Cyclic strain is known to influence many aspects of vascular cell biology, including macromolecular biosynthesis, cell proliferation, and cell morphology. The simulation of the cyclic strain associated with the vasculature in situ has been carried out mostly using devices that manipulated flat membranes on which the cells of choice are cultured. The purpose of this work was to create an apparatus wherein cyclic strains consistent with those found in native blood vessels could be applied to intact three-dimensional (tubular) specimens perfused ex vivo. The cyclic strain protocols using our apparatus may be any combination of axial stretch and twist. Concurrently, the perfusion flow and shear stress are controlled as desired. Vessel diameter, intraluminal pressure, volume flow, and regional strain are measured and stored on line. To illustrate the application of the device, we present hemodynamic and kinematic data collected from a human saphenous vein segment perfused under steady-flow conditions while subjected to cyclic stretch and twist.
The biomechanical milieu of the coronary arteries is unique in that they experience mechanical deformations of twisting, bending, and stretching due to their tethering to the epicardial surface. Spatial variations in stresses caused by these deformations could account for the heterogeneity of atherosclerotic plaques within the coronary tree. The goal of this work was to utilize previously reported shear moduli to calculate a shear strain parameter for a Fung-type exponential model of the arterial wall and determine if this single constant can account for the observed behavior of arterial segments under torsion. A Fung-type exponential strain-energy function was adapted to include a torsional shear strain term. The material parameter for this term was determined from previously published data describing the relationship between shear modulus and circumferential stress and longitudinal stretch ratio. Values for the shear strain parameter were determined for three geometries representing the mean porcine left anterior descending coronary artery dimensions plus or minus one standard deviation. Finite element simulation of triaxial biomechanical testing was then used to validate the model. The mean value calculated for the shear strain parameter was 0.0759+/-0.0009 (N=3 geometries). In silico triaxial experiments demonstrated that the shear modulus is directly proportional to the applied pressure at a constant longitudinal stretch ratio and to the stretch ratio at a constant pressure. Shear moduli determined from these simulations showed excellent agreement to shear moduli reported in literature. Previously published models describing the torsional shear behavior of porcine coronary arteries require a total of six independent constants. We have reduced that description into a single parameter in a Fung-type exponential strain-energy model. This model will aid in the estimation of wall stress distributions of vascular segments undergoing torsion, as such information could provide insight into the role of mechanical stimuli in the localization of atherosclerotic plaque formation.
By applying experimental concepts and principles originally established in the study of blood vessel biomechanics, we are exploring various aspects of lower urinary tract function, dysfunction, and treatment effects on tissue properties and performance. We demonstrate here the feasibility of using a modified ex vivo vascular perfusion apparatus for urethral functional studies. Through administration of various pharmacologic agents, and against applied luminal pressures, we demonstrate control over urethral smooth and striated muscle contractile elements. The ability to measure such physiologic responses provides the basis for performing novel functional studies pertaining to the role of each component in overall urethral function and biomechanics. Therefore, the use of this system to evaluate ex vivo physiology and biomechanical properties will advance the understanding of underlying principles of both normal and abnormal urethral function.
Certain arteries (e.g., coronary, femoral, etc.) are exposed to cyclic flexure due to their tethering to surrounding tissue beds. It is believed that such stimuli result in a spatially variable biomechanical stress distribution, which has been implicated as a key modulator of remodeling associated with atherosclerotic lesion localization. In this study we utilized a combined ex vivo experimental/computational methodology to address the hypothesis that local variations in shear and mural stress associated with cyclic flexure influence the distribution of early markers of atherogenesis. Bilateral porcine femoral arteries were surgically harvested and perfused ex vivo under pulsatile arterial conditions. One of the paired vessels was exposed to cyclic flexure (0–0.7 cm−1) at 1 Hz for 12 h. During the last hour, the perfusate was supplemented with Evan's blue dye-labeled albumin. A custom tissue processing protocol was used to determine the spatial distribution of endothelial permeability, apoptosis, and proliferation. Finite element and computational fluid dynamics techniques were used to determine the mural and shear stress distributions, respectively, for each perfused segment. Biological data obtained experimentally and mechanical stress data estimated computationally were combined in an experiment-specific manner using multiple linear regression analyses. Arterial segments exposed to cyclic flexure had significant increases in intimal and medial apoptosis (3.42±1.02 fold, p=0.029) with concomitant increases in permeability (1.14±0.04 fold, p=0.026). Regression analyses revealed specific mural stress measures including circumferential stress at systole, and longitudinal pulse stress were quantitatively correlated with the distribution of permeability and apoptosis. The results demonstrated that local variation in mechanical stress in arterial segments subjected to cyclic flexure indeed influence the extent and spatial distribution of the early atherogenic markers. In addition, the importance of including mural stresses in the investigation of vascular mechanopathobiology was highlighted. Specific example results were used to describe a potential mechanism by which systemic risk factors can lead to a heterogeneous disease.
The biaxial tensile testing results reported here are, to our knowledge, the first given for the human infrarenal aorta and reinforce the importance of determining the functional form of W from experimental data. Such information may be useful for the clinician or researcher in identifying key changes in the biomechanical response of abdominal aorta in the presence of an aneurysm.
