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

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.