Physiological angiogenesis in electrically stimulated skeletal muscle in rabbits: Characterization of capillary sprouting by ultrastructural 3‐D reconstruction study

Abstract

Physiological angiogenesis occurs in electrically stimulated skeletal muscles. It is known to start as capillary sproutings, but has not yet been well characterized as ordinary angiogenesis. To characterize the sprouting process during physiological angiogenesis, we carried out an ultrastructural 3-D reconstruction study for the extensor digitorum longus of three adult rabbits under electrical stimulation for 7 days. In addition, hemodynamic and morphological studies were carried out after stimulation for 3, 7, and 14 days. The electrical stimulation induced a twofold increase in femoral artery blood flow and tissue blood flow. This was associated with an increase in capillary density of the muscle by more than twofold at 7 and 14 days. Sproutings frequently appeared at 7 days (4.3 +/- 1.4 x 10(3) sproutings per mm3, 13.3 +/- 6.9 microm in length). All sprouting tips consisted of endothelial cytoplasmic protrusions (ECP). Besides sproutings, there were communicating networks consisting segmentally of ECP (11.6 +/- 5.6 x 10(3) networks per mm3). Endothelial cytoplasmic protrusions began to appear at 3 days, were frequent at 7 days, and disappeared at 14 days, which corresponded well to the changes in blood flow and capillary density. We consider that in physiological angiogenesis, sproutings start as ECP, which contact other capillaries to form networks and become hollowed to form new capillary networks.

Increased angiogenic response but deficient arteriolization and abnormal microvessel ultrastructure in critical leg ischaemia

“…Immunohistochemistry using Ki67, a proliferation marker16, revealed no active cell proliferation. Furthermore, TEM of CLI muscle showed no evidence of active angiogenesis such as capillary sprouting24 or transcapillary pillars25. In addition, the nuclei of the endothelial cells were abnormal, with less chromatin content and an osmophilic nuclear membrane, which suggested increased lipid in the nuclear membrane.…”

Modelling capillary oxygen supply capacity in mixed muscles: Capillary domains revisited

“…1B) generate a space-filling alternative (Egginton & Ross, 1989 thereby allowing the exploration of the local influences associated with microvascular remodelling, as well as any mismatch between angiogenesis and local O 2 demand (Degens et al, 1992(Degens et al, , 2002(Degens et al, , 2006(Degens et al, , 2008Egginton et al, 2001;Wüst et al, 2009a). This gives Voronoi polygons an advantage in assessing the efficacy of applications to pathological scenarios, such as ischaemia, where potential therapeutic interventions include strength training (Deveci & Egginton, 2002;Suzuki et al, 2000), endurance exercise (Ahmed et al, 1997;Scott et al, 2009), electrical stimulation (Ebina et al, 2002), and alterations in muscle temperature (Egginton et al, 2001;Egginton, 2002). In addition to their ability to reproduce robust versions of the aforementioned global measures, Voronoi polygons have the capacity to provide indices of capillary supply to individual fibres, with both direct contact and indirect influence, and to fibres of different metabolic activities.…”

A Murine Model of Muscle Training by Neuromuscular Electrical Stimulation

“…First, it provides a reproducible experimental model in which physiological adaptations, such as myofiber hypertophy and muscle strengthening 6 , angiogenesis [7][8][9] , growth factor secretion [9][10][11] , and muscle precursor cell activation 12 are well documented. Such physiological responses may be carefully titrated using different parameters of stimulation (for Cochrane review, see 13 ).…”