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 journalArticlepeer-review

63 Scopus citations


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
Issue number2
StatePublished - 2002
Externally publishedYes

ASJC Scopus subject areas

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


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