Preservation and functional maintenance of lung allograft / 器官移植

As the final resolution for end-stage lung disease, lung transplantation can not only significantly prolong the survival, but also remarkably improve the quality of life of recipients. In recent decades, with the advancement of surgical techniques, immunosuppressants and post-transplantation management, the quantity of lung transplantation has been surged around the globe. However, the shortage of donor lung has severely restricted the development of lung transplantation. It is necessary to develop innovative approaches to expand the donor pool. The number of donors and effective preservation and functional maintenance of potential donor lungs play a key role in expanding the donor pool. The quality of donor lung is a critical precondition to ensure the long-term survival of lung transplant recipients. Preservation and functional maintenance of donor lung are of significance for guaranteeing the quality of lung allograft. In this article, research progresses on the management and maintenance of donor lung before procurement, the procurement of donor lung and the preservation and functional maintenance of lung allograft were reviewed, aiming to provide reference for the development of lung transplantation in clinical practice.

Impact of protamine injected into ascending aorta on C3a and C5a concentration in infants underwent cardiopulmonary bypass / 中国综合临床

Objective To observe and evaluate the changes in plasma C3a and C5a concentration after injecting protamine via two different pathways:ascending aorta and superior vena cava.Methods Sixty children with age under 1-year-old who underwent cardiopulmonary bypass were randomly divided into two groups:experimental group(injecting protamine via ascending aorta,n =30)and control group(injecting protamine viasuperior vena cava,n =30;).The plasma concentration of C3a and C5a were measured by ELISA at prior to protamine injected(Time 1)and 1 hour after the protamine injected(Time 2).Results In experimental group,there was no statistical difference on C3a and C5a concentration before and after injection of protamine[C3a:(18.762±3.792) μg/L vs(19.554±3.453) μg/L,t =-0.846,P =0.20; C5a:(0.843±0.159) μg/L vs (0.825±0.119) μg/L,t =0.496,P =0.31].In control group,C3 a concentration increased from(18.780±3.864) μg/L to(22.961±3.501) g/L,C5a concentration increased from(0.839±0.157) μg/L to(0.979±0.116)μg/L after injection of protamine,and the differences were significant(t =-4.392,-3.928,respectively,P ＜0.01).The level of C3a concentration in experimental group was significantly higher than that in control group[(19.554±3.453) μg/L vs.(22.961±3.501) μμg/L,ι =3.795,P < 0.01]after injection of protamine for 1 h and the level of C5a concentration exhibited the same change[(0.825±0.119) μg/L vs.(0.979±0.116)μg/L,t =-5.075,P ＜0.01].Conclusion The levels of C3a and C5a concentration of infants underwent cardiopulmonary bypass are decreased significantly after protamine injected via ascending aorta compated with via superior vena cava.

Allogeneic single lung transplantation in 7 cases / 中国组织工程研究

The present case report was designed to summarize the clinical experience of operative technique. lung preservation, lung perfusion, and perioperative management. Of 7 cases who underwent allogenic single lung transplantation (LT), 3 were idiopathic pulmonary fibrosis, 2 were chronic obstructive pulmonary disease, 1 was silicosis, emphysema, and bulla, and I was tuberculosis in both sides and presented with destroyed lung in one side. All donors were already brain death. Donor lungs were well preserved utilizing Euro-Colins liquid or low-potassium dextran solution. Donors and recipients were matched in blood type. Of 7 cases selected,5 received single right lung transplantation, and 2 received single left LT. End-to-end anastomosis was performed for pulmonary branches and pulmonary arteries. while atrium-to-atrium anastomosis was performed for pulmonary vein. Antibiotics and immunosuppressants were routinely used prior to and subsequent to LT. Following LT, heart and lung function, usage of antibiotics, and adjustment of immunosuppressant were monitored. Stomal complications regarding bronchus and pulmonary artery and vein did not appear in any patient. Five cases survived for about 2 months, one for approximately 1 year, and one for nearly 2 years. Four cases died of multi-organ failure caused by pulmonary infection, and one of severe pulmonary hemorrhage caused by aspergillus sydowi infection. Rejection occurred in 6 cases. One case sufiered from rejection three times. Selection of indication, selection and preservafton of donor lung, LT operation and pre-and post-operative management of LT have acquired satisfactory achievements. High mortality occurred in patients with preoperative poor cardiac and pulmonary functions and postoperative severe infections accompany with application of immunosuppressant.

