University of Wisconsin solution with butanedione monoxime and calcium improves rat lung preservation

Background. A limitation to fully using lung transplantation for patients w ith end-stage lung diseases is short, safe preservation time (4 to 6 hours) . Our goal is to extend this to 24 hours or more, which would greatly impro ve clinical lung transplantation. Methods. We used the isolated perfused rat lung to test how two preservatio n solutions (low potassium dextran and University of Wisconsin solution) af fected quality of lungs after 6, 12, and 24 hours of preservation. Also, we tested modifications of the University of Wisconsin solution, including re versing the ratio of Na/K, the addition of 1.5 mmol/L calcium, and the comb ination of calcium and butanedione monoxime, agents that improve cardiac pr eservation. After preservation at 4 degrees C, lungs were reperfused at 37 degrees C with a physiologically balanced solution. Pulmonary artery now ra te, airway peak inspiratory pressure, and tissue edema were used to assess degree of preservation and reperfusion injury. Results. Low potassium dextran solution gave poor preservation (decreased p ulmonary artery now, tissue edema) after 12 hours of cold storage. There we re no differences between regular and reversed Na/K ratio University of Wis consin solutions at 12 or 24 hours of preservation. Addition of calcium had no beneficial effect on lung preservation. However, University of Wisconsi n solution with calcium and butanedione monoxime gave excellent 24-hour col d storage, with pulmonary artery flow rate, tissue edema, and airway peak i nspiratory pressure equal to control (0 hours of preservation) lungs. Conclusions. The University of Wisconsin solution appears capable of lung p reservation for up to 24 hours if modified to contain calcium and butanedio ne monoxime. The mechanism of action of butanedione monoxime may be related to the suppression of smooth muscle contraction resulting in vasodilation of the cold-stored lung on reperfusion. (C) 1999 by The Society of Thoracic Surgeons.