{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,3]],"date-time":"2026-07-03T17:14:06Z","timestamp":1783098846737,"version":"3.54.6"},"reference-count":52,"publisher":"Oxford University Press (OUP)","issue":"5","license":[{"start":{"date-parts":[[2022,9,1]],"date-time":"2022-09-01T00:00:00Z","timestamp":1661990400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"name":"Belgian Foundation for Cardiac Surgery"},{"name":"Fondation Mont-Godinne"},{"name":"Fondation Mont-Godinne"},{"name":"Belgian Foundation for Cardiac Surgery"},{"name":"Fondation Mont-Godinne"},{"name":"Fondation Mont-Godinne"}],"content-domain":{"domain":["www.atsjournals.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2022,9,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Rationale<\/jats:title>\n                    <jats:p>Donor brain death\u2013induced lung injury may compromise graft function after transplantation. Establishing strategies to attenuate lung damage remains a challenge because the underlying mechanisms remain uncertain.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>The effects of tacrolimus pretreatment were evaluated in an experimental model of brain death\u2013induced lung injury.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Brain death was induced by slow intracranial infusion of blood in anesthetized pigs after randomization to tacrolimus (orally administered at 0.25 mg\u2009\u22c5\u2009kg\u22121 twice daily the day before the experiment and intravenously at 0.05 mg\u2009\u22c5\u2009kg\u22121 1 h before the experiment; n\u2009=\u20098) or placebo (n\u2009=\u20099) 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 score (LIS).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Measurements and Main Results<\/jats:title>\n                    <jats:p>Tacrolimus pretreatment prevented increases in pulmonary arterial pressure, pulmonary vascular resistance, and pulmonary capillary pressure and decreases in systemic arterial pressure and thermodilution cardiac output associated with brain death. After brain death, the ratio of PaO2 to Fi \u00a0O2 decreased, which was prevented by tacrolimus. Tacrolimus pretreatment prevented increases in the ratio of IL-6 to IL-10, VCAM1 (vascular cell adhesion molecule 1), circulating concentrations of IL-1\u03b2, and glycocalyx-derived molecules. Tacrolimus partially decreased apoptosis (Bax [Bcl2-associated X apoptosis regulator]\u2013to\u2013Bcl2 [B-cell lymphoma-2] ratio [P\u2009=\u20090.07] and number of apoptotic cells in the lungs [P\u2009&amp;lt;\u20090.05]) but failed to improve LIS.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Immunomodulation through tacrolimus pretreatment prevented pulmonary capillary hypertension as well as the activation of inflammatory and apoptotic processes in the lungs after brain death; however, LIS did not improve.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1164\/rccm.202201-0033oc","type":"journal-article","created":{"date-parts":[[2022,5,13]],"date-time":"2022-05-13T10:54:13Z","timestamp":1652439253000},"page":"584-595","update-policy":"https:\/\/doi.org\/10.1164\/crossmarkpolicies","source":"Crossref","is-referenced-by-count":9,"title":["Tacrolimus Prevents Mechanical and Humoral Alterations in Brain Death\u2013induced Lung Injury in Pigs"],"prefix":"10.1093","volume":"206","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8506-8239","authenticated-orcid":false,"given":"Asmae","family":"Belhaj","sequence":"first","affiliation":[{"name":"Service de Chirurgie Cardiovasculaire, Thoracique et Transplantation Pulmonaire, CHU UCL Namur and"},{"name":"Service de Biologie Clinique, CHU UCL Namur, Universit\u00e9 Catholique de Louvain, Yvoir, Belgique; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laurence","family":"Dewachter","sequence":"additional","affiliation":[{"name":"Service de Biologie Clinique, CHU UCL Namur, Universit\u00e9 Catholique de Louvain, Yvoir, Belgique; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emeline","family":"Hupkens","sequence":"additional","affiliation":[{"name":"Service de Biologie Clinique, CHU UCL Namur, Universit\u00e9 Catholique de Louvain, Yvoir, Belgique; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Myriam","family":"Remmelink","sequence":"additional","affiliation":[{"name":"Laboratoire de Physiologie et Pharmacologie, Facult\u00e9 de M\u00e9decine and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laurence","family":"Galanti","sequence":"additional","affiliation":[{"name":"Service d\u2019Anatomopathologie, H\u00f4pital Erasme, Universit\u00e9 Libre de Bruxelles, Bruxelles, Belgique"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sandrine","family":"Rorive","sequence":"additional","affiliation":[{"name":"Laboratoire de Physiologie et Pharmacologie, Facult\u00e9 de M\u00e9decine and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christian","family":"Melot","sequence":"additional","affiliation":[{"name":"Service de Biologie Clinique, CHU UCL Namur, Universit\u00e9 Catholique de Louvain, Yvoir, Belgique; 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