HSP90 Inhibitor Improves Lung Protection in Porcine Model of Donation After Circulatory Arrest.

Autor:	Nasir BS; Centre de Recherche du Centre Hospitalier de l'Université de Montréal (CRCHUM), Montréal, Quebec, Canada; Department of Surgery, Faculty of Medicine, Université de Montréal, Montréal, Quebec, Canada., Landry C; Centre de Recherche du Centre Hospitalier de l'Université de Montréal (CRCHUM), Montréal, Quebec, Canada., Menaouar A; Centre de Recherche du Centre Hospitalier de l'Université de Montréal (CRCHUM), Montréal, Quebec, Canada., Germain JF; Centre de Recherche du Centre Hospitalier de l'Université de Montréal (CRCHUM), Montréal, Quebec, Canada., Der Sarkissian S; Centre de Recherche du Centre Hospitalier de l'Université de Montréal (CRCHUM), Montréal, Quebec, Canada; Department of Surgery, Faculty of Medicine, Université de Montréal, Montréal, Quebec, Canada., Stevens LM; Centre de Recherche du Centre Hospitalier de l'Université de Montréal (CRCHUM), Montréal, Quebec, Canada; Department of Surgery, Faculty of Medicine, Université de Montréal, Montréal, Quebec, Canada., Aceros H; Centre de Recherche du Centre Hospitalier de l'Université de Montréal (CRCHUM), Montréal, Quebec, Canada., Cailhier JF; Centre de Recherche du Centre Hospitalier de l'Université de Montréal (CRCHUM), Montréal, Quebec, Canada; Department of Medicine, Faculty of Medicine, Université de Montréal, Montréal, Quebec, Canada., Leduc C; Centre de Recherche du Centre Hospitalier de l'Université de Montréal (CRCHUM), Montréal, Quebec, Canada; Department of Pathology and Cellular Biology, Faculty of Medicine, Université de Montréal, Montréal, Quebec, Canada., Liberman M; Centre de Recherche du Centre Hospitalier de l'Université de Montréal (CRCHUM), Montréal, Quebec, Canada; Department of Surgery, Faculty of Medicine, Université de Montréal, Montréal, Quebec, Canada., Noiseux N; Centre de Recherche du Centre Hospitalier de l'Université de Montréal (CRCHUM), Montréal, Quebec, Canada; Department of Surgery, Faculty of Medicine, Université de Montréal, Montréal, Quebec, Canada. Electronic address: noiseuxn@videotron.ca., Ferraro P; Centre de Recherche du Centre Hospitalier de l'Université de Montréal (CRCHUM), Montréal, Quebec, Canada; Department of Surgery, Faculty of Medicine, Université de Montréal, Montréal, Quebec, Canada.
Jazyk:	angličtina
Zdroj:	The Annals of thoracic surgery [Ann Thorac Surg] 2020 Dec; Vol. 110 (6), pp. 1861-1868. Date of Electronic Publication: 2020 Jul 09.
DOI:	10.1016/j.athoracsur.2020.05.079
Abstrakt:	Background: Ischemia-reperfusion associated with prolonged warm ischemia during donation after circulatory death (DCD) induces acute lung injury. The objective of this study was to combine ex vivo lung perfusion (EVLP) and a heat shock protein-90 inhibitor (HSP90i) to recondition DCD organs and prevent primary graft dysfunction. Methods: Pigs (55 to 65 kg) were anesthetized, ventilated, and hemodynamically monitored. Cardiac arrest was induced with potassium chloride, and animals were left nonventilated for 2 hours. Lungs were procured and perfused in an EVLP platform for 4 hours by using a cellular perfusate. In the study group, the perfusate contained HSP90i and its transport vehicle (n = 4). In the control group, the perfusate contained only the transport vehicle (n = 4). Gas exchange, airway pressures, and compliance were measured. Pulmonary edema was assessed by bronchoscopy and weight measurement. Lung biopsy samples were obtained for histologic analyses and protein expression measurements. Results: The use of HSP90i reduced lung weight gain to 8.4 ± 3.4% vs 26.6 ± 6.2% in the control group (P < .05). There was reduced edema formation. The ratio of the partial pressure of arterial oxygen to the fraction of inspired oxygen at the end of EVLP was 423 ± 65 in the study group vs 339 ± 25 mm Hg in the control group, but this difference was not statistically significant. Lactate metabolism, pulmonary vascular resistance, and pulmonary arterial pressure improved during EVLP with the use of the HSP90i. Conclusions: The use of HSP90i with EVLP improves the lung reconditioning process. Further research is required to confirm whether these findings translate to benefit once transplanted and observed in vivo. Successful pharmacologic inhibitors may expand the donor pool in the context of DCD donors. (Copyright © 2020 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
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