Tuesday September 13, 2022 - 16:25 to 17:25
Effects of tacrolimus on mechanical and humoral determinants of brain death-induced lung injury
Asmae Belhaj1,2, Laurence Dewachter2, Benoit Rondelet1,2.
11Department of Cardio-Vascular, Thoracic Surgery and Lung Transplantation, CHU UCL Namur, Université Catholique de Louvain, Yvoir, Belgium; 2Laboratory of Physiology and Pharmacology, Faculty of Medicine, Université Libre de Bruxelles, Brussels, Belgium
Background: Donor brain death-induced lung injury may compromise graft function after transplantation. The mechanisms of this particular form of neurogenic lung edema and its possible prevention by immunomodulator Tacrolimus remain incompletely understood.
Methods and Results: Brain death was induced, by slow intracranial infusion of blood, in anesthetized pigs after randomisation to placebo (n=9) or to Tacrolimus (n=8). One, three, five and seven hours after brain death, pulmonary artery pressure (Pap), wedged Pap (Papo), right atrial pressure (Pra), effective pulmonary capillary pressure (Pcap), systemic artery pressure (Psa) and thermodilution cardiac output (Q) were measured. Blood and lung tissue were sampled and lung injury scored on pathological examination.
Brain death was associated with marked increases in Pap, PVR and Pcap, decreases in Psa and Q with growing need for Noradrenaline while Ppao and Pra remained in a physiological range. Arterial O2 pressure to fraction of inspired O2(PaO2/FiO2) decreased. Brain death was associated with increased lung injury score together with increased gene expressions of interleukin (IL)-6 and IL-1b, heme-oxygenase-1, signal transducer and activator of transcription-3. Lung tissue pro-inflammatory IL-6/IL-10 ratio was decreased and pro-apoptotic Bax/Bcl2 ratio was increased. Tacrolimus partially corrected pulmonary hypertension and lung tissue biological perturbations. PaO2/FiO2 was inversely correlated to PCP and lung injury score. Serum IL-6 and IL-1b were correlated to PCP.
Conclusion: Brain death induced lung injury is related to effective pulmonary capillary hypertension with normal PAWP and pro-inflammatory and pro-apoptotic biological changes all partially reversed by preventive Tacrolimus treatment.
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