Jennifer K W Chesnutt

Artery Buckling: New Phenotypes, Models, and Applications

Arteries are under significant mechanical loads from blood pressure, flow, tissue tethering, and body movement. It is critical that arteries remain patent and stable under these loads. This review summarizes the common forms of buckling that occur in blood vessels including cross-sectional collapse, longitudinal twist buckling, and bent buckling. The phenomena, model analyses, experimental measurements, effects on blood flow, and clinical relevance are discussed. It is concluded that mechanical buckling is an important issue for vasculature, in addition to wall stiffness and strength, and requires further studies to address the challenges. Studies of vessel buckling not only enrich vascular biomechanics but also have important clinical applications.

Tortuosity Triggers Platelet Activation and Thrombus Formation in Microvessels

Tortuous blood vessels are often seen in humans in association with thrombosis, atherosclerosis, hypertension, and aging. Vessel tortuosity can cause high fluid shear stress, likely promoting thrombosis. However, the underlying physical mechanisms and microscale processes are poorly understood. Accordingly, the objectives of this study were to develop and use a new computational approach to determine the effects of venule tortuosity and fluid velocity on thrombus initiation. The transport, collision, shear-induced activation, and receptor-ligand adhesion of individual platelets in thrombus formation were simulated using discrete element method. The shear-induced activation model assumed that a platelet became activated if it experienced a shear stress above a relative critical shear stress or if it contacted an activated platelet. Venules of various levels of tortuosity were simulated for a mean flow velocity of 0.10 cm s(-1), and a tortuous arteriole was simulated for a mean velocity of 0.47 cm s(-1). Our results showed that thrombus was initiated at inner walls in curved regions due to platelet activation in agreement with experimental studies. Increased venule tortuosity modified fluid flow to hasten thrombus initiation. Compared to the same sized venule, flow in the arteriole generated a higher amount of mural thrombi and platelet activation rate. The results suggest that the extent of tortuosity is an important factor in thrombus initiation in microvessels.

Platelet size and density affect shear-induced thrombus formation in tortuous arterioles

Thrombosis accounts for 80% of deaths in patients with diabetes mellitus. Diabetic patients demonstrate tortuous microvessels and larger than normal platelets. Large platelets are associated with increased platelet activation and thrombosis, but the physical effects of large platelets in the microscale processes of thrombus formation are not clear. Therefore, the objective of this study was to determine the physical effects of mean platelet volume (MPV), mean platelet density (MPD) and vessel tortuosity on platelet activation and thrombus formation in tortuous arterioles. A computational model of the transport, shear-induced activation, collision, adhesion and aggregation of individual platelets was used to simulate platelet interactions and thrombus formation in tortuous arterioles. Our results showed that an increase in MPV resulted in a larger number of activated platelets, though MPD and level of tortuosity made little difference on platelet activation. Platelets with normal MPD yielded the lowest amount of mural thrombus. With platelets of normal MPD, the amount of mural thrombus decreased with increasing level of tortuosity but did not have a simple monotonic relationship with MPV. The physical mechanisms associated with MPV, MPD and arteriole tortuosity play important roles in platelet activation and thrombus formation.

Simulation of the microscopic process during initiation of stent thrombosis

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.

Computational simulation of platelet interactions in the initiation of stent thrombosis due to stent malapposition

Coronary stenting is one of the most commonly used approaches to open coronary arteries blocked due to atherosclerosis. Stent malapposition can induce thrombosis but the microscopic process is poorly understood. The objective of this study was to determine the platelet-level process by which different extents of stent malapposition affect the initiation of stent thrombosis. We utilized a discrete element model to computationally simulate the transport, adhesion, and activation of thousands of individual platelets and red blood cells during thrombus initiation in stented coronary arteries. Simulated arteries contained a malapposed stent with a specified gap distance (0, 10, 25, 50, or 200 μm) between the struts and endothelium. Platelet-level details of thrombus formation near the proximal-most strut were measured during the simulations. The relationship between gap distance and amount of thrombus in the artery varied depending on different conditions (e.g., amount of dysfunctional endothelium, shear-induced activation of platelets, and thrombogenicity of the strut). Without considering shear-induced platelet activation, the largest gap distance (200 μm) produced no recirculation and less thrombus than the smallest two gap distances (0 and 10 μm) that created recirculation downstream of the strut. However, with the occurrence of shear-induced platelet activation, the largest gap distance produced more thrombus than the two smallest gap distances, but less thrombus than an intermediate gap distance (25 μm). A large gap distance was not necessarily the most thrombogenic, in contrast to implications of some computational fluid dynamics studies. The severity of stent malapposition affected initial stent thrombosis differently depending on various factors related to fluid recirculation, platelet trajectories, shear stress, and endothelial condition.

