Document Detail


The nitric oxide donor S-nitroso-N-acetylpenicillamine (SNAP) increases free radical generation and degrades left ventricular function after myocardial ischemia-reperfusion.
MedLine Citation:
PMID:  14659604     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
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:
Type:  Comparative Study; Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Resuscitation     Volume:  59     ISSN:  0300-9572     ISO Abbreviation:  Resuscitation     Publication Date:  2003 Dec 
Date Detail:
Created Date:  2003-12-08     Completed Date:  2004-04-15     Revised Date:  2013-03-05    
Medline Journal Info:
Nlm Unique ID:  0332173     Medline TA:  Resuscitation     Country:  Ireland    
Other Details:
Languages:  eng     Pagination:  345-52     Citation Subset:  IM    
Affiliation:
The Cardiovascular Center, Department of Internal Medicine, College of Medicine, University of Iowa Hospital, 200 Hawkins Drive, Iowa City, IA 52242, USA.
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MeSH Terms
Descriptor/Qualifier:
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:
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:
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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