Increased shear rate drives arteriolar collateral remodeling after acute microocclusion but might not concern venular collateral remodeling
Authors: Xiang Weiwei , Reglin Bettina , Rong Wenwei , Nitzsche Bianca , Maibier Martin , Guimarães Pedro , Ruggeri Alfredo , Secomb Timothy W. , Pries Axel R. 
Published: November 2023

IntroductionCollateral circulation provides protection against ischemic injury of the tissue in vascular obstructive diseases. However, processes and mechanisms underlying the establishment of functional collateral flow after arteriolar occlusion are not fully understood yet. In vivo investigation of these processes is complicated by the difficulty to repeatedly observe evoked adaptive changes in most animal models. In addition, almost no studies on vascular responses to venular occlusion have been conducted yet. Here, using intravital videomicroscopy at frequent time points, collateral remodeling after acute arteriolar and venular occlusion is studied in the ex ovo chick chorioallantoic membrane (CAM) model.MethodsWhite leghorn chicken eggs were cracked open on embryonic day 3 (E3) and its content was transferred into petri dishes. On E14, an arteriole (venule) with a diameter of 50–70 μm feeding (draining) an arteriolo‐arteriolar (venulo‐venular) anastomosis was occluded using laser irradiation. Before and up to 24 hours after occlusion, adaptive changes in the occlusion region were videorecorded at hourly intervals. For both the occluded and the un‐occluded vessel trees contributing to the anastomosis, adaptive changes in the 2 vessel segments adjacent to the anastomosis were analyzed by semi‐automatically measuring vessel diameter and blood flow velocities (spatial correlation analysis) off‐line. A ‘pseudo shear rate’ (PSR = blood flow velocity/vessel diameter) and blood flow rate were calculated.ResultsImmediately after occlusion of both arterioles and venules, reversal of blood flow direction was observed in the 2 vessel segments directly adjacent to the occlusion site thus extending the un‐occluded vessel tree. This helped to recover perfusion downstream of the occlusion site in the arteriolar tree and to re‐establish draining of blood flow upstream of the occlusion site in the venular tree, respectively. Diameter adaptation in response to flow reversal re‐established a harmonious decrease (increase) of arteriolar (venular) diameter along the extended non‐occluded flow pathway within 24 hours after occlusion. Inner diameter of all 4 vessel segments analyzed increased after occlusion. PSR showed a two‐phase change and almost returned to the pre‐occlusion value. In arterioles, PSR exhibited two summits, immediately after occlusion and a few hours later. In contrast, in venules PSR decreased sharply immediately after occlusion, slightly increased during the following few hours and then fell to a second bottom value. Changes in blood flow were similar to changes of vessel diameter.ConclusionsOur data suggest, that an increased shear rate drives collateral remodeling after acute arteriolar occlusion but not after venular occlusion. In addition, transfer of metabolic information may play a role in evoking collateral diameter increase in phases of decreased shear rate.Support or Funding InformationThis project is funded by a Marie Curie grant from the European Commission in the framework of the REVAMMAD ITN (Initial Training Research network) with a project number 316990.