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T₁ 映射可检测到药物对压力超负荷肥厚小鼠弥漫性心肌纤维化的抑制作用。

T₁ mapping detects pharmacological retardation of diffuse cardiac fibrosis in mouse pressure-overload hypertrophy.

机构信息

British Heart Foundation Centre of Research Excellence, National Heart and Lung Institute.

出版信息

Circ Cardiovasc Imaging. 2014 Mar;7(2):240-9. doi: 10.1161/CIRCIMAGING.113.000993. Epub 2014 Jan 14.

DOI:10.1161/CIRCIMAGING.113.000993
PMID:24425501
Abstract

BACKGROUND

Diffuse interstitial fibrosis is present in diverse cardiomyopathies and associated with poor prognosis. We investigated whether magnetic resonance imaging-based T1 mapping could quantify the induction and pharmacological suppression of diffuse cardiac fibrosis in murine pressure-overload hypertrophy.

METHODS AND RESULTS

Mice were subjected to transverse aortic constriction or sham surgery. The angiotensin receptor blocker losartan was given to half the animals. Cine-magnetic resonance imaging performed at 7 and 28 days showed hypertrophy and remodeling and systolic and diastolic dysfunction in transverse aortic constriction groups as expected. Late gadolinium-enhanced magnetic resonance imaging revealed focal signal enhancement at the inferior right ventricular insertion point of transverse aortic constriction mice concordant with the foci of fibrosis in histology. The extracellular volume fraction, calculated from pre- and postcontrast T1 measurements, was elevated by transverse aortic constriction and showed direct linear correlation with picrosirius red collagen volume fraction, thus confirming the suitability of extracellular volume fraction as an in vivo measure of diffuse fibrosis. Treatment with losartan reduced left ventricular dysfunction and prevented increased extracellular volume fraction, indicating that T1 mapping is sensitive to pharmacological prevention of fibrosis.

CONCLUSIONS

Magnetic resonance imaging can detect diffuse and focal cardiac fibrosis in a clinically relevant animal model of pressure overload and is sensitive to pharmacological reduction of fibrosis by angiotensin receptor blockade. Thus, T1 mapping can be used to assess antifibrotic therapeutic strategies.

摘要

背景

弥漫性间质纤维化存在于多种心肌病中,并与预后不良相关。我们研究了基于磁共振成像的 T1 映射是否可以定量评估压力超负荷肥厚的小鼠模型中心房弥漫性纤维化的诱导和药物抑制。

方法和结果

小鼠接受升主动脉缩窄或假手术。一半的动物给予血管紧张素受体阻滞剂氯沙坦。在第 7 天和第 28 天进行心脏电影磁共振成像显示,升主动脉缩窄组出现了预期的肥厚和重塑,以及收缩和舒张功能障碍。钆延迟增强磁共振成像显示,升主动脉缩窄小鼠的右心室下插入点出现局灶性信号增强,与组织学中的纤维化灶一致。从预对比和后对比 T1 测量计算的细胞外容积分数升高,升主动脉缩窄组升高,并与苦味酸红胶原容积分数呈直接线性相关,因此证实细胞外容积分数作为弥漫性纤维化的体内测量是合适的。氯沙坦治疗可降低左心室功能障碍并预防细胞外容积分数升高,表明 T1 映射对纤维化的药物预防具有敏感性。

结论

磁共振成像可以在压力超负荷的临床相关动物模型中检测到弥漫性和局灶性心脏纤维化,并且对血管紧张素受体阻断的纤维化减少具有敏感性。因此,T1 映射可用于评估抗纤维化治疗策略。

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