Ex-vivo biomechanical characterization of arteriovenous fistulas
Renal Failure, also known as kidney failure, is a medical condition in which the kidneys in the body are not able to adequately filter waste products from the blood, leading to elevated blood pressure. Frequent formation of vascular access is required for patients undergoing hemodialysis treatment for renal failure. Arteriovenous fistula (AVF), formed by connecting an artery and a vein is considered the gold standard method for vascular access. Despite this, AVFs fail in the early stages of maturation or require secondary interventions. These failures are believed to be caused by changes in the biomechanical properties of the AVFs over time. Using a pre-clinical model, we hypothesized that treating AVFs with the anti-fibrotic agent β-aminopropionitrile (BAPN) results in a decrease in AVF stiffness. This hypothesis was tested by conducting mechanical pressure-inflation testing on epigastric veins, AVFs formed by joining the right epigastric vein to the femoral artery, and AVFs treated with BAPN originated from Sprague Dawley rat subjects. AVFs were modeled as thin-walled nonlinear elastic vessels using a two dimensional Fung model. Histology analysis was conducted for assessing collagen, elastin and SMA cross-linking, while biological changes on the BAPN treated AVFs were compared to the controls and a correlation with biomechanical parameters was evaluated. Mechanical testing revealed that AVFs treated with BAPN exhibited a smaller mean outer diameter, lower wall thickness, and lower circumferential and axial stretch ratios compared to the untreated AVFs.
The maximum tangential modulus (MTM) was evaluated to quantify the material stiffness, resulting in a lower MTM for the BAPN treated AVFs compared to the untreated AVFs. Collagen and smooth muscle cell actin (SMA) cross-linking was reduced in the BAPN treated AVFs compared to the veins as BAPN successfully inhibited the formation of new cross-linkages. Staining for elastin did not reveal any changes in the BAPN treated AVFs relative to the vein specimens. Our results suggest that BAPN treatment affects the mechanical strength and structural architecture of AVFs, resulting in decreased crosslinking of collagen and SMA, which may play an important role during thrombosis and stenosis of the fistula during hemodialysis.