The Effect of Local Alcohol Delivery in Reducing Intimal Hyperplasia Induced by Vascular Injury and the Clinical Implications
Abstract:Local delivery of pharmacological agents into the vessel wall has been extensively studied to prevent restenosis after coronary angioplasty. Alcohol solution was found to affect cellular responses to growth stimulation. The effects of local delivery of alcohol solution using specially designed catheter on intimal proliferation were initially studied in animals, including rabbits and pigs. In rabbits, the neointimal areas of alcohol treated iliac arteries after balloon denudation were significantly less than those of control segments in both 10% and 15% groups. In addition, a method of quantifying phenotypic conversion of smooth muscle cells was chosen. The volume fraction of the synthetic organelles of vascular smooth muscle of the control vessels were significantly greater than those of paired 10% and 15% alcohol treated arteries in both intima and media. In pigs study, loca l delive ry of 15% ethanol with a local delive ry ba lloon c atheter wa s per for me d in cor onary a rte ries af ter balloon dilata tion. Simila r to the r abbit study, the ne ointima l a re as we re significa ntly sma ller in the alc ohol tr eated ar te ria l segme nts than in the untr eated se gments. SMC pr olife ra tive activity wa s signific antly lowe r in alcohol tr ea ted a rte ries than in untr eated ar te rie s at 4 and 8 da ys af te r injury by both br omode oxyur idune a nd pr olife rating c ell nuc lea r antigen staining method. Based on the animal studies, a pilot study of 46 patients with in-stent restenosis was treated with 15% alcohol solution using InfusaSleeve (LocalMed, Palo Alto, CA), a local delivery device after successful balloon dilatation. According to the initial length of restenotic lesion before the alcohol delivery, there were 15 patients with lesion length < 10 mm, 13 with lesion length 10-20 mm and 14 with length > 20 mm. Target vessel revascularization rate in these 3 groups were 7% (1 / 15), 15% (2 / 13) and 7 / 14 (50%) (P < 0.02). Another human study using a different local delivery catheter, Infiltrator (IVT, San Diego, CA) was performed in 18 patients with de novo coronary lesions. After successful balloon dilatation, three separate groups of 6 patients received 5%, 10% and 15% alcohol solution respectively. In-stent neointimal volume at 9 months were 39±19, 27±10, and 13± 12 mm3 in 5%, 10% and 15% treatment groups respectively. (p <0.05). No patient need repeat revascularization. In conclusion, local delivery of alcohol solution is a promising vascular pharmacological method in reducing intimal proliferation and hence restenosis after vascular injury.
Document Type: Review Article
Affiliations: Division of Cardiovascular Medicine, University of Southern, California 1355, San Pablo Street, Suite 117, Los Angeles, CA 90089, USA.
Publication date: 2004-03-01
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