Oxygen and Pancreas Preservation: Reply

Abstract

Is simple oxygen bubbling without the presence of perfluorodecalin (PFD) really enough? Accepting the amazing speculation of Mirbolooki and Lakey would mean to question not only our findings about the simple handling and efficacy of the one-layer method (OLM) but also all previous studies demonstrating the beneficial effect of human pancreas storage in oxygenated PFD (1, 2). Their skepticism is stimulated by the absence of significant data about PFD oxygen saturation, tissue oxygen tension, and oxygen consumption, which are essential to characterize positive and negative effects of PFD-based pancreas preservation. Considerations that omitting the University of Wisconsin (UW)-layer may accelerate oxygen release into the ambient atmosphere were actually disproved by measurement of oxygen tension in PFD precharged for OLM (Fig. 1). After 20 hours of storage, 8.0±0.1% of the initial oxygen content of fully oxygenated PFD was lost. This corresponds to previously published data determined in PFD precharged for the static two-layer method (TLM) (2).FIGURE 1.: Partial oxygen tension determined sequentially in 500 mL of PFD stored for 30 hours at 4°C in a closed 1000 mL-wide mouth jar. PFD precharged with 100% oxygen for 30 min at a rate of 2000 mL/min was stored alone (OLM, open circles, n=3) or covered with 300 mL of UW solution (TLM, filled squares, n=3). Data are means±SE calculated from three different measurements.Doubts about the efficiency of PFD-based pancreas oxygenation are supported by the remarkable observation made in pigs that only 15% of total pancreatic volume is oxygenated during TLM storage (3). This finding is in conflict with generally accepted data obtained from canine pancreases which indicate a close relationship between pancreas oxygenation, tissue oxygen pressure, ATP generation and graft function (4). This contradiction may be explained by species-dependent differences with regard to pancreas size and texture which is particularly relevant for unregularly formed and fibrous human pancreases often covered by significant amounts of fat. These conditions may aggrevate diffusion of adenosine from the UW-layer into the tissue as well as oxygen penetration into the pancreatic core. It suggests a significant advantage of OLM providing a contact area with oxygenated PFD which can be twice compared to TLM. In fact, compared to unstored organs a significant reduction of islet yield was found in TLM- but not in OLM-preserved pig pancreases. However, whether a pancreas is fixed at the interface between PFD and a UW-layer or not seems to be of minor importance considering the different qualities of numerous oxygen-dissolving substances which are represented by the common term perfluorocarbon (PFC) (5). For example, PFCs with lower gravity could generally reduce mechanical stress and simplify organ handling during shipment although our data do not confirm the assumption that the risk of physical tissue injury correlates with slight differences in buoyancy as present in OLM and TLM. Furthermore, if the inert and lipophobic characteristics of oxygen carriers could be substantially reduced, enhanced substance diffusion and oxygen release in deeper tissue layers may increase islet isolation outcome from oxygenated pancreases. The realization of comparative studies about the effect of PFC characteristics such as purity, density or percentage of cis- and trans-isomers will be important to identify PFCs with optimized pancreas-preserving characteristics. Daniel Brandhorst1 Reinhard G. Bretzel2 Heide Brandhorst1 1Department of Oncology, Radiology & Clinical Immunology, University Hospital, 75185 Uppsala, Sweden, 2Third Medical Department, University Hospital, 35385 Giessen, Germany