Emerging pharmacological treatments to prevent abdominal aortic aneurysm growth and rupture

Abdominal aortic aneurysm (AAA) is a local expansion of the abdominal aorta wall caused by a complex multifactorial maladaptive vascular remodeling. Despite recent advances in the management of cardiovascular diseases, there currently is no established drug therapy for AAA. Since the probability of death from a ruptured AAA still remains high, preventive elective repair of AAAs larger than 5.5 cm in luminal diameter is considered the best treatment option. However, perioperative complications are problematic as elective AAA repair comes with numerous intrinsic risks. Impelled by the need of improving AAA therapy, significant efforts have been made to identify pharmacological tools that would slow down AAA enlargement and lower the risk of rupture, thereby reducing the necessity of surgical intervention. In this review, we discuss recent findings addressing molecular targets that could potentially treat AAA, particularly addressing: statins, classical renin angiotensin system (RAS) blockers, the protective arm of RAS, renin inhibitors, tetracyclines, interleukin-1 beta inhibition, anti-angiogenic agents and urocortins

The influence of anesthesia and fluid-structure interaction on simulated shear stress patterns in the carotid bifurcation of mice

Background: Low and oscillatory wall shear stresses (WSS) near aortic bifurcations have been linked to the onset of atherosclerosis. In previous work, we calculated detailed WSS patterns in the carotid bifurcation of mice using a Fluid-structure interaction (FSI) approach. We subsequently fed the animals a high-fat diet and linked the results of the FSI simulations to those of atherosclerotic plaque location on a within-subject basis. However, these simulations were based on boundary conditions measured under anesthesia, while active mice might experience different hemodynamics. Moreover, the FSI technique for mouse-specific simulations is both time- and labor-intensive, and might be replaced by simpler and easier Computational Fluid Dynamics (CFD) simulations. The goal of the current work was (i) to compare WSS patterns based on anesthesia conditions to those representing active resting and exercising conditions; and (ii) to compare WSS patterns based on FSI simulations to those based on steady-state and transient CFD simulations. Methods: For each of the 3 computational techniques (steady state CFD, transient CFD, FSI) we performed 5 simulations: 1 for anesthesia, 2 for conscious resting conditions and 2 more for conscious active conditions. The inflow, pressure and heart rate were scaled according to representative in vivo measurements obtained from literature. Results: When normalized by the maximal shear stress value, shear stress patterns were similar for the 3 computational techniques. For all activity levels, steady state CFD led to an overestimation of WSS values, while FSI simulations yielded a clear increase in WSS reversal at the outer side of the sinus of the external carotid artery that was not visible in transient CFD-simulations. Furthermore, the FSI simulations in the highest locomotor activity state showed a flow recirculation zone in the external carotid artery that was not present under anesthesia. This recirculation went hand in hand with locally increased WSS reversal. Conclusions: Our data show that FSI simulations are not necessary to obtain normalized WSS patterns, but indispensable to assess the oscillatory behavior of the WSS in mice. Flow recirculation and WSS reversal at the external carotid artery may occur during high locomotor activity while they are not present under anesthesia. These phenomena might thus influence plaque formation to a larger extent than what was previously assumed. (C) 2016 Elsevier Ltd. All rights reserved

Inverse modelling of image-based patient-specific blood vessels : zero-pressure geometry and in vivo stress incorporation

In vivo visualization of cardiovascular structures is possible using medical images. However, one has to realize that the resulting 3D geometries correspond to in vivo conditions. This entails an internal stress state to be present in the in vivo measured geometry of e.g. a blood vessel due to the presence of the blood pressure. In order to correct for this in vivo stress, this paper presents an inverse method to restore the original zero-pressure geometry of a structure, and to recover the in vivo stress field of the final, loaded structure. The proposed backward displacement method is able to solve the inverse problem iteratively using fixed point iterations, but can be significantly accelerated by a quasi-Newton technique in which a least-squares model is used to approximate the inverse of the Jacobian. The here proposed backward displacement method allows for a straightforward implementation of the algorithm in combination with existing structural solvers, even if the structural solver is a black box, as only an update of the coordinates of the mesh needs to be performed

A multi-angle plane wave imaging approach for high frequency 2D flow visualization in small animals: simulation study in the murine arterial system

To preclinically investigate the role of hemodynamics in atherogenesis, mouse models are particularly useful due to the rapid disease development. As such, murine blood flow visualization has become an important tool, with current US systems equipped with traditional 1D flow imaging techniques, lacking spatial and/or temporal resolution to accurately resolve in-vivo flow fields. Hence, we investigated multi-angle plane wave imaging for ultrafast, 2D vector flow visualization and compared this approach with conventional pulsed Doppler in the setting of a mouse aorta with abdominal aortic aneurysm. For this purpose, we used a multiphysics model which allowed direct comparison of synthetic US images with the true flow field behind the image. In case of the abdominal aorta, we showed the mean flow estimation improved 9 % when using 2D vector Doppler compared to conventional Doppler, but still underestimated the true flow because the full spatial velocity distribution remained unknown. We also evaluated a more challenging measurement location, the mesenteric artery (aortic side branch), often assessed in a short-axis view close to the origin of the branch to avoid the smaller dimensions downstream. Even so, complex out-ofplane flow dynamics hampered a reliable flow assessment for both techniques. Hence, both cases illustrated the need for 3D vascular imaging, allowing acquisition of the full 3D spatial velocity profile

Synchrotron-based visualization and segmentation of elastic lamellae in the mouse carotid artery during quasi-static pressure inflation

This dataset contains images that were obtained during quasi-static pressure inflation of mouse carotid arteries. Images were taken with phase propagation imaging at the X02DA TOMCAT beamline of the Swiss Light Source synchrotron at the Paul Scherrer Institute in Villigen, Switzerland. Scans of n=12 left carotid arteries (n-6 Apoe-deficient mice, n=6 wild-type mice, all on a C57Bl6J background) were taken at pressure levels of 0, 10, 20, 30, 40, 50, 70, 90 and 120 mmHg. For analysis we selected 75 images from the center of each stack (starting at the center of the stack, and skipping 2 of every three images in both cranial and caudal axial directions) for each sample and for each pressure level, resulting in a total of 75 x 12 x 9 = 8100 analyzed images from 108 different scans. Segmentation, 3D visualization and geometric analysis is presented in the corresponding manuscript. Files are uploaded in 16bit .tif format and are named: mouseid_pressurelevel_stacknumber, with mouseid consisting of either Apoe (Apoe-deficient) or Bl (wild-type) and the mouse number, pressurelevel varies from P0 to P120 and stacknumber indicates which image from the stack has been uploaded