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Ann Thorac Surg. 2002 Feb;73(2):575-81.

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

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  • 1Division of Cardiothoracic Surgery, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts 02215, USA.

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.

PMID:
11845877
[PubMed - indexed for MEDLINE]
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