Published Online
on May 20, 2002

A more recent version of this article appeared on June 11, 2002

This Article Full Text (PDF) All Versions of this Article: 105/23/2779    most recent 01.CIR.0000017432.19415.3Ev1 Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Baek, S. H. Articles by March, K. L. Search for Related Content PubMed Articles by Baek, S. H. Articles by March, K. L. Related Collections Cardiovascular Pharmacology Restenosis Catheter-based coronary and valvular interventions: other

Submitted on May 31, 2001
Revised on March 18, 2002
Accepted on March 19, 2002

Augmentation of Intrapericardial Nitric Oxide Level by a Prolonged-Release Nitric Oxide Donor Reduces Luminal Narrowing After Porcine Coronary Angioplasty

Sang Hong Baek MD, PhD, Joseph A. Hrabie PhD, Larry K. Keefer PhD, Dongming Hou MD, PhD, Naomi Fineberg PhD, Rodney Rhoades PhD, and Keith L. March MD, PhD^*

From the Department of Medicine, Division of Cardiology (S.H.B., D.H., N.F., K.L.M.) and Department of Physiology (R.R.), Indiana University Medical Center, Indianapolis, Ind; the Intramural Research Support Program, SAIC-Frederick (J.A.H.), and Laboratory of Comparative Carcinogenesis (L.K.K.), National Cancer Institute at Frederick, Frederick, Md; and the RL Roudebush VA Medical Center, Indianapolis, Ind (K.L.M.).

^* To whom correspondence should be addressed. E-mail: kmarch{at}iupui.edu.

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 -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.

Key words: angioplasty • restenosis • pericardium • nitric oxide • coronary disease

This article has been cited by other articles:

				J. Perree, T. G. van Leeuwen, R. Kerindongo, J. A. E. Spaan, and E. VanBavel Function and Structure of Pressurized and Perfused Porcine Carotid Arteries: Effects of in Vitro Balloon Angioplasty Am. J. Pathol., November 1, 2003; 163(5): 1743 - 1750. [Abstract] [Full Text] [PDF]

				K. Kumar, K. Nguyen, S. Waxman, B. D. Nearing, G. A. Wellenius, S. X. Zhao, and R. L. Verrier Potent antifibrillatory effects of intrapericardial nitroglycerin in the ischemic porcine heart J. Am. Coll. Cardiol., May 21, 2003; 41(10): 1831 - 1837. [Abstract] [Full Text] [PDF]

				M. Rubart and D. P. Zipes NO Hope for Patients With Atrial Fibrillation Circulation, November 26, 2002; 106(22): 2764 - 2766. [Full Text] [PDF]