Document Detail

Vascular response to zotarolimus-coated balloons in injured superficial femoral arteries of the familial hypercholesterolemic Swine.
MedLine Citation:
PMID:  21953371     Owner:  NLM     Status:  MEDLINE    
BACKGROUND: Drug-coated balloons are rapidly emerging as a therapeutic alternative for the interventional treatment of peripheral vascular disease. The purpose of this study was to test the hypothesis that an angioplasty balloon coated with the mTOR inhibitor zotarolimus (ZCB) would inhibit neointimal hyperplasia in a novel injury-based superficial femoral artery model in the familial hypercholesterolemic swine.
METHODS AND RESULTS: A total of 44 familial hypercholesterolemic swine were included (12 designated to study tissue pharmacokinetics and 32 to study safety and efficacy). Fogarty balloon denudation was performed in all superficial femoral artery segments, followed by balloon angioplasty. In the pharmacokinetic study, a total of 24 ZCBs (300 μg/cm(2)) were used. Zotarolimus was detected in arterial tissue at 5 minutes (162 ng/mg of tissue), 24 hours (5.9 ng/mg of tissue), and 28 days (0.007 ng/mg of tissue) after ZCB inflation. In the safety and efficacy study, superficial femoral artery segments were randomized to either high-dose (600 μg/cm(2), n=16), low-dose (300 μg/cm(2), n=16), or paired uncoated balloons (high-dose ZCB control, n=16; low-dose ZCB control, n=16). At 28 days, the percentage of angiographic stenosis was similar among all tested groups. Histological analysis demonstrated a reduction in neointimal formation in both ZCB groups compared with controls (high-dose ZCB 44% reduction, P=0.007; low-dose ZCB 22% reduction, P=0.08). There was no evidence of delayed arterial healing or vascular toxicity in any of the ZCB groups.
CONCLUSIONS: The single delivery of zotarolimus via coated balloon is feasible, and therapeutic levels are maintained up to 28 days. The ZCB technology appears to be effective in the reduction of neointimal proliferation in the superficial femoral artery of the familial hypercholesterolemic swine.
Juan F Granada; Krzysztof Milewski; Hugh Zhao; John J Stankus; Armando Tellez; Michael S Aboodi; Greg L Kaluza; Christian G Krueger; Renu Virmani; Lewis B Schwartz; Alexander Nikanorov
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2011-09-27
Journal Detail:
Title:  Circulation. Cardiovascular interventions     Volume:  4     ISSN:  1941-7632     ISO Abbreviation:  Circ Cardiovasc Interv     Publication Date:  2011 Oct 
Date Detail:
Created Date:  2011-10-19     Completed Date:  2012-02-08     Revised Date:  2014-07-30    
Medline Journal Info:
Nlm Unique ID:  101499602     Medline TA:  Circ Cardiovasc Interv     Country:  United States    
Other Details:
Languages:  eng     Pagination:  447-55     Citation Subset:  IM    
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MeSH Terms
Angioplasty, Balloon*
Clinical Protocols
Femoral Artery / drug effects*,  pathology,  radiography,  surgery
Hyperlipoproteinemia Type II / pathology,  physiopathology,  therapy*
Infusion Pumps, Implantable / utilization
Models, Animal
Neointima / etiology*,  prevention & control
Postoperative Complications*
Sirolimus / administration & dosage,  adverse effects,  analogs & derivatives*,  pharmacology
TOR Serine-Threonine Kinases / antagonists & inhibitors
Reg. No./Substance:
0/zotarolimus; EC protein, human; EC Serine-Threonine Kinases; W36ZG6FT64/Sirolimus

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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