Augmentation of intrapericardial nitric oxide level by a prolonged-release nitric oxide donor reduces luminal narrowing after porcine coronary angioplasty.
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.


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.
Baek
Sang Hong
SH
Department of Medicine, Division of Cardiology, Indiana University Medical Center, Indianapolis, Ind, USA.
Hrabie
Joseph A
JA
Keefer
Larry K
LK
Hou
Dongming
D
Fineberg
Naomi
N
Rhoades
Rodney
R
March
Keith L
KL
D015906:Angioplasty, Balloon, Coronary / Q000009:adverse effects*; D000818:Animals; D023903:Coronary Restenosis / Q000209:etiology / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D003692:Delayed-Action Preparations; D004305:Dose-Response Relationship, Drug; D009569:Nitric Oxide / Q000096:biosynthesis; D020030:Nitric Oxide Donors / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology*; D010496:Pericardium / Q000378:metabolism*; D011073:Polyamines / Q000008:administration & dosage / Q000494:pharmacology; D012711:Serum Albumin, Radio-Iodinated / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology*; D013552:Swine
C118196:(131)I-labeled diazeniumdiolated albumin; D003692:Delayed-Action Preparations; D020030:Nitric Oxide Donors; D011073:Polyamines; D012711:Serum Albumin, Radio-Iodinated; C005391:diethylenetriamine; D009569:Nitric Oxide