Structural and functional changes in the microvasculature of disused skeletal muscle

Abstract

Skeletal muscle and its microvasculature can exhibit remarkable plasticity in response to decreased functional demand (i.e., muscle disuse). Since the microvascular adaptation to disuse does seem to not depend solely on reduced demand, this review examines the various factors that may be responsible for the observed regression of microvascular structure and function during disuse. There are several animal models of muscle disuse; their common feature is that they are associated with a variety of confounding effects that make the interpretation of the "pure" disuse effect challenging. As well, in clinical studies, the effect of disuse can be difficult to separate from that of various pathologies. Regardless of methodological difficulties, degeneration of the capillary wall, capillary loss, arteriolar remodelling, reduced resting state blood flow, and reduced arteriolar responsiveness to acute vasodilative and vasoconstrictive stimuli have all been observed in disused muscles. The level, and presence/absence of these changes may depend on many factors including the duration of disuse, degree of muscle atrophy, residual muscle activity, microvascular blood flow, release of vasoactive agents from the degenerating muscle, muscle type, and the particular pathology associated with the muscle withering in humans. It is the present challenge to discover the presence/absence of key agents (possibly originating at the interface between the blood stream and the vascular wall, within the extracellular matrix, or the muscle fibres themselves) that alter the intra- and/or inter-cellular signalling to explain the mechanism of adaptation of the microvasculature to skeletal muscle disuse.

Regression of capillary network in atrophied soleus muscle induced by hindlimb unweighting

“…This was the case in our study. Although earlier reports (13,31,32) indicated the decrease of the C/F ratio after HU, they did not focus on the regression of anastomoses. Our 3D observation clearly indicates that the regression of microvessels in HU is greater in the anastomoses than in capillaries, resulting in a significant decrease in blood flow in the capillary network.…”

“…Previous studies have reported that muscle atrophy is associated with a decrease in the C/F ratio (13,31,32) or in the capillary # Significant difference between control and HU groups(P Ͻ 0.05). †Significant difference between capillaries and anastomoses (P Ͻ 0.05).…”

“…C/F ratio was increased by the augmentation of muscle activity, e.g., exercise or electrical stimulation (9,14,20,25), and was decreased by disuse (14, 31, 33). Histological sections from earlier studies of capillary remodeling in skeletal muscle with disuse atrophy demonstrate a decrease in capillary luminal diameter (16,36) and in the C/F ratio (13, 31, 32) despite an increase in capillary density (13,31,32).Although the regression of anastomoses in atrophied skeletal muscle has not been well studied, it was demonstrated that reduction of the number of anastomosis decreases the net flow greatly in a coronary capillary network by a simulation study (17). Tortuosity is characteristic of muscular capillaries, but its change after disuse has received little attention.…”

“…C/F ratio was increased by the augmentation of muscle activity, e.g., exercise or electrical stimulation (9,14,20,25), and was decreased by disuse (14,31,33). Histological sections from earlier studies of capillary remodeling in skeletal muscle with disuse atrophy demonstrate a decrease in capillary luminal diameter (16,36) and in the C/F ratio (13,31,32) despite an increase in capillary density (13,31,32).…”

Low-flow vascular remodeling in the metabolic syndrome X

“…Another common cause of reduced blood flow to skeletal muscle is atrophy of skeletal muscle, resulting in reduced oxygen demand and thus reduced perfusion (26). To determine whether low flow remodeling was due to a loss of muscle mass in the OZR, several key muscles of the hindlimb were removed and weighed.…”