Twenty-hour canine lung preservation using newly developed solutions containing trehalose.
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Analysis of Variance↗
Biomedical subjects
H Yokomise
Publications and source records attributed to H Yokomise.
Inhibition of reperfusion injury by rADF/human thioredoxin in canine lung transplantation.
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Amino Acid Sequence↗
High-dose irradiation prevents rejection of canine tracheal allografts.
We investigated the possibility of immunosuppressant-free transplantation of the trachea using high doses of 60Co gamma irradiation of the graft before transplantation. Twenty mongrel dogs were used. Five rings of the trachea were removed from the donors and irradiated with 60Co gamma rays. Five corresponding rings were removed from the thoracic trachea of the recipient dogs, and the irradiated trachea was transplanted. Five animals were placed in each of four dosage groups: group A, no irradiation; group B, 20,000 cGy; group C, 50,000 cGy; and group D, 100,000 cGy. The anastomotic site and graft were covered with a pedicled greater omentum graft. No immunosuppressants were given. In group A, all the animals died within 1 month of tracheal stenosis caused by graft rejection. In groups B and C, one animal in each group survived for a long period, but all the others died of tracheal stenosis caused by graft rejection. In group D (100,000 cGy), the graft became incorporated into the recipient tissue in four of the five animals, and three are still alive (more than 1 year later). These findings indicate that allotransplantation of the trachea without the use of immunosuppressants is possible with pretransplantation irradiation of the graft at the dose of 100,000 cGy.
Animals↗
Effects of trehalose in canine lung preservation.
BACKGROUND: The effect of trehalose on the preservation of canine lungs was studied with the use of Euro-Collins solution (ECS). METHODS: In group 1, five lungs were perfused and preserved with a modified ECS in which trehalose (35.0 gm/L) was used instead of glucose. In group 2, six lungs were perfused and preserved with a modified ECS in which glucose was replaced by 70.0 gm/L trehalose. In group 3, six lungs were perfused and preserved with ECS. After preservation for 12 hours, left lung transplantation was performed. RESULTS: The PaO2 values in groups 1 and 2 at 130 minutes after reperfusion were 264.9 and 257.5 mm Hg, respectively. These PaO2 values were significantly higher than the corresponding PaO2 value in group 3 (114.8 mm Hg). All the transplanted lungs in groups 1 and 2 had normal structures on histologic examination, whereas five of the group 3 lungs showed severe pulmonary edema. CONCLUSIONS: These findings show that trehalose is effective in the preservation of lungs for 12 hours.
Animals↗
Effects of trehalose in preservation of canine lung for transplants.
The effect of trehalose, a non-reducing disaccharide which stabilizes and protects membranes, in the preservation of canine lungs was examined when Euro-Collins solution was basically used as a preservant. In group I, five lungs were perfused and preserved in an Euro-Collins solution modified by replacing the glucose with 35.0 g/L of trehalose. Five control lungs (group II) were perfused and preserved with Euro-Collins solution containing 35.0 g/L glucose. In both groups, no vasodilators were used. After preservation for 12 hours, left lung allotransplantation was performed. At 10, 40, 70, and 130 minutes after reperfusion, the right pulmonary artery was clamped for 10 minutes and four parameters were measured: arterial oxygen tension, mean pulmonary arterial pressure, peak inspiratory pressure, and wet/dry weight ratios. The transplanted lung was also examined histologically. At 10, 40, 70, and 130 minutes after reperfusion, oxygen-tension levels from group I were 263.2 +/- 19.2, 283.4 +/- 14.0, 277.5 +/- 19.9 and 264.9 +/- 26.2 mmHg, respectively. In group II, the corresponding values were 191.2 +/- 33.9, 188.0 +/- 40.3, 153.4 +/- 40.0 and 134.7 +/- 49.4 mmHg, respectively. At 70 and 130 minutes the difference were significant (p < 0.05). All transplanted lungs from group I showed normal histology, whereas four dogs in group II developed severe pulmonary edema and one had a partially edematous lung. These findings suggest that simple substitution of trehalose for glucose has a beneficial effect on preservation of canine lung for 12 hours.
