Development of Low Potassium Solution (EP4 Solution) for Long‐Term Preservation of a Lung Transplant: Evaluation in Primate and Murine Lung Transplant Model

Abstract

The results of recent studies on long‐term preservation using low potassium flush solution, which was originally produced in our department, are presented and discussed. In the primate model, a lung preserved for 24 h with EP4 solution retained sufficient function in single lung allotransplantation. In the murine experiments, we have evaluated the ion transport properties across alveolar epithelial cells in the transplanted lung using the tools of alveolar fluid clearance tests. The alveolar fluid clearance rate, which can be inhibited by 10‐3M ouabain, is also well preserved for the first 24 h, indicating that the alveolar epithelial Na‐K‐ATPase is still functioning and that the 72 h preservation decreases those function of Na‐K‐ATPase in a time‐dependent manner. In conclusion, because 24 h hypothermic preservation with EP4 solution did not show any obvious disadvantage on primate lung allografts and the cellular and molecular viability of the preserved lung flushed with EP4 solution could be retained for 24 h, this kind of solution with extracellular electrolyte composition can be applicable in the clinical settings.

Improving the viability of tissue‐resident stem cells using an organ‐preservation solution

“…Our ECF-type solution was prepared in collaboration with Cell Science Technology (Sendai, Japan). This ECF-type solution is based on the organ-preservation solution developed for lung transplantation [12]. Because many potential solutions can be used for tissue preservation, we chose the solutions to be compared according to the following criteria: (a) the solution has been previously used for tissue preservation and/or transportation for experimental purpose; (b) the solution is chemically defined; and (c) the solution does not contain additives that can affect the stem/progenitor characteristics such as recombinant growth factors and animal serum.…”

“…These preservation solutions are classified into two groups: intracellular fluid (ICF)-type preservation solutions (high potassium/low sodium ratio) and extracellular fluid (ECF)-type preservation solutions (low potassium/high sodium ratio) [10]. Earlier investigations exploring the use of preservation solutions for transplantation have usually employed ICF-type solutions [10]; however, more recent studies have suggested the improved functionality of the organs preserved in ECF-type solutions [11][12][13][14]. We previously demonstrated the improved viability and function of alveolar type II (ATII) cells, one of the stem/progenitor cells in lung [2], in an ECF-type solution over an ICF-type solution [15].…”