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Load-Dependent Changes in Left Ventricular Structure and Function in a Pathophysiologically Relevant Murine Model of Reversible Heart Failure
Circulation: Heart Failure ( IF 9.7 ) Pub Date : 2018-05-01 , DOI: 10.1161/circheartfailure.117.004351
Carla J. Weinheimer 1 , Attila Kovacs 1 , Sarah Evans 1 , Scot J. Matkovich 1 , Philip M. Barger 1 , Douglas L. Mann 1
Affiliation  

Background: To better understand reverse left ventricular (LV) remodeling, we developed a murine model wherein mice develop LV remodeling after transverse aortic constriction (TAC) and a small apical myocardial infarct (MI) and undergo reverse LV remodeling after removal of the aortic band.
Methods and Results: Mice studied were subjected to sham (n=6) surgery or TAC+MI (n=12). Two weeks post-TAC+MI, 1 group underwent debanding (referred to as heart failure debanding [HF-DB] mice; n=6), whereas the aortic band remained in a second group (heart failure [HF] group; n=6). LV remodeling was evaluated by 2D echocardiography at 1 day, 2 weeks and 6 weeks post-TAC+MI. The hearts were analyzed by transcriptional profiling at 4 and 6 weeks and histologically at 6 weeks. Debanding normalized LV volumes, LV mass, and cardiac myocyte hypertrophy at 6 weeks in HF-DB mice, with no difference in myofibrillar collagen in the HF and HF-DB mice. LV ejection fraction and radial strain improved after debanding; however, both remained decreased in the HF-DB mice relative to sham and were not different from HF mice at 6 weeks. Hemodynamic unloading in the HF-DB mice was accompanied by a 35% normalization of the HF genes at 2 weeks and 80% of the HF genes at 4 weeks.
Conclusions: Hemodynamic unloading of a pathophysiologically relevant mouse model of HF results in normalization of LV structure, incomplete recovery of LV function, and incomplete reversal of the HF transcriptional program. The HF-DB mouse model may provide novel insights into mechanisms of reverse LV remodeling.


中文翻译:

在可逆性心力衰竭的病理生理相关小鼠模型中左心室结构和功能的负荷依赖性变化。

背景:为了更好地了解左心室逆转(LV)重塑,我们开发了一种小鼠模型,其中小鼠在横向主动脉缩窄(TAC)和小根尖心肌梗塞(MI)后发展为LV重塑,并在去除主动脉带后进行反向LV重塑。
方法和结果:研究的小鼠接受了假手术(n = 6)或TAC + MI(n = 12)。TAC + MI后两周,解散一组(称为心力衰竭解散[HF-DB]小鼠; n = 6),而第二组保留主动脉带(心衰[HF]组; n = 6)。 6)。在TAC + MI后1天,2周和6周通过二维超声心动图评估LV重塑。在第4周和第6周通过转录谱分析对心脏进行分析,并在第6周通过组织学分析。在HF-DB小鼠中,在6周时消除标准化的LV体积,LV质量和心肌细胞肥大,而在HF和HF-DB小鼠中,肌原纤维胶原蛋白没有差异。解散后,左室射血分数和径向应变得到改善;然而,与假手术相比,HF-DB小鼠中的这两种都保持下降,并且与HF小鼠在第6周时没有差异。
结论: HF的病理生理相关小鼠模型的血流动力学卸除可导致LV结构正常化,LV功能恢复不完全以及HF转录程序逆转不完全。HF-DB小鼠模型可以提供有关反向LV重塑机制的新颖见解。
更新日期:2018-05-16
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