Anesthesia↗
Preparation of in-vivo rat lung model for ischemia-reperfusion injury.
An in-vivo rat lung model for ischemia-reperfusion injury was prepared. The left lung was collapsed after hilar stripping, and the left main pulmonary artery and bronchus were clamped. After the determined period of clamping the left main pulmonary artery and bronchus were declamped and the right main pulmonary artery was clamped. Arterial gas analyses were performed, 1, 10, and 20 minutes after reperfusion. The wet/dry lung eight ratio was calculated and lungs were histologically examined. Before clamping, PaO2 was 102-155 mmHg in all animals. The experimental animals were divided into 4 groups; Group I: temperature 19 degrees C, humidity 55% and duration of clamping 120 minutes (n = 2); Group II: 23 degrees C, 55% and 120 minutes (n = 4); Group III: 23 degrees C, 55% and 90 minutes (n = 5); Group IV: 23 degrees C, 65% and 75 minutes (n = 9). In Group IV, PaO2 decreased significantly in all 9 animals immediately after reperfusion, and at 1, 10, and 20 minutes it was 53.2 +/- 6.1 mmHg, 53.4 +/- 10.2 mmHg, and 67.0 +/- 10.2 mmHg, respectively. Pulmonary edema was observed histologically in 7 of the 9 animals. In-vivo rat lung models for ischemia-reperfusion injury are affected by the surrounding conditions. We established a stable model by setting ischemic time, temperature, and humidity at 75 minutes, 23 degrees C, and 65%, respectively.
Animals↗
[Present world status and problems resolved in lung transplantation: from the surgical view].
We have summarized the results of international data from many institutes. In 1983 in Toronto, Canada, Cooper performed that first successful clinical case lung-transplantation. Subsequently, there have been more than 1,500 cases of lung transplantation. One reason for Cooper's success was the use of cyclosporin, the other was the performing of omentopexy. Among the total lung transplant cases, single lung transplant comprised 66%, bilateral sequential lung transplant comprised 26%, and en-blocdouble lung-transplant, (8%). Of the 1,540 recipients, the most common underlying of sease was emphysema (360 cases), followed by fibrosis (289 cases), cystic fibrosis (206 cases), alpha-1 antitripsin deficiency (210 cases) and rare diseases including pulmonary hypertension, lymphagiomyomatosis and sarcoidosis. The survival rate of all patients was 68% at 1 year, and 60% at two years.
Adolescent↗
Effect of preoperative irradiation on wound healing after bronchial anastomosis in mongrel dogs.
To determine the endurable radiation dose before bronchial anastomosis, the bronchial circulation of mongrel dogs was assessed after bronchoplastic surgery conducted after various single doses of radiation. Plastic surgery of the right main bronchus was carried out 1 week after cobalt 60 irradiation to the right hilar region. Bronchial blood flow was measured with laser Doppler velocimetry 7, 14, and 30 days after operation. Animals were killed 30 days after operation and the region of the bronchial anastomosis was examined histologically. The animals were divided into five groups: group A (control group without irradiation), group B (8 Gy irradiation), group C (16 Gy), group D (19 Gy), and group E (24 Gy). Wound healing of the anastomosed bronchus was excellent in groups A and B. In group A, bronchial blood flow did not drop below 80% of the preoperative level throughout the postoperative observation period. In group B, bronchial blood flow on day 7 after operation was only 65% of the preoperative level, but blood flow had returned to the preoperative level by day 30. In groups C, D, and E, bronchial blood flow was less than 60% of the preoperative level on day 30. There was a high prevalence of radiation-induced morbidity in the region of anastomosis in groups C, D, and E. Postoperative recovery of bronchial blood flow and wound healing of the anastomosed bronchus were thus delayed in dogs that had received high doses of radiation before operation. We conclude that the safe dose of preoperative radiation in clinically used fractionation is 36 Gy or less (corresponding to a single dose of 16 Gy or less in dogs).
