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Ann Thorac Surg 2002;73:575-581
© 2002 The Society of Thoracic Surgeons

Original article: cardiovascular

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

Renato Faro, PhDa, Yoshiya Toyoda, MDa, James D. McCully, PhDa, Prakash Jagtap, PhDb, Eva Szabo, MDb, Laszlo Virag, MD, PhDb, Cesario Bianchi, MD, PhDa, Sidney Levitsky, MDa, Csaba Szabo, MD, PhDb, Frank W. Sellke, MD*a

a Division of Cardiothoracic Surgery, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, USA
b Inotek Corporation, Beverly, Massachusetts, USA

Accepted for publication September 22, 2001.

* Address reprint requests to Dr Sellke, Division of Cardiothoracic Surgery, Beth Israel Deaconess Medical Center, Harvard Medical School, 110 Francis St, No. LMOB Suite 2A, Boston, MA 02215, USA
e-mail: fsellke{at}caregroup.harvard.edu

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.


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Ann. Thorac. Surg. 2002 73: 581. [Extract] [Full Text] [PDF]



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