• Journal of Chest Surgery
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• v.27 no.9
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• pp.723-731
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• 1994

We have modified the isolated perfused working rabbit lung model [IPWL] by perfusing the isolated lung with a hollow fiber membrane deoxygenator.For assessment the stored lung was ventilated with FIO2 0.4 and perfused with 37$^{\circ}$C deoxygenated circulating blood at a rate 5ml/kg/min for several hours until lung failure.We chose to compare our developing solution which contained low potassium and pentastarch with the modified Euro-Collins solution .Experiments were divided into four groups[n=6] based on the type of flushing preservation solution and preservation time.The flushed lungs were then preserved into same solution at 8~10$^{\circ}$C with 100% O2 inflated condition for 1 or 20 hours.These following results were obtained.The IPWL model requires only one animal per experiment and allows for the continuous assessment of aerodynamic performance. This should therefore be used as screening test in lung preservation.One hour preservation groups, there were no significant difference in recovery rates of PaO2, PAP and Paw. Survival time in the one hour preservation groups were very significant long in the Group II[LPPS, p<0.01]. Twenty hours preservation groups, there were no significant difference in the recovery rates of PAP and Paw between Group III[m-ECS] and Group IV[NS], but PaO2 was significantly worse at onset of reperfusion in Group III when compared with Group IV [p<0.05]. And also survival time in the 20 hours preservation groups were significant long in the Group IV [p<0.05].

• Journal of Chest Surgery
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• v.33 no.5
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• pp.377-384
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• 2000

Background: Numerous studies of safe, long term preservation for lung transplantation have been performed using ex vivo models or in vivo single lung transplantation models. However, a safe preservation time which is applicable for clinical use is difficult to determine. We prepared LPDG solution for lung preservation study. In this study we examined the efficacy of LPDG(low potassium dextran glucose) solution in 24-hour lung preservation by using a sequential bilateral canine lung allotransplant model. Material and Method: Seven bilateral lung transplant procedures were performed using weight-matched pairs(24 to 25kg) of adult mongrel dogs. The donor lungs were flushed with LPDG solution and maintained hyperinflated with 100% oxygen at 1$0^{\circ}C$ for a planned ischemic time of 24 hours for the lung implanted first. After sequential bilateral lung transplantation, dogs were maintained on ventilators for 3 hours: arterial resistance were determined if the recipients hourly after bilateral reperfusion and compared with pretransplant-recipient values, which were used as controls. After 2hours of reperfusion, the chest X-ray, computed tomogram and lung perfusion scan were performed for assessmint of early graft lung function. Pathological examinations for ultrastructural findings of alveolar structure and endothelial structure of pulmonary artery were performed. Result: Five of seven experiments successfully finished the whole assessments after bilateral reperfusion for three hours. Arterial oxygen tension in the recipients was markedly decrased 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 perservation and reperfusion. Conclusion : This study suggests that LPDG solution provides excellent preservation in a canine model in which the dog is completely dependent on the function of the transplanted lung.

• Journal of Chest Surgery
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• v.7 no.2
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• pp.145-152
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• 1974

The effect of reticuloendothelial hyperfunction on hypothermic preservation of lung was studied in dogs. In order to evaluate the viability after hemodynamic_ load in preserved isolated lung, observations were made on the rate of increase in weight, degree of edema,compliance and surface activity of lung. The results obtained as follows: l. In the group of activating of the reticuloendothelial system by injection of sodium thiosulfate intravenously before pneumonectomy and infusion of naphthionine through the pulmonary artery before hypothermic preservation of isolated lung the limit of preservation was eight hours whereas four hours in non-treated control group. 2.Therefore the method of activating of the reticuloendothelial system before and after pulmonary resection seems effective in preserving for prolonging the period of preservation of lung by means of inhibition of pulmonary edema. 3. Pulmonary surface activity is expected to be valuable as a method in evaluation of the viability of preserved lung along with compliance and rate of increase in weight of lung.

• Journal of Chest Surgery
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• v.28 no.12
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• pp.1096-1106
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• 1995

