Lung Transplantation: Clinical and experimental studies

Sammanfattning: During the past 15 years lung transplantation has been established as a therapeutic option for patients with end-stage pulmonary disease. The results have improved over time and some transplantation centers now show 1-year survival rates above 80%. The number of donors has remained relatively constant during later years but the demand is increasing resulting in longer waiting times and an increasing number of patients dying on active waiting lists. Better lung preservation allowing longer cold ischemic times would potentially increase the donor pool and also improve immediate postoperative lung function. Paper I describes an experimental big animal model for evaluation of donor lungs in vivo. With this method we could show good preservation for 12 hours using a low-potassium-dextran-glucose solution (Perfadex). Another potential way of increasing the number of donors would be to accept organs from non-heart-beating donors i e dead from cardiac arrest. These donors will have died without systemic anticoagulation and will have been subjected to cardiopulmonary resuscitation with risk of traumatic injury to the lungs and aspiration. Paper III describes an ex vivo method for functional evaluation of donor lungs. There was good correlation between measurements of gas exchange in vivo and ex vivo. Paper II describes the physiological background for using gas exchange for CO2 in evaluating lung perfusion abnormalities. Acute graft failure represents a significant cause of early morbidity and mortality after lung transplantation, accounting for about 25% of all deaths in the first postoperative month. When conventional intensive care fails treatment options include re-transplantation and ECMO. Paper IV describes another approach, induced hypothermia to reduce metabolic needs, in the treatment of two patients in respiratory failure fulfilling established ECMO-criteria. Both patients could be stabilized and eventually discharged from the hospital with normal arterial blood gases. A finding in studies on hypothermia has been an increased pulmonary vascular resistance as is also seen early after lung transplantation. It was our concern that the combination of the two would prove detrimental to right ventricular function. The study presented in paper V did not show an increased work load on the right ventricle. Paper VI is a retrospective study of the first 39 lung transplantations performed in Lund between Jan 1990 and Dec 1995. Mean follow-up was 2.1 years. One-year survival was 87% and 2-year survival 83%. This compares favorably with other, larger transplant centers.