Characterization of the Changes in Cardiac Structure and Function in Mice Treated With Anthracyclines Using Serial Cardiac Magnetic Resonance Imaging.
Characterization of the Changes in Cardiac Structure and Function in Mice Treated With Anthracyclines Using Serial Cardiac Magnetic Resonance Imaging.
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DOI：
10.1161/circimaging.115.003584
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发表时间：
2016-12
期刊：
影响因子：
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通讯作者：
Neilan TG
中科院分区：
文献类型：
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作者：
Farhad H;Staziaki PV;Addison D;Coelho-Filho OR;Shah RV;Mitchell RN;Szilveszter B;Abbasi SA;Kwong RY;Scherrer-Crosbie M;Hoffmann U;Jerosch-Herold M;Neilan TG
蒽环类药物对心脏有毒性作用；然而，目前还没有足够的数据来描述在使用这些药物后心脏结构和功能的一系列变化。本研究的目的是利用心脏磁共振(CMR)来表征蒽环类药物对小鼠的心脏毒性。这是一项纵向的CMR和组织学研究，将45只野生型雄性小鼠随机分为阿霉素(DOX，n=30，每周5 mg/kg DOX，共5周)和安慰剂(n=15)。在基线和随机分组后5、10和20周进行CMR检查。主要的测量指标包括左心室射血分数(LVEF)、心肌水肿(多回波短轴自旋回波采集)和心肌纤维化(Look-Locker梯度回波)。与安慰剂相比，DOX治疗的小鼠在5周时心肌水肿增加(T2值为32±4比21±3毫秒，P<；0.05)，随后在10周时LVEF降低(54±6比63±5%，P<；0.05)，心肌纤维化增加(细胞外体积为0.34±0.03比0.27±0.03，P<；0.05)。早期(5周)的水肿增加和亚急性(10周)的纤维化增加之间有很强的相关性(r=0.9，P<；0.001)。水肿和纤维化的增加都可以预测晚期阿霉素诱导的小鼠死亡率(P<；0.001)。我们的数据表明，在小鼠中，AIC与早期心脏水肿增加和随后的心肌纤维化增加有关。早期的水肿增加和亚急性的纤维化增加是密切相关的，两者都是晚期死亡率的预测因素。
Anthracyclines are cardiotoxic; however, there are limited data characterizing the serial changes in cardiac structure and function after anthracyclines. The aim of this study was to use cardiac magnetic resonance (CMR) to characterize anthracycline-induced cardiotoxicity (AIC) in mice. This was a longitudinal CMR and histological study of 45 wild-type male mice randomized to doxorubicin (DOX, n=30, 5 mg/kg of DOX/week for 5 weeks) or placebo (n=15). A CMR was performed at baseline and at 5, 10 and 20 weeks after randomization. Measures of primary interest included left ventricular ejection fraction (LVEF), myocardial edema (multi-echo short-axis spin-echo acquisition) and myocardial fibrosis (Look-Locker gradient-echo). In DOX-treated mice vs. placebo, there was an increase in myocardial edema at 5 weeks (T2 values of 32±4 vs. 21±3 msec, P < 0.05); followed by a reduction in LVEF (54±6 vs. 63±5%, P < 0.05) and an increase in myocardial fibrosis (extracellular volume of 0.34±0.03 vs. 0.27±0.03, P < 0.05) at 10 weeks. There was a strong association between the early (5 weeks) increase in edema and the sub-acute (10 weeks) increase in fibrosis (r = 0.90, P < 0.001). Both the increase in edema and fibrosis predicted the late DOX-induced mortality in mice (P < 0.001). Our data suggest that, in mice, AIC is associated with an early increase in cardiac edema and a subsequent increase in myocardial fibrosis. The early increase in edema and sub-acute increase in fibrosis are strongly linked and are both predictive of late mortality.