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

Abstract

Objectives: 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. Materials and methods: 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). Immunohistolabelling of cell proliferation and histomorphometry were serially performed in perfusion fixed SFA samples. Results: at 24h, 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 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 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 ± 0.3mm) vessels (p<0.05). Conclusions: 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. © 2002 Elsevier Science Ltd. All rights reserved.