Weekly doxorubicin increases coronary arteriolar wall and adventitial thickness.
Weekly doxorubicin increases coronary arteriolar wall and adventitial thickness.
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DOI：
10.1371/journal.pone.0057554
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Hundley WG
中科院分区：
文献类型：
--
作者：
Eckman DM;Stacey RB;Rowe R;D'Agostino R Jr;Kock ND;Sane DC;Torti FM;Yeboah J;Workman S;Lane KS;Hundley WG
阿霉素 (DOX) 与包括心肌梗塞在内的过早心血管事件有关。本研究旨在确定每周给予 DOX 是否会影响冠状动脉内侧和/或外膜壁增厚。 32只25.1±2.4周龄的雄性Sprague-Dawley大鼠随机分为三组，每周腹腔注射生理盐水（生理盐水，n = 7），或低剂量（1.5 mg/kg至1.75 mg/kg，n = 14）或高剂量（2.5 mg/kg，n = 11）阿霉素。对动物进行2-12周的治疗，并按照预先指定的时间间隔（2、4、7或10周以上）处死动物，以获得冠状动脉管腔直径、内壁厚度、外膜壁厚度和总壁厚度（内膜厚度+外膜厚度）的组织病理学评估。所有组的管腔直径相似（盐水：315±34 µm，低 DOX：286±24 µm，高 DOX：242±27 µm；p = 0.22）。与每周注射盐水的动物相比，每周注射 2.5 mg/kg DOX 的动物的内侧厚度（23±2μm vs. 13±3μm；p = 0.005）和总壁厚度（51±4μm vs. 36±5μm；p = 0.022）分别增加。在管腔直径标准化后（p<0.05 至 p<0.001）并调整年龄、体重和总累积 DOX 剂量（p = 0.02 至 p = 0.01）后，这些增加以及外膜增厚变得更加突出。接受低剂量 DOX 的动物在管腔直径归一化并考虑年龄、体重和总累积 DOX 剂量后，外膜和总壁厚度趋于增加（分别为 p = 0.06 和 0.09）。总之，这些数据表明，每周用较高剂量的 DOX 治疗大鼠会增加冠状动脉内侧、外膜和总壁厚度。未来的研究有必要确定 DOX 相关的冠状动脉效应是否可逆或可预防，是否会加剧 DOX 已知的心肌病效应，影响静息或应激诱导的心肌灌注改变，或导致心肌梗塞的发生。
Doxorubicin (DOX) is associated with premature cardiovascular events including myocardial infarction. This study was performed to determine if the weekly administration of DOX influenced coronary arteriolar medial and/or adventitial wall thickening. Thirty-two male Sprague-Dawley rats aged 25.1± 2.4 weeks were randomly divided into three groups and received weekly intraperitoneal injections of normal saline (saline, n = 7), or low (1.5 mg/kg to 1.75 mg/kg, n = 14) or high (2.5 mg/kg, n = 11) doses of DOX. The animals were treated for 2–12 weeks, and euthanized at pre-specified intervals (2, 4, 7, or 10+ weeks) to obtain histopathologic assessments of coronary arteriolar lumen diameter, medial wall thickness, adventitial wall thickness, and total wall thickness (medial thickness + adventitial thickness). Lumen diameter was similar across all groups (saline: 315±34 µm, low DOX: 286±24 µm, high DOX: 242±27 µm; p = 0.22). In comparison to animals receiving weekly saline, animals receiving weekly injections of 2.5 mg/kg of DOX experienced an increase in medial (23±2µm vs. 13±3µm; p = 0.005), and total wall thickness (51±4µm vs. 36±5µm; p = 0.022), respectively. These increases, as well as adventitial thickening became more prominent after normalizing for lumen diameter (p<0.05 to p<0.001) and after adjusting for age, weight, and total cumulative DOX dose (p = 0.02 to p = 0.01). Animals receiving low dose DOX trended toward increases in adventitial and total wall thickness after normalization to lumen diameter and accounting for age, weight, and total cumulative DOX dose (p = 0.06 and 0.09, respectively). In conclusion, these data demonstrate that weekly treatment of rats with higher doses of DOX increases coronary arteriolar medial, adventitial, and total wall thickness. Future studies are warranted to determine if DOX related coronary arteriolar effects are reversible or preventable, exacerbate the known cardiomyopathic effects of DOX, influence altered resting or stress-induced myocardial perfusion, or contribute to the occurrence of myocardial infarction.
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影响因子：
7.4
作者：
Csanyi, Gabor;Taylor, W. Robert;Pagano, Patrick J.
通讯作者：
Pagano, Patrick J.
DOI：
10.1093/jnci/djk029
发表时间：
2007-02-07
期刊：
JOURNAL OF THE NATIONAL CANCER INSTITUTE
影响因子：
--
作者：
Swerdlow, Anthony J.;Higgins, Craig D.;Linch, David C.
通讯作者：
Linch, David C.
影响因子：
9.3
作者：
Dalla Pozza R;Beyerlein A;Thilmany C;Weissenbacher C;Netz H;Schmidt H;Bechtold S
通讯作者：
Bechtold S
影响因子：
3.7
作者：
Bar-Joseph H;Ben-Aharon I;Tzabari M;Tsarfaty G;Stemmer SM;Shalgi R
通讯作者：
Shalgi R
影响因子：
45.3
作者：
Aleman, BMP;van den Belt-Dusebout, AW;van Leeuwen, FE
通讯作者：
van Leeuwen, FE