Functional recovery of the microcirculation during skeletal muscle regeneration

Abstract

Skeletal muscle has a remarkable capacity to regenerate following injury, and although muscle regeneration has been studied extensively, little is known about the recovery of the skeletal muscle microcirculation during regeneration. To determine the restoration of blood flow regulation during skeletal muscle regeneration, this dissertation explored the recovery of vasomotor responses to physiological agonists and of functional vasodilation in response to muscle contraction. A novel injury model in the mouse gluteus maximus muscle was developed to study the microcirculation in vivo using intravital microscopy at welldefined time points (5, 10, 21 and 35 days) post injury compared to uninjured Control muscles. Studies encompassed feed arteries and the principal branches (1st, 2nd and 3rd order) of arteriolar networks comprising the resistance vasculature. Vasomotor responses to agonists and active force developed by muscle fibers recovered by 21d, however functional vasodilation required [about]35d to recover. This research provides novel insight into when and to what extent blood flow regulation is restored during skeletal muscle regeneration and provides novel perspective towards developing therapeutic strategies for restoring skeletal muscle function during recovery from injury.