| Background Lung transplantation has evolved from anexperimental procedure to an accepted therapeutical option for patients with endstage pulmonary disease. Nowadays, the introduction of immunosuppression drugs and improved lung preservation solutions has diminished the incidence of severe graft dysfunction. Many early problems could be solved and long-term survival results are very promising. But optimizing posttransplantation graft function is still a continuing challenge in lung transplantation. Ischemia -reperfusion injury and the resulting primary graft dysfunction remains a persistent cause of early graft loss in lung transplantation because the function of the transplanted lung is particularly susceptible to the deleterious effects of it. There has been a great deal of attention focused on ischemia-reperfusion injury in the transplanted lung. The manifestations of pulmonary ischemia -reperfusion injury can be characterized by increased pulmonary vascular resistance, decreased oxygenation capacity, worsened compliance, and edema formation. The pathophysiology of ischemia -reperfusion injury is complex and involves the generation and release of inflammatory cytokines, accumulation and infiltration ofneutrophils and macrophages, release of oxygen free radicals, activation of proteases, and generation of nitric oxide (NO). Aprotinin, a nonspecific serine protease inhibitor that is presently in wide clinical use for minimizing perioperative blood loss in cardiac operations, has dose-dependent effects on coagulation, fibrinolysis, and inflammatory variables. Aprotinin has been shown to protect against the damage of ischemia and reperfusion by suppressing the release of lysosomal enzymes and bradykinin, and inhibiting their activities. It can also inhibit the production of superoxides and peroxides which are originated from the human polymorphonuclear leukocytes. Previous studies with aprotinin have shown it to improve myocardial, hepatic, and renal viability after a period of ischemia followed by reperfusion .Objective In this study, we investigated whether aprotinin can provide protection against the adverse effects of ischemia and reperfusion in the lung during lung transplantation in a canine single lung transplantation model.Method Twenty male canines, weighing 15å¤2.5kg, were randomly divided into two groups. In each group canines were randomly assigned to donors(n=5) and recipients(n=5). Left lung transplantation was performed. The average ischemia time was about 90 minutes. Recipients received either aprotinin 25U/kg i.v. infusion(Group I) or equivalent volumes of 5% glucose i.v.(Group II, control) before reperfusion. Lung tissue samples were obtained one hour after reperfusion. Blood samples were obtained before ischemia (T0), 30 min (Ti), 60 min (T2) and 120 min (T3) after reperfusion. The-6-pulmonary water content, tissue myeloperoxidase(MPO) activity, content of MDA and nitric oxide(NO) were measured. The lung were also performed with microscopic examination. Serum levels of tumor necrosis factor alpha (TNF-a), interleukin-6 (IL-6) and interleukin-8 (IL-8) were detected using enzyme-linked immunosorbent assay. The influences of aprotinin on cytokines production were observed.Results The pulmonary water content were significantly lower in group 1(73. 65% 4. 31%) than in control (81. 33% 3. 67%)group (P <0.05) . Tissue MPO activity were significantly lower in group I(0.21 0.05 A OD/min . g) than in control (0.37 0.10 A OD/min . g)group(P<0.05). Content of MDA were significantly lower in group I(0. 17 0. 004nmol/mgprot) than in control (0. 29 0. 010 nmol/mgprot)group (P<0.05) . Content of NO were significantly lower in group I(12. 60 8. 73 mol/gprot) than in control(35. 09 13. 73 P mol/gprot) group (P<0.05). Microscopic examination showed that there were severe leukocyte infiltration and edema formation in alveolar space in group II, but the changes were less severe in group I. Serum levels of IL-6 were significantly lower at time point T2 and T3 in... |
PDF Full Text Request