Human sinoatrial node structure: 3D microanatomy of sinoatrial conduction pathways

Abstract

Introduction 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. Methods 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. Results 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. Conclusions 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.

Redundant and diverse intranodal pacemakers and conduction pathways protect the human sinoatrial node from failure

“…Near-infrared optical mapping is currently the only reliable method to delineate activation and conduction within the intramural human SAN complex structure (12 to 27 mm long, 3 to 8 mm wide, and 1 to 3 mm deep) (1, 2, 33) that is obscured to clinical surface electrode mapping by the surrounding atria (2, 7). We optically mapped human hearts ( n = 11, 34 to 69 years old, five females) from patients with a variety of recorded comorbidities, ranging from no diseases to chronic hypertension, diabetes, or acute heart failure (table S1).…”

“…The SAN is a collection of specialized cardiomyocytes located at the junction of the right atria and the superior vena cava (2, 6, 7). To efficiently keep the heart beating, the SAN requires a sophisticated ability to maintain uninterrupted function during internal or external perturbations, known as biological robustness (8).…”

Three‐dimensional Integrated Functional, Structural, and Computational Mapping to Define the Structural “Fingerprints” of Heart‐Specific Atrial Fibrillation Drivers in Human Heart Ex Vivo

“…In this study, we have further refined fibrosis identification in CE‐MRI images via histological staining of the same heart,24 and extended the fiber orientation analysis to the whole human atria imaged using CE‐MRI. We also developed a novel computational framework to estimate 3D wall thickness across both atrial chambers 25.…”

Atrial fibrillation driver mechanisms: Insight from the isolated human heart

“…During mapping, both right and whole intact atria are coronary-perfused and superfused with 37°C oxygenated Tyrode’s solution under constantly maintained pH (7.35) and pressure (55 mmHg) to preserve physiological conditions. Due to these precautions, we were able to maintain stable conduction and repolarization, as well as normal sinus rhythm in preparations with intact sinoatrial node, in the entire atrial human preparation for 6–8 hours(7;8;31;32) with all electrophysiological parameters in clinical range.…”

“…This is currently impossible in clinical procedures, but our group has the unique opportunity and required experience to test these types of clinical mapping systems ex vivo using the recently validated coronary-perfused human atria model(7;8;32). Combining clinical mapping techniques with high-resolution optical mapping in ex vivo human heart experiments could validate the accuracy of current in vivo techniques and refine the characteristics of AF drivers seen by these techniques.…”