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
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
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