Local delivery of NO-donor molsidomine post-PTA improves haemodynamics, wall mechanics and histomorphometry in atherosclerotic porcine SFA.

Abstract

we investigated the therapeutic effect of angioplasty with local drug delivery (LDD) of the wall-accumulating NO-donor molsidomine (M) in the superficial femoral arteries (SFA) of atherosclerotic swine. atherosclerotic Pietrin swines (n=14) underwent PTA-LDD-M (4 mg/2 ml) vs contralateral PTA-LDD-Placebo in the SFA using a channelled balloon angioplasty catheter. Invasive and colour Doppler energy (CDE) assessments of haemodynamics and wall mechanics were performed at 24 h (n=4) and 5 months (n=10). Immuno-histolabelling of cell proliferation and histomorphometry were serially performed in perfusion fixed SFA samples. at 24 h, PCNA-positive nuclei revealed 33+/-14 and 12+/-3 proliferating cells/mm2 at placebo and molsidomine PTA-LDD sites, respectively (p<0.001). At 5 months, PTA-LDD-M vessels, compared with PTA-LDD-P, had increased compliance (66+/-9 vs 11+/-4 ml/mmHg) and lowered impedance (0.11+/-0.05 vs 0.45+/-0.14 mmHg/ml x min(-1)) (p<0.05). CDE revealed low, middle and high velocity peaks at 7.5, 20 and 35, and 8, 15 and 22 cm x s(-1) in systolic and diastolic flows, respectively; and PTA-LDD-M prevented emergence of restenosis-associated increases in low blood velocities (p<0.01). PTA-LDD-M inhibited restenotic intimal thickening and medial thinning which decreased mean lumenal diameter in placebo-treated (2.6+/-0.3) as compared to molsidomine-treated (3.4+/-0.3 mm) vessels (p<0.05). in the atherosclerotic porcine SFA model, PTA-LDD with molsidomine consistently improved haemodynamic wall mechanics, lowered cell proliferation and prevented late lumen loss observed with PTA-LDD with placebo.