Anastomosis, Surgical↗
[Surgical therapy with adjuvant radiotherapy of thymoma: results of 104 cases].
One hundred and four cases of thymomas were treated between 1967 and 1991 at the Chest Disease Institute, Kyoto University. Forty-two cases were clinical stage I, 12 cases were stage II, 42 cases were stage III and 8 cases were stage IV. Nineteen patients had MG, 17 patients had SVC syndrome. Ninety-six cases were surgically resected combined with radiation therapy. Overall survival was 77.9% at 5 years and 62.5% at 10 years. The survival of 62 cases of invasive thymoma was 77.5% at 5 years and 54.8% at 10 years. We've got better prognosis when total or subtotal resection of invasive thymoma could be accomplished, i.e. 88.8% at 5 years and 72.6% at 10 years.
Female↗
Successful 12-hour lung preservation with trehalose.
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Animals↗
Omentopexy for revascularization of free tracheal grafts in rats.
In rats, we examined the effect of an omentum wrapping on the vascularization of the trachea and on regeneration of the mucosal epithelium in the very early stage after free tracheal grafting. Two pieces of trachea were obtained from each donor rat. One piece was transplanted into the peritoneal cavity of the recipient rat and wrapped with omentum. The other piece was transplanted subcutaneously into the abdominal wall, without omentopexy. Recipients were sacrificed at random on days 1, 2, 3, and 4 after operation (5 rats/day). The increase of blood vessels rose significantly earlier in the omentopexy tracheas than in those without omentopexy (p less than 0.01), with all the former showing a normal ciliated, columnar epithelium in the membranous region of the trachea on day 4, accompanied by excellent epithelial regeneration in the cartilaginous region. These results suggest that omentopexy causes revascularization to occur earlier and to be completed in a shorter time, and that it also promotes epithelial regeneration following free tracheal grafting.
Animals↗
Laser Doppler velocimetry measurement of canine mucosal circulation response to bronchial artery reperfusion after lung transplantation.
Left lung transplantation accompanied by reestablishment of the circulation of the bronchial arteries by simultaneous transplantation of part of the aorta was performed on seven dogs. Mucosal circulation of the bronchi at the anastomosis was evaluated using laser Doppler velocimetry (LDV). Since the donor lung must maintain blood supply through the bronchial arteries, the donor aorta from its ascending portion to the descending portion below the outlet for the last bronchial artery was retained with the lung graft. The distal end of the left brachiocephalic artery was sutured to the side of the recipient aorta when the blood supply to the bronchial arteries was to be restored. The LDV values before reperfusion of the bronchial arteries were 20 to 65% (mean: 42.8%) of the preoperative value. Since the LDV values increased to 36 to 125% (mean: 79.9%) of the control, blood flow to the bronchial mucosa increased evidently. Four out of seven dogs died one to two days after the operation due to bleeding and operative stress. One dog was sacrificed on the 4th postoperative day and another on the 16th. The last dog died 40 days after surgery. The unfavorable course of the LDV values in these three dogs suggest that the method used does not ensure an adequate blood supply to the bronchial arteries in the long term.
Animals↗
Combination use of suboptimal dose of FK 506 and cyclosporine in canine lung transplantation.
