Vessel Wall Histologic Changes in a Porcine Model of Arteriovenous Fistula Stenosis Treated with Percutaneous Transluminal Angioplasty

Abstract

Purpose: To describe the immunohistologic changes in arteriovenous fistula stenosis treated using plain old balloon angioplasty (POBA) versus paclitaxel drug-coated balloons (DCBs).

Materials and methods: Castrated male Yorkshire pigs (n = 12) 4-5 months old had chronic kidney disease induced with renal artery embolization. Twenty-eight days later, a side-to-end anastomosis was created between the left common carotid artery and ipsilateral external jugular vein. Four weeks later, a juxta-anastomotic stenosis was treated with balloon angioplasty (percutaneous transluminal angioplasty [PTA]) or DCB, and animals were euthanized at 4 (POBA [n = 6]) and 42 days (POBA [n = 3] or DCB [n = 3]) for histomorphometric analysis with immunohistochemical staining for CD68 (macrophages), FSP-1 (fibroblasts), α-smooth muscle cell (SMC) actin, CD-31 (endothelial), proliferation (Ki-67), and apoptosis (terminal deoxynucleotidyl transferase dUTP nick end labeling [TUNEL]).

Results: Two animals died at 14 and 28 days after PTA. There was a significant increase in the lumen (P = .0431), neointima (P = .0156 at Day (D) 4 and P < .001 at D42), and neointima/media + adventitia (N/M + A) ratio (P = .0061 at D4 and P = .0032 at D42). DCB-treated vessels showed a significant decrease in the N/M + A ratio (P = .0386) and cell density in the intima (P = .0113) compared with those treated with POBA. Endothelial cells were significantly increased at 4 days (P = .0034) and 42 days (P = .012), macrophages were significantly increased at 14 days (P = .0094), fibroblasts were significantly increased at 4 days (P = .0025) and 42 days (P < .001), and SMCs were significantly increased at 28 days (P = .004). Ki-67 staining peaked at 28 days (P = .0018), and TUNEL staining decreased at 4 days (P = .0012), 14 days (P = .0062), and 42 days (P = .04).

Conclusions: After PTA, the lumen vessel area increases with fibroblast and SMCs peaking at 4, followed by macrophages, SMCs, and proliferation.