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Lidocaine Administration Controls MicroRNAs Alterations Observed After Lung Ischemia–Reperfusion Injury

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Rancan, Lisa PhD*; Simón, Carlos PhD†; Marchal-Duval, Emmeline MSc*; Casanova, Javier PhD‡; Paredes, Sergio Damian PhD§; Calvo, Alberto MD*; García, Cruz PhD*; Rincón, David MD†; Turrero, Agustín PhD‖; Garutti, Ignacio PhD‡; Vara, Elena PhD*. Lidocaine Administration Controls MicroRNAs Alterations Observed After Lung Ischemia–Reperfusion Injury. Anesthesia & Analgesia 123(6):p 1437-1447, December 2016. | DOI: 10.1213/ANE.0000000000001633

Abstract

BACKGROUND: Ischemia–reperfusion injury (IRI) is associated with morbidity and mortality. MicroRNAs (miRNAs) have emerged as regulators of IRI, and they are involved in the pathogenesis of organ rejection. Lidocaine has proven anti-inflammatory activity in several tissues but its modulation of miRNAs has not been investigated. This work aims to investigate the involvement of miRNAs in lung IRI in a lung auto-transplantation model and to investigate the effect of lidocaine. METHODS: Three groups (sham, control, and Lidocaine), each comprising 6 pigs, underwent a lung autotransplantation. All groups received the same anesthesia. In addition, animals of lidocaine group received a continuous intravenous administration of lidocaine (1.5 mg/kg/h) during surgery. Lung biopsies were taken before pulmonary artery clamp, before reperfusion, 30 minutes postreperfusion (Rp-30), and 60 minutes postreperfusion (Rp-60). Samples were analyzed for different miRNAs (miR-122, miR-145, miR-146a, miR-182, miR-107, miR-192, miR-16, miR-21, miR-126, miR-127, miR142-5p, miR152, miR155, miR-223, and let7) via the use of reverse-transcription quantitative polymerase chain reaction. Results were normalized with miR-103. RESULTS: The expression of miR-127 and miR-16 did not increase after IRI. Let-7d, miR-21, miR-107, miR-126, miR-145, miR-146a, miR-182, and miR-192 significantly increased at the Rp-60 (control versus sham P < .001). miR-142-5p, miR-152, miR-155, and miR 223 significantly increased at the Rp-30 (control versus sham P < .001) and at the Rp-60 (control versus. sham P < .001). The administration of lidocaine was able to attenuate these alterations in a significant way (control versus Lidocaine P < .001). CONCLUSIONS: Lung IRI caused dysregulation miRNA. The administration of lidocaine reduced significantly miRNAs alterations.

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