Biomechanical Phenotyping of Central Arteries in Health and Disease: Advantages of and Methods for Murine Models

Abstract

The stiffness and structural integrity of the arterial wall depends primarily on the organization of the extracellular matrix and the cells that fashion and maintain this matrix. Fundamental to the latter is a delicate balance in the continuous production and removal of structural constituents and the mechanical state in which such turnover occurs. Perturbations in this balance due to genetic mutations, altered hemodynamics, or pathological processes result in diverse vascular phenotypes, many of which have yet to be well characterized biomechanically. In this paper, we emphasize the particular need to understand regional variations in the biaxial biomechanical properties of central arteries in health and disease and, in addition, the need for standardization in the associated biaxial testing and quantification. As an example of possible experimental methods, we summarize testing protocols that have evolved in our laboratory over the past 8 years. Moreover, we note advantages of a four fiber family stress – stretch relation for quantifying passive biaxial behaviors, the use of stored energy as a convenient scalar metric of the associated material stiffness, and the utility of appropriate linearizations of the nonlinear, anisotropic relations both for purposes of comparison across laboratories and to inform computational fluid-solid-interaction models. We conclude that, notwithstanding prior advances, there remain many opportunities to advance our understanding of arterial mechanics and mechanobiology, particularly via the diverse genetic, pharmacological, and surgical models that are, or soon will be, available in the mouse.

Beyond Burst Pressure: Initial Evaluation of the Natural History of the Biaxial Mechanical Properties of Tissue-Engineered Vascular Grafts in the Venous Circulation Using a Murine Model

“…Color images available online at www.liebertpub.com/tea formulation of an appropriate nonlinear constitutive relation for the evolving TEVG. 27 Indeed, there is also a need to delineate better the separate evolution of the TEVG and adaptation of the adjacent IVC (which will require tracking axial fiducial markers on each segment during biaxial testing). Finally, there is a need to elucidate the fundamental mechanobiological principles involved in neotissue formation in the hope of understanding their impact on vascular tissue regeneration and the development of graft-related complications such as the formation of TEVG stenosis.…”

Local Versus Global Mechanical Effects of Intramural Swelling in Carotid Arteries

“…5) and compared experimental results (symbols; present data) and theoretical predictions (lines, with constitutive relations based primarily on data from Ref. [10] augmented with the swelling) for all three extents of swelling. The top panel shows the predicted behavior for the control solution ( Ã ¼ 1), the middle panel for the 33% solution ( Ã ¼ 1:09), and the bottom panel for the 3.3% solution ( Ã ¼ 1:33).…”

“…Pressure-diameter tests were performed in each of these 1 three solutions at room temperature using a modified version of the protocol described by Ref. [10]. Specifically, each cannulated vessel was placed horizontally within a testing chamber (Living Systems Instrumentation, Albans, VT) with one cannula set at a fixed position and the other connected to a custom externally mounted micrometer to control and measure axial lengths.…”

“…All animal care and experiments were approved by the Yale University Institutional Animal Care and Use Committee. Following established methods in our laboratory [10], male C57BL/6 mice were euthanized at 10-18 weeks of age via an overdose of Beuthanasia. The right and left common carotid arteries were excised, carefully cleaned of excess perivascular tissue, mounted on custom glass cannula, and secured with 6-O suture.…”

“…The material parameters, mass fractions, and deposition stretches were taken from Ref. [13], that is, based on a larger data base for the passive behavior of murine control arteries [10].…”