Simulation of Particle Separation on an Inclined Electric Curtain

Electric curtains have been shown in experiments to successfully remove charged dust particles from a surface using phase-modulated oscillating electric fields on parallel electrodes. Experimental limitations on charge and velocity measurement of individual particles have restricted understanding of the physical mechanism of this phenomenon. A discrete-element method for simulating particle motion in electric curtains is discussed and applied to study particle motion induced by an upward-traveling wave on an inclined electric curtain. The upward particle motion induced by the traveling wave is opposed by downward gravitational motion. Particles are influenced by van der Waals adhesion and electrostatic interaction, both to the surface and to each other. These different effects result in a complex particle flow that sometimes leads to separation of particles of different sizes but, in other cases, leads to particles moving together in one direction.

Effect of red blood cells on platelet activation and thrombus formation in tortuous arterioles

Thrombosis is a major contributor to cardiovascular disease, which can lead to myocardial infarction and stroke. Thrombosis may form in tortuous microvessels, which are often seen throughout the human body, but the microscale mechanisms and processes are not well understood. In straight vessels, the presence of red blood cells (RBCs) is known to push platelets toward walls, which may affect platelet aggregation and thrombus formation. However in tortuous vessels, the effects of RBC interactions with platelets in thrombosis are largely unknown. Accordingly, the objective of this work was to determine the physical effects of RBCs, platelet size, and vessel tortuosity on platelet activation and thrombus formation in tortuous arterioles. A discrete element computational model was used to simulate the transport, collision, adhesion, aggregation, and shear-induced platelet activation of hundreds of individual platelets and RBCs in thrombus formation in tortuous arterioles. Results showed that high shear stress near the inner sides of curved arteriole walls activated platelets to initiate thrombosis. RBCs initially promoted platelet activation, but then collisions of RBCs with mural thrombi reduced the amount of mural thrombus and the size of emboli. In the absence of RBCs, mural thrombus mass was smaller in a highly tortuous arteriole compared to a less tortuous arteriole. In the presence of RBCs however, mural thrombus mass was larger in the highly tortuous arteriole compared to the less tortuous arteriole. As well, smaller platelet size yielded less mural thrombus mass and smaller emboli, either with or without RBCs. This study shed light on microscopic interactions of RBCs and platelets in tortuous microvessels, which have implications in various pathologies associated with thrombosis and bleeding.

Contributions of platelet activation and collision to thrombus formation in tortuous venules

Vessel tortuosity is often seen in humans in association with various conditions, including thrombosis.1–3 Thrombosis is a major contributor to cardiovascular disease, which is the leading cause of death in the U.S. Tortuosity can increase shear stress that can activate platelets, which can lead to thrombosis.4 A fundamental gap exists in understanding how vessel tortuosity regulates thrombosis through such microscale physical mechanisms. Solving this problem is essential to assess the risk of thrombosis and to develop new treatment strategies.© 2012 ASME

Mesoscale Analysis of Blood Flow

Blood flow in the cardiovascular system and its interaction with the vessel walls plays a crucial role in health and disease. Individual blood cells play varied and vital roles in the circulation, including transport of nutrients and dissolved gases (red blood cells), fighting infections and disease (white blood cells), and healing of wounds (platelets). Malfunctioning of blood cells can result in pathologies such as sickle cell disease (red blood cells), ischemia (white blood cells), atherosclerosis (white blood cells and platelets) and thrombosis (platelets and red blood cells). To better understand the behavior of blood cells and their role in health and disease, microscale models that capture the dynamics of individual cells and their interactions with other cells/vessel walls can be very useful. However, since even micro-volumes of blood contain extremely large numbers of cells, connecting blood flow phenomena to cell dynamics and cell–cell/cell–wall interactions limits the usefulness of micro-scale models. Mesoscale models that do not model individual cells in detail, but allow for the treatment of large numbers of cells can provide important insights into the impact of the particulate nature of blood; such mesoscale models can represent transport phenomena, aggregation/disaggregation of cell clusters, collisional interactions of cells with each other and with walls and other phenomena important to healthy and pathological states in the circulation. This chapter describes the important features of such mesoscale models of blood; the treatment of the particulate nature of blood and the modeling and simulation of cell–cell and cell–surface interactions are covered. The examples presented illustrate the state of the art in mesoscale modeling of blood flow.