Acute methamphetamine exposure inhibits cardiac contractile function.
Acute methamphetamine exposure inhibits cardiac contractile function.
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DOI：
10.1016/j.toxlet.2009.05.015
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发表时间：
2009-09-10
影响因子：
3.5
通讯作者：
Ren, Jun
中科院分区：
文献类型：
--
作者：
Turdi, Subat;Schamber, Robbie M.;Roe, Nathan D.;Chew, Herbert G., Jr.;Culver, Bruce;Ren, Jun
甲基安非他明是一种常见的滥用物质，据报告对包括心血管系统在内的身体机能产生有害影响，但对其作用机制知之甚少。本研究旨在研究甲基苯丙胺对离体全心脏和单个心肌细胞收缩功能的直接影响。将来自成年FVB小鼠的鼠心脏和分离的心肌细胞暴露于各种浓度的甲基苯丙胺30分钟，然后分别使用Langendroff装置和IonOptix Myocam®系统评估机械功能。分析心肌收缩特性，包括左室压力发展和下降的最大速度（± dP/dt）、最大缩短幅度（PS）、最大缩短/再舒张速度（± dLdt）、达到PS的时间（TPS）、达到90%再舒张的时间（TR 90）、静息和电刺激时细胞内Ca 2+的增加以及细胞内Ca 2+的衰减。结果表明，急性甲基苯丙胺暴露可降低± dP/dt、PS和细胞内Ca ~（2+）升高，而不影响± dLdt、TPS、TR_（90）、静息Ca ~（2+）和细胞内Ca ~（2+）衰减。此外，甲基苯丙胺取消肾上腺素能激动剂去甲肾上腺素引起的心肌细胞正性收缩反应，包括PS，± dLdt升高和TR 90缩短，而不影响TPS。蛋白质印迹分析显示肌浆网（内）Ca 2 +-ATP酶（SERCA 2a）和受磷蛋白表达无变化，与急性甲基苯丙胺暴露后Na+-Ca 2+交换水平上调相关。此外，甲基苯丙胺促进明显的心肌细胞蛋白质损伤的羰基形成。综上所述，这些结果表明甲基苯丙胺在心肌和分离的心肌细胞中的直接心脏抑制作用，可能与蛋白质损伤和抑制肾上腺素能反应有关。
Methamphetamine, a commonly seen substance of abuse, has been reported to exert detrimental effect on bodily function including the cardiovascular system although its mechanism of action is poorly understood. This study was designed to examine the direct impact of methamphetamine on isolated whole heart and single cardiomyocyte contractile function. Murine hearts and isolated cardiomyocytes from adult FVB mice were exposed to various concentrations of methamphetamine for 30 min prior to the assessment of mechanical function using a Langendroff apparatus and an IonOptix Myocam® system, respectively. Cardiac contractile properties analyzed included maximal velocity of left ventricular pressure development and decline (± dP/dt), peak shortening amplitude (PS), maximal velocity of shortening/relengthening (± dLdt), time-to-PS (TPS), time-to-90% relengthening (TR90), resting and electrically-stimulated increase of intracellular Ca2+ as well as intracellular Ca2+ decay. Our results revealed that acute methamphetamine exposure depressed ± dP/dt, PS and rise of intracellular Ca2+ without affecting ± dLdt, TPS, TR90, resting intracellular Ca2+ and intracellular Ca2+ decay. Furthermore, methamphetamine nullified the adrenergic agonist norepinephrine-elicited positive cardiomyocyte contractile response, including elevated PS, ± dLdt and shortened TR90 without affecting TPS. Western blot analysis showed unchanged expression of sarco(endo)plasmic reticulum Ca2+-ATPase (SERCA2a) and phospholamban, associated with upregulated Na+-Ca2+ exchanger levels following acute methamphetamine exposure. In addition, methamphetamine promoted overt cardiomyocyte protein damage evaluated by carbonyl formation. Taken together, these results demonstrate direct cardiac depressant effect of methamphetamine in myocardium and isolated cardiomyocytes, possibly associated with protein damage and dampened adrenergic response.
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影响因子：
2.7
作者：
JACOBS, LJ
通讯作者：
JACOBS, LJ
DOI：
10.1081/clt-120026521
发表时间：
2003-01-01
期刊：
JOURNAL OF TOXICOLOGY-CLINICAL TOXICOLOGY
影响因子：
--
作者：
Wijetunga, M;Seto, T;Schatz, I
通讯作者：
Schatz, I
DOI：
10.1196/annals.1432.017
发表时间：
2008-01-01
期刊：
DRUG ADDICTION: RESEARCH FRONTIERS AND TREATMENT ADVANCES
影响因子：
--
作者：
Ruffoli, Riccardo;Soldani, Paola;Fornai, Francesco
通讯作者：
Fornai, Francesco
影响因子：
8.3
作者：
Wang, Y;Hayashi, T;Lin, SZ
通讯作者：
Lin, SZ
影响因子：
2.2
作者：
Maeno, Y;Iwasa, M;Nagao, M
通讯作者：
Nagao, M