Brief bubble, and subsequent intermittent surface oxygenation is a simple and effective alternative for membrane oxygenation to maintain aerobic metabolism during hypothermic machine perfusion in kidneys
Tom Darius1,2, Martial Vergauwen2, Louis Maistriaux2,3, Robin Evrard2,4, Matteo Mueller5, Andrea Schlegel5, Philipp Dutkowski5, Pierre Gianello2, Michel Mourad1,2.
1Department of Surgery, Surgery and Abdominal Transplant Unit, University Clinics Saint-Luc, Université catholique de Louvain, Brussels, Belgium; 2Institut de recherche expérimentale et clinique (IREC), Pôle de Chirurgie Exp et Transplantation, Université catholique de Louvain, Brussels, Belgium; 3Institut de recherche expérimentale et clinique (IREC), Pôle de Morphologie , Université catholique de Louvain, Brussels, Belgium; 4Institut de recherche expérimentale et clinique (IREC), Neuro Musclo-Skeletal lab (NMSK), Université catholique de Louvain, Brussels, Belgium; 5Department of Surgery and Transplantation, Swiss HPB Center , University Hospital Zurich, Zurich, Switzerland
Introduction: Brief bubble, and subsequent surface oxygenation is an alternative oxygenation technique for membrane-oxygenated kidneys during HMP. The aim of this study was to evaluate the metabolic effect of interruption of surface oxygenation (mimicking organ transport) during HMP as compared to continuous surface and membrane oxygenation in a pig kidney ex vivo preservation model.
Methods: A kidney of a ±40 kg pig was exposed to 30 minutes of warm ischemia and preserved according to one of the following study groups: 1) 22h HMP+intermittent surface oxygenation (30 min at start, 4h interruption followed by 17h30 surface oxygenation) during 22h HMP (n=12), 2) 22h HMP+continuous membrane oxygenation (n=6), and 3) 22h HMP+continuous surface oxygenation (n=7). Brief O2 uploading of the perfusion fluid before kidney perfusion was obtained either by a hollow fiber membrane oxygenator (study group 2) or by direct bubble oxygenation (study group 1 and 3).
Results: O2 uploading of the perfusion fluid by minimum 15 minutes of direct bubble oxygenation was as efficient as membrane oxygenation to achieve pO2 levels above 450-500 mmHg (at 4°C) before connecting the kidney to the perfusion device (Figure 1).
Metabolic analysis (i.e. lactate, succinate, glutamate, ATP, ADP, AMP, NADH, NAD+ and Flavin Mononucleotide (FMN)) on end-preservation cortical and medullar tissue biopsies demonstrated a similar mitochondrial protection/preservation in all study groups (Figure 2). FMN measurement by fluorescence demonstrated no difference between all study groups during the first 270 minutes of preservation, however perfusate FMN levels were significantly higher at the end of the preservation period in the membrane-oxygenated groups as compared by both surface-oxygenated HMP groups.
Conclusion: Brief bubble and intermittent surface oxygenation of the perfusate during standard HMP at procurement site might be an effective, user-friendly, and less expensive preservation strategy to protect mitochondria when compared with membrane-oxygenated kidneys eliminating the need for a membrane oxygenator and oxygen source during transport.
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