Poly(ADP-Ribose) polymerase inhibition reduces reperfusion injury after heart transplantation

Détails

ID Serval
serval:BIB_B7B9C02D833E
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Institution
Titre
Poly(ADP-Ribose) polymerase inhibition reduces reperfusion injury after heart transplantation
Périodique
Circulation Research
Auteur⸱e⸱s
Szabo  G., Bahrle  S., Stumpf  N., Sonnenberg  K., Szabo  E. E., Pacher  P., Csont  T., Schulz  R., Dengler  T. J., Liaudet  L., Jagtap  P. G., Southan  G. J., Vahl  C. F., Hagl  S., Szabo  C.
ISSN
1524-4571 (Electronic)
Statut éditorial
Publié
Date de publication
01/2002
Volume
90
Numéro
1
Pages
100-6
Notes
Journal Article
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, P.H.S. --- Old month value: Jan 11
Résumé
The aim of the present study was to investigate the effects of the novel poly(ADP-ribose) polymerase (PARP) inhibitor PJ34 (N-(6-oxo-5,6-dihydro-phenanthridin-2-yl)-N,N-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.
Mots-clé
Adenosine Diphosphate/metabolism Adenosine Monophosphate/metabolism Adenosine Triphosphate/metabolism Animals Coronary Circulation Enzyme Inhibitors/*pharmacology Heart/drug effects/physiopathology *Heart Transplantation Immunohistochemistry Intercellular Adhesion Molecule-1/analysis Male Myocardial Reperfusion Injury/*prevention & control Myocardium/chemistry/metabolism/pathology P-Selectin/analysis Phenanthrenes/*pharmacology Phosphocreatine/metabolism Poly(ADP-ribose) Polymerases/*antagonists & inhibitors/metabolism Rats Rats, Inbred Lew Time Factors
Pubmed
Web of science
Création de la notice
24/01/2008 17:01
Dernière modification de la notice
20/08/2019 15:25
Données d'usage