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 journalArticle

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

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Organ Preservation
Brain Death
Lung Transplantation
Tissue Donors
Lung
Interleukin-8
Extravascular Lung Water
Reperfusion
E-Selectin
Positive-Pressure Respiration
Therapeutics
Swine
Transplantation
Ligands
Transplants
Cold Ischemia
CXC Chemokines
Warm Ischemia
CC Chemokines
Diabetes Insipidus

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

Cite this

A standardized model of brain death, donor treatment, and lung transplantation for studies on organ preservation and reconditioning. / Valenza, Franco; Coppola, Silvia; Froio, Sara; Ruggeri, Giulia Maria; Fumagalli, Jacopo; Villa, Alessandro Maria; Rosso, Lorenzo; Mendogni, Paolo; Conte, Grazia; Lonati, Caterina; Carlin, Andrea; Leonardi, Patrizia; Gatti, Stefano; Stocchetti, Nino; Gattinoni, Luciano.

In: Intensive Care Medicine Experimental, Vol. 2, No. 1, 12, 01.12.2014.

Research output: Contribution to journalArticle

Valenza, Franco ; Coppola, Silvia ; Froio, Sara ; Ruggeri, Giulia Maria ; Fumagalli, Jacopo ; Villa, Alessandro Maria ; Rosso, Lorenzo ; Mendogni, Paolo ; Conte, Grazia ; Lonati, Caterina ; Carlin, Andrea ; Leonardi, Patrizia ; Gatti, Stefano ; Stocchetti, Nino ; Gattinoni, Luciano. / A standardized model of brain death, donor treatment, and lung transplantation for studies on organ preservation and reconditioning. In: Intensive Care Medicine Experimental. 2014 ; Vol. 2, No. 1.
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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.",
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author = "Franco Valenza and Silvia Coppola and Sara Froio and Ruggeri, {Giulia Maria} and Jacopo Fumagalli and Villa, {Alessandro Maria} and Lorenzo Rosso and Paolo Mendogni and Grazia Conte and Caterina Lonati and Andrea Carlin and Patrizia Leonardi and Stefano Gatti and Nino Stocchetti and Luciano Gattinoni",
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T1 - A standardized model of brain death, donor treatment, and lung transplantation for studies on organ preservation and reconditioning

AU - Valenza, Franco

AU - Coppola, Silvia

AU - Froio, Sara

AU - Ruggeri, Giulia Maria

AU - Fumagalli, Jacopo

AU - Villa, Alessandro Maria

AU - Rosso, Lorenzo

AU - Mendogni, Paolo

AU - Conte, Grazia

AU - Lonati, Caterina

AU - Carlin, Andrea

AU - Leonardi, Patrizia

AU - Gatti, Stefano

AU - Stocchetti, Nino

AU - Gattinoni, Luciano

PY - 2014/12/1

Y1 - 2014/12/1

N2 - 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.

AB - 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.

KW - Brain death

KW - Lung transplantation

KW - Organ preservation/methods

KW - Reperfusion injury

KW - Tissue and organ procurement

KW - Ventilator-induced lung injury

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