Key points 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. Abstract 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.
The pathology of thrombophlebitis primarily results from the obliteration of venous valves in the lower extremities. The objective of this study was to develop a prosthetic venous valve that could be implanted in the human femoral system to ameliorate the deleterious effects of thrombophlebitis. Prosthetic venous valves were produced from two materials: Pellethane valves were fabricated from a dip-casting process; umbilical vein valves were produced by a fixation process. The valves were evaluated as implants within the external jugular veins of 10 research dogs. Each animal was implanted with one Pellethane valve in one external jugular vein and one umbilical vein venous valve in the contralateral jugular vein. Each valve was positioned over a stainless-steel cylinder that had been implanted into the jugular veins in such a manner that there existed no blood-cylinder interaction. Patency of the valves was determined by X-ray venography at 24, 48, and 72 h and at 5 and 8 days postoperatively. All of the umbilical vein venous valves were occluded by the end of 48 h, whereas two of the Pellethane venous valves remained patent for at least 5 days but were occluded at 8 days. The results of this study suggest the possibility of success of Pellethane valve implants in the venous circulation and indicate future directions for study.
The objective of this study was to compare the surface thrombogenicities of endothelial cell-seeded small-diameter vascular grafts with those of nonseeded contralateral grafts under conditions of acute controlled low blood flows through the grafts in a canine carotid artery model. Autologous venous endothelial cells seeded in the preclots onto 6 cm sections of 4 mm (internal diameter) double-velour Dacron grafts covered 15% and 80% of graft luminal surfaces at 3 and 5 weeks postsurgically, respectively. Contralateral nonseeded control graft lumina had pannus ingrowth of endothelium across the anastomoses only. There were significant differences in initial carotid graft blood flow rates between seeded and control grafts at both 3 and 5 weeks postsurgically. When blood flow was reduced to 30% of the initial flow levels for 4 hours through these grafts, endothelial cell-seeded grafts maintained patencies and mean blood flow returned to 63.3% and 93% of initial flow levels at 3 and 5 weeks postsurgically, respectively. Few thrombi accumulated. In contrast, thrombi accumulated on nonseeded graft lumina during restricted blood flow. Some nonseeded grafts occluded during low flows, and the ratios of final flow to initial flow were only 28% at 3 weeks and 20% at 5 weeks in these nonseeded grafts. These data demonstrate the efficacy of seeding autologous endothelial cells on small-diameter grafts in this canine model. If technically successful, endothelial cell seeding may provide a protocol for enhancement of the long-term implantation success of small-diameter vascular grafts used for human vascular repair and replacements.
Despite numerous advances in biomaterials design and utilization, the perfect artificial small-vessel substitute has yet to be developed. Dacron and expanded polytetrafluoroethylene (PTFE) are two materials potentially appropriate for use as small-vessel prostheses. We report the patencies of endothelial cell-seeded and nonseeded 4 mm I.D. Dacron grafts and two designs of nonseeded 4 mm I.D. PTFE (Gore-Tex and Impra) in the carotid position in dogs. All graft lengths exceeded the calculated maximum critical length for the material being tested. Dacron grafts, both endothelial cell-seeded and nonseeded, achieved higher patencies than both designs of PTFE. Endothelial cell-seeded Dacron grafts achieved the highest patencies. Endothelium was present to a significant extent only on endothelial cell-seeded Dacron grafts. There was little pannus ingrowth or midgraft pseudointima on nonseeded Dacron or on patent PTFE grafts although thrombus-free surface areas of patent PTFE grafts were high. These comparative data support the utility of endothelial cell seeding in achieving high patencies of small-diameter vascular grafts.
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