| The nitric oxide donor S-nitroso-N-acetylpenicillamine (SNAP) increases free radical generation and degrades left ventricular function after myocardial ischemia-reperfusion. | |
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MedLine Citation:
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PMID: 14659604 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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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. |
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Authors:
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Yi Zhang; Loyd R Davies; Sean M Martin; William J Coddington; Francis J Miller; Garry R Buettner; Richard E Kerber |
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Publication Detail:
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Type: Comparative Study; Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S. |
Journal Detail:
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Title: Resuscitation Volume: 59 ISSN: 0300-9572 ISO Abbreviation: Resuscitation Publication Date: 2003 Dec |
Date Detail:
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Created Date: 2003-12-08 Completed Date: 2004-04-15 Revised Date: 2013-03-05 |
Medline Journal Info:
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Nlm Unique ID: 0332173 Medline TA: Resuscitation Country: Ireland |
Other Details:
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Languages: eng Pagination: 345-52 Citation Subset: IM |
Affiliation:
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The Cardiovascular Center, Department of Internal Medicine, College of Medicine, University of Iowa Hospital, 200 Hawkins Drive, Iowa City, IA 52242, USA. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals Disease Models, Animal Dogs Dose-Response Relationship, Drug Echocardiography Electron Spin Resonance Spectroscopy Female Free Radicals / metabolism* Immunohistochemistry Infusions, Intravenous Lipid Peroxidation / drug effects, physiology Male Myocardial Ischemia / drug therapy*, pathology* Myocardial Reperfusion / methods* Nitric Oxide Donors / adverse effects, pharmacology Probability Reference Values Risk Factors S-Nitroso-N-Acetylpenicillamine / adverse effects*, pharmacology* Sensitivity and Specificity Ventricular Function, Left Ventricular Remodeling |
| Grant Support | |
ID/Acronym/Agency:
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CA84462/CA/NCI NIH HHS; HL03669/HL/NHLBI NIH HHS; HL53284/HL/NHLBI NIH HHS; HL62984/HL/NHLBI NIH HHS; K08 HL003669/HL/NHLBI NIH HHS; K08 HL003669-03/HL/NHLBI NIH HHS; K08 HL003669-04/HL/NHLBI NIH HHS; K08 HL003669-05/HL/NHLBI NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Free Radicals; 0/Nitric Oxide Donors; 79032-48-7/S-Nitroso-N-Acetylpenicillamine |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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