title: Development of a preclinical model of donation after circulatory determination of death for translational application.
abstract: BACKGROUND
  Extracorporeal membranous oxygenation is proposed for abdominal organ procurement from donation after circulatory determination of death (DCD). In France, the national Agency of Biomedicine supervises the procurement of kidneys from DCD, specifying the durations of tolerated warm and cold ischemia. However, no study has determined the optimal conditions of this technique. The aim of this work was to develop a preclinical model of DCD using abdominal normothermic oxygenated recirculation (ANOR). In short, our objectives are to characterize the mechanisms involved during ANOR and its impact on abdominal organs.
  
  
  METHODS
  We used Large White pigs weighing between 45 and 55 kg. After 30 minutes of potassium-induced cardiac arrest, the descending thoracic aorta was clamped and ANOR set up between the inferior vena cava and the abdominal aorta for 4 hours. Hemodynamic, respiratory and biochemical parameters were collected. Blood gasometry and biochemistry analysis were performed during the ANOR procedure.
  
  
  RESULTS
  Six ANOR procedures were performed. The surgical procedure is described and intraoperative parameters and biological data are presented. Pump flow rates were between 2.5 and 3 l/min. Hemodynamic, respiratory, and biochemical objectives were achieved under reproducible conditions. Interestingly, animals remained hemodynamically stable following the targeted protocol. Arterial pH was controlled, and natremia and renal function remained stable 4 hours after the procedure was started. Decreased hemoglobin and serum proteins levels, concomitant with increased lactate dehydrogenase activity, were observed as a consequence of the surgery. The serum potassium level was increased, owing to the extracorporeal circulation circuit.
  
  
  CONCLUSIONS
  Our ANOR model is the closest to clinical conditions reported in the literature and will allow the study of the systemic and abdominal organ impact of this technique. The translational relevance of the pig will permit the determination of new biomarkers and protocols to improve DCD donor management.
authors.affiliation: INSERM U1082, CHU de Poitiers, rue de la Milétrie, B.P. 577, F-86021 Cedex Poitiers, France ; CHU de Poitiers, Service de Chirurgie cardio-thoracique, Poitiers F-86000, France.
authors.forename: Géraldine
authors.initials: G
authors.lastname: Allain
authors.affiliation: INSERM U1082, CHU de Poitiers, rue de la Milétrie, B.P. 577, F-86021 Cedex Poitiers, France ; CHU de Poitiers, Service de Réanimation chirurgicale, Poitiers F-86000, France.
authors.forename: Thomas
authors.initials: T
authors.lastname: Kerforne
authors.affiliation: INSERM U1082, CHU de Poitiers, rue de la Milétrie, B.P. 577, F-86021 Cedex Poitiers, France ; CHU de Montpellier, Service d'Urologie et de transplantation rénale, Montpellier F-34295, France.
authors.forename: Rodolphe
authors.initials: R
authors.lastname: Thuret
authors.affiliation: INSERM U1082, CHU de Poitiers, rue de la Milétrie, B.P. 577, F-86021 Cedex Poitiers, France ; CHU de Poitiers, Service d'Urologie, Poitiers F-86000, France.
authors.forename: Pierre-Olivier
authors.initials: PO
authors.lastname: Delpech
authors.affiliation: INSERM U1082, CHU de Poitiers, rue de la Milétrie, B.P. 577, F-86021 Cedex Poitiers, France ; CHU de Poitiers, Service d'Urologie, Poitiers F-86000, France.
authors.forename: Thibaut
authors.initials: T
authors.lastname: Saint-Yves
authors.affiliation: INSERM U1082, CHU de Poitiers, rue de la Milétrie, B.P. 577, F-86021 Cedex Poitiers, France ; CHU de Poitiers, Service de Réanimation chirurgicale, Poitiers F-86000, France ; CHU de Montpellier, Service d'Urologie et de transplantation rénale, Montpellier F-34295, France.
authors.forename: Michel
authors.initials: M
authors.lastname: Pinsard
authors.affiliation: INSERM U1082, CHU de Poitiers, rue de la Milétrie, B.P. 577, F-86021 Cedex Poitiers, France ; Université de Poitiers, Faculté de Médecine et de Pharmacie, Poitiers F-86000, France ; CHU Poitiers, Service de Biochimie, Poitiers F-86000, France ; IBISA Platform 'Experimental Surgery and Transplantation', INRA, Domaine expérimental du Magneraud, Surgères F-17700, France.
authors.forename: Thierry
authors.initials: T
authors.lastname: Hauet
authors.affiliation: INSERM U1082, CHU de Poitiers, rue de la Milétrie, B.P. 577, F-86021 Cedex Poitiers, France ; CHU Poitiers, Service de Biochimie, Poitiers F-86000, France.
authors.forename: Sébastien
authors.initials: S
authors.lastname: Giraud
authors.affiliation: INSERM U1082, CHU de Poitiers, rue de la Milétrie, B.P. 577, F-86021 Cedex Poitiers, France ; CHU de Poitiers, Service de Chirurgie cardio-thoracique, Poitiers F-86000, France ; Université de Poitiers, Faculté de Médecine et de Pharmacie, Poitiers F-86000, France ; IBISA Platform 'Experimental Surgery and Transplantation', INRA, Domaine expérimental du Magneraud, Surgères F-17700, France.
authors.forename: Christophe
authors.initials: C
authors.lastname: Jayle
authors.affiliation: INSERM U1082, CHU de Poitiers, rue de la Milétrie, B.P. 577, F-86021 Cedex Poitiers, France ; GH Pitié-Salpêtrière, AP-HP, Service d'Urologie et de transplantation rénale, Paris F-75013, France ; UPMC Université Paris VI, Paris F-75013, France.
authors.forename: Benoît
authors.initials: B
authors.lastname: Barrou
keywords: Animal model; Donation after circulatory determination of death; Extracorporeal membrane oxygenation; Ischemia/reperfusion injury; Organ donor management