Department of Medicine, Section of Critical Care Medicine, Rady Faculty of Health Sciences, University of Manitoba, Winnipeg, Manitoba, Canada.
Department of Medical Biophysics, Schulich School of Medicine and Dentistry, Western University, London, Ontario, Canada.
J Physiol. 2021 Apr;599(8):2149-2168. doi: 10.1113/JP281172. Epub 2021 Mar 18.
The capillary module, consisting of parallel capillaries from arteriole to venule, is classically considered as the building block of complex capillary networks. In skeletal muscle, this structure fails to address how blood flow is regulated along the entire length of the synchronously contracting muscle fibres. Using intravital video microscopy of resting extensor digitorum longus muscle in rats, we demonstrated the capillary fascicle as a series of interconnected modules forming continuous columns that align naturally with the dimensions of the muscle fascicle. We observed structural heterogeneity for module topology, and functional heterogeneity in space and time for capillary-red blood cell (RBC) haemodynamics within a module and between modules. We found that module RBC haemodynamics were independent of module resistance, providing direct evidence for microvascular flow regulation at the level of the capillary module. The capillary fascicle is an updated paradigm for characterizing blood flow and RBC distribution in skeletal muscle capillary networks.
Capillary networks are the fundamental site of oxygen exchange in the microcirculation. The capillary module (CM), consisting of parallel capillaries from terminal arteriole (TA) to post-capillary venule (PCV), is classically considered as the building block of complex capillary networks. In skeletal muscle, this structure fails to address how blood flow is regulated along the entire length of the synchronously contracting muscle fibres, requiring co-ordination from numerous modules. It has previously been recognized that TAs and PCVs interact with multiple CMs, creating interconnected networks. Using label-free intravital video microscopy of resting extensor digitorum longus muscle in rats, we found that these networks form continuous columns of linked CMs spanning thousands of microns, herein denoted as the capillary fascicle (CF); this structure aligns naturally with the dimensions of the muscle fascicle. We measured capillary-red blood cell (RBC) haemodynamics and module topology (n = 9 networks, 327 modules, 1491 capillary segments). The average module had length 481 μm, width 157 μm and 9.51 parallel capillaries. We observed structural heterogeneity for CM topology, and functional heterogeneity in space and time for capillary-RBC haemodynamics within a module and between modules. There was no correlation between capillary RBC velocity and lineal density. A passive inverse relationship between module length and haemodynamics was remarkably absent, providing direct evidence for microvascular flow regulation at the level of the CM. In summary, the CF is an updated paradigm for characterizing RBC distribution in skeletal muscle, and strengthens the theory of capillary networks as major contributors to the signal that regulates capillary perfusion.
由小动脉到小静脉的平行毛细血管组成的毛细血管模块，经典上被认为是复杂毛细血管网络的构建块。在骨骼肌中，这种结构无法解释血流如何在同步收缩的肌纤维的整个长度上进行调节，这需要多个模块的协调。先前已经认识到，小动脉和小静脉与多个毛细血管模块相互作用，形成相互连接的网络。我们使用大鼠伸趾长肌休息时的无标记活体视频显微镜，发现这些网络形成了连续的、相互连接的毛细血管模块列，我们将其命名为毛细血管束（CF）；这种结构与肌束的尺寸自然对齐。我们测量了毛细血管-红细胞（RBC）的血液动力学和模块拓扑结构（n=9 个网络、327 个模块、1491 个毛细血管段）。平均模块长度为 481μm，宽度为 157μm，有 9.51 个平行毛细血管。我们观察到 CM 拓扑结构的异质性，以及模块内和模块之间毛细血管-RBC 血液动力学的空间和时间功能异质性。毛细血管 RBC 速度与线密度之间没有相关性。模块长度与血液动力学之间的被动负相关关系显著缺失，为毛细血管水平的微血管流量调节提供了直接证据。总之，CF 是一种用于描述骨骼肌 RBC 分布的更新范例，并且加强了毛细血管网络作为调节毛细血管灌注信号的主要贡献者的理论。
