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Open Access Research

Development of a preclinical model of donation after circulatory determination of death for translational application

Géraldine Allain12, Thomas Kerforne13, Rodolphe Thuret14, Pierre-Olivier Delpech15, Thibaut Saint-Yves15, Michel Pinsard134, Thierry Hauet1678*, Sébastien Giraud17, Christophe Jayle1268 and Benoît Barrou1109

Author Affiliations

1 INSERM U1082, CHU de Poitiers, rue de la Milétrie, B.P. 577, F-86021 Cedex Poitiers, France

2 CHU de Poitiers, Service de Chirurgie cardio-thoracique, Poitiers F-86000, France

3 CHU de Poitiers, Service de Réanimation chirurgicale, Poitiers F-86000, France

4 CHU de Montpellier, Service d’Urologie et de transplantation rénale, Montpellier F-34295, France

5 CHU de Poitiers, Service d’Urologie, Poitiers F-86000, France

6 Université de Poitiers, Faculté de Médecine et de Pharmacie, Poitiers F-86000, France

7 CHU Poitiers, Service de Biochimie, Poitiers F-86000, France

8 IBISA Platform ‘Experimental Surgery and Transplantation’, INRA, Domaine expérimental du Magneraud, Surgères F-17700, France

9 GH Pitié-Salpêtrière, AP-HP, Service d’Urologie et de transplantation rénale, Paris F-75013, France

10 UPMC Université Paris VI, Paris F-75013, France

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Transplantation Research 2014, 3:13  doi:10.1186/2047-1440-3-13

Published: 14 June 2014

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.

Keywords:
Animal model; Donation after circulatory determination of death; Extracorporeal membrane oxygenation; Ischemia/reperfusion injury; Organ donor management