Tracheal allotransplantation after varying terms of cryopreservation.
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Animals↗
Biomedical subjects
M Aoe
Publications and source records attributed to M Aoe.
Expression of endothelin-1 and effects of an endothelin receptor antagonist, TAK-044, at reperfusion after cold preservation in a canine lung transplantation model.
BACKGROUND: Rapid increase of pulmonary vascular resistance (PVR) early after reperfusion remains a major issue in clinical lung transplantation. A potent vasoconstrictor peptide, endothelin- plays an important role in various pulmonary pathophysiologic conditions and might induce increased PVR. We investigated the expression and influence of endothelin-1, and the effects of an ETA and ETB nonselective endothelin receptor antagonist, TAK-044, at reperfusion after cold preservation in a canine lung transplantation model. METHODS: Left single lung allotransplantation procedures were performed in three groups of animals. In group I (n=5) lungs were preserved for 12 hours; in group II (n=5) lungs were preserved for 18 hours; and in group III (n=6) lungs were also preserved for 18 hours, and TAK-044 (5 mg/kg) was administered just before reperfusion. All donor lungs were flushed and preserved with low-potassium dextran glucose solution at 4 degrees C. RESULTS: Six hours after reperfusion, arterial oxygen tension (mm Hg, inspired oxygen fraction=1.0) was 512.9+/-34.7 in group I, 152.4+/-46.7 in group II, and 509.6+/-29.0 in group III; PVR index (dyne x sec x cm(-5) x m2) was 1130+/-142 in group I, 1820+/-142 in group II, and 1287+/-191 in group III. Plasma endothelin-1 level was elevated significantly, and endothelin-1-like immunoreactivity was found in a variety of pulmonary vascular tissue and was seen less with immunohistochemical evaluation in group II in bronchial tissue. CONCLUSIONS: These results suggest that endothelin-1 is expressed as a result of ischemia-reperfusion injury and may worsen early graft function. TAK-044 is beneficial in protecting the graft from high pulmonary vascular resistance and pulmonary edema during the early posttransplantation stage.
Animals↗
[A case report of dumbbell neurogenic tumor of the superior mediastinum].
A 15-year-old female was admitted because of the superior mediastinum mass on chest X-rays and sensory loss of ulnar side of the left arm. Computed tomographic scanning and magnetic resonance imaging revealed that the tumor was dumbbell-shaped and invaded the vertebral canal through the intervertebral foramen between C 7 and Th 1. At first laminectomy of vertebrae (C 6-Th 1) was made in a prone position and intra-spinal portion of the tumor was resected. Then the patient was placed in a supine position and the chest was opened by left hemicollar incision and sternotomy to the 2nd intercostal space. The tumor was divided into two parts at the level of 1st rib and completely removed. The pathological diagnosis was schwannoma. This procedure is safe and useful for dumbbell type tumor located in superior mediastinum, especially in case of large tumor from neck to the thoracic cavity.
Adolescent↗
EPC-K1 is effective in lung preservation in an ex vivo rabbit lung perfusion model.
BACKGROUND: L-Ascorbic acid 2-[3,4-dihydro-2,5,7,8-tetramethyl-2-(4,8,12-trimethyltridecyl)-2H -1-benzopyran-6yl-hydrogen phosphate] potassium salt (EPC-K1) is a phosphate diester of alpha-tocopherol and ascorbic acid. It has been reported that EPC-K1 inhibits lipid peroxidation and phospholipase A2. We hypothesized that EPC-K1 might enhance lung preservation and reduce the degree of posttransplantation lung dysfunction. METHODS: Eighteen rabbits were divided into three groups, as follows: group 1, no preservation (n = 6); groups 2 (n = 6) and 3 (n = 6), 24 hours of preservation at 8 degrees C. Low-potassium dextran-1% glucose solution was used for flushing and immersion in all groups, but EPC-K1 (0.5 mg/L) was added to the solution used in group 3. After storage the left lung was reperfused with autologous blood and ventilated using a membrane oxygenator in an isolated rabbit lung reperfusion model. The grafts used in the group 1 rabbits were perfused for 5 hours to confirm the reliability of this model, and the grafts used in the group 2 and 3 rabbits were perfused for 2 hours. Pulmonary arterial pressure, airway pressure, blood gas analysis, and the lipid peroxide level of the perfusate were assessed. The lipid peroxide levels of the lung tissue before and after storage and the wet-dry weight ratio of the perfused lung were determined in groups 2 and 3. RESULTS: Superior graft function was noted in group 3 in terms of all indices. The lipid peroxide level in the perfusate and the wet-dry weight ratio were also suppressed in group 3. The lipid peroxide level in the lung tissue did not change during storage in either group. CONCLUSIONS: The administration of EPC-K1 in the flush and preservation solution helps enhance lung graft function and suppresses lipid peroxidation after reperfusion.
Animals↗
[Four cases of thymoma associated with pure red cell aplasia].
Thymomas associated with pure red cell aplasia (PRCA) constituted only 3.3% of 122 thymomas treated in our department from 1963 to March, 1995. Four patients with this disease (2 men and 2 women, mean age: 58 years, range: 41 to 66 years old) are reported. Auto-antibodies were found in all 4 cases, increase of T cell in two, suppression of erythropoietin production in one, and antibody to EB virus in one. Operation was performed in all cases (two thymothymectomies, one extended thymothymectomy, and one thymomectomy), and 3 of 4 patients were in the progressive stage of Masaoka's classification (I, III, IVa, and IVb each). As for the pathological findings, mixed type was found in three cases and lymphocyte predominant type in one. Two patients died from radiation pneumonia. As for PRCA, postoperative therapy was effective (100%) in all patients.
