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Szabó, Gábor; Bährle, Susanne; Stumpf, Nicole; Sonnenberg, Karin; Szabó, Éva; Pacher, Pál; Csont, Tamás; Schulz, Richard; Dengler, Thomas J.; Liaudet, Lucas; Jagtap, Prakash G.; Southan, Garry J.; Vahl, Christian F.; Hagl, Siegfried; Szabó, Csaba

Poly(ADP-Ribose) Polymerase Inhibition Reduces Reperfusion Injury After Heart Transplantation

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  • Media type: E-Article
  • Title: Poly(ADP-Ribose) Polymerase Inhibition Reduces Reperfusion Injury After Heart Transplantation
  • Contributor: Szabó, Gábor; Bährle, Susanne; Stumpf, Nicole; Sonnenberg, Karin; Szabó, Éva; Pacher, Pál; Csont, Tamás; Schulz, Richard; Dengler, Thomas J.; Liaudet, Lucas; Jagtap, Prakash G.; Southan, Garry J.; Vahl, Christian F.; Hagl, Siegfried; Szabó, Csaba
  • imprint: Ovid Technologies (Wolters Kluwer Health), 2002
  • Published in: Circulation Research
  • Language: English
  • DOI: 10.1161/hh0102.102657
  • ISSN: 0009-7330; 1524-4571
  • Keywords: Cardiology and Cardiovascular Medicine ; Physiology
  • Origination:
  • Footnote:
  • Description: <jats:p> The aim of the present study was to investigate the effects of the novel poly(ADP-ribose) polymerase (PARP) inhibitor PJ34 ( <jats:italic>N</jats:italic> -(6-oxo-5,6-dihydro-phenanthridin-2-yl)- <jats:italic>N</jats:italic> , <jats:italic>N</jats:italic> -dimethylacetamide) on myocardial and endothelial function after hypothermic ischemia and reperfusion in a heterotopic rat heart transplantation model. After a 1-hour ischemic preservation, reperfusion was started either after application of placebo or PJ34 (3 mg/kg). The assessment of left ventricular pressure–volume relations, total coronary blood flow, endothelial function, myocardial high energy phosphates, and histological analysis were performed at 1 and 24 hours of reperfusion. After 1 hour, myocardial contractility and relaxation, coronary blood flow, and endothelial function were significantly improved and myocardial high energy phosphate content was preserved in the PJ34-treated animals. Improved transplant function was also seen with treatment with another, structurally different PARP inhibitor, 5-aminoisoquinoline. The PARP inhibitors did not affect baseline cardiac function. Immunohistological staining confirmed that PJ34 prevented the activation of PARP in the transplanted hearts. The activation of P-selectin and ICAM-1 was significantly elevated in the vehicle-treated heart transplantation group. Thus, pharmacological PARP inhibition reduces reperfusion injury after heart transplantation due to prevention of energy depletion and downregulation of adhesion molecules and exerts a beneficial effect against reperfusion-induced graft coronary endothelial dysfunction. </jats:p>
  • Access State: Open Access