Wu Haotian, Li Li, Niu Pei, Huang Xu, Liu Jinyi, Zhang Fengshun, Shen Wenzeng, Tan Wenchang, Wu Yiling, Huo Yunlong
School of Basic Medical Sciences, Nanjing University of Traditional Chinese Medicine, Nanjing, China.
Hebei Yiling Pharmaceutical Research Institute, Shijiazhuang, China.
Physiol Rep. 2017 Jun;5(12). doi: 10.14814/phy2.13311.
Animal models are of importance to investigate basic mechanisms for ischemic heart failure (HF). The objective of the study was to create a rabbit model through multiple coronary artery ligations to investigate the postoperative structure-function remodeling of the left ventricle (LV) and coronary arterial trees. Here, we hypothesize that the interplay of the degenerated coronary vasculature and increased ventricle wall stress relevant to cardiac fibrosis in vicinity of myocardial infarction (MI) precipitates the incidence and progression of ischemic HF Echocardiographic measurements showed an approximately monotonic drop of fractional shortening and ejection fraction from 40% and 73% down to 28% and 58% as well as persistent enlargement of LV cavity and slight mitral regurgitation at postoperative 12 weeks. Micro-CT and histological measurements showed that coronary vascular rarefaction and cardiac fibrosis relevant to inflammation occurred concurrently in vicinity of MI at postoperative 12 weeks albeit there was compensatory vascular growth at postoperative 6 weeks. These findings validate the proposed rabbit model and prove the hypothesis. The post-MI rabbit model can serve as a reference to test various drugs for treatment of ischemic HF.
动物模型对于研究缺血性心力衰竭(HF)的基本机制具有重要意义。本研究的目的是通过多次冠状动脉结扎建立兔模型,以研究左心室(LV)和冠状动脉树的术后结构-功能重塑。在此,我们假设退化的冠状动脉血管与心肌梗死(MI)附近与心脏纤维化相关的心室壁应力增加之间的相互作用会促使缺血性HF的发生和发展。超声心动图测量显示,术后12周时,缩短分数和射血分数从40%和73%大致呈单调下降至28%和58%,同时左心室腔持续扩大且有轻微二尖瓣反流。微型计算机断层扫描(Micro-CT)和组织学测量显示,术后12周时,在MI附近同时发生了与炎症相关的冠状动脉血管稀疏和心脏纤维化,尽管术后6周时有代偿性血管生长。这些发现验证了所提出的兔模型并证明了该假设。心肌梗死后兔模型可作为测试各种治疗缺血性HF药物的参考。