Pharmacological Reconditioning of Marginal Donor Rat Lungs Using Inhibitors of Peroxynitrite and Poly (ADP-ribose) Polymerase During Ex Vivo Lung Perfusion.

Détails

ID Serval
serval:BIB_7AFCEFB8854D
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
Pharmacological Reconditioning of Marginal Donor Rat Lungs Using Inhibitors of Peroxynitrite and Poly (ADP-ribose) Polymerase During Ex Vivo Lung Perfusion.
Périodique
Transplantation
Auteur(s)
Wang X., Wang Y., Parapanov R., Abdelnour E., Gronchi F., Perentes J.Y., Piquilloud L., Ris H.B., Letovanec I., Liaudet L., Krueger T.
ISSN
1534-6080 (Electronic)
ISSN-L
0041-1337
Statut éditorial
Publié
Date de publication
07/2016
Peer-reviewed
Oui
Volume
100
Numéro
7
Pages
1465-1473
Langue
anglais
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't
Publication Status: ppublish
Résumé
Donor lungs obtained after prolonged warm ischemia (WI) may be unsuitable for transplantation due to the risk of reperfusion injury, but could be reconditioned using ex-vivo lung perfusion (EVLP). Key processes of reperfusion injury include the formation of reactive oxygen species (ROS)/nitrogen species (RNS) and the activation of poly(adenosine diphosphate-ribose) polymerase (PARP). We explored whether rat lungs obtained after WI could be reconditioned during EVLP using the ROS/RNS scavenger Mn(III)-tetrakis (4-benzoic acid) porphyrin chloride (MnTBAP) or the PARP inhibitor 3-aminobenzamide (3-AB).
Rat lungs obtained after 3 hours cold ischemia (CI group, control), or 1 hour WI plus 2 hours CI (WI group) were placed in an EVLP circuit for normothermic perfusion for 3 hours. Lungs retrieved after WI were treated or not with 3-AB (1 mg/mL) or MnTBAP (0.3 mg/mL), added to the perfusate. Measurements included physiological variables (lung compliance, vascular resistance, oxygenation capacity), lung weight gain, levels of proteins, lactate dehydrogenase, protein carbonyl (marker of ROS), 3-nitrotyrosine (marker of RNS), poly(adenosine diphosphate-ribose) (PAR, marker of PARP activation) and IL-6, in the bronchoalveolar lavage or the lung tissue, and histology.
In comparison to the CI group, the lungs from the WI group displayed higher protein carbonyls, 3-nitrotyrosine, PAR, lactate dehydrogenase and proteins in bronchoalveolar lavage, lung weight gain, perivascular edema, as well as reduced static compliance, but similar oxygenation. All these alterations were markedly attenuated by 3-AB and MnTBAP.
After EVLP, lungs obtained after WI exhibit oxidative stress, PARP activation, and tissue injury, which are suppressed by pharmacological inhibitors of ROS/RNS and PARP.

Mots-clé
Animals, Benzamides/chemistry, Cold Ischemia, Extracorporeal Circulation, Interleukin-6/metabolism, Lung/drug effects, Lung/pathology, Lung/surgery, Male, Metalloporphyrins/chemistry, Perfusion/methods, Peroxynitrous Acid/antagonists & inhibitors, Peroxynitrous Acid/chemistry, Poly(ADP-ribose) Polymerase Inhibitors/chemistry, Poly(ADP-ribose) Polymerases/chemistry, Rats, Rats, Sprague-Dawley, Reactive Nitrogen Species/metabolism, Reactive Oxygen Species/metabolism, Transplantation Conditioning/methods
Pubmed
Web of science
Création de la notice
01/07/2016 11:20
Dernière modification de la notice
13/03/2018 11:58
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