Catalytic peroxynitrite decomposition improves reperfusion injury after heart transplantation

Gábor Szabó, Sivakkanan Loganathan, Béla Merkely, John T. Groves, Matthias Karck, Csaba Szabo, Tamás Radovits

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11 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)1443-1449
Number of pages7
JournalJournal of Thoracic and Cardiovascular Surgery
Volume143
Issue number6
DOIs
StatePublished - Jun 2012

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ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Surgery
  • Pulmonary and Respiratory Medicine

Cite this

Szabó, G., Loganathan, S., Merkely, B., Groves, J. T., Karck, M., Szabo, C., & Radovits, T. (2012). Catalytic peroxynitrite decomposition improves reperfusion injury after heart transplantation. Journal of Thoracic and Cardiovascular Surgery, 143(6), 1443-1449. https://doi.org/10.1016/j.jtcvs.2012.02.008