Abstract
The dynamic properties of the heart differ based on the regions that effectively circulate blood throughout the body with each heartbeat. These properties, including the inter-beat interval (IBI) of autonomous beat activity, are retained even in in vitro tissue fragments. However, details of beat dynamics have not been well analyzed, particularly at the sub-mm scale, although such dynamics of size are important for regenerative medicine and computational studies of the heart. We analyzed the beat dynamics in sub-mm tissue fragments from atria and ventricles of hearts obtained from chick embryos over a period of 40 h. The IBI and contraction speed differed by region and atrial fragments retained their values for a longer time. The major finding of this study is synchronization of these fragment pairs physically attached to each other. The probability of achieving this and the time required differ for regional pairs: atrium–atrium, ventricle–ventricle, or atrium–ventricle. Furthermore, the time required to achieve 1:1 synchronization does not depend on the proximity of initial IBI of paired fragments. Various interesting phenomena, such as 1:n synchronization and a reentrant-like beat sequence, are revealed during synchronization. Finally, our observation of fragment dynamics indicates that mechanical motion itself contributes to the synchronization of atria.
Highlights
The heart comprises two types of chambers, atria and ventricles, which aid in the circulation of blood in the body through contraction–relaxation cycles in a synchronized manner, called the heartbeat [1,2]
We investigated the synchronization of the following tissue fragment pairs at sub–mm scale with regional variations: atrium–atrium (A–A), ventricle–ventricle (V–V), and atrium–ventricle (A–V)
Cx43 enhances the synchronization of primary cultured cardiomyocytes of rat, so a faster synchronization time for V–V may be induced by an increased amount of Cx43 at the V–V interface [16]
Summary
The heart comprises two types of chambers, atria and ventricles, which aid in the circulation of blood in the body through contraction–relaxation cycles in a synchronized manner, called the heartbeat [1,2]. Once the delicately balanced difference degrades, an electrical or mechanical disturbance is induced, which is recognized as a disease state, i.e., arrhythmia generating an irregular heartbeat These regional differences are important for constructing heart tissues from pluripotent stem cells using engineering approaches [5,6]. We investigated the dynamics of contraction of sub-mm tissue fragments obtained from atria and ventricles on porous filter inserts in 6-well tissue culture plates for over 40 h, using a home-built imaging platform inside an incubator The fragments in this size range displayed simple rhythmic beats and retained their contractile behavior over tens of hours, which is an indication of vitality [13,14]. Moving toward the integration of computational studies of the entire heart function on a sub-cellular scale to simulate heart disease and its therapeutic control [30], an understanding of heart dynamics in a tissue–size model with regional differences might reveal connections between electrical and mechanical properties and help us understand the mechano–electric feedback system [31,32]
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