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

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

Research output: Contribution to journalArticle

58 Citations (Scopus)

Abstract

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 γ-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.

Original languageEnglish
Pages (from-to)2779-2784
Number of pages6
JournalCirculation
Volume105
Issue number23
DOIs
StatePublished - Jun 11 2002

Fingerprint

Nitric Oxide Donors
Angioplasty
Nitric Oxide
Swine
Pericardium
Coronary Vessels
Molecular Weight
Tunica Intima
Platelet Aggregation Inhibitors
Bovine Serum Albumin
Vasodilator Agents
Vascular Smooth Muscle
Smooth Muscle Myocytes
Blood Vessels
Half-Life
Albumins
Hemodynamics
Cell Proliferation
Injections

Keywords

  • Angioplasty
  • Coronary disease
  • Nitric oxide
  • Pericardium
  • Restenosis

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine

Cite this

Augmentation of intrapericardial nitric oxide level by a prolonged-release nitric oxide donor reduces luminal narrowing after porcine coronary angioplasty. / Baek, Sang Hong; Hrabie, Joseph A.; Keefer, Larry K.; Hou, Dongming; Fineberg, Naomi; Rhoades, Rodney; March, Keith L.

In: Circulation, Vol. 105, No. 23, 11.06.2002, p. 2779-2784.

Research output: Contribution to journalArticle

Baek, Sang Hong ; Hrabie, Joseph A. ; Keefer, Larry K. ; Hou, Dongming ; Fineberg, Naomi ; Rhoades, Rodney ; March, Keith L. / Augmentation of intrapericardial nitric oxide level by a prolonged-release nitric oxide donor reduces luminal narrowing after porcine coronary angioplasty. In: Circulation. 2002 ; Vol. 105, No. 23. pp. 2779-2784.
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abstract = "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 γ-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.",
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AU - Baek, Sang Hong

AU - Hrabie, Joseph A.

AU - Keefer, Larry K.

AU - Hou, Dongming

AU - Fineberg, Naomi

AU - Rhoades, Rodney

AU - March, Keith L.

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N2 - 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 γ-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.

AB - 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 γ-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.

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