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(Stroke. 2007;38:1924.)
© 2007 American Heart Association, Inc.

Original Contributions

Complex Hemodynamics at the Apex of an Arterial Bifurcation Induces Vascular Remodeling Resembling Cerebral Aneurysm Initiation

Hui Meng, PhD; Zhijie Wang, MS; Yiemeng Hoi, MS; Ling Gao, PhD; Eleni Metaxa, BS; Daniel D. Swartz, PhD John Kolega, PhD

From the Toshiba Stroke Research Center (H.M., Z.W., Y.H., L.G., E.M., D.D.S., J.K.) and the Departments of Mechanical and Aerospace Engineering (H.M., Z.W., Y.H., E.M.), Neurosurgery (H.M., L.G., D.D.S.), Pediatrics (D.D.S.), and Pathology and Anatomical Sciences (J.K.), University at Buffalo, State University of New York, Buffalo.

Correspondence to Hui Meng, PhD, Toshiba Stroke Research Center, State University of New York at Buffalo, 447 Biomedical Research Building, 3435 Main St, Buffalo, NY. E-mail huimeng{at}buffalo.edu

Background and Purpose— Arterial bifurcation apices are common sites for cerebral aneurysms, raising the possibility that the unique hemodynamic conditions associated with flow dividers predispose the apical vessel wall to aneurysm formation. This study sought to identify the specific hemodynamic insults that lead to maladaptive vascular remodeling associated with aneurysm development and to identify early remodeling events at the tissue and cellular levels.

Methods— We surgically created new branch points in the carotid vasculature of 6 female adult dogs. In vivo angiographic imaging and computational fluid dynamics simulations revealed the detailed hemodynamic microenvironment for each bifurcation, which were then spatially correlated with histologic features showing specific tissue responses.

Results— We observed 2 distinct patterns of vessel wall remodeling: (1) hyperplasia that formed an intimal pad at the bifurcation apex and (2) destructive remodeling in the adjacent region of flow acceleration that resembled the initiation of an intracranial aneurysm, characterized by disruption of the internal elastic lamina, loss of medial smooth muscle cells, reduced proliferation of smooth muscle cells, and loss of fibronectin.

Conclusions— Strong localization of aneurysm-type remodeling to the region of accelerating flow suggests that a combination of high wall shear stress and a high gradient in wall shear stress represents a "dangerous" hemodynamic condition that predisposes the apical vessel wall to aneurysm formation.

Key Words: wall shear stress • gradient • intimal hyperplasia • intracranial aneurysm

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