Peterson L M, McPheeters M, Barwick L, Gu S, Rollins A M, Jenkins M W
Biomedical Engineering Department, Case Western Reserve University, Cleveland, Ohio 44106, USA.
Annu Int Conf IEEE Eng Med Biol Soc. 2012;2012:1382-5. doi: 10.1109/EMBC.2012.6346196.
Several studies have shown that altering blood flow early in development leads to congenital heart defects. In these studies the perturbations to hemodynamics were very gross manipulations (vessel ligation, conotruncal banding, etc.) that would be inappropriate for probing the delicate mechanisms responsible for mechanically-transduced signaling. Also, these perturbations lacked feedback from a monitoring system to determine the exact degree of alteration and the location of its effect. Here, we employed optical pacing (OP) to alter the heart rate in quail embryos and optical coherence tomography (OCT) to measure the resultant shear forces on the endocardium. OP is a new technique utilizing pulsed 1.851 µm infrared laser light to noninvasively capture the heart rate to the pulse frequency of the laser without the use of exogenous agents. To measure shear stress on the endocardium, we extended our previous OCT algorithms to enable the production of 4-D shear maps. 4-D shear maps allowed observation of the spatial and temporal distribution of shear stress. Employing both OCT and OP, we were able to develop perturbation protocols that increase regurgitant flow and greatly modify the oscillatory shear index (OSI) in a region of the heart tube where future valves will develop. Regurgitant flow has been linked with valve development and precise perturbations may allow one to determine the role of hemodynamics in valvulogenesis.
多项研究表明，在发育早期改变血流会导致先天性心脏缺陷。在这些研究中，对血流动力学的扰动是非常粗略的操作（血管结扎、圆锥干束带等），不适用于探究负责机械转导信号的精细机制。此外，这些扰动缺乏来自监测系统的反馈，无法确定改变的确切程度及其影响位置。在此，我们采用光学起搏（OP）来改变鹌鹑胚胎的心率，并利用光学相干断层扫描（OCT）来测量心内膜上产生的剪切力。OP是一种新技术，利用脉冲1.851 µm红外激光在不使用外源试剂的情况下无创地将心率捕捉到激光的脉冲频率。为了测量心内膜上的剪应力，我们扩展了之前的OCT算法，以生成4D剪应力图。4D剪应力图能够观察剪应力的空间和时间分布。通过同时使用OCT和OP，我们能够制定扰动方案，增加反流并极大地改变未来瓣膜将发育的心管区域的振荡剪切指数（OSI）。反流与瓣膜发育有关，精确的扰动可能使人们能够确定血流动力学在瓣膜发生中的作用。
