Catalytic peroxynitrite decomposition improves reperfusion injury after heart transplantation

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-reperfus...

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Main Authors: Szabó, Gábor (Author) , Loganathan, Sivakkanan (Author) , Karck, Matthias (Author) , Radovits, Tamás (Author)
Format: Article (Journal)
Language:English
Published: 2012
In: The journal of thoracic and cardiovascular surgery
Year: 2012, Volume: 143, Issue: 6, Pages: 1443-1449
ISSN:1097-685X
DOI:10.1016/j.jtcvs.2012.02.008
Online Access:Verlag, Volltext: http://dx.doi.org/10.1016/j.jtcvs.2012.02.008
Verlag, Volltext: http://www.sciencedirect.com/science/article/pii/S0022522312001882
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Author Notes:Gábor Szabó, Sivakkanan Loganathan, Béla Merkely, John T. Groves, Matthias Karck, Csaba Szabó and Tamás Radovits
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Summary: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.
Item Description:Available online 6 March 2012
Gesehen am 22.06.2018
Physical Description:Online Resource
ISSN:1097-685X
DOI:10.1016/j.jtcvs.2012.02.008