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

Background: 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 +/- 5.9 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 alpha), interleukin-1 beta (IL-1 beta), interleukin-6 (IL-6), interferon gamma (IFN gamma), 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 < 0.05), and diabetes insipidus occurred. Lung-protective ventilation strategy was applied: 9 h after brain death induction, PaO2 was 192 +/- 12 mmHg at positive end-expiratory pressure (PEEP) 8.0 +/- 1.8 cmH(2)O and FiO(2) of 40%; wet-to-dry ratio (W/D) was 5.8 +/- 0.5, and extravascular lung water (EVLW) was 359 +/- 80 mL. Procured lungs were cold-stored for 471 +/- 24 min (Ischemia) at the end of which W/D was 6.1 +/- 0.9. Left lungs were transplanted and reperfused (warm ischemia 98 +/- 14 min). Six hours after controlled reperfusion, PaO2 was 192 +/- 23 mmHg (PEEP 8.7 +/- 1.5 cmH(2)O, FiO(2) 40%), W/D was 5.6 +/- 0.4, and EVLW was 366 +/- 117 mL. Levels of IL-8 rose at the end of donor management (BD, P < 0.05); CCL2-MCP-1, IL-8, HMGB-1, and SELE were significantly altered after reperfusion (Graft, P < 0.05). 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.