Abstract

PURPOSE: To evaluate the therapeutic effects of local molsidomine delivery via a hydrogel-coated angioplasty balloon catheter during overstretch angioplasty in atherosclerotic swine iliac vessels. Molsidomine is retained in the arterial wall after local delivery for more than 72 hr and is slowly metabolized into linsidomine, releasing nitric oxide (NO).
METHODS: A hydrogel-coated angioplasty balloon catheter was used to both deliver drug locally (150 mg molsidomine or placebo in the contralateral vessel) and dilate iliac vessels in nine Pietrin pigs that had been on an atherogenic diet for 5 months. Animals were killed at 3 hr (n = 2), 24 hr (n = 3) and 3 months (n = 3) after treatment. Iliac arteries were examined for wall pulsatility, histomorphometry, cell proliferation and platelet aggregation.
RESULTS: No significant therapeutic effects were detected 3 hr after treatment. At 24 hr, wall pulsatility, thromboresistance and vascular cell homeostasis were significantly restored in the molsidomine-treated versus placebo group. At 3 months, molsidomine inhibited restenotic lesion development, except in scarred areas of histologically detectable adventitial/medial dissection.
CONCLUSION: Local delivery of concentrated molsidomine from a hydrogel-coated angioplasty balloon catheter resulted in early NO-dependent vasodilation/stress normalization and antithrombotic and antiproliferative effects. In the medium term, molsidomine inhibited restenosis in the absence of vessel dissection.