Efficacy of local molsidomine delivery from a hydrogel-coated angioplasty balloon catheter in the atherosclerotic porcine model.
OBJECTIVE
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.


CONCLUSIONS
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.
Rolland
Pierre H
PH
School of Medicine, Faculté de Medicine, 27, Hemodynamics and Cardiovascular Mechanics Laboratory, Bld Jean-Moulin, F-13385 Marseille Cedex 5, France. Ph.Rolland@medecine.univ-mrs.fr
Mekkaoui
Choukri
C
Palassi
Maria
M
Friggi
Alain
A
Moulin
Guy
G
Piquet
Philippe
P
Bartoli
Jean-Michel
JM
D000704:Analysis of Variance; D000800:Angioplasty, Balloon / Q000295:instrumentation; D000818:Animals; D001161:Arteriosclerosis / Q000188:drug therapy*; D004195:Disease Models, Animal; D016503:Drug Delivery Systems / Q000295:instrumentation*; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate; D007083:Iliac Artery; D008855:Microscopy, Electron, Scanning; D008981:Molsidomine / Q000008:administration & dosage*; D018709:Statistics, Nonparametric; D013552:Swine; D014665:Vasodilator Agents / Q000008:administration & dosage*
D014665:Vasodilator Agents; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate; D008981:Molsidomine