Hyperelastic remodeling in the intrauterine growth restricted (IUGR) carotid artery in the near-term fetus

Abstract

A constitutive model for a fiber reinforced hyperelastic material was applied to understand arterial fiber remodeling in a sheep model of Intrauterine Growth Restriction (IUGR). IUGR is associated altered hemodynamics characterized by increased resistance to blood flow in the placenta and elevated fetal arterial pressure and pulsatility. The constitutive model describes the collagen contribution to the mechanics within the arterial wall in both control and IUGR carotid artery through defining the material modulus and the orientation of the microstructure. A sheep model of placental insufficiency induced IUGR (PI-IUGR) was created by exposure of the pregnant ewe to elevated ambient temperatures. Experimental data was collected using pressure–diameter measurements to measure passive compliance in control and PI-IUGR carotid arteries. The constitutive model was optimized to fit the experimental data predicting the material parameters. Specifically, the collagen fiber predicted angle (γ) in the control artery was 49.9° from the circumferential axis while the PI-IUGR was 16.6° with a 23.5% increase in fiber orientation (κ). Quantitative assessment of collagen fiber orientation in secondary harmonic generation images confirmed the shift in orientation between the two groups. Together these suggest vascular remodeling of the ECM fiber orientation plays a major role in arterial stiffening in the PI-IUGR near-term fetal sheep.

Thoracic and abdominal aortas stiffen through unique extracellular matrix changes in intrauterine growth restricted fetal sheep

“…Fetal and placental weights and lengths were obtained and recorded as previously described (10,11). The thoracic aortas (control n ϭ 11; PI-IUGR n ϭ 10) were dissected from the base of the aortic arch to the diaphragm.…”

“…The dissected aortas were tested for stiffness using transmural pressure and diameter as previously described (10,11). In brief, the aorta was cannulated and sutured into a custom arteriography chamber and tested for passive compliance measuring transmural pressure, axial stretch, and vessel diameter.…”

“…Three representative fixed test samples of control and PI-IUGR thoracic and abdominal aortas were processed for imaging. Samples were rehydrated using PBS and then dissected and oriented for imaging in the circumferential-axial plane and imaged using laser confocal second harmonic generation (SHG) to visualize collagen and elastin content as previously described (11). Images were quantified for collagen fiber orientation and dispersion using a previously validated custom-written ImageJ analysis macro OrientationJ (30).…”

“…The aortic walls were analyzed using the Gasser et al constitutive model as previously described (11,17). Experimental arterial walls were modeled as single layer fiber reinforced isochoric hyperelastic material.…”

Changes in Aortic Wall Structure, Composition, and Stiffness With Continuous-Flow Left Ventricular Assist Devices

“…8 Uniaxial extension was applied at a constant crosshead speed of 0.5 mm/s, executing 5 successive preconditioning cycles to a prescribed elastin and collagen activation strain. The tensile force and specimen length were continuously recorded (10 Hz, Testworks 4 software).…”