Development of New Organ Preservation Solutions in Kyoto University

ABSTRACT

Although lung transplantation (LTx) has been established as a therapeutic approach for end-stage respiratory failure, several problems remain to be solved. In addition to the serious problem of donor shortage, primary graft failure, which is mostly caused by ischemia-reperfusion injury, a serious problem, and represents one of the most frequent causes of early mortality. The development of a highly reliable organ preservation solution that reduces ischemia-reperfusion injury will improve the functioning of transplanted organs and alleviate the donor shortage. We first evaluated the importance of saccharides and electrolytes in the lung preservation solution. We proved the superiority of trehalose, a non-reducing disaccharide, and the efficiency of the extracellular-type (low potassium) ion composition, and we also developed an extracellular-type trehalose containing Kyoto (ET-Kyoto) solution. Furthermore, several agents for vascular endothelial protection were evaluated, and finally, a more effective solution named "new ET-Kyoto solution" was developed, by adding N-acetylcysteine, dibutyryl adenosine 3', 5'-cyclic monophosphate, and nitroglycerin to the "conventional" ET-Kyoto solution. The new ET-Kyoto solution enabled canine LTx to last up to 30 hours. ET-Kyoto solution has so far been used and produced good results in five clinical LTx throughout Japan and South Korea. Although it was initially developed for lung preservation, its effectiveness in the preservation of various organs/ tissues, such as the trachea, kidney, skin/muscle flap, amputated digits, liver, and pancreas, has also been experimentally and clinically shown. In this paper, clinical and experimental findings with ET-Kyoto solution have been accumulated to further analyze its effect, safety, and chemical stability. We hope to provide ET-Kyoto solution as the standard organ/tissue preserving solution throughout the world.