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The nitric oxide donor S-nitroso-N-acetylpenicillamine (SNAP) increases free radical generation and degrades left ventricular function after myocardial ischemia-reperfusion.

Publication ,  Journal Article
Zhang, Y; Davies, LR; Martin, SM; Coddington, WJ; Miller, FJ; Buettner, GR; Kerber, RE
Published in: Resuscitation
December 2003

BACKGROUND: During reperfusion of ischemic myocardium nitric oxide (NO) reacts with superoxide radicals to form cardiotoxic peroxynitrite, which causes lipid peroxidation. Our hypothesis was that infusion of a NO donor S-nitroso-N-acetylpenicillamine (SNAP) during ischemia-reperfusion would exacerbate the oxidative damage to the myocardium by increased formation of nitrogen radicals. METHODS AND RESULTS: In 19 open-chest dogs, left anterior descending (LAD) coronary occlusion (15 min)-reperfusion (15 min) sequences were created. Using electron paramagnetic resonance (EPR), we monitored the coronary sinus concentration of ascorbate free radical (Ascz*-), a measure of free radical generation (total oxidative flux). Seven control dogs (Group 1) received intravenous saline infusion during occlusion-reperfusion, while 12 dogs received SNAP infusion (Group 2: 2.5 microg/min per kg SNAP, and Group 3: 5 microg/min per kg SNAP). Left ventricular fractional area shortening was determined by echocardiography. Dogs in Group 3 receiving a high dose of SNAP (5 microg/min per kg) demonstrated a higher Ascz*- concentration increase than the control group. Percent fractional area shortening in Group 1 declined from 77+/-4.0 (baseline) to 54+/-9.0% during ischemia (P<0.05), and then fully recovered to 74+/-3.7% with reperfusion. In the SNAP-treated dogs, the percent fractional area shortening during reperfusion was significantly lower than baseline in Group 2 (55+/-3.9 vs. baseline 74+/-4.4%, P<0.05) and in Group 3 (49+/-5.0 vs. baseline 71+/-4.5%, P<0.01). In five additional dogs, nitrotyrosine immunohistochemistry showed heavy staining of the ischemic-reperfused myocardium. CONCLUSIONS: The NO donor SNAP increased free radical concentration and exacerbated myocardial oxidative damage after ischemia-reperfusion.

Duke Scholars

Published In

Resuscitation

DOI

ISSN

0300-9572

Publication Date

December 2003

Volume

59

Issue

3

Start / End Page

345 / 352

Location

Ireland

Related Subject Headings

  • Ventricular Remodeling
  • Ventricular Function, Left
  • Sensitivity and Specificity
  • S-Nitroso-N-Acetylpenicillamine
  • Risk Factors
  • Reference Values
  • Probability
  • Nitric Oxide Donors
  • Myocardial Reperfusion
  • Myocardial Ischemia
 

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Zhang, Y., Davies, L. R., Martin, S. M., Coddington, W. J., Miller, F. J., Buettner, G. R., & Kerber, R. E. (2003). The nitric oxide donor S-nitroso-N-acetylpenicillamine (SNAP) increases free radical generation and degrades left ventricular function after myocardial ischemia-reperfusion. Resuscitation, 59(3), 345–352. https://doi.org/10.1016/s0300-9572(03)00240-5
Zhang, Yi, Loyd R. Davies, Sean M. Martin, William J. Coddington, Francis J. Miller, Garry R. Buettner, and Richard E. Kerber. “The nitric oxide donor S-nitroso-N-acetylpenicillamine (SNAP) increases free radical generation and degrades left ventricular function after myocardial ischemia-reperfusion.Resuscitation 59, no. 3 (December 2003): 345–52. https://doi.org/10.1016/s0300-9572(03)00240-5.
Zhang Y, Davies LR, Martin SM, Coddington WJ, Miller FJ, Buettner GR, et al. The nitric oxide donor S-nitroso-N-acetylpenicillamine (SNAP) increases free radical generation and degrades left ventricular function after myocardial ischemia-reperfusion. Resuscitation. 2003 Dec;59(3):345–52.
Zhang, Yi, et al. “The nitric oxide donor S-nitroso-N-acetylpenicillamine (SNAP) increases free radical generation and degrades left ventricular function after myocardial ischemia-reperfusion.Resuscitation, vol. 59, no. 3, Dec. 2003, pp. 345–52. Pubmed, doi:10.1016/s0300-9572(03)00240-5.
Zhang Y, Davies LR, Martin SM, Coddington WJ, Miller FJ, Buettner GR, Kerber RE. The nitric oxide donor S-nitroso-N-acetylpenicillamine (SNAP) increases free radical generation and degrades left ventricular function after myocardial ischemia-reperfusion. Resuscitation. 2003 Dec;59(3):345–352.
Journal cover image

Published In

Resuscitation

DOI

ISSN

0300-9572

Publication Date

December 2003

Volume

59

Issue

3

Start / End Page

345 / 352

Location

Ireland

Related Subject Headings

  • Ventricular Remodeling
  • Ventricular Function, Left
  • Sensitivity and Specificity
  • S-Nitroso-N-Acetylpenicillamine
  • Risk Factors
  • Reference Values
  • Probability
  • Nitric Oxide Donors
  • Myocardial Reperfusion
  • Myocardial Ischemia