Tacrolimus Prevents Mechanical and Humoral Alterations in Brain Death–induced Lung Injury in Pigs

Autor: Asmae Belhaj, Laurence Dewachter, Emeline Hupkens, Myriam Remmelink, Laurence Galanti, Sandrine Rorive, Christian Melot, Robert Naeije, Benoît Rondelet
Přispěvatelé: UCL - SSS/IREC/MONT - Pôle Mont Godinne, UCL - SSS/IRSS - Institut de recherche santé et société, UCL - (MGD) Service de chirurgie cardio-vasculaire et thoracique, UCL - (MGD) Laboratoire de biologie clinique
Rok vydání: 2022
Předmět:
Zdroj: American journal of respiratory and critical care medicine, Vol. 206, no. 5, p. 584-595 (2022)
ISSN: 1535-4970
1073-449X
Popis: Donor brain death-induced lung injury may compromise graft function after transplantation. Establishing strategies to attenuate lung damage remains a challenge because the underlying mechanisms remain uncertain. The effects of tacrolimus pretreatment were evaluated in an experimental model of brain death-induced lung injury. Brain death was induced by slow intracranial infusion of blood in anesthetized pigs after randomization to tacrolimus (orally administered at 0.25 mg. kg-1 BID the day before the experiment and intravenously at 0.05 mg. kg-1 one hour before the experiment; n=8) or placebo (n=9) pretreatment. Hemodynamic measurements were performed 1, 3, 5 and 7 hours after brain death. After euthanasia of the animals, lung tissue was sampled for pathobiological and histological analysis, including lung injury scoring (LIS). Tacrolimus pretreatment prevented increases in pulmonary artery pressure, pulmonary vascular resistance and pulmonary capillary pressure and decreases in systemic artery pressure and thermodilution cardiac output associated with brain death. After brain death, the ratio of the partial arterial O2 pressure to the inspired O2 fraction (PaO2/FiO2) decreased, which was prevented by tacrolimus. Tacrolimus pretreatment prevented increases in the interleukin (IL)-6-to-IL-10 ratio, vascular cell adhesion molecule-1, circulating levels of IL-1β, IL-6-to-IL-10 ratio and glycocalyx-derived molecules. Tacrolimus partially decreased apoptosis [Bax-to-Bcl2 ratio (p=0.07) and the number of apoptotic cells in the lungs (p
Databáze: OpenAIRE
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