We experienced 7 cases of left single lung transplantation in 14 mongrel dogs and analyzed graft lung function by hemodynamics, blood gas analysis, chest X-ray, biopsy and perfusion lung scan. We performed right pulmonary artery cuff[PA cuff for analysis of graft lung function in 3 cases. The donor lungs were flushed with modified Euro-Collins solution[n=3 or low potassium dextran glucose solution[n=4 and preserved for 4 to 5 hours[n=4 or 24 hours[n=3 at 10o C and implanted to the dogs with similar weight . Assessment of left graft lung was done by occluding the right pulmonary artery for 10 minutes using PA cuff. Assessment for graft lung function was done immediately after an operation and after 3 days, 7days and 3 weeks postoperatively. Four dogs survived for 3days, 7days[2 cases and 3 weeks respectively. Other three dogs expired within 3 hours of reperfusion. Immediate perfusion scans of left lung in four survived dogs after reperfusion were 42.1%, 36% , 11% and 5.9% respectively, and another dog with 4.8% perfusion to left lung was dead due to left atrial thrombi after 3 hours reperfusion. In one case among three acute rejections follow-up perfusion scan was done on 3rd and 11th postoperative day and the result decreased from 36% perfusion immediate postoperatively to 21% and 15% respectively. Three expired dogs postoperatively couldn`t tolerate occlusion of right pulmonary artery with above 40 mmHg of mean pulmonary artery pressure. On the other hand, three survival dogs postoperatively tolerated occlusion of right pulmonay artery with less than 30 mmHg of mean pulmonary artery pressure. and one dog couldn`t tolerate same procedure immediate postopertively but in 2 hours reperfusion later tolerated with 29 mmHg of mean pulmonary artery pressure.In conclusion we couldn`t compare the effect of two flushing solutions but low potassium dextran glucose solution showed relatively safe preservation effect in cases with preservation of more than 20 hours. Also canine left single lung transplantation model with PA cuff indicated useful method for the assessment of graft lung function with effect of lung preservation.

• Journal of Chest Surgery
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• v.30 no.3
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• pp.253-253
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• 1997

Hypothermia during lung preservation decreases metabolic processes. After the rabbit lung was flushed with modified Euro-Collins solution, heart-lung block was harvested and the left lung was assessed after ligation of the right pulmonary artery and right main-stem bronchus. Heart-lung block was immersed in the same solution for 6 hours. The modified Euro-Collins solution and storage temperature of group 1(10 cases) was 4t, roup 2(10 cases) was l0℃. On completion of the storage period, the left lung was ventilated and reperfused with blood u:high used a cross-circulating paracorporeal rabbit as a "biologic deoxygenator" for 60 minutes. Pulmonary artery pressure, airway pressure, difference in oxygen tension between mow and outflow perfusate and degree of pulmonary edema were assessed at 10-minute intervals while the left lung was ventilated at 0.8 of the inspired oxygen fraction. The mean pulmonary venous oxygen tensions at 10 and 60 minutes after reperfusion were 209.52±42.46 and 103.48± 15.96 mmHg in group I versus 247.78±36.19 and 147.91 ± 11.07 mmHg in group II(p=0.049, (0.0001). The mean alveolar-arterial oxygen differences at 20 and 60 minutes after reperfusion were 357. 95± 12.84 and 437.31 14.26 mmHg in group I versus 310.88±3).47 and )90.93± 15.86 mmHg in group II (p=0.0092, (0.0001). The mean pulmonary arterial pressures at 10 and 60 minutes after reperfusion were 40.56± 18.66 and 87. 2± 17.22 mmHg in group I versus 31.22±6.84 and 65.78± 11.02 mmHg in group rl (p : 0.048, 0.0062). The mean pulmonary vascular resistances at 10 and 60 minutes after reperfusion were 2.69±0.85 and 4.36±0.86 mmHg/ml/min in group I versus 1.99±0.39 and 3.29±0.55 mmHg/ml/min in group II(p : 0.0323, 0.0062). There were no difference between groups in peak airway pressure, lung compliance and degree of pulmonary edema. In conclusion that preservation of lung at l0℃ was superior to preservation at 4℃.

• Journal of Chest Surgery
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• v.30 no.10
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• pp.949-960
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• 1997

Background. Limited ischemic tolerance of the lung has remained one of the factors that limits the expansion of pulmonary transplantation as a treatment for end-stage pulmonary disease. 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. In this. study, we examined the efficacy of L DG solution in lung preservation longer than 20 hours by comparison with modified Euro-Collins solution. Iwethods. Thirty-(our adult mongrel dogs were divided into two groups. Donor lungs were flushed with LPDG solution(n=9) or modified Euro-Collins(MEC) solution(n=8) and stored for 24 hours at 1$0^{\circ}C$. All donor lungs were perfused through the pulmonary arteries with solutions containing prostaglandin El and verapamil. Left canine lung allotransplantations wereperformed. Assessment(hemodynamic indices and arterial blood gas analysis) of left implanted lung was made by occluding the right pulmonary artery for ten minutes using pulmonary artery Cuff. Assessment was repeated at the interval of 30 minutes, one hour, and two hours later after reperfusion and then chest X-ray, computed tomogram and lung perfusion scan were obtained. In survival dogs follow-up studies were done with assessment with chest X-ray, computed tomogram of the chest and lung perfusion scan on 7th day postoperatively. After preservation above 20 hours, pathological examinations for ultrastructural findings on right lung were performed in each group. Results. With respect to arterial oxygen tension, LPDG group was superior to MEC but there was no statistical significance for 2 hours after reperfusion. Mean pulmonary artery pressure was less increased(p < 0.05) and cardiac output higher(p <0.05) than MEC group until 2 hours after reperfusion. After 2 hours of reperfusion, both groups showed transplanted lung function deteriorated gradually. Perfusion scan of the transplanted lung in LPDG group showed better perfusion rate in immediate post-reperfusion, 3 days and 7 days later respectively but there was no statistical significance and corelation with PaO2 and computed tomoRravhic views. In scanning electron microscopy of pulmonary artery after preservation, LPDG group relatively shows less irregular protrusion of the inner surface of endothelial cell of poulmonary artery than MEC group. Conclusions, e concluded that LPDG solution can offer safe lung preservation above 20 hours with adequate immunosuppressive therapy and prevention of the infection.

