Human sinoatrial node structure: 3D microanatomy of sinoatrial conduction pathways.
Human sinoatrial node structure: 3D microanatomy of sinoatrial conduction pathways.
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DOI：
10.1016/j.pbiomolbio.2015.12.011
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发表时间：
2016-01
影响因子：
3.8
通讯作者：
Fedorov VV
中科院分区：
文献类型：
--
作者：
Csepe TA;Zhao J;Hansen BJ;Li N;Sul LV;Lim P;Wang Y;Simonetti OP;Kilic A;Mohler PJ;Janssen PM;Fedorov VV
尽管对人类窦房结（SAN）的广泛研究已经进行了世纪，但特定的窦房结传导通路（SACP）的结构-功能特征仍然是未知的和有争议的。我们报告了一种新的方法，直接分析SAN的微观结构在光学映射的人的心脏与临床病史的SAN功能障碍。对两个分离的供体心脏进行冠状动脉灌注和光学标测。将平行于心外膜的组织学切片（间隔约13-21μm）的结构分析与光学图相结合，以创建SAN复合体的3D计算重建。通过对结构张量的三维特征分析获得了高分辨率的纤维场，并利用纤维跟踪方法分析了SACP的微结构。光学标测显示，在心脏#1中，通过靠近界嵴的外侧SACP，心房的SAN激活正常，但在患病心脏#2中，持续性SAN出口阻滞。3D结构分析显示功能上观察到的SAN边界由SAN和心房之间的纤维化、脂肪和/或不连续纤维组成，其仅由SACP区域中的几个分支肌纤维束穿过。计算3D纤维追踪显示SACP的肌纤维束在SAN #1和心房之间形成连续连接，但在SAN #2中，SACP区域肌纤维束由于纤维化和脂肪而不连续。我们开发了一种新的综合功能，结构和计算方法，首次允许对人类SACP的专门3D微观结构的分辨率。这种综合方法的应用将揭示特殊SAN显微解剖在维持窦性心律中的作用。
Despite a century of extensive study on the human sinoatrial node (SAN), the structure-to-function features of specialized SAN conduction pathways (SACP) are still unknown and debated. We report a new method for direct analysis of the SAN microstructure in optically-mapped human hearts with and without clinical history of SAN dysfunction. Two explanted donor human hearts were coronary-perfused and optically-mapped. Structural analyses of histological sections parallel to epicardium (~13-21μm intervals) were integrated with optical maps to create 3D computational reconstructions of the SAN complex. High-resolution fiber fields were obtained using 3D Eigen-analysis of the structure tensor, and used to analyze SACP microstructure with a fiber-tracking approach. Optical mapping revealed normal SAN activation of the atria through a lateral SACP proximal to the crista terminalis in Heart #1 but persistent SAN exit block in diseased Heart #2. 3D structural analysis displayed a functionally-observed SAN border composed of fibrosis, fat, and/or discontinuous fibers between SAN and atria, which was only crossed by several branching myofiber tracts in SACP regions. Computational 3D fiber-tracking revealed that myofiber tracts of SACPs created continuous connections between SAN #1 and atria, but in SAN #2, SACP region myofiber tracts were discontinuous due to fibrosis and fat. We developed a new integrative functional, structural and computational approach that allowed for the resolution of the specialized 3D microstructure of human SACPs for the first time. Application of this integrated approach will shed new light on the role of the specialized SAN microanatomy in maintaining sinus rhythm.