左心房胶原纤维二维重构定量研究的一种方法

A Novel Method for Quantitative Analysis of Two Dimensional Collagen Remodeling in Left Atrium Induced by Left Ventricular Pressure Overload

背景心房压力超负荷所致胶原重构,尤其是胶原纤维的异质性分布是心房颤动发生的重要原因之一,但目前尚未见到对此病理生理过程进行定量分析的报道。目的尝试建立一种能够对心房胶原纤维二维分布情况进行定量描述的方法。方法采用兔腹主动脉肾上段缩窄方法建立左心室压力超负荷模型;按照狭窄程度不同,分为假手术组(无狭窄,n=14),左室肥厚组(50%～60%狭窄,n=16)和心力衰竭组(70%～80%狭窄,n=12)。术后8周,对存活动物(心力衰竭组死亡5只,其余各组无死亡)通过心脏超声、有创血流动力学检测对左心室和左心房结构和功能进行评价。心肌组织胶原分析采用苦味酸天狼猩红染色。利用具有自动角度识别功能的Continuity软件结合圆分布统计分析,对心房胶原纤维的二维分布进行定量分析。采用的圆分布变量为两类,一类为反映胶原纤维角度向量圆分布集中趋势的参数(平均向量长度和集中参数),另一类为反映胶原纤维圆分布离散趋势的参数(圆分布方差和圆分布标准差)。结果腹主动脉肾上段缩窄为50%～60%可形成明显的左心室肥厚及左心房扩大和心房肌细胞肥大;缩窄为70%～80%时,产生明显左心功能衰竭,伴有左心房内径明显增大[(14.7±3.1)vs(6.5±0.9)mm,P<0.01]。压力超负荷左心功能处于代偿期时,左心房胶原纤维平均向量长度、集中参数、圆分布方差和标准差均与假手术组无统计学差异,提示左心功能代偿期时心房胶原分布的异质性并未明显增强;当左心功能失代偿并且心房出现明显扩大时,左心房胶原纤维平均向量长度和集中参数明显降低,而圆分布方差和标准差增大,提示压力超负荷伴左心房明显扩大时心房胶原分布异质性增强。结论由左心房压力超负荷引起的心房胶原纤维二维分布异质性增高的现象,能够采用自动角度识别结合圆分布统计分析进行定量描述。

Background Pressure overload induced atrial collagen remodeling, and increased spatial heterogeneity of collagen fiber organization, leading to atrial fibrillation. However, there has been no quantitative method to describe this dynamic change. Objective To establish a novel method to quantify the two dimensional organization of collagen fiber in atrium. Methods Superrenal aortic coarctation was carried out to establish ex- perimental model of left ventricular （LV） pressure overload. According to the degree of stenosis, the animals were divided into sham （no stenosis, n= 14）, hypertrophy （50%-60% aortic stenosis, n= 16） and heart failure group （aortic 70%-80% stenosis, n=12）. Eight weeks after operation, transthoracie and invasive LV catheterization was performed to evaluate structural and functional changes of LV and left atrium in survival aminals. Collagen was measured by piero-sirius red staining. We used Continuity, a software with function of automatic angle recognition, combined with circular statistical method to quantify two dimensional atrial collagen fiber organization, Which generated two categories of parameters, one in term of central tendency of collagen vectors （length of mean vector, yon Wiese concentration）, another to delineate the dispersion tendency of collagen vectors （circular variance and circular standard deviation）. Results Obvious LV hypertrophy and enlargement of left atrium was observed with 50%-60% aortic coarctation. Severe LV systolic and diastolic dysfunction was found after 70% -80% aortic coarctation accompanied by prominent left atrial enlargement [（14.7±3.1） vs （6.5±0.9）mm, P〈0.01]. In compensated hypertrophy, no differences in 4 parameters （length of mean vector, von Wiese concentration, circular variance and circular standard deviation） derived from circular statistics was found, indicating no differences in left atrial collagen orientation. However, when LV failure and severe left atrial enlargement occurred, length of mean vector and yon Wiese concentration were significantly increased, and circular variance and standard deviation were significantly decreased, indicating obvious two dimensional heterogeneity of collagen fibers. Conclusion Automatic angle recognition combined with circular statistics is a novel method to quantify two dimensional heterogeneity of collagen fiber orientation and organization in pressure overloaded left atrium.