• Journal of Chest Surgery
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• v.27 no.5
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• pp.345-352
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• 1994

We have performed left lung transplantation followed by ligation of right pulmonary artery in 14 dogs at the Chest Disease Research Institute, Yonsei University College of Medicine from May 1992 to February 1994. Excised left lung was perfused with 1500cc of 4$^{\circ}$C cold Euro-Collin`s[E-C] solution at a pressure of 30cmH2O through main pulmonary artery and preserved in 4$^{\circ}$C cold E-C solution for one hour. Left lung transplantation were proceeded in order of left atrium, left main bronchus, left pulmonary artery and right pulmonary artery ligation as usual method. The femoral artery and pulmonary artery pressures were monitored for more than 5 hours after the transplantations in 14 dogs. Six recipient dogs had elevated mean pulmonary artery pressure to greater than 30mmHg after the left lung transplantation and ligation of right pulmonary artery. The cause of elevated mean pulmonary artery pressure was due to inadequate preservation resulting in ischemic damage to donor lungs in 3 cases, and inadequate surgical techniques in 3 cases. Two recipient dogs without surgical complications died immediate post-operatively due to hemorrhagic shock. The bleeding focuses were LA anastomotic site in one case and femoral artery puncture site in another case. The remaining 6 recipient dogs showed mean pulmonary arterial pressure less than 30mmHg. However, one dog had spontaneous pneumothorax in post-operative 4 days, and another dog had rejection phenomenon in post-operative 5 days which was confirmed by pathologic findings of extracted transplanted lung. One dog succumbed of severe hemoptysis which was due to lung abscess with pin point stenosis of bronchial anastomosis in post-operative 38 days. In conclusion, elevated mean pulmonary arterial pressure greater than 30mmHg in immediate postoperative period can be due to inadequate preservation of extracted lung or poor surgical techniques. And the two dogs succumbed of hemorrhagic shock even though the mean pulmonary arterial pressure was less than 30mmHg. It is thought that careful preservation of the extracted donor lung in 4oC E-C solution and complete surgical techniques are the most important factors early and late complications.

• Tuberculosis and Respiratory Diseases
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• v.46 no.4
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• pp.512-522
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• 1999

Background: Due to the paucity of suitable donor organs for lung allotransplantation, a number of techniques have been developed to improve the lung preservation. Ultrastructural studies of the morphologic changes of the flushing, preservation and reperfusion injury in donor lungs have rarely been reported. Methods: Adult dogs (n=46) were matched as donors and recipients for the single lung transplantation. The donor lungs were preserved after flushing with preservation solution and transplanted after 20-hours of preservation at $10^{\circ}C$. Ultrastructural features of the lung were examined after flushing, preservation and 2 hours after lung transplantation (reperfusion) respectively. Results: Electron microscopy after flushing showed focal alveolar collapse and mild swelling of type I epithelial cells. After preservation both type I epithelial cells and endothelial cells were swollen and destroyed focally. The endothelial cells showed protrusion of tactile-like structures into the lumina, blebs or vacuoles of the cytoplasm After reperfusion the lung tissue showed fibrin material in the alveoli, prominent type I epithelial cell swelling with fragmented cytoplasmic debris and marked endothelial cell swelling with vacuoles or tactile-like projections. The alveolar macrophages showed active phagocytosis. Scanning electron microscopic examination of the pulmonary parenchyma showed focally alveolar collapse and focal consolidation after the preservation and more prominent changes after the reperfusion procedure. The lungs preserved with low potassium dextran glucose solution, with additional prostaglandin $E_1(PGE_1)$ and verapamil(VP) showed relatively well preserved ultrastructures compared with those which were preserved with modified Euro-Collins or University of Wisconsin, and with additional $PGE_1$ and/or VP. Conclusion: The ultrastructural changes associated with flushing were mild in severity, the donor lungs were injured during the preservation, and further damage was occurred during the reperfusion. The reperfusion injury resulted in prominent pulmonary parenchymal alterations with a pattern of acute lung injury.

