EPC-K1 is effective in lung preservation in an ex vivo rabbit lung perfusion model

L-Ascorbic acid 2-[3,4-dihydro-2,5,7,8-tetramethyl-2-(4,8,12-trimethyltridecyl)-2H -1-benzopyran-6yl-hydrogen phosphate] potassium salt (EPC-K1) is a phosphate diester of alpha-tocopherol and ascorbic acid. It has been reported that EPC-K1 inhibits lipid peroxidation and phospholipase A2. We hypothesized that EPC-K1 might enhance lung preservation and reduce the degree of posttransplantation lung dysfunction.

Eighteen rabbits were divided into three groups, as follows: group 1, no preservation (n = 6); groups 2 (n = 6) and 3 (n = 6), 24 hours of preservation at 8 degrees C. Low-potassium dextran-1% glucose solution was used for flushing and immersion in all groups, but EPC-K1 (0.5 mg/L) was added to the solution used in group 3. After storage the left lung was reperfused with autologous blood and ventilated using a membrane oxygenator in an isolated rabbit lung reperfusion model. The grafts used in the group 1 rabbits were perfused for 5 hours to confirm the reliability of this model, and the grafts used in the group 2 and 3 rabbits were perfused for 2 hours. Pulmonary arterial pressure, airway pressure, blood gas analysis, and the lipid peroxide level of the perfusate were assessed. The lipid peroxide levels of the lung tissue before and after storage and the wet-dry weight ratio of the perfused lung were determined in groups 2 and 3.

Superior graft function was noted in group 3 in terms of all indices. The lipid peroxide level in the perfusate and the wet-dry weight ratio were also suppressed in group 3. The lipid peroxide level in the lung tissue did not change during storage in either group.

The administration of EPC-K1 in the flush and preservation solution helps enhance lung graft function and suppresses lipid peroxidation after reperfusion.