The immunosuppressive potency and the side effects of combination therapy with FK 506 and cyclosporine A were studied in dogs that had undergone lung transplantation. The animals were divided into four groups: group A (one third optimal FK 506 dose: FK 506, 0.03 mg/kg intramuscularly) (n = 5), group B (one third optimal cyclosporine dose: cyclosporine 6 mg/kg orally) (n = 5), group C (one third FK 506 and one third cyclosporine optimal doses): FK 506, 0.03 mg/kg intramuscularly plus cyclosporine 6 mg/kg orally) (n = 5), and group D (half FK 506 plus half cyclosporine optimal doses: FK 506, 0.05 mg/kg intramuscularly, plus cyclosporine, 10 mg/kg orally) (n = 10). Assessments including chest x-ray film, fiberoptic bronchoscopy, hematologic and biochemical tests, FK 506 and cyclosporine blood trough level measurement, right pulmonary artery occlusion test, and histopathologic observations were performed. In group A two of five dogs survived 28 days and three died on postoperative days 7, 14, and 21. In group B one dog survived 28 days and four died on postoperative days 9 (two dogs), 14, and 21. Histologic examination showed severe rejection in both group A and group B. In group C all five dogs survived 28 days but showed mild rejection. In group D one dog died of intestinal bleeding on postoperative day 7 and nine survived 28 days. No pathologic changes were observed except in one case of mild rejection. The ventilation function of the transplanted lung was poor in groups A, B, and C but good in group D. No abnormal rise of FK 506 and cyclosporine trough levels was observed. There were no significant side effects and abnormal hematologic and biochemical data except in one dog in group D. We concluded (1) the combination of FK 506, 0.03 mg/kg, and cyclosporine, 6 mg/kg, is much more effective than either drug used singly, (2) the combination of FK 506, 0.05 mg/kg, and cyclosporine, 10 mg/kg, prevents rejection with tolerable side effects, and (3) no worse side effects are caused by combination therapy with FK 506 and cyclosporine than by either one used singly.
Animals↗
The role of dextran 40 and potassium in extended hypothermic lung preservation for transplantation.
We have previously demonstrated that a low-potassium dextran solution provides superior and more reliable preservation of lungs for 12 hours than that provided by the commonly used Euro-Collins solution. This study was designed to examine the individual contributions of dextran 40 and a low (extracellular) potassium concentration to lung preservation. In a randomized, blinded study using an in vivo canine single-lung transplant model, lungs preserved with low-potassium dextran solution (K+, 4 mmol/L; dextran 40, 20 gm/L) were compared to lungs preserved with low-potassium, no-dextran solution (K+, 4 mmol/L) and high-potassium dextran solution (K+, 123 mmol/L; dextran 40, 20 gm/L). The lungs were assessed immediately and 3 days after transplantation. The low-potassium dextran solution provided excellent immediate pulmonary function with little variability (arterial oxygen tension, 519 +/- 12 mm Hg, measured on the transplanted lung alone, inspired oxygen fraction = 1.0, n = 6). Removing the dextran 40 from the flush solution (low-potassium group) led to a significant deterioration in pulmonary function (arterial oxygen tension, 243 +/- 78 mm Hg, n = 6, p less than 0.01). The high-potassium dextran solution provided extremely poor preservation (arterial oxygen tension, 176 +/- 79 mm Hg; n = 6; p less than 0.01). Two animals in this group died within 6 hours of operation. Viability of the transplanted bronchus was significantly improved with the two solutions containing dextran 40. These results indicate that dextran 40 and low potassium concentration both contribute significantly to the uniformly excellent 12-hour lung preservation seen with the low-potassium dextran solution.
Animals↗
The immunosuppressive effect of FK 506 on canine lung transplantation.
