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

57 Citations (Scopus)

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
Externally publishedYes

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Poly Adenosine Diphosphate Ribose
Ligases
Reperfusion
Swine
Myocardial Reperfusion Injury
N-(oxo-5,6-dihydrophenanthridin-2-yl)-N,N-dimethylacetamide hydrochloride
Ventricular Pressure
Reperfusion Injury
Myocardial Ischemia
Ischemia
Myocardial Infarction
Pressure
Control Groups

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Surgery

Cite this

Faro, R., Toyoda, Y., McCully, J. D., Jagtap, P., Szabo, E., Virag, L., ... 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

Myocardial protection by PJ34, a novel potent poly (ADP-Ribose) synthetase inhibitor. / Faro, Renato; Toyoda, Yoshiya; McCully, James D.; Jagtap, Prakash; Szabo, Eva; Virag, Laszlo; Bianchi, Cesario; Levitsky, Sidney; Szabo, Csaba; Sellke, Frank W.

In: Annals of Thoracic Surgery, Vol. 73, No. 2, 2002, p. 575-581.

Research output: Contribution to journalArticle

Faro, R, Toyoda, Y, McCully, JD, Jagtap, P, Szabo, E, Virag, L, Bianchi, C, Levitsky, S, Szabo, C & Sellke, FW 2002, 'Myocardial protection by PJ34, a novel potent poly (ADP-Ribose) synthetase inhibitor', Annals of Thoracic Surgery, vol. 73, no. 2, pp. 575-581. https://doi.org/10.1016/S0003-4975(01)03329-X
Faro, Renato ; Toyoda, Yoshiya ; McCully, James D. ; Jagtap, Prakash ; Szabo, Eva ; Virag, Laszlo ; Bianchi, Cesario ; Levitsky, Sidney ; Szabo, Csaba ; Sellke, Frank W. / Myocardial protection by PJ34, a novel potent poly (ADP-Ribose) synthetase inhibitor. In: Annals of Thoracic Surgery. 2002 ; Vol. 73, No. 2. pp. 575-581.
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