Effect of Nitric Oxide and Cytokines for Reperfusion Lung Injury in Living-donor Lung Transplantation

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We have succeeded a living-donor lober lung transplantation (LDLLT) at Okayama University Hospital in 1998, which was the first lung transplantation (LT) in Japan. The acute phase mortality rate of LT is higher than that of heart transplantation. A major cause of the death is reperfusion lung injury (RLI) and the treatment has not been established. Although nitric oxide (NO) inhalation therapy is supposed to improve oxygenation and prevent RLI and post-transplant pulmonary hypertension (PH), the usage is controversial. Patients undergoing LDLLT tend to develop PH because of the small size of the implanted lungs. The management of LDLLT is less understood. In order to improve the survival rate of LDLLT, we have established the treatment of LDLLT with inhalation NO and managed the patients. The overall actuarial survivals of LDLLT recipients have been reported as 70%, 54%, and 45% at 1, 3, and 5 years, respectively from the International Society for Heart and Lung Transplant registry. Be … More tween October 1998 and April 2004, we performed LDLLT in 30 critically ill patients with various lung diseases. All 30 recipients were discharged and are currently alive, with a follow-up period of 1 to 66 months. In spite of the complicated managements of LDLLT, 100% survival during the observation period is noteworthy. LDLLT can be applied to both pediatric and adult patients with very limited life expectancies. It might provide better survival than conventional cadaveric LT. We also studied intra-operative serum levels of key cytokines and polymorphonuclear elastase (PMN-E) in patients undergoing LDLLT surgery with cardiopulmonary bypass (CPB) in order to understand the pathophysiologic role. The NO inhalation started before the reperfusion. LDLLT patients demonstrated significant elevations of serum interleukin-6 (IL-6) and PMN-E during and after CPB. IL-6 production increased significantly after CPB. Serum tumor necrosis factor- α did not change significantly. It is expected to find new treatments to prevent ischemia-reperfusion lung injury in LT. Less