Department of Cardiac Surgery, Faculty of Medical Science, State University of Campinas, Campinas, UNICAMP, Brazil.
Eur J Cardiothorac Surg. 2010 Feb;37(2):368-75. doi: 10.1016/j.ejcts.2009.06.011. Epub 2009 Nov 27.
Heart failure is a common and often fatal disease. Numerous animal models are used to study its aetiology, progression and treatment. This article aims to demonstrate two minimally invasive models of congestive heart failure in a rabbit model and a precise method to assess cardiac performance.
Fifty New Zealand White rabbits underwent cervicotomy incision and were then divided into three groups. Aortic regurgitation (AR group) was induced in 17 animals by catheter lesion through the right carotid artery, proximal aortic constriction (AC group) was created in 17 animals by metallic clip placement in the ascending aorta through a neck incision, while 16 animals served as controls (CO group). Eight weeks later, myocardial function and contractility indices were assessed by sonomicrometry crystals. Hearts were then collected for morphometric measurements and left ventricular tissues were subjected to immunohistochemical analysis of fibrosis, necrosis and apoptosis. Statistical analysis was by analysis of variance (ANOVA) with a Dunnett's post hoc test or by Kruskal-Wallis test with Dunn's post hoc test as appropriate, with significance at p< or =0.05.
The model of aortic regurgitation indicated early stages of heart failure by volume overload with increased end-diastolic and end-systolic volumes, stroke volume, cardiac output and pressure-volume loop areas. The elastance was higher in the control group compared with that in the AC and AR groups (131.00+/-51.27 vs 88.77+/-40.11 vs 75.29+/-50.70; p=0.01). The preload recruitable stroke work was higher in the control group compared with that in the AC and AR groups (47.70+/-14.19 vs 33.87+/-7.46 vs 38.58+/-9.45; p=0.01). Aortic constriction produced left ventricular concentric hypertrophy. Fibrosis appeared in both heart failure models and was elevated by aortic constriction when compared with that in controls. Necrosis and apoptosis indices were very low in all the groups. Clinical signs of congestive heart failure were not present.
The two heart failure models we describe were relatively simple to create and maintain, minimally invasive, accurate, inexpensive and, importantly, had a low mortality rate. These models rapidly induced deterioration of contractility indices and onset of fibrosis, the hallmarks of early myocardial dysfunction associated with heart failure. Sonomicrometry assessments were able to detect early contractility changes prior to clinical signs.
心力衰竭是一种常见且通常致命的疾病。大量动物模型被用于研究其病因、进展和治疗。本文旨在展示两种微创型兔心力衰竭模型，并提供一种精确评估心功能的方法。
50 只新西兰白兔行颈部切口，然后分为三组。17 只动物通过右侧颈动脉导管损伤诱导主动脉瓣反流（AR 组），17 只动物通过颈部切口金属夹放置于升主动脉创建近端主动脉缩窄（AC 组），16 只动物作为对照组（CO 组）。8 周后，应用超声心动图微测技术评估心肌功能和收缩力指标。收集心脏进行形态学测量，并对左心室组织进行纤维化、坏死和凋亡的免疫组织化学分析。统计分析采用方差分析（ANOVA），并进行 Dunnett 事后检验或 Kruskal-Wallis 检验及 Dunn 事后检验，以 p<或=0.05 为差异有统计学意义。
主动脉瓣反流模型通过容量超负荷导致舒张末期和收缩末期容积、每搏量、心输出量和压力-容积环面积增加，表现为心力衰竭的早期阶段。与 AC 组和 AR 组相比，对照组的弹性更高（131.00+/-51.27 比 88.77+/-40.11 比 75.29+/-50.70；p=0.01）。与 AC 组和 AR 组相比，对照组的预负荷可收缩功更高（47.70+/-14.19 比 33.87+/-7.46 比 38.58+/-9.45；p=0.01）。主动脉缩窄导致左心室向心性肥厚。两种心力衰竭模型均出现纤维化，并与对照组相比纤维化增加。所有组的坏死和凋亡指数均非常低。所有组均无充血性心力衰竭的临床体征。
我们描述的两种心力衰竭模型创建和维持相对简单，微创、准确、经济实惠，重要的是死亡率低。这些模型迅速导致收缩力指数恶化和纤维化发生，纤维化是心力衰竭相关早期心肌功能障碍的标志。超声心动图微测技术能够在出现临床体征之前检测到早期收缩力变化。
