Combining in vivo and in vitro biomechanical data reveals key roles of perivascular tethering in central artery function

Abstract

Considerable insight into effectors of cardiovascular function can be gleaned from controlled studies on mice, especially given the diverse models that are available. Toward this end, however, there is a need for consistent and complementary methods of in vivo and in vitro data analysis, synthesis, and interpretation. The overall objective of this study is twofold. First, we present new semi-automated methods to quantify in vivo measurements of vascular function in anesthetized mice as well as new approaches to synthesize these data with those from in vitro biaxial mechanical characterizations. Second, we contrast regional differences in biomechanical behaviors along the central vasculature by combining biaxial strains measured in vivo with data on the unloaded geometry and biaxial material properties measured in vitro. Results support the hypothesis that the healthy ascending aorta stores significant elastic energy during systole, which is available to work on the heart and blood during diastole, particularly during periods of physical exertion, and further suggest that perivascular tethering allows arteries to work at lower values of wall stress and material stiffness than often assumed. The numerous measurements of vascular function and properties provided herein can also serve as reference values for normal wild-type male and female mice, to which values for myriad genetic, surgical, and pharmacological models can be compared in future studies.

Mechanical stresses associated with flattening of human femoropopliteal artery specimens during planar biaxial testing and their effects on the calculated physiologic stress–stretch state

“…Another limitation is that current analysis neglected the effects of perivascular tethering on the outer surface of the FPA wall, which likely affected the assessment of physiologic stressstretch conditions. Additional experiments are needed to quantify perivascular tethering effects (Ferruzzi et al 2018) in human FPAs, and to determine whether they change with age and disease. While these and other limitations are being addressed, current analysis provides a better understanding of the effects associated with flattening of the FPA specimens during planar biaxial testing, and offers a set of adjusted constitutive parameters that can be used to model the physiologic FPA behavior in subjects of different ages.…”

H19 is not hypomethylated or upregulated with age or sex in the aortic valves of mice

“…An exemplary PW Doppler scan and corresponding flow profile traces are shown in Figure A and B. VevoLAB software was used to analyze M‐mode cardiac cycles (~9 per image) and extract PW Doppler images. A custom MATLAB script was used to isolate and average PW Doppler cardiac cycles (~10–30 per image) in order to compute the systolic transvalvular pressure gradient and peak systolic velocity (PSV) (Ferruzzi et al ). Ejection fraction to velocity ratio (EFVR), a metric used as an indicator of valve disease, was calculated as EFVR = (ejection fraction)/(4*(PSV) 2 ) (Cattaneo et al ).…”

Genetic ablation of serotonin receptor 2B improves aortic valve hemodynamics of Notch1 heterozygous mice in a high-cholesterol diet model

“…AV jet velocity profiles were estimated by aortic pulsed-wave Doppler imaging. A custom MATLAB script was implemented to determine the maximum systolic velocity and mean pressure gradient [31]. Three images were analyzed per mouse yielding a total of~100 cardiac cycles that were quantified and averaged to reliably quantify AV hemodynamic characteristics.…”