A standardized model of brain death, donor treatment, and lung transplantation for studies on organ preservation and reconditioning

We set a model of brain death, donor management, and lung transplantation for studies on lung preservation and reconditioning before transplantation.Methods Ten pigs (39.7\u2009\ub1\u20095.9 Kg) were investigated. Five animals underwent brain death and were treated as organ donors; the lungs were then procured and cold stored (Ischemia). Five recipients underwent left lung transplantation and post-reperfusion follow-up (Graft). Cardiorespiratory and metabolic parameters were collected. Lung gene expression of cytokines (tumor necrosis factor alpha (TNF\u3b1), interleukin-1 beta (IL-1\u3b2), interleukin-6 (IL-6), interferon gamma (IFN\u3b3), high mobility group box-1 (HMGB-1)), chemokines (chemokine CC motif ligand-2 (CCL2-MCP-1), chemokine CXC motif ligand-10 (CXCL-10), interleukin-8 (IL-8)), and endothelial activation markers (endothelin-1 (EDN-1), intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), selectin-E (SELE)) was assessed by real-time polymerase chain reaction (PCR). Results Tachycardia and hypertension occurred during brain death induction; cardiac output rose, systemic vascular resistance dropped (P\u2009<\u20090.05), and diabetes insipidus occurred. Lung-protective ventilation strategy was applied: 9 h after brain death induction, PaO2 was 192\u2009\ub1\u200912 mmHg at positive end-expiratory pressure (PEEP) 8.0\u2009\ub1\u20091.8 cmH2O and FiO2 of 40%; wet-to-dry ratio (W/D) was 5.8\u2009\ub1\u20090.5, and extravascular lung water (EVLW) was 359\u2009\ub1\u200980 mL. Procured lungs were cold-stored for 471\u2009\ub1\u200924 min (Ischemia) at the end of which W/D was 6.1\u2009\ub1\u20090.9. Left lungs were transplanted and reperfused (warm ischemia 98\u2009\ub1\u200914 min). Six hours after controlled reperfusion, PaO2 was 192\u2009\ub1\u200923 mmHg (PEEP 8.7\u2009\ub1\u20091.5 cmH2O, FiO2 40%), W/D was 5.6\u2009\ub1\u20090.4, and EVLW was 366\u2009\ub1\u2009117 mL. Levels of IL-8 rose at the end of donor management (BD, P\u2009<\u20090.05); CCL2-MCP-1, IL-8, HMGB-1, and SELE were significantly altered after reperfusion (Graft, P\u2009<\u20090.05). Conclusions We have set a standardized, reproducible pig model resembling the entire process of organ donation that may be used as a platform to test in vivo and ex vivo strategies of donor lung optimization before transplantation