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

Franco Valenza, Silvia Coppola, Sara Froio, Giulia Maria Ruggeri, Jacopo Fumagalli, Alessandro Maria Villa, Lorenzo Rosso, Paolo Mendogni, Grazia Conte, Caterina Lonati, Andrea Carlin, Patrizia Leonardi, Stefano Gatti, Nino Stocchetti, Luciano Gattinoni

Research output: Contribution to journalArticlepeer-review

Abstract

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 (TNFα), interleukin-1 beta (IL-1β), interleukin-6 (IL-6), interferon gamma (IFNγ), 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 cmH2O and FiO2 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 cmH2O, FiO2 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.

Original languageEnglish
Article number12
JournalIntensive Care Medicine Experimental
Volume2
Issue number1
DOIs
Publication statusPublished - Dec 1 2014

Keywords

  • Brain death
  • Lung transplantation
  • Organ preservation/methods
  • Reperfusion injury
  • Tissue and organ procurement
  • Ventilator-induced lung injury

ASJC Scopus subject areas

  • Critical Care and Intensive Care Medicine

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