Tortuosity Triggers Platelet Activation and Thrombus Formation in Microvessels

Chesnutt, Jennifer K.W.; Han, Hugang

doi:10.1115/1.4005478

Cited by 49 publications

(54 citation statements)

References 60 publications

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“…Aneurysm asymmetry is another factor that is related to increased rupture risk (Fillinger et al 2004; Doyle et al 2009). Buckling deformation changes the blood flow in the aneurysm, which can alter the wall shear stress and affects intra-lumen thrombus distribution (Chesnutt and Han 2011; Chesnutt and Han 2013). While some of these changes are similar to normal arteries (Han 2012), they may be severe in aneurysms.…”

Section: Discussionmentioning

confidence: 99%

Mechanical instability of normal and aneurysmal arteries

Lee¹,

Sanyal²,

Xiao³

et al. 2014

Journal of Biomechanics

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Tortuous arteries associated with aneurysms have been observed in aged patients with atherosclerosis and hypertension. However, the underlying mechanism is poorly understood. The objective of this study was to determine the effect of aneurysms on arterial buckling instability and the effect of buckling on aneurysm wall stress. We investigated the mechanical buckling and post-buckling behavior of normal and aneurysmal carotid arteries and aorta’s using computational simulations and experimental measurements to elucidate the interrelationship between artery buckling and aneurysms. Buckling tests were done in porcine carotid arteries with small aneurysms created using elastase treatment. Parametric studies were done for model aneurysms with orthotropic nonlinear elastic walls using finite element simulations. Our results demonstrated that arteries buckled at a critical buckling pressure and the post-buckling deflection increased nonlinearly with increasing pressure. The presence of an aneurysm can reduce the critical buckling pressure of arteries, although the effect depends on the aneurysm’s dimensions. Buckled aneurysms demonstrated a higher peak wall stress compared to unbuckled aneurysms under the same lumen pressure. We conclude that aneurysmal arteries are vulnerable to mechanical buckling and mechanical buckling could lead to high stresses in the aneurysm wall. Buckling could be a possible mechanism for the development of tortuous aneurysmal arteries such as in the Loeys-Dietz syndrome.

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Section: Discussionmentioning

confidence: 99%

Mechanical instability of normal and aneurysmal arteries

Lee¹,

Sanyal²,

Xiao³

et al. 2014

Journal of Biomechanics

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“…Artery buckling could be a possible mechanism for the tortuous arteries observed often in aged populations and in patients with cardiovascular diseases [4][5][6]. The loss of stability could alter blood flow and arterial wall stress [7][8][9]. It is believed that the alteration in flow around the curved regions can trigger the development of atherosclerosis [10][11][12].…”

Section: Introductionmentioning

confidence: 99%

Stability of Carotid Artery Under Steady-State and Pulsatile Blood Flow: A Fluid–Structure Interaction Study

Khalafvand

Han

2015

Journal of Biomechanical Engineering

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It has been shown that arteries may buckle into tortuous shapes under lumen pressure, which in turn could alter blood flow. However, the mechanisms of artery instability under pulsatile flow have not been fully understood. The objective of this study was to simulate the buckling and post-buckling behaviors of the carotid artery under pulsatile flow using a fully coupled fluid-structure interaction (FSI) method. The artery wall was modeled as a nonlinear material with a two-fiber strain-energy function. FSI simulations were performed under steady-state flow and pulsatile flow conditions with a prescribed flow velocity profile at the inlet and different pressures at the outlet to determine the critical buckling pressure. Simulations were performed for normal (160 ml/min) and high (350 ml/min) flow rates and normal (1.5) and reduced (1.3) axial stretch ratios to determine the effects of flow rate and axial tension on stability. The results showed that an artery buckled when the lumen pressure exceeded a critical value. The critical mean buckling pressure at pulsatile flow was 17-23% smaller than at steady-state flow. For both steady-state and pulsatile flow, the high flow rate had very little effect (<5%) on the critical buckling pressure. The fluid and wall stresses were drastically altered at the location with maximum deflection. The maximum lumen shear stress occurred at the inner side of the bend and maximum tensile wall stresses occurred at the outer side. These findings improve our understanding of artery instability in vivo.

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“…Our shear-induced platelet activation model, as developed and applied in [16, 30, 31], assumed that a platelet became activated if it experienced a shear stress above a critical shear stress ( T crit ). This model was in agreement with in vivo and in vitro observations of shear-induced platelet activation and aggregation that occurred within milliseconds [12, 32, 33].…”

Section: Methodsmentioning

confidence: 99%

Simulation of the microscopic process during initiation of stent thrombosis

Chesnutt

Han

2015

Computers in Biology and Medicine

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Objective Coronary stenting is one of the most commonly used approaches to open coronary arteries blocked due to atherosclerosis. However, stent struts can induce stent thrombosis due to altered hemodynamics and endothelial dysfunction, and the microscopic process is poorly understood. The objective of this study was to determine the microscale processes during the initiation of stent thrombosis. Methods We utilized a discrete element computational model to simulate the transport, collision, adhesion, and activation of thousands of individual platelets and red blood cells in thrombus formation around struts and dysfunctional endothelium. Results As strut height increased, the area of endothelium activated by low shear stress increased, which increased the number of platelets in mural thrombi. These thrombi were generally outside regions of recirculation for shorter struts. For the tallest strut, wall shear stress was sufficiently low to activate the entire endothelium. With the entire endothelium activated by injury or denudation, the number of platelets in mural thrombi was largest for the shortest strut. The type of platelet activation (by high shear stress or contact with activated endothelium) did not greatly affect results. Conclusions During the initiation of stent thrombosis, platelets do not necessarily enter recirculation regions or deposit on endothelium near struts, as suggested by previous computational fluid dynamics simulations. Rather, platelets are more likely to deposit on activated endothelium outside recirculation regions and deposit directly on struts. Our study elucidated the effects of different mechanical factors on the roles of platelets and endothelium in stent thrombosis.

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Tortuosity Triggers Platelet Activation and Thrombus Formation in Microvessels

Cited by 49 publications

References 60 publications

Mechanical instability of normal and aneurysmal arteries

Mechanical instability of normal and aneurysmal arteries

Stability of Carotid Artery Under Steady-State and Pulsatile Blood Flow: A Fluid–Structure Interaction Study

Simulation of the microscopic process during initiation of stent thrombosis

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