Document Detail

Augmentation of intrapericardial nitric oxide level by a prolonged-release nitric oxide donor reduces luminal narrowing after porcine coronary angioplasty.
MedLine Citation:
PMID:  12057994     Owner:  NLM     Status:  MEDLINE    
BACKGROUND: Nitric oxide (NO) is a potent vasodilator and antiplatelet agent that suppresses vascular smooth muscle cell proliferation. Hypothesizing that generating NO in the pericardial space would reduce luminal narrowing after coronary angioplasty without affecting systemic hemodynamics, we have determined the effect of a novel NO donor on vascular healing after balloon overstretch. METHODS AND RESULTS: Diazeniumdiolated bovine serum albumin (D-BSA; molecular weight 74 kDa, half-life for NO release 20 days) was radioiodinated and found by intravital gamma-imaging to have a longer residence time in pig pericardium than a low-molecular-weight (0.5 kDa) analogue (22 versus 4.6 hours, respectively). Intrapericardial injection of D-BSA immediately before 30% overstretch of normal left anterior descending and left circumflex coronary arteries dose dependently reduced the intimal/medial area ratio by up to 50% relative to controls treated with underivatized albumin when measured 2 weeks after intervention. Positive remodeling was also noted, which increased luminal area relative to control. CONCLUSIONS: Perivascular exposure of coronary arteries to NO via intrapericardial D-BSA administration reduced flow-restricting lesion development after angioplasty in pigs without causing significant systemic effects. The data suggest that intrapericardial delivery of NO donors for which NO release rates and pericardial residence times are matched and optimized might be a beneficial adjunct to coronary angioplasty.
Sang Hong Baek; Joseph A Hrabie; Larry K Keefer; Dongming Hou; Naomi Fineberg; Rodney Rhoades; Keith L March
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Circulation     Volume:  105     ISSN:  1524-4539     ISO Abbreviation:  Circulation     Publication Date:  2002 Jun 
Date Detail:
Created Date:  2002-06-11     Completed Date:  2002-06-25     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  0147763     Medline TA:  Circulation     Country:  United States    
Other Details:
Languages:  eng     Pagination:  2779-84     Citation Subset:  AIM; IM    
Department of Medicine, Division of Cardiology, Indiana University Medical Center, Indianapolis, Ind, USA.
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MeSH Terms
Angioplasty, Transluminal, Percutaneous Coronary / adverse effects*
Coronary Restenosis / etiology,  metabolism,  pathology,  prevention & control*
Delayed-Action Preparations
Dose-Response Relationship, Drug
Nitric Oxide / biosynthesis
Nitric Oxide Donors / administration & dosage,  pharmacokinetics,  pharmacology*
Pericardium / metabolism*
Polyamines / administration & dosage,  pharmacology
Serum Albumin, Radio-Iodinated / administration & dosage,  pharmacokinetics,  pharmacology*
Grant Support
Reg. No./Substance:
0/(131)I-labeled diazeniumdiolated albumin; 0/Delayed-Action Preparations; 0/Nitric Oxide Donors; 0/Polyamines; 0/Serum Albumin, Radio-Iodinated; 10102-43-9/Nitric Oxide; 111-40-0/diethylenetriamine

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