Characterization of Critical Hemodynamics Contributing to Aneurysmal Remodeling at the Basilar Terminus in a Rabbit Model

Abstract

Background and Purpose-Hemodynamic insult by bilateral common carotid artery ligation has been shown to induce aneurysmal remodeling at the basilar terminus in a rabbit model. To characterize critical hemodynamics that initiate this remodeling, we applied a novel hemodynamics-histology comapping technique. Methods-Eight rabbits received bilateral common carotid artery ligation to increase basilar artery flow. Three underwent sham operations. Hemodynamic insult at the basilar terminus was assessed by computational fluid dynamics. Bifurcation tissue was harvested on day 5; histology was comapped with initial postligation hemodynamic fields of wall shear stress (WSS) and WSS gradient. Results-All bifurcations showed internal elastic lamina loss in periapical regions exposed to accelerating flow with high WSS and positive WSS gradient. Internal elastic lamina damage happened 100% of the time at locations where WSS was Ͼ122 Pa and WSS gradient was Ͼ530 Pa/mm. The degree of destructive remodeling accounting for internal elastic lamina loss, medial thinning, and luminal bulging correlated with the magnitude of the hemodynamic insult. Conclusions-Aneurysmal

Aneurysmal Remodeling in the Circle of Willis after Carotid Occlusion in an Experimental Model

“…This creates a local hemodynamic environment with high WSS and positive WSS gradient, not dissimilar to that of bifurcation apices. 35 Based on the observed aneurysmal changes present in tortuous PComs, we speculate that high WSS and positive WSS gradient at outer curves may have triggered IEL damage 24 and aneurysmal remodeling, 19 contributing to the progressive development of tortuosity as well as segmental dilation. The relationship between tortuosity and segmental dilation and their respective etiologies should be further elucidated.…”

“…Our previous studies of BT aneurysm formation in the same model (rabbit BCCA-L) have demonstrated that aneurysmal remodeling is a maladaptive response to elevated hemodynamic stresses. 22,24 Through detailed hemodynamics-histology mapping, we found that IA initiation at the BT (defined by regions of IEL loss) was associated with high WSS combined with positive WSS gradient above a threshold. 24,33 This hemodynamic condition, often associated with bifurcation apices, 34 has been recognized to independently cause de novo IA formation.…”

“…22,24 Through detailed hemodynamics-histology mapping, we found that IA initiation at the BT (defined by regions of IEL loss) was associated with high WSS combined with positive WSS gradient above a threshold. 24,33 This hemodynamic condition, often associated with bifurcation apices, 34 has been recognized to independently cause de novo IA formation. 21,22,24,35 Kono et al 36 further provided clinical evidence that de novo BT aneurysms could be triggered by unphysiologically high local WSS and WSS gradient generated by proximal stenoses.…”

“…18 Experimentally, we have performed unilateral and bilateral CCA ligation (BCCA-L) in rabbits and observed a drastic flow increase in the BA 19 and de novo IA initiation at the BT. [20][21][22][23][24] Aneurysm formation was shown to be a direct, maladaptive response to elevated hemodynamic stresses. This localized response was dose dependent on blood flow increase 20 and was sustained beyond the normalization of the inciting hemodynamic insult; that is, after returning wall shear stress (WSS) to baseline levels.…”

Changes in Hemodynamics After Placing Intracranial Stents

“…15) A combination of high WSS and positive WSSG represents dangerous hemodynamics likely to induce aneurysm remodeling. 16) RRT is a recently emerged, additional hemodynamic factor to describe the slow flow motion near the aneurysm wall. 9) WSSG and RRT could be recognized as H. Tanemura et al…”