Allo-transplantation of the Lung Preserved 24 Hour with UW Solution and the Preventive Effect of Flush with Leukocyte-depleted Blood before Reperfusion.

The purpose of this study was to evaluate the possibility of clinical use of a 24 hour preserved donor lung with UW solution and the effects of the flush with Leukocyte depleted before reperfusion. The left canine lung was used for allotransplantation and dogs were divided into 4 groups. The donor lungs preserved for 24 hours with UW solution (Group 1 and 2) or EC solution (Group 3 and 4) were transplanted in mongrel dogs. Moreover, the flush with Leukocytedepleted blood for 30-60 minutes was performed in Group 2 and 4. The severity of reperfusion injury at 60 minutes of reperfusion was assessed and the graft funchion was observed for 14 days. The Pa02 value at 60 minutes of reperfusion was 345 ± 132, 261 ± 161, 312 ± 120, 152 146 Torr, static compliance was 31.2 ± 4.5, 27.8 ± 5.0, 22.2 ± 9.0, 17.6 ± 6.1, and dynamic compliance was 13.9 ± 1.9, 14.2 ± 1.9, 10.9 ± 1.8, 11.7 ± 1.5 ml/cmH20, respectively. There were no significant differences among the groups. And no significant deterioration was seen in these parameters as compared with the figures before harvesting. Pulmonary vascular resistance (PVR) was 1824 650, 2100 ± 564, 3830 ± 1549, 4553 ± 1819 dyne*sec*cm' respectively. Group 1 and 2 showed significantly lower PVR than Group 3 and 4. Tissue Lipid Peroxide was 0.75 ± 0.15, 0.85 ± 0.21, 1.52 ± 0.85, 0.70 ± 0.27 nmolMDA/mg pt, and the ability of superoxide generation of neutrophils (SOX) was 4697 ± 1886, 4466 ± 1760, 6934 ± 156, 3125 ± 725 respectively at 60 minutes of reperfuison. Group 1, 2 and 4 showed better results than Group 3. There was a significant decrease in SOX of Group 4 as compared with Group 3. Recipients were administered Cyclospoline A (20 mg/kg/day) and Azachiopurine (2 mg/kg/day). The survival rates were 100% (6/6), 57% (4/7), 0% (0/4), 0% (0/4) respectively. And 4 of 6 in Group 1 and 3 of 7 in Group 2 functioned well with Pa02 of 354 ± 66, 317 ± 178 Torr at sacrifice (10 to 21 POD). And a slight rise in PVR was recognized in both groups as compared with the figures before harvesting. (2524 ± 894, 2947 ± 381 respectively) Histological examination after 60 minutes of reperfusion revealed mild interstitial edema in Group 1 and 2. Severe alveolar edema, marked vascular congestion, and perivascular extravasation were seen in Group 3 and 4. But the grade of vascular congestion was slightly lower in Group 4 as compared with that in Group 3. At sacrifice survivors showed rejection in three dogs and none in four dogs, in which interstitial thickening, diffues perivascular cuffmg was seen. There was no significant difference between Group 1 and 2. The data suggest that UW solution may prepare the 24-hourpreserved donor lung for succesful lung transplantation. And the flush with leukocyte depleted blood showed attenuation of the tissue lipid peroxidation and superoxide generation of neutrophils in the lung preserved with EC but not with UW. The flush with leukocytedepleted blood may play a role in attenuation of neutrophils related reperfusion injury. Introduction Lung transplantation in human being was first performed in 1963. After the development of Cyclosporine, lung transplantation has become recognized as the only possible way of therapy for many patients suffering from the end-stage of lung diseases. However, the shortage of suitable donor organs is one of the restricting factors in clinical application of lung transplantation. Recent studies focused on the technique of longer preservation and better quality of the donor lung. In recent years, there has been growing evidence that University of Wisconsin solution is superior to EuroCollins solution for preservation of the liver, the kidney and the pancreas. But there were a few reports about the donor lung. In our previous study, We have demonstrated the superiority of UW solution to EC solution for 24-hour lung preservation in vitro canine model." In this model lower PVR and better compliance were observed, whereas Pa02 values were not significantly better. The estimation of oxygenation is controversial about this model because of no oxygen consumption. And the duration of reperfusion was limited. The mutual factors between recipients and grafts such as the circulating neutrophils' effects to the endothelium were unclear. And the survival times depending on the following reperfusion injury, implantation response and immunological rejection were not estimated. Therefore, the 1st purpose of this study was to clarify the possibility of 24 hour preservation with UW solution in vivo model, though it is costly and time consuming. It is well known that the important role of leukocytes and its production of toxic metabolites in reperfusion injury.2-5) It contributes to damage to the pulmonary vascular endothelium, which results in leukocyte sequestration, vasospasm, hemorrhage and lung edema.") The other factors such as Leukotriene, and Thromboxane affect the advances in lung injury. Therefore, peripheral blood leukocyte depletion after ischemia is useful to attenuate the reperfusion injury."