The immunosuppressive potency of FK 506 was studied after left lung transplantation in adult mongrel dogs in comparison with cyclosporine. Fiberoptic bronchoscopy, bronchial mucosal blood flow measurement with laser Doppler velocimetry, and chest x-ray and pathologic examinations were performed. Group A had no immunosuppression (n = 5); group B received FK 506 (0.10 mg/kg/day intramuscularly (n = 5); group C received cyclosporine (20 mg/kg/day orally) (n = 5). In group A four dogs died of rejection on the seventh to the twenty-first postoperative days. Another one was killed on the fourteenth postoperative day because bronchial dehiscence occurred at the anastomosis. In group B one died of alveolar rejection on the seventh postoperative day. The remaining four survived 28 days and were put to death. In group C all five dogs survived 28 days and were put to death. In group A bronchial stenosis or dehiscence at the anastomosis was found in every one during the early postoperative period. In group B stenosis did not develop in any of the dogs, including the one that died on the seventh postoperative day. In group C slight stenosis was seen in one dog, severe narrowing in another, and good healing in the remaining three. The transplanted lungs were almost normal histologically in four animals of group B, and one showed alveolar phase rejection. In all animals of group A severe rejection was observed, and in group C two of five animals showed vascular phase rejection, two latent phase, and one fibrosis. Histologic examination of the bronchial anastomosis in group B showed almost normal bronchial epithelium and slight submucosal infiltration of mononuclear cells. In group A there was desquamation of epithelium and mild to moderate mononuclear cell infiltration. In group C hyperplasia of the epithelium was observed in two animals, an abscess at the site of anastomosis in one, and mild to moderate mononuclear cell infiltration in all five. With use of laser Doppler velocimetry, bronchial blood flow in group B was found to be the same as in group C. Laser Doppler velocimetry values reached preoperative levels by the twenty-eighth postoperative day in both groups. Although diarrhea developed in two dogs of group B, no other significant side effect of FK 506 was seen.
Animals↗
Optimal dose of FK 506 in canine lung allotransplantation.
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Animals↗
A new method for carinal reconstruction: an experimental study.
We developed a new procedure for carinal reconstruction which can be used for lesions of the carina invading the left main bronchus. Twelve mongrel dogs were used. A Y-shaped bronchial graft was autotransplanted from the bifurcation of the right upper bronchus to form a new carina with or without an omentopexy. Six animals survived 10 days to 11 months. In these animals healing of the bronchial anastomotic sites was excellent, and the integrity of the grafts was well preserved. Although the results of this preliminary report were not satisfactory in all cases, intensive perioperative care will improve the outcome of this new procedure.
Animals↗
The effect of PGE1 and temperature on lung function following preservation.
We studied the effect of a vasodilator (prostaglandin E1) as well as flush (F) and storage (S) temperatures (4 degrees C or 10 degrees C) on lung preservation in an isolated rabbit lung perfusion model. Low-potassium dextran (LPD) or Euro-Collins (E-C) solution was used as flush solution. Six groups of six animals were studied: group 1 (LPD, 4 degrees C F-S), group 2 (LPD with PGE1, 4 degrees C F-S), group 3 (E-C with PGE1, 4 degrees C F-S), group 4 (LPD, 10 degrees C F-S), group 5 (LPD with PGE1, 10 degrees C F-S), group 6 (E-C with PGE1, 10 degrees C F-S). After 18-hr preservation, left lungs alone were ventilated, and reperfused with fresh venous blood. PaO2, PaCO2, pulmonary artery pressure (PAP), tracheal pressure (Pt) during reperfusion, and wet/dry weight (W/D) ratios were measured. PaO2 after LPD with or without PGE1 was significantly higher than after E-C with PGE1 at 4 degrees C (95.8 +/- 11.5 mmHg in group 1 or 102.7 +/- 8.6 in group 2 vs. 41.8 +/- 10.5 in group 3, P less than 0.01) and at 10 degrees C (119.3 +/- 2.3 in group 4 or 131.1 +/- 6.2 in group 5 vs. 54.6 +/- 5.2 in group 6, P less than 0.01). PaCO2, PAP, Pt, and W/D ratios in the LPD groups were lower than in the E-C groups. LPD/PGE1 and LPD alone produced similar pulmonary preservation. PaO2 of lungs flushed with LPD and preserved at 10 degrees C was higher than that of lungs stored at 4 degrees C. We conclude that LPD solution is superior to E-C solution in this ex vivo rabbit lung preservation model, even when PGE1 is used. A moderate dose of PGE1 did not improve the performance of LPD as a flush solution. Pulmonary preservation with LPD at 10 degrees C is superior to preservation at 4 degrees C.
Alprostadil↗