Abstract
Introduction: Arteriovenous fistula (AVF) nonmaturation is associated with postoperative fibrosis and an increase in lysyl oxidase (LOX) expression. Objective: The purpose of this study was to determine whether unidirectional periadventitial delivery of β-aminoproprionitrile (BAPN) using bilayer poly lactic-co-glycolic acid nanofiber scaffolds is a feasible approach to reduce AVF fibrosis and encourage adaptive vascular remodeling. Methods: AVFs were created in thirty Sprague Dawley rats (200-350 g) of both sexes by an end-to-side anastomosis of the epigastric vein to the femoral artery. BAPN-loaded (b-BAPN) (n=10) or vehicle (b-VEH) (n=10) scaffolds (5 mm x 5 mm) were wrapped around the juxta-anastomotic zone of the epigastric vein immediately after anastomosis. AVFs without treatment were used as an additional control (n=10). Changes in lumen diameter were followed-up weekly using ultrasound. Flow was calculated using the pulse-wave velocity and lumen diameter. AVFs were collected at 21 days for histomorphometric analysis and to assess fibrosis. Results: b-BAPN significantly increased dilation of AVFs at day 14 (185.9%) compared to b-VEH (135.5%; p=0.0006) and control AVFs (113.6%; p<0.0001). The treatment (214.2%) had a significant difference compared to b-VEH (135.5%; p<0.0001) and AVF controls (122%; p<0.0001) at day 21 as well. In addition, blood flow was significantly enhanced in the treatment group (38.13 mL/min) versus b-VEH (9.436 mL/min; p=0.0002) and AVF controls (16.11 mL/min; p<0.0001). Histomorphometric analysis confirmed the ultrasound findings. Treatment with b-BAPN significantly increased lumen area compared to control AVFs (354,127 μm 2 vs. 95,580 μm 2 ; p=0.0048). While there was no difference in intimal growth (p=0.5460), b-BAPN significantly reduced luminal occlusion with respect to control AVFs (0.0611 vs. 0.2067; p=0.0002). Finally, b-BAPN (49.48%) significantly reduced the fibrosis percent area compared to b-VEH (72.14%; p=0.0016) and control AVFs (74.5%; p=0.0007). Conclusion: Periadventitial LOX inhibition prevents AVF postoperative fibrosis and promotes adaptive vascular remodeling.
