Document Detail


Catalytic peroxynitrite decomposition improves reperfusion injury after heart transplantation.
MedLine Citation:
PMID:  22401641     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
OBJECTIVE: Peroxynitrite, a reactive nitrogen species, has been implicated in the development of ischemia-reperfusion injury. The present study investigated the effects of the potent peroxynitrite decomposition catalyst FP15 on myocardial and endothelial function after hypothermic ischemia-reperfusion in a heterotopic rat heart transplantation model.
METHODS: After a 1-hour ischemic preservation and implantation of donor hearts, reperfusion was started after application of vehicle (5% glucose solution) or FP15 (0.3 mg/kg). The assessment of left ventricular pressure-volume relations, total coronary blood flow, endothelial function, immunohistochemical markers of nitro-oxidative stress, and myocardial high-energy phosphates was performed at 1 and 24 hours of reperfusion.
RESULTS: After 1 hour of reperfusion, myocardial contractility (maximal slope of systolic pressure increment at 140 μL left ventricular volume: 5435 ± 508 mm Hg/s vs 2346 ± 263 mm Hg/s), coronary blood flow (3.98 ± 0.33 mL/min/g vs 2.74 ± 0.29 mL/min/g), and endothelial function were significantly improved, nitro-oxidative stress was reduced, and myocardial high-energy phosphate content was preserved in the FP15-treated animals compared with controls.
CONCLUSIONS: Pharmacologic peroxynitrite decomposition reduces reperfusion injury after heart transplantation as the result of reduction of nitro-oxidative stress and prevention of energy depletion and exerts a beneficial effect against reperfusion-induced graft cardiac and coronary endothelial dysfunction.
Authors:
Gábor Szabó; Sivakkanan Loganathan; Béla Merkely; John T Groves; Matthias Karck; Csaba Szabó; Tamás Radovits
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2012-03-07
Journal Detail:
Title:  The Journal of thoracic and cardiovascular surgery     Volume:  143     ISSN:  1097-685X     ISO Abbreviation:  J. Thorac. Cardiovasc. Surg.     Publication Date:  2012 Jun 
Date Detail:
Created Date:  2012-05-18     Completed Date:  2012-07-11     Revised Date:  2013-04-16    
Medline Journal Info:
Nlm Unique ID:  0376343     Medline TA:  J Thorac Cardiovasc Surg     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1443-9     Citation Subset:  AIM; IM    
Copyright Information:
Copyright © 2012 The American Association for Thoracic Surgery. Published by Mosby, Inc. All rights reserved.
Affiliation:
Department of Cardiac Surgery, University of Heidelberg, Heidelberg, Germany. gabor.szabo@urz.uni-heidelberg.de
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MeSH Terms
Descriptor/Qualifier:
Adenosine Diphosphate / metabolism
Adenosine Monophosphate / metabolism
Adenosine Triphosphate / metabolism
Animals
Biological Markers / metabolism
Coronary Circulation / drug effects
Disease Models, Animal
Endothelium, Vascular / drug effects*,  metabolism,  physiopathology
Energy Metabolism / drug effects
Heart Transplantation / adverse effects*
Immunohistochemistry
Male
Metalloporphyrins / pharmacology*
Myocardial Reperfusion Injury / etiology,  metabolism,  physiopathology,  prevention & control*
Myocardium / metabolism*
Oxidative Stress / drug effects
Peroxynitrous Acid / metabolism*
Poly Adenosine Diphosphate Ribose / metabolism
Rats
Rats, Inbred Lew
Time Factors
Tyrosine / analogs & derivatives,  metabolism
Vasodilation / drug effects
Ventricular Function, Left / drug effects
Ventricular Pressure / drug effects
Grant Support
ID/Acronym/Agency:
R37 GM036298/GM/NIGMS NIH HHS
Chemical
Reg. No./Substance:
0/Biological Markers; 0/FeCl tetrakis-2-(triethyleneglycolmonomethylether)pyridylporphyrin; 0/Metalloporphyrins; 14691-52-2/Peroxynitrous Acid; 26656-46-2/Poly Adenosine Diphosphate Ribose; 3604-79-3/3-nitrotyrosine; 55520-40-6/Tyrosine; 56-65-5/Adenosine Triphosphate; 58-64-0/Adenosine Diphosphate; 61-19-8/Adenosine Monophosphate
Comments/Corrections

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