Nguyen, Phuc Hoang (2014-08). Integrating Biomechanics, Hemodynamics, and Vascular Adaptation to Relate Mechanisms of Vascular Adaptation to Arterial Pulsatile Pressure in Health and Disease. Doctoral Dissertation.
Thesis
The inherent complexity of the mammalian systemic arterial system has presented numerous challenges to relating basic vascular biology to clinically-relevant derangements of blood pressures and flows. The field of biomechanics has identified how local changes in pulsatile blood pressures and flows lead to changes in local endothelial shear stress and circumferential wall stress. The field of mechanobiology has identified how local changes in wall circumferential stress and endothelial shear stress lead to changes in arterial radii, wall thicknesses and stiffnesses. The field of pulsatile hemodynamics has identified how changes in local radii, wall thicknesses and stiffnesses lead to changes in the complex distributions of pressures and flows throughout an arterial network. These three fields have primarily been studied in isolation, and yet the properties of a single vessel emerge from the interaction of these three processes. The effect of adaptation of one artery on hemodynamics, stress, and structure of all other vessels in the network makes the arterial system a complex adaptive system that is difficult to study experimentally. This dissertation addresses this unmet need by integrating hemodynamics, vessel mechanics, and vascular adaptation by developing a novel framework with mathematical models at different scales. Allowing arteries simultaneously to adapt to mechanical stresses in a computational model of the human systemic arterial system, the present work illustrated that simple arterial adaptation to wall circumferential and endothelial shear stresses are sufficient to explain nine salient features of the cardiovascular system when traversing away from the aortic root towards the peripheral arteries: decrease in lumen radii, wall thicknesses, vessel compliances, shear stresses, wall stresses and pulsatile flows, and increase in wall stiffnesses, pulse wave velocities, and pulsatile pressures. In addition, it revealed that pulse pressure homeostasis emerges to mechanical perturbations such as reduced ejection fraction, increased peripheral resistance and aortic coarctation. Finally, it illustrated how changes in sensitivity of arterial adaptation to pulsatile wall stress can lead to manifestations of disease states such as increased pulse wave velocity and isolated systolic hypertension. The governing principles leading to the emergence of complex, adaptive behavior in the systemic arterial system have thus been identified.