Development of New Organ Preservation Solutions in Kyoto University

Although lung transplantation (LTx) has been established as a therapeutic approach for end-stage respiratory failure, several problems remain to be solved. In addition to the serious problem of donor shortage, primary graft failure, which is mostly caused by ischemia-reperfusion injury, a serious problem, and represents one of the most frequent causes of early mortality. The development of a highly reliable organ preservation solution that reduces ischemia-reperfusion injury will improve the functioning of transplanted organs and alleviate the donor shortage. We first evaluated the importance of saccharides and electrolytes in the lung preservation solution. We proved the superiority of trehalose, a non-reducing disaccharide, and the efficiency of the extracellular-type (low potassium) ion composition, and we also developed an extracellular-type trehalose containing Kyoto (ET-Kyoto) solution. Furthermore, several agents for vascular endothelial protection were evaluated, and finally, a more effective solution named "new ET-Kyoto solution" was developed, by adding N-acetylcysteine, dibutyryl adenosine 3', 5'-cyclic monophosphate, and nitroglycerin to the "conventional" ET-Kyoto solution. The new ET-Kyoto solution enabled canine LTx to last up to 30 hours. ET-Kyoto solution has so far been used and produced good results in five clinical LTx throughout Japan and South Korea. Although it was initially developed for lung preservation, its effectiveness in the preservation of various organs/ tissues, such as the trachea, kidney, skin/muscle flap, amputated digits, liver, and pancreas, has also been experimentally and clinically shown. In this paper, clinical and experimental findings with ET-Kyoto solution have been accumulated to further analyze its effect, safety, and chemical stability. We hope to provide ET-Kyoto solution as the standard organ/tissue preserving solution throughout the world.

The Effects of addition of Cyclic Adenosine Monophosphate and NItric Oxide in Low Potassium Dextran Solution for Lung Preservation in an Isolated Rabbit Lung Perfusion Model / 대한흉부외과학회지

BACKGROUND: During organ preservation and reperfusion, both cyclic adenosine monophos-phate(cAMP) and nitric oxide(NO) play a central role in maintaining pulmonary vascular homeostasis. However , both cAMP and NO levels decline markedly during pulmonary ischemia and reperfusion. In this study we prepared a new solution in which a cAMP analog(dibutyryl cAMP, db-cAMP) and a nitric oxide donor (nitroglycerin, NTG) were added to the conventional low potassium dextran(LPD) solution. We investigated the effects of addition of cAMP and/or NO in LPD solution for lung preservation and compared the effectiveness of the solutions. MATERIAL AND METHOD: Rabbit lung grafts(six per group) were studied in an isolated lung perfusion model. The heart-lung blocks were harvested after flushing in situ with only LPD solution(group I, n = 6), plus NTG(group II, n = 6), plus db-cAMP(group III, n = 6), or plus NTG and db-cAMP(group IV, n = 6), and were preserved at 10degreesC for 24 hours. The stored lungs were ventilated with 100% oxygen and reperfused with fresh venous blood at 38degreesC for 30 minutes. We assessed the lung functions and subsequent lung edema. Tumor necrosis factor alpha(TNF-alpha) and nitrite/nitrate(total NO production) levels were also measured. In addition, we evaluated histologic and ultrastructual changes of the reperfused lungs. RESULT: Although Group IV demonstrated the best lung preservation, the differences were not significant among group II, III and IV. Group Irevealed the worst lung functions and severe pulmonary edema(p<0.05 versus all other groups). Although group II showed better lung preservation than in group III, the differences were not significant. TNF-alpha release was significantly reduced in group IV than in group I after reperfusion(p<0.01). NO levels were significantly increased in groups II and IV than in groups I and III after reperfusion(p<0.001). However , there were no significant differences between groups I and III or between groups II and IV. NO levels decreased gradually in groups I and III(p<0.05). Histologic and ultrastructual studies showed better preservation of the alveolar-capillary barrier in groups II, III and IV than in group I. CONCLUSION: This study demonstrate that both of db-cAMP and NTG had beneficial effects on lung preservation with LPD solution, and there was no difference in the effect of each component. Especially, we expect that combined supplementation of db-cAMP and NTG will preserve better vascular homeostasis and minimize reperfusion inj ury after ischemic cold storage.

