Computer simulation of arterial blood flow

Computer models have been widely used to simulate pressure and flow propagation in the arterial system. While experimentation involving the human arterial system is difficult and impractical, computer models offer an attractive alternative for the study of arterial hemodynamics. The purpose of the present study was to develop a computer model of the whole systemic circulation and to use this model to study pressure and flow propagation under normal flow conditions, as well as under conditions of arterial disease;The mathematical model used to describe flow in an arterial segment was based on the one-dimensional continuity and momentum equations. The model includes nonlinearities arising from the convective acceleration term and the pressure-area relationship. The mathematical model also includes a seepage term for the modeling of small branches, as well as a body force term for the modeling of gravitational and external acceleration forces. Arterial segments that do not branch are terminated using modified windkessel lumped impedances. Arterial stenoses are modeled using an empirical pressure drop-flow relationship. The problem was solved numerically by employing either an explicit finite difference scheme, or a finite element scheme based on the Galerkin method;The physiological model consisted of 55 arterial segments and included most major arteries. The majority of the parameter data were obtained from the literature. Under normal flow conditions, the model predicted satisfactorily the major characteristics of pressure and flow throughout the arterial system. Tests were also run to assess the influence of model parameters, such as those related to boundary conditions, nonlinearities, and the wall shear stress model, on the model predictions;Finally, the model was used to study cases of medical interest, such as the effect of various forms of cardiovascular disease on pressure and flow waveforms. The cases studied include the effect of arterial stenoses on the mean flow and the pulsatility of the flow, the effect of heart valvular disease on central and peripheral pressure waveforms, as well as the effect of arteriosclerosis and hypertension on peripheral pressure pulse formation. The results were in reasonably good agreement with published experimental findings, suggesting that the computer model can be used to gain valuable information on the hemodynamics of the human arterial system

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

On the Estimation of Total Arterial Compliance from Aortic Pulse Wave Velocity

Total arterial compliance (C T) is a main determinant of cardiac afterload, left ventricular function and arterio-ventricular coupling. C T is physiologically more relevant than regional aortic stiffness. However, direct, in vivo, non-invasive, measurement of C T is not feasible. Several methods for indirect C T estimation require simultaneous recording of aortic flow and pressure waves, limiting C T assessment in clinical practice. In contrast, aortic pulse wave velocity (aPWV) measurement, which is considered as the "gold standard” method to assess arterial stiffness, is noninvasive and relatively easy. Our aim was to establish the relation between aPWV and C T. In total, 1000 different hemodynamic cases were simulated, by altering heart rate, compliance, resistance and geometry using an accurate, distributed, nonlinear, one-dimensional model of the arterial tree. Based on Bramwell-Hill theory, the formula $$C_{\text{T}} = k \cdot {\text{aPWV}}^{ - 2}$$ was found to accurately estimate C T from aPWV. Coefficient k was determined both analytically and by fitting C T vs. aPWV data. C T estimation may provide an additional tool for cardiovascular risk (CV) assessment and better management of CV diseases. C T could have greater impact in assessing elderly population or subjects with elevated arterial stiffness, where aPWV seem to have limited prognostic value. Further clinical studies should be performed to validate the formula in viv

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

Unravelling the aortic microstructure : synchrotron-based quasi-static pressure inflation of the mouse carotid artery

The contribution of the aortic microstructure to the mechanical behavior of the aortic wall is poorly understood. Several high-resolution techniques have been proposed to visualize elastic lamellae or collagen fibers, but most have a limited field of view and are challenging to perform in pressurized conditions. In recent experiments we visualized the micro-structure of mouse aortas using phase propagation imaging – a synchrotron-based technique that yielded 3D images on which separate lamellar layers could be identified (unpublished data, manuscript in preparation). In the experimental study that is presented here we used phase propagation imaging to quantify, for the first time, the unfolding of aortic lamellae during quasi-static pressure inflation experiments. Six wild type and six ApoE-/- mice, all male and on a C57Bl6/J background, were used for this study. The left carotid artery was harvested immediately after sacrifice and mounted on a dedicated synchrotron-compatible pressure inflation device. During the experiment pressure was increased quasi-statically with a syringe pump and maintained at a constant level during each imaging step. After two initial loops of 0-120 mmHg to precondition the vessel, scans were taken at pressure levels of 0, 10, 20, 30, 40, 50, 70, 90 and 120 mmHg while the axial stretch was kept at the in vivo value. Phase propagation was performed at 25m source-to-sample distance, 25 cm sample-todetector distance and at 21 keV. A scientific CMOS detector (pco.Edge 5.5) was used in combination with a 4x magnifying visible-light optics and a 20 μm thick scintillator. The effective pixel size was 1.625 x 1.625 μm2. During post-processing the images were skeletonized and a bi-directional graph was generated in Matlab. Using a modified Dijkstra algorithm in which lower weights were assigned to the edges closest to the center of the vessel, we created a Matlab-based algorithm that allows us to automatically segment the main micro-structural features each of the three lamellar layers in the carotid artery. The algorithm exploits the edge connectivity and the shortest path constraints, and weights of edges belonging to the shortest path are subsequently increased order to allow for the detection of subsequent layers. After filtering and de-trending the signal, the undulation of each layer was quantified from the prominence of the peaks in the signal. Both in ApoE-/- and wild type mice we were able to quantify how the increased straightening of the lamellar layers in response to the increasing pressure related to the change in vessel diameter that is quantified in traditional biomechanical experiments. In future work we intend to use the synchrotroncompatible pressure-inflation device in order to experimentally determine the microstructural material properties of aortic lamellae and the interlamellar space