Beneficial Effects of Nitric Oxide in Lung and Liver Transplantation

Lung transplantation is an evolutionary procedure from its experimental origin in the twentieth century and is now recognized as an established and routine life-saving intervention for a variety of end-stage pulmonary diseases refractory to medical management. Despite the success and continuous refinement in lung transplantation techniques, the widespread application of this important life-saving procedure is severely hampered by poor allograft quality offered from donors-after-brain-death. This has necessitated the use of lung allografts from donors-after-cardiac-death (DCD) as an additional source to expand the pool of donor lungs. Unlike other solid organs, the lung may be ideally suitable for DCD due to its tolerance for warm ischemia at substantial time intervals because of its low metabolic requirement, in addition to being normally well-perfused and its alveoli filled with oxygen. However, primary graft dysfunction (PGD), allograft rejection and other post-transplant complications arising from unavoidable ischemia-reperfusion injury (IRI) of transplanted lungs, increase morbidity and mortality of lung transplant recipients annually. In the light of this worrying trend, nitric oxide (NO), a selective pulmonary vasodilator, has been identified as a suitable agent that attenuates lung IRI and prevents PGD when administered directly to lung donors prior to donor lung procurement, or to recipients during and after transplantation, or administered indirectly through lung preservation solutions. This chapter presents a historical account of clinical lung transplantation and discusses the lung as an ideal organ for DCD. Next, the author highlights IRI and its clinical effects in lung transplantation, and finally discusses preservation solutions suitable for lung transplantation, and the protective effects and mechanisms of NO in preclinical and clinical lung transplantation. A section of the chapter also discusses the therapeutic effect of NO in experimental and clinical liver transplantation.