| Cerebral aneurysms are often found at arterial bifurcation apices, raising the possibility that the unique hemodynamics associated with flow dividers predispose the wall to aneurysm formation. To identify the specific hemodynamics that lead to such mal-adaptive response, we developed a mapping system to correlate the flow field with vascular remodeling in canine created carotid bifurcations. In this study, carotid bifurcations were surgically created using two naive common carotid arteries in dogs. Next, in vivo angiography and computational fluid dynamics (CFD) simulations revealed the detailed hemodynamic microenvironment for each bifurcation, which were then spatially overlaid and correlated with histological features. Histology and immunohistochemistry were performed to explore the cellular and molecular alterations involved in the remodeling. We observed destructive remodeling in the flow acceleration region adjacent to the impingement that resembles the initiation of an intracranial aneurysm, characterized by disruption of internal elastic lamina, loss of endothelial and smooth muscle cells, elevated nitrotyrosine (marker of peroxynitrite) and MMP expressions. The strong localization of aneurysmal remodeling suggests that a combination of high wall shear stress (WSS) and high, positive spatial gradient in wall shear stress (WSSG) represents a "dangerous" hemodynamic condition that predisposes an apical vessel wall to aneurysm formation. |
