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Dynamic flow alterations dictate leukocyte adhesion and response to endovascular interventions
Yoram Richter, … , Philip Seifert, Elazer R. Edelman
Yoram Richter, … , Philip Seifert, Elazer R. Edelman
Published June 1, 2004
Citation Information: J Clin Invest. 2004;113(11):1607-1614. https://doi.org/10.1172/JCI21007.
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Article Cardiology

Dynamic flow alterations dictate leukocyte adhesion and response to endovascular interventions

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Abstract

Although arterial bifurcations are frequent sites for obstructive atherosclerotic lesions, the optimal approach to these lesions remains unresolved. Benchtop models of arterial bifurcations were analyzed for flow disturbances known to correlate with vascular disease. These models possess an adaptable geometry capable of simulating the course of arterial disease and the effects of arterial interventions. Chronic in vivo studies evaluated the effect of flow disturbances on the pattern of neointimal hyperplasia. Acute in vivo studies helped propose a mechanism that bridges the early mechanical stimulus and the late tissue effect. Side-branch (SB) dilation adversely affected flow patterns in the main branch (MB) and, as a result, the long-term MB patency of stents implanted in pig arteries. Critical to this effect is chronic MB remodeling that seems to compensate for an occluded SB. Acute leukocyte recruitment was directly influenced by the changes in flow patterns, suggesting a link between flow disturbance on the one hand and leukocyte recruitment and intimal hyperplasia on the other. It is often impossible to simultaneously maximize the total cross-sectional area of both branches and to minimize flow disturbance in the MB. The apparent trade-off between these two clinically desirable goals may explain many of the common failure modes of bifurcation stenting.

Authors

Yoram Richter, Adam Groothuis, Philip Seifert, Elazer R. Edelman

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Figure 6

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Lesion composition. High-magnification images of one of the sections of ...
Lesion composition. High-magnification images of one of the sections of a chronic (14-day) lesion. A blue dot in each image denotes the location of the lateral wall. (A) Carstairs’ fibrin stain demonstrates high concentrations of fibrin around the stent struts, particularly on the lateral wall. (B) Smooth-muscle cell α-actin stain shows tightly packed smooth muscle inside along the lumen (inside of the hoop in C), with areas poor in smooth-muscle cells in the crescent region on the lateral wall. (C) Ver Hoeff’s elastin stain shows a cellular, dense region of relatively uniform thickness (inside yellow circle) and an ECM-rich, sparse crescent region located on the lateral wall. (D and E) False-colored enhancement of fibrin concentration (green) highlights the difference in ECM away from the struts in the flow divider (D) and the lateral wall (E).

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