Pharmacological Reconditioning of Marginal Donor Rat Lungs Using Inhibitors of Peroxynitrite and Poly (ADP-ribose) Polymerase During Ex Vivo Lung Perfusion. Issue 7 (July 2016)

• Record Type: Journal Article
• Authors: Wang, Xingyu; Wang, Yabo; Parapanov, Roumen; Abdelnour, Etienne; Gronchi, Fabrizio; Perentes, Jean Yannis; Piquilloud, Lise; Ris, Hans-Beat; Letovanec, Igor; Liaudet, Lucas; Krueger, Thorsten
• Is Part Of: Transplantation. Volume 100:Issue 7(2016)
• Publication Date: 2016-07
• Subjects: Transplantation of organs, tissues, etc -- Periodicals; Transplantation immunology -- Periodicals; 617.95
• DOI: 10.1097/TP.0000000000001183
• Languages: English
• ISSNs: 0041-1337

Abstract

Abstract : Background: 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). Methods: 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. Results: 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. Conclusions: 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. Abstract : Donor rat lungs after warm ischemia (WI) and reconditioning using ex-vivo lung perfusion with the ROS/RNS scavenger MnTBAP or the PARP inhibitor 3-AB show reduced oxidative stress, PARP activation and tissue injury as compared to WI reconditioned without these compounds. Oxygenation and pulmonary vascular resistance were stable with 3-AB but not MnTBAP treatment.