• Journal of Chest Surgery
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• v.29 no.9
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• pp.931-939
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• 1996

An experimental comparative study was done to determine the protective effects of three preservation solutions on isolated rabbit heart-lung bloc during acute ischemia and reperfusion of the lung during lung transplantation. Thirty Isolated rabbit heart-lung blocs were divided into 3 groups , group I(n:9) was preserved with Hartmann's solution, group II(n: 10) with modified University of Wisconsin solution, and group III(n: 1 1) with Kosin solution. The isolated heart-lung blocs were washed with Hartmann's so ution. Aftar infusion of each preservation solution into pulmonary artery, the heart-lung bloc was stored at 4'c cold preservation solution for each group for 4 hours and .then the heart-lung blocs were reventilated and reperfused. The changes of weight of heart-lung blocs, airway pressure, percent change of PCO2, level of lactate and adenosine deaminase(ADA) and microscopic structure of the lung parenchyme were evaluated. Results were as follows 1. A change of weight of the heart lung bloc after reperfusion was lowest in group 111(p< .05) 2. The airway pressure increased after reperfusion in group I but decreased in group II, and II. Especially in group II, post-reperfusion airway pressure returned to level lower than that of en-bloc resection. 3. Pulmonary artery pressure during reperfusion after 4 hour preservation was lowest in group III, and pulmonary artery pressure in group II was higher than in group I(P> 0.1). 4. The level of lactate and ADA in the lung tissue were higher in group III than in group I and II(P< .05) 5. The percent change of PCO2 in perfusate was slightly higher in group III than group I and II. 6. Microscopic changes in lung tissue after reperfusion were diffuse pulmonary edema, expansion of inter- stitial tissue, focal aggregation of erythrocytes, and basement membrane abnormalities, but no differences were found among the three groups. In conclusion, the protective effects of modified University of Wisconsin solution and Kosin solution were slightly superior to Hartmann's solution.

• Journal of Chest Surgery
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• v.30 no.3
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• pp.253.1-262
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• 1997

Hypothermia during lung preservation decreases metabolic processes. After the rabbit lung was flushed with modified Euro-Collins solution, heart-lung block was harvested and the left lung was assessed after ligation of the right pulmonary artery and right main-stem bronchus. Heart-lung block was immersed in the same solution for 6 hours. The modified Euro-Collins solution and storage temperature of group 1(10 cases) was 4t, roup 2(10 cases) was l$0^{\circ}C$. On completion of the storage period, the left lung was ventilated and reperfused with blood u:high used a cross-circulating paracorporeal rabbit as a "biologic deoxygenator" for 60 minutes. Pulmonary artery pressure, airway pressure, difference in oxygen tension between mow and outflow perfusate and degree of pulmonary edema were assessed at 10-minute intervals while the left lung was ventilated at 0.8 of the inspired oxygen fraction. The mean pulmonary venous oxygen tensions at 10 and 60 minutes after reperfusion were 209.52$\pm$42.46 and 103.48$\pm$ 15.96 mmHg in group I versus 247.78$\pm$36.19 and 147.91 $\pm$ 11.07 mmHg in group II(p=0.049, (0.0001). The mean alveolar-arterial oxygen differences at 20 and 60 minutes after reperfusion were 357. 95$\pm$ 12.84 and 437.31 14.26 mmHg in group I versus 310.88$\pm$3).47 and )90.93$\pm$ 15.86 mmHg in group II (p=0.0092, (0.0001). The mean pulmonary arterial pressures at 10 and 60 minutes after reperfusion were 40.56$\pm$ 18.66 and 87. 2$\pm$ 17.22 mmHg in group I versus 31.22$\pm$6.84 and 65.78$\pm$ 11.02 mmHg in group rl (p : 0.048, 0.0062). The mean pulmonary vascular resistances at 10 and 60 minutes after reperfusion were 2.69$\pm$0.85 and 4.36$\pm$0.86 mmHg/ml/min in group I versus 1.99$\pm$0.39 and 3.29$\pm$0.55 mmHg/ml/min in group II(p : 0.0323, 0.0062). There were no difference between groups in peak airway pressure, lung compliance and degree of pulmonary edema. In conclusion that preservation of lung at l$0^{\circ}C$ was superior to preservation at 4$^{\circ}C$.}C$.