Local drug delivery from intravascular stents for modulating the arterial response to balloon dilatation injury
Abstract
Local drug delivery from intravascular stents was investigated for modulating the arterial response to injury. Twelve rabbits underwent balloon dilatation of both external iliac arteries and received either a heparin treated (HT) or dexamethasone treated (DMT) stent in one artery and an untreated stent (UT) in the contralateral artery. The HT was a coating of heparin - benzalkonium chloride in cellulose acetate nitrate polymer (CAN) and the DMT was a coating of dexamethasone in CAN. Arteriograms recorded before dilatation (control), immediately after stenting and six months after stenting were quantitatively analyzed, and at six months, the arteries were harvested for qualitative histopathology and quantitative morphometry. There were no significant differences in the control arteriographic diameters among the treatment groups. All arteries had larger arteriographic diameters immediately after stenting than control (average increase of 10-12%, p $<$ 0.05), without significant differences among the treatment groups. All arterial responses included neointimal hyperplasia and all arteries had smaller six month arteriographic diameters than control (average decrease of 14-41%, p $<$ 0.005). There was less neointimal hyperplasia in arteries receiving DMT stents, with the cross sectional wall areas 20-25% less, on average, than arteries receiving UT stents (p $<$ 0.01). There were no significant differences in the six month arteriographic diameters or histologic diameters of arteries receiving DMT stents compared to UT stents. All arteries receiving HT stents exhibited a foreign body inflammatory reaction, with animal to animal variability in the quantitative results. These arteries, on average, had about 2X larger cross sectional wall areas (p $<$ 0.001), 32-41% smaller six month arteriographic diameters (p $<$ 0.01) and 20% smaller histologic diameters (p ${\simeq}$ 0.005) than arteries receiving UT or DMT stents. The DMT stents should be studied further to clarify their potential for limiting neointimal hyperplasia and helping reduce human restenosis. Stents coated with only CAN should be investigated to help determine the cause of the inflammatory reaction. Stents treated with a combination of dexamethasone and heparin should also be investigated for locally delivering dexamethasone, locally delivering heparin without causing inflammation and possible synergistic benefit.
Degree
Ph.D.
Advisors
Tacker, Purdue University.
Subject Area
Biophysics|Anatomy & physiology|Animals|Veterinary services
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