Induction of aneurysmogenic high positive wall shear stress gradient by wide angle at cerebral bifurcations, independent of flow rate

Abstract

OBJECTIVE Endothelium adapts to wall shear stress (WSS) and is functionally sensitive to positive (aneurysmogenic) and negative (protective) spatial WSS gradients (WSSG) in regions of accelerating and decelerating flow, respectively. Positive WSSG causes endothelial migration, apoptosis, and aneurysmal extracellular remodeling. Given the association of wide branching angles with aneurysm presence, the authors evaluated the effect of bifurcation geometry on local apical hemodynamics. METHODS Computational fluid dynamics simulations were performed on parametric bifurcation models with increasing angles having: 1) symmetrical geometry (bifurcation angle 60°-180°), 2) asymmetrical geometry (daughter angles 30°/60° and 30°/90°), and 3) curved parent vessel (bifurcation angles 60°-120°), all at baseline and double flow rate. Time-dependent and time-averaged apical WSS and WSSG were analyzed. Results were validated on patient-derived models. RESULTS Narrow symmetrical bifurcations are characterized by protective negative apical WSSG, with a switch to aneurysmogenic WSSG occurring at angles ≥ 85°. Asymmetrical bifurcations develop positive WSSG on the more obtuse daughter branch. A curved parent vessel leads to positive apical WSSG on the side corresponding to the outer curve. All simulations revealed wider apical area coverage by higher WSS and positive WSSG magnitudes, with increased bifurcation angle and higher flow rate. Flow rate did not affect the angle threshold of 85°, past which positive WSSG occurs. In curved models, high flow displaced the impingement area away from the apex, in a dynamic fashion and in an angle-dependent manner. CONCLUSIONS Apical shear forces and spatial gradients are highly dependent on bifurcation and inflow vessel geometry. The development of aneurysmogenic positive WSSG as a function of angular geometry provides a mechanotransductive link for the association of wide bifurcations and aneurysm development. These results suggest therapeutic strategies aimed at altering underlying unfavorable geometry and deciphering the molecular endothelial response to shear gradients in a bid to disrupt the associated aneurysmal degeneration.

Surrounding vascular geometry associated with basilar tip aneurysm formation

“…We also found larger P1-P1 angles to be associated with BTA presence. These results are consistent with the findings by Lauric et al that wide bifurcation angles are aneurysmogenic 29 . In order to control for the possibility that aneurysm formation could affect the surrounding vessel geometry (by increasing the P1-P1 angle), we included a subgroup analysis with small (width ≤ 3 mm) aneurysms only and a sensitivity analysis with the vascular angles excluded, and arrived at similar findings.…”

Long time-scale study of von Willebrand factor multimers in extensional flow

“…At a scale local to a given protein, flow conditions and rates can exhibit more significant variationspatially and temporallythan might be derived from considering average blood flow through the entire blood vessel (41). Even at the vessel scale, flow near bifurcations (42) and narrowing blood vessels, particularly associated with stenosis or other partial blockages, can generate extensional flow with a high strain rate. Table 2 reports that exposure to extensional flow with strain rate ∈̇= 4000 s −1 will likely drive unraveling in less than 160 ms; while such a flow rate may seem highly pathological, it may not be for very short duration events at the individual vWF protein scale.…”

Unraveling Kinetics of Collapsed Polymers in Extensional Flow

“…In blood, many regions of the vasculature experience relatively low strain rate extensional flow (ϵ̇ = 100 – 400 s –1 ). However, near vessel bifurcations and in narrowing blood vessel regions, such as those caused by build-up on the vessel wall, strain rates of extension are higher, with reported upper limits of order ϵ̇ = 1000 – 3000 s –1 . , Nonetheless, such rates are still less than half of the estimated critical strain rate for vWF in blood, emphasizing the need for knowledge about behavior in extensional flow with strain rates well under the critical value . Furthermore, in any closed-loop flow systemlike bloodflow is periodic; for example, any given volume element of blood passes through the complete vasculature in approximately 30–60 s. Thus, vWF proteins are repeatedly exposed to multiple regions of extensional flow, some with potentially elevated ϵ̇ that is nonetheless well under the critical strain rate.…”