Myocardial protection by PJ34, a novel potent poly (ADP-Ribose) synthetase inhibitor

Renato Faro, Yoshiya Toyoda, James D. McCully, Prakash Jagtap, Eva Szabo, Laszlo Virag, Cesario Bianchi, Sidney Levitsky, Csaba Szabo, Frank W. Sellke

    Research output: Contribution to journalArticle

    59 Scopus citations

    Abstract

    Background. The activation of poly (ADP-ribose) synthetase plays an important role in the pathogenesis leading to myocardial ischemia-reperfusion injury. The aim of this study was to determine if a novel potent inhibitor of poly (ADP-ribose) synthetase, PJ34, provides myocardial protection. Methods. Pigs were subjected to 60 minutes of regional ischemia followed by 180 minutes of reperfusion. Ten mg/kg of PJ34 (PJ34; n = 6) was administrated intravenously (treated group) from 15 to 5 minutes before reperfusion followed by 3 mg/kg/hour of PJ34 from 5 minutes before reperfusion to the end of 180 minutes reperfusion. Control pigs (n = 7) received vehicle only. Arterial and left ventricular pressure and coronary flow were monitored. Results. The PJ34 showed significant reduction on infarct size (37.5% ± 4.5% and 50.5% ± 4.8% of the area at risk) for PJ34 and control pigs groups, respectively, (p < 0.05). Significant reduction in postsystolic shortening, as well as improvement on segment shortening, and positive first derivative of pressure over time (+dP/dt) maximum were also observed in PJ34 versus control pigs (p < 0.05). Conclusions. Our results suggest that PJ34 provides cardioprotection by decreasing myocardial infarct size and enhancing postischemic regional and global functional recovery.

    Original languageEnglish (US)
    Pages (from-to)575-581
    Number of pages7
    JournalAnnals of Thoracic Surgery
    Volume73
    Issue number2
    DOIs
    StatePublished - 2002

    ASJC Scopus subject areas

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

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    Faro, R., Toyoda, Y., McCully, J. D., Jagtap, P., Szabo, E., Virag, L., Bianchi, C., Levitsky, S., Szabo, C., & Sellke, F. W. (2002). Myocardial protection by PJ34, a novel potent poly (ADP-Ribose) synthetase inhibitor. Annals of Thoracic Surgery, 73(2), 575-581. https://doi.org/10.1016/S0003-4975(01)03329-X