Obstruction-Induced Pulmonary Vascular Remodeling

Abstract

Pulmonary obstruction occurs in many common forms of congenital heart disease. In this study, pulmonary artery (PA) banding is used as a model for pulmonary stenosis. Significant remodeling of the vascular bed occurs as a result of a prolonged narrowing of the PAs, and here we quantify the biophysical and molecular changes proximal and distal to the obstruction. Main and branch PAs are harvested from banded and sham rabbits and their mechanical properties are assessed using a biaxial tensile tester. Measurements defined as initial and stiff slopes are taken, assuming a linear region at the start and end of the J-shaped stress-strain curves, along with a transitional knee point. Collagen, elastin assays, Movat’s pentachrome staining, and Doppler protocols are used to quantify biochemical, structural, and physiological differences. The banded main PAs have significantly greater initial slopes while banded branch PAs have lower initial slopes; however, this change in mechanical behavior cannot be explained by the assay results as the elastin content in both main and branch PAs is not significantly different. The stiff slopes of the banded main PAs are higher, which is attributed to the significantly greater amounts of insoluble collagen. Shifting of the knee points reveals a decreased toe region in the main PAs but an opposite trend in the branch PAs. The histology results show a loss of integrity of the media, increase in ground substance, and dispersion of collagen in the banded tissue samples. This indicates other structural changes could have led to the mechanical differences in banded and normal tissue.

Structural and Functional Differences Between Porcine Aorta and Vena Cava

“…The variability in the stress-stretch behavior of vena cava in this study ranges from 32% to 42%, and the closest comparison is uniaxial ovine vena cava with variability of up to $23% within an individual [36]. Finally, the choice of a sixth-order polynomial was used to obtain the tangent modulus [41]. However, we acknowledge that the use of a fifth-order polynomial has been used to successfully determine the tangent modulus [53].…”

“…Collagen content was expressed as microgram of collagen per milligram of wet tissue weight. Elastin content was measured using Fastin elastin assay kit (Biocolor, Ltd.) [39][40][41]. Following manufacture's protocols, our assays measured soluble tropoelastins and insoluble elastin that was solubilized into a-elastin polypeptides.…”

“…Biaxial Tensile Test. A custom-designed biaxial tensile testing device was used to mechanically test the tissue samples following protocols described previously [39][40][41]. Briefly, tissue deformation, stretch, was measured by tracking four carbon marker dots on the tissue with a CCD camera during a tension control protocol using a custom LABVIEW program [42].…”

Glycosaminoglycans contribute to extracellular matrix fiber recruitment and arterial wall mechanics

“…The high stress region was chosen such that the adventitial collagen fibers are recruited. Transition stress/strain was then calculated as the intersection of the bilinear curve fit to the initial and stiff regions of the stress-strain curves (Chow et al 2011). For treated samples, the transition points of the circumferential (p=0.04) and longitudinal (p=0.002) directions are at significantly lower strain measurements, indicating earlier stiffening behavior of the arterial wall (Fig.…”

Pulmonary artery stents in the recent era

“…Surgical repair may itself cause or exacerbate pulmonary artery stenosis secondary to scar formation, vascular distortion, folding or external compression, with a recurrence rate of 35–40% . Unless treated early in life, long standing stenosis of one or both pulmonary arteries can lead to poor distal vascular growth as well as right ventricular hypertension and progressive pulmonary insufficiency .…”