Protective Effects of Ulinastatin on Rabbit Lung Transplantation / 中国医师杂志

Objective To explore the protective effects of Ulinastatin on lung transplantation. Methods Orthotopic pulmonary autograft transplantation models of 24 New Zealand rabbits were established and randomly divided into four groups: groupⅠ (control group,n=6), groupⅡ(given 6000U/kg UTI 30min before ischemia, n=6), groupⅢ(given 12000U/kg UTI 30min before ischemia, n=6), groupⅣ(given 12000U/kg UTI respectively 30min before ischemia and during reperfusion, n=6). Then blood samples were taken from left and right atrium respectively before ischemia, and 30min after reperfusion for white blood cells counting. lung tissue DMA content was measured and lung biopsy were performed respectively before ischemia and 2h after reperfusion. Results Compared with groupⅠ, in groups Ⅱ,Ⅲ and Ⅳ, the white cell ratio of right atrium/left atrium was significantly lower, the ratio of wet/dry lung tissue weight and lung tissue DMA content were lower, and the pathological lesion was less. Conclusion Ulinastatin has protective effects on rabbit lung transplantation.

24-hour Lung Preservation Study in a Canine Sequential Bilateral Lung Tranplant Model / 대한이식학회지

BACKGROUND: Numerous studies on safe, long term preservation for lung transplantation has been performed for the purpose of developing ideal preservation solution with extracellular type or intracellular type solutions and overcoming the shortage of donors. We prepared LPDG (low potassium dextran glucose)solution for lung preservation study. In this study we examined the efficacy of LPDG solution in 24-hour lung preservation by using of a sequential bilateral canine lung allotransplant model. METHOD: Seven bilateral lung transplant procedures were performed using weight-matched pairs (23 to 26 Kg) of adult mongrel dogs. The donor lungs were flushed with LPDG solution and maintained hyperinflated with 100% oxygen at 10oC for a planned ischemic time of 24 hours for the lung implanted first. After sequential bilateral lung transplantation, dogs were maintained on a ventilator for 3 hours: arterial oxygen tension, pulmonary artery pressure, and pulmonary vascular resistance were determined in the recipients hourly after bilateral reperfusion and compared with pretransplant-recipient values, which used as controls. After 2 hours of reperfusion, the chest X-ray, computed tomogram and lung perfusion scan were performed for assessment of early graft lung function. And pathological examinations for ultrastructural findings of alveolar structure and endothelial structure of pulmonary artery were performed. RESULTS: Five dogs of seven experiments had successfully finished the whole assessments after bilateral reperfusion for three hours. Arterial oxygen tension in the recipients was markedly decreased in immediate reperfusion period but gradually recovered after reperfusion for three hours. The pulmonary artery and pulmonary vascular resistance showed singificant elevation (p<0.05 versus control values) but also recovered after reperfusion for three hours (p<0.05 versus immediate period value). The ultrastructural findings of alveolar structure and endothelial structure of pulmonary artery showed reversible mild injury in 24 hours of lung preservation and reperfusion. CONCLUSIONS: The present study suggests that LPDG solution provide excellent preservation and transplanted lung function after 24 hours of preservation in a canine model in which the dog is completely dependent on the fuction of transplanted lung.

An Experimental Model of Isolated Lung Block for Evaluation of Pulmonary Preservation after Ischemia / 대한흉부외과학회지

During the last 30 years, major organ transplantation has become popular, even in Korea, such as kidney, liver, etc. After the successful clinical cardiac transplantation in Korea, many cases of cardiac transplantation are being performed in some centers. But lung transplantation has a lot of obstacles, especially donor shortage and decreased tolerability of the lung to ischemia-reperfusion injury. Usually it was considered that the maximum safety margin of ischemic time in lung transplantation was about 4 to 6 hours. So, many investigators have tried to develop better preservation methods and experimental model for evaluation of effectiveness in those various methods. But most of those methods had several drawbacks in clinical and experimental settings. So we developed an easily-controllable, reliable, and inexpensive experimental model of isolated rabbit lung block. Using these model, we evaluated its effectiveness and reliability for the experiment of ischemia-reperfusion injury in lung transplantation.