American Journal of Transplantation 2013; 13: 3290 Wiley Periodicals Inc.
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Copyright 2013 The American Society of Transplantation and the American Society of Transplant Surgeons doi: 10.1111/ajt.12495
Letter to the Editor
Normothermic Acellular Ex Vivo Liver Perfusion (NEVLP) Reduces Liver and Bile Duct in DCD Liver Grafts To the Editor: We welcome the comments from Martins (1) and op den Dries et al (2) and the opportunity to further discuss our results. It is important to develop a large animal model that closely resembles ischemic type biliary stricture (ITBS) in donation after cardiac death (DCD) grafts. The studies by Brunner et al (3) and Hansen et al (4) investigated common bile duct biopsies in humans after cold storage and reperfusion. In both studies, the biopsies were taken from the most distal part of the common bile duct, which is usually not used for the anastomosis. Common bile duct biopsies are susceptible to changes that are independent from ITBS in the setting of DCD organ retrieval. Distal common bile duct biopsies might include tissue that has been devascularized during organ retrieval, has been mechanically manipulated during portal dissection or bile duct catheterization. In addition, ITBS more often affects intrahepatic bile ducts than the extrahepatic biliary system and common bile duct biopsies might not be representative for ITBS. In our study, only intrahepatic bile ducts were used for histologic evaluation, which we believe better reflects the ITBS. In our study, bile flow was not a marker of bile function. Bilirubin concentration in the bile better reflected bile duct injury. It is possible that injured biliary mucosa secretes serum-like fluid, which falsely increases the bile volume. In addition, during ex vivo reperfusion, bile flow might be changed in all groups because of the lack of hormonal or neurogen stimulation, and nonphysiologic levels of bile precursors. Oxygen extraction during ex vivo perfusion was calculated using the oxygen content of the perfusate at the inflow and at the outflow, multiplied by the flow (reverse Fick method; VO2 ¼ Q[CaO2 CvO2]). We used Kelman’s equation (5) to calculate hemoglobin saturation of the blood perfusate at the corresponding PO2. Since pigs of comparable size were
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used in all groups, we did not present the data as per gram liver weight. M. U. Boehnert1, J. C. Yeung2, J. M. Knaak1, N. Selzner 3 and M. Selzner1, 1 Multi Organ Transplant Program, Department of Surgery, Toronto General Hospital, University of Toronto, Toronto, Canada 2 Multi Organ Transplant Program, Department of Medicine, Toronto General Hospital, University of Toronto, Toronto, Canada 3 Toronto Lung Transplant Program, University of Toronto, Toronto, Canada Corresponding author: Markus Selzner [email protected]
Disclosure The authors of this manuscript have no conflicts of interest to disclose as described by the American Journal of Transplantation.
References 1. Martins PNA. Normothermic machine preservation as an approach to decrease biliary complications of DCD liver grafts. Am J Transplant 2013; 13: 3287–3288. 2. op den Dries S, Karimian N, Weeder PD, Porte RJ. Normothermic acellular machine perfusion and bile duct injury in pig livers retrieved after cardiac death. Am J Transplant 2013; 13: 3289. 3. Brunner SM, Junger H, Ruemmele P, et al. Bile duct damage after cold storage of deceased donor livers predicts biliary complications after liver transplantation. J Hepatol 2013; 58: 1133– 1139. 4. Hansen T, Hollemann D, Pitton MB, et al. Histological examination and evaluation of donor bile ducts received during orthotopic liver transplantation—A morphological clue to ischemic-type biliary lesion? Virchows Archiv 2012; 461: 41–48. 5. Kelman GR. Digital computer subroutine for the conversion of oxygen tension into saturation. J Appl Physiol 1966; 21: 1375– 1376.
C
Copyright 2013 The American Society of Transplantation and the American Society of Transplant Surgeons doi: 10.1111/ajt.12495
Letter to the Editor
Normothermic Acellular Ex Vivo Liver Perfusion (NEVLP) Reduces Liver and Bile Duct in DCD Liver Grafts To the Editor: We welcome the comments from Martins (1) and op den Dries et al (2) and the opportunity to further discuss our results. It is important to develop a large animal model that closely resembles ischemic type biliary stricture (ITBS) in donation after cardiac death (DCD) grafts. The studies by Brunner et al (3) and Hansen et al (4) investigated common bile duct biopsies in humans after cold storage and reperfusion. In both studies, the biopsies were taken from the most distal part of the common bile duct, which is usually not used for the anastomosis. Common bile duct biopsies are susceptible to changes that are independent from ITBS in the setting of DCD organ retrieval. Distal common bile duct biopsies might include tissue that has been devascularized during organ retrieval, has been mechanically manipulated during portal dissection or bile duct catheterization. In addition, ITBS more often affects intrahepatic bile ducts than the extrahepatic biliary system and common bile duct biopsies might not be representative for ITBS. In our study, only intrahepatic bile ducts were used for histologic evaluation, which we believe better reflects the ITBS. In our study, bile flow was not a marker of bile function. Bilirubin concentration in the bile better reflected bile duct injury. It is possible that injured biliary mucosa secretes serum-like fluid, which falsely increases the bile volume. In addition, during ex vivo reperfusion, bile flow might be changed in all groups because of the lack of hormonal or neurogen stimulation, and nonphysiologic levels of bile precursors. Oxygen extraction during ex vivo perfusion was calculated using the oxygen content of the perfusate at the inflow and at the outflow, multiplied by the flow (reverse Fick method; VO2 ¼ Q[CaO2 CvO2]). We used Kelman’s equation (5) to calculate hemoglobin saturation of the blood perfusate at the corresponding PO2. Since pigs of comparable size were
3290
used in all groups, we did not present the data as per gram liver weight. M. U. Boehnert1, J. C. Yeung2, J. M. Knaak1, N. Selzner 3 and M. Selzner1, 1 Multi Organ Transplant Program, Department of Surgery, Toronto General Hospital, University of Toronto, Toronto, Canada 2 Multi Organ Transplant Program, Department of Medicine, Toronto General Hospital, University of Toronto, Toronto, Canada 3 Toronto Lung Transplant Program, University of Toronto, Toronto, Canada Corresponding author: Markus Selzner [email protected]
Disclosure The authors of this manuscript have no conflicts of interest to disclose as described by the American Journal of Transplantation.
References 1. Martins PNA. Normothermic machine preservation as an approach to decrease biliary complications of DCD liver grafts. Am J Transplant 2013; 13: 3287–3288. 2. op den Dries S, Karimian N, Weeder PD, Porte RJ. Normothermic acellular machine perfusion and bile duct injury in pig livers retrieved after cardiac death. Am J Transplant 2013; 13: 3289. 3. Brunner SM, Junger H, Ruemmele P, et al. Bile duct damage after cold storage of deceased donor livers predicts biliary complications after liver transplantation. J Hepatol 2013; 58: 1133– 1139. 4. Hansen T, Hollemann D, Pitton MB, et al. Histological examination and evaluation of donor bile ducts received during orthotopic liver transplantation—A morphological clue to ischemic-type biliary lesion? Virchows Archiv 2012; 461: 41–48. 5. Kelman GR. Digital computer subroutine for the conversion of oxygen tension into saturation. J Appl Physiol 1966; 21: 1375– 1376.
