The relaxation kinetics of the intracellular calcium transients were significantly longer in myocytes from ecstasy-treated rats. Ecstasy significantly increased nitrotyrosine content in the left ventricle. Proteomic analysis revealed increased nitration of contractile proteins (troponin-T, tropomyosin alpha-1 chain, myosin light polypeptide, and myosin regulatory light chain), mitochondrial proteins (Ub-cytochrome-c reductase and ATP synthase), and sarcoplasmic reticulum calcium ATPase.ConclusionThe repeated binge administration of ecstasy produces eccentric LV dilation and dysfunction that is accompanied by oxidative stress. These functional responses may result from the redox modification of proteins involved in excitation-contraction coupling and/or mitochondrial energy production. Together, these results indicate that ecstasy has the potential to produce serious cardiac toxicity and ventricular dysfunction.