Effects of fp15, a peroxynitrite decomposition catalyst on cardiac and pulmonary function after cardiopulmonary bypass

Tamás Radovitsa, Carsten J. Beller, John T. Groves, Béla Merkely, Matthias Karck, Csaba Szabó, Gábor Szabó

    Research output: Contribution to journalArticle

    9 Scopus citations

    Abstract

    OBJECTIVE: Peroxynitrite, a toxic nitrogen species, has been implicated in the development of ischemia/reperfusion injury. The aim of the present study was to investigate the effects of the potent peroxynitrite decomposition catalyst, FP15, on myocardial, endothelial, and pulmonary function in an experimental model of cardioplegic arrest and extracorporal circulation. METHODS: Twelve anesthetized dogs underwent hypothermic cardiopulmonary bypass. After 60 min of hypothermic cardiac arrest, reperfusion was started and either saline vehicle (control, n = 6) or FP15 (n = 6) was administered. Left-ventricular preload-recruitable stroke work (PRSW) was measured by a combined pressure-volume conductance catheter at baseline and after 60 min of reperfusion. Left anterior descending (LAD) coronary (CBF) and pulmonary blood flow (PBF), endothelium-dependent vasodilatation to acetylcholine (ACh), and alveolo-arterial O2 gradient were determined. RESULTS: The administration of FP15 led to a significantly better recovery of PRSW (given as percent of baseline: 93 ± 9 vs 62 ± 6%, p < 0.05). CBF was also significantly higher in the FP15 group (44 ± 6 vs 25 ± 4 ml min-1, p < 0.05). Injection of ACh resulted in a significantly higher increase in CBF (70 ± 6 vs 35 ± 5%, p < 0.05) in the FP15-treated animals. The alveolo-arterial O2 gradient was significantly lower after FP15 administration (83 ± 7 vs 49 ± 6 mmHg, p < 0.05). Catalytic peroxynitrite decomposition did not affect baseline cardiovascular and pulmonary functions. CONCLUSIONS: Application of FP15 improves myocardial, endothelial, and pulmonary function after cardiopulmonary bypass with hypothermic cardiac arrest. The observed protective effects imply that catalytic peroxynitrite decomposition could be a novel therapeutic option in the treatment of ischemia/reperfusion injury.

    Original languageEnglish (US)
    Pages (from-to)391-396
    Number of pages6
    JournalEuropean Journal of Cardio-thoracic Surgery
    Volume41
    Issue number2
    DOIs
    StatePublished - 2012

    Keywords

    • Cardiopulmonary bypass
    • Endothelial function
    • FP15
    • Ischemia/reperfusion injury
    • Peroxynitrite

    ASJC Scopus subject areas

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

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