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

Journal Article (Journal Article)

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.

Full Text

Duke Authors

Cited Authors

  • Zhang, Y; Davies, LR; Martin, SM; Coddington, WJ; Miller, FJ; Buettner, GR; Kerber, RE

Published Date

  • December 2003

Published In

Volume / Issue

  • 59 / 3

Start / End Page

  • 345 - 352

PubMed ID

  • 14659604

Pubmed Central ID

  • PMC4343200

International Standard Serial Number (ISSN)

  • 0300-9572

Digital Object Identifier (DOI)

  • 10.1016/s0300-9572(03)00240-5


  • eng

Conference Location

  • Ireland