Cape E G, Vanauker M D, Sigfússon G, Tacy T A, del Nido P J
Cardiac Dynamics Laboratory, Division of Cardiology, Children's Hospital of Pittsburgh, Pennsylvania 15213, USA.
J Am Coll Cardiol. 1997 Jul;30(1):247-54. doi: 10.1016/s0735-1097(97)00048-x.
The objective of this study was to show elevations in septal shear stress in response to morphologic abnormalities that have been associated with discrete subaortic stenosis (SAS) in children. Combined with the published data, this critical connection supports a four-stage etiology of SAS that is advanced in this report.
Subaortic stenosis constitutes up to 20% of left ventricular outflow obstruction in children and frequently requires surgical removal, and the lesions may reappear unpredictably after the operation. The etiology of SAS is unknown. This study proposes a four-stage etiology for SAS that I) combines morphologic abnormalities, II) elevation of septal shear stress, III) genetic predisposition and IV) cellular proliferation in response to shear stress.
Morphologic structures of a left ventricular outflow tract were modeled based on measurements in patients with and without SAS. Septal shear stress was studied in response to changes in aortoseptal angle (AoSA) (120 degrees to 150 degrees), outflow tract convergence angle (45 degrees, 22.5 degrees and 0 degree), presence/location of a ventricular septal defect (VSD) (3-mm VSD; 2 and 6 mm from annulus) and shunt velocity (3 and 5 m/s).
Variations in AoSA produced marked elevations in septal shear stress (from 103 dynes/cm2 for 150 degrees angle to 150 dynes/cm2 for 120 degrees angle for baseline conditions). This effect was not dependent on the convergence angle in the outflow tract (150 to 132 dynes/cm2 over full range of angles including extreme case of 0 degree). A VSD enhanced this effect (150 to 220 dynes/cm2 at steep angle of 120 degrees and 3 m/s shunt velocity), consistent with the high incidence of VSDs in patients with SAS. The position of the VSD was also important, with a reduction of the distance between the VSD and the aortic annulus causing further increases in septal shear stress (220 and 266 dynes/cm2 for distances of 6 and 2 mm from the annulus, respectively).
Small changes in AoSA produce important changes in septal shear stress. The levels of stress increase are consistent with cellular flow studies showing stimulation of growth factors and cellular proliferation. Steepened AoSA may be a risk factor for the development of SAS. Evidence exists for all four stages of the proposed etiology of SAS.
本研究的目的是表明，儿童中与离散性主动脉瓣下狭窄（SAS）相关的形态学异常会导致室间隔剪切应力升高。结合已发表的数据，这一关键联系支持了本报告中提出的SAS四阶段病因学。
主动脉瓣下狭窄占儿童左心室流出道梗阻的20%，常需手术切除，且病变在术后可能不可预测地复发。SAS的病因尚不清楚。本研究提出了SAS的四阶段病因学，即：I）形态学异常，II）室间隔剪切应力升高，III）遗传易感性，IV）对剪切应力的细胞增殖反应。
根据有或无SAS患者的测量结果，对左心室流出道的形态结构进行建模。研究了室间隔剪切应力对主动脉-室间隔角（AoSA）（120度至150度）、流出道会聚角（45度、22.5度和0度）、室间隔缺损（VSD）的存在/位置（3毫米VSD；距瓣环2和6毫米）以及分流速度（3和5米/秒）变化的反应。
AoSA的变化导致室间隔剪切应力显著升高（基线条件下，从150度角时的103达因/平方厘米到120度角时的150达因/平方厘米）。这种效应不依赖于流出道的会聚角（在包括0度极端情况的整个角度范围内为150至132达因/平方厘米）。VSD增强了这种效应（在120度陡坡角和3米/秒分流速度下为150至220达因/平方厘米），这与SAS患者中VSD的高发生率一致。VSD的位置也很重要，VSD与主动脉瓣环之间距离的减小会导致室间隔剪切应力进一步增加（距瓣环6毫米和2毫米时分别为220和266达因/平方厘米）。
AoSA的微小变化会导致室间隔剪切应力发生重要变化。应力增加水平与显示生长因子刺激和细胞增殖的细胞流动研究一致。AoSA变陡可能是SAS发生的一个危险因素。所提出的SAS病因学的所有四个阶段都有证据支持。
