Poster U5 - Mechanisms of Solute Mass Transport in Abdominal Aortic Aneurysms

Introduction: Abdominal aortic aneurysm (AAA) is a progressive, potentially life-threatening aortic disease characterized by dilation of the aortic diameter by more than 50%. AAAs are thought to be present in as many as 1,000,000 people in the United States [1], and their rupture accounts for 10-15,000 deaths annually. Rupture becomes increasingly likely as the lesion wall weakens, which can be caused by reduced bioavailability of both O2, which is needed for smooth muscle contraction, and nitric oxide (NO), which serves as a pivotal regulator of homeostasis, participating in vascular tone modulation, smooth muscle cell relaxation, and inhibition of proliferation and migration of vascular smooth muscle cells. Decreased availability of these molecules has been proposed as an important mechanism in AAA development and progress [2]. Unfortunately, most AAAs present with large amounts of deposited intraluminal thrombus (ILT), which creates a diffusion barrier around the aneurysm bulge lumen that impedes transport of these crucial small molecules from blood to the vessel wall. Accordingly, as a first step towards understanding the relations between AAA flow fields, O2 and NO transport, and rupture risk, we have developed a computational technique for analyzing luminal blood flow and O2 and NO transport in a patient-based model of a thrombosed AAA.

Materials and

Methods: The model includes separate layers for the aneurysm lumen, thrombus, and wall. In the lumen it allows for simultaneous convection and diffusion of both molecules. In ILT it allows for diffusion of both molecules without convection but consumption only of NO, and in the wall it allows for diffusion and consumption of both molecules. Coupled Navier-Stokes and scalar transport equations were solved by Direct Numerical Simulation (DNS) in the lumen layer, assuming a steady inlet flow rate but allowing for physiologically realistic turbulence development. The inlet and outlet flow rates were chosen to match time-averaged physiologic Reynolds numbers. O2 and NO consumption in the wall were described by Michaelis-Menten kinetics. O2 partial pressure at the inlet and the outermost surface of the wall layer was assumed to be 90 mmHg and 55 mmHg, respectively. NO concentration at the inlet was taken to be 0 nM, and NO production was assumed to occur only at the wall endothelium and to be proportional to the local wall shear stress. NO was also assumed to be consumed through interactions with oxyhemoglobin, free oxygen, and smooth muscle cells. At the outlets, concentration gradients for both O2 and NO normal to the boundaries were assumed to be zero.

Results, Conclusions, and Discussions: Our computations in the sample model illustrate reduced bioavailability of oxygen and nitric oxide, especially in the presence of thrombus. Streamlines colored by velocity magnitude illustrating the local hemodynamics are shown in Figure 1b. In wall regions covered with thrombus, there was no NO production because the endothelium experiences zero wall shear stress. Consequently, there is a large variation in NO concentration between aortic wall regions with thrombus and regions without (Figure 1a). Oxygen concentration at the wall inner surface was significantly reduced in the presence of ILT (Figure 1c). The magnitude of the reduction in wall O2 increased with increasing ILT thickness, but only up to a thickness of 5 mm, beyond which O2 concentration varied little (Figure 2). Very surprisingly, varying the turbulence intensity over several orders of magnitude had little effect on the wall O2 concentration distribution (Figure 2). Most importantly, to explain the physical mechanisms underlying this unexpected observation we develop an argument based on the mass transport resistance and the Damkohler number, which governs the ratio of convective transport rate to consumption rate.

Conclusions: We show that intraluminal thrombus plays a crucial role in the transport of the small molecules O2 and NO in our illustrative patient-specific AAA model, and we describe the physical mechanisms underlying this transport. In addition, we have developed a modeling framework which health professionals can use to estimate vessel wall oxygen and nitric oxide concentration in patient-specific models. An illustrative patient-specific AAA model is used to demonstrate our framework.

Acknowledgements (Optional): The authors thank Dassault Systèmes for use of their cloud-based cluster.

References:
1. Mussa, F.F., J. Vasc. Surg., 2015, 62(3), pp.774-778.
2. Gao, Ling, et al., Hypertension 59.1 (2012): pp.158-166.