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(Circulation. 2002;105:2779.)
© 2002 American Heart Association, Inc.

Basic Science Reports

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; 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.).

Correspondence to Keith March, MD, PhD, Indiana Center for Vascular Biology and Medicine, 1B441, 975 W Walnut St, Indianapolis, IN 46202. 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

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