Adult↗
[One-stage bilateral lung volume reduction surgery with median sternal incision for diffuse pulmonary emphysema].
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Aged↗
[PCR-RFLP analysis of epithelium in canine cryopreserved tracheal allograft].
In this study, we investigated whether the regenerated epithelia were recipient phenotype or donor phenotype using PCR-RFLP (polymerase chain reaction-restriction fragment length polymorphism) method. Preoperatively 24 mongrel dogs were classified to 14 types by PCR-RFLP result from peripheral blood. The PCR-RFLP result of peripheral blood agreed to that of recipient epithelia. The cryopreserved tracheal allotransplantation was performed among the five pairs in which we could distinguish donor from recipient by PCR-RFLP. The epithelia of graft at 10 days after transplantation showed donor phenotype, but the epithelia at postoperative 20 days or more showed recipient phenotype. These results showed that allogenic epithelium remained in early post-transplant time and was gradually omitted. The epithelia migrated gradually from the anastomotic site, and the graft was covered with regenerated epithelia showing recipient phenotype within about 50 post-transplant days.
Animals↗
The effect of combination therapy with EPC-K1 and low-dose cyclosporine to pulmonary allograft after rat lung transplantation.
BACKGROUND: EPC-K1, a diester of alpha-tocopherol and ascorbic acid, has a hydroxyl radical scavenging effect and also has antiinflammatory properties through its phospholipase A2 inhibitory effect. With a view to decreasing the total dose of cyclosporine, the effect of a combination of EPC-K1 and cyclosporine on rejection was investigated by use of a rat orthotopic left lung transplantation model. METHODS: Orthotopic left lung transplantation was performed with brown Norway rats as donors and Lewis rats as recipients. Recipients were assigned to one of four experimental groups. Control group animals were given no immunosuppression. The EPC-K1 group received continuous intraperitoneal infusion of EPC-K1 (5 mg/kg/day) by osmotic pump on postoperative days (POD) 0 through 6. The cyclosporine group received cyclosporine (1.25 mg/kg/day) intramuscularly on POD 1 through 6. The EPC-K1 + cyclosporine group received both EPC-K1 and cyclosporine in the same manner as the EPC-K1 and cyclosporine groups. Recipients were killed on POD 7, and the transplanted lungs were examined histologically and graded in a blinded fashion (grade 0 to 4). The effect of EPC-K1 and cyclosporine treatment on the primary immune response was examined by mixed lymphocyte reaction (MLR) between brown Norway rat stimulator cells (treated with mitomycin) added to Lewis rat responder lymphocytes. RESULTS: Control group animals exhibited the severe destructive changes of grade 4 lung rejection. The EPC-K1 + cyclosporine group showed significantly less graft rejection compared with the EPC-K1 group and the cyclosporine group (p < 0.01). In MLR assay, the EPC-K1 + cyclosporine group (793 +/- 210 cpm) showed significantly suppressed lymphocyte proliferation compared with the control group (2188 +/- 360 cpm), EPC-K1 group (1869 +/- 541 cpm), and cyclosporine group (1873 +/- 326 cpm) (p < 0.01). CONCLUSION: EPC-K1 significantly improves effects of cyclosporine at lower doses both in preventing pulmonary allograft rejection and in suppressing lymphocyte proliferation in MLR.
Animals↗
Efficacy of combining donor-specific presensitization with a simultaneous single injection of tacrolimus on pulmonary allografts.
BACKGROUND: We investigated the effects of combining donor-specific presensitization with a simultaneous injection of tacrolimus by use of a fully allogeneic rat lung allograft model. METHODS: Lungs from Brown Norway donor rats were orthotopically transplanted into Lewis recipient rats. Seven days before transplantation, allograft recipients received a transfusion of donor splenocytes (1 x 10(8) cells, intravenously), tacrolimus (3 or 1.5 mg/kg, intramuscularly), or a combination. No posttransplantation immunosuppression was given. In the transplantation study, graft survival was evaluated, and histologic characteristics of acute rejection were graded. In the in vitro studies, mixed lymphocyte reaction assays were used to investigate the effects of pretreatment on immune response. RESULTS: The graft survival evaluation disclosed that untreated rats rejected the allografts at 4.6 +/- 0.2 days. Donor splenocyte transfusion alone accelerated the graft rejection (3.3 +/- 0.2 days). Tacrolimus (3 mg/kg) alone moderately improved the graft survival (8.7 +/- 0.6 days). When donor splenocyte transfusion was combined with tacrolimus, graft survival was significantly increased to 29.6 +/- 12.0 days. In a mixed lymphocyte reaction assay, peripheral blood lymphocytes obtained from animals pretreated with donor splenocyte transfusion alone seemed to be hyperresponsive against the donor lymphocytes. In contrast, donor splenocyte transfusion with tacrolimus significantly suppressed the proliferative response against the donor lymphocytes but not against third-party lymphocytes obtained from naive Wistar King A rats. CONCLUSION: These data demonstrate that donor-specific presensitization with a simultaneous single injection of tacrolimus prevented both sensitization and graft rejection and induced donor-specific unresponsiveness.
Animals↗
Effect of a single injection of high-dose FK506 on lung transplantation in rats.
Orthotopic left lung grafts from Brown Norway (BN) donors were transplanted to Lewis (LEW) rat recipients which had been treated with a single dose of FK506 10mg/kg body weight intramuscularly on postoperative day 3. Although the lungs were rejected with a median survival time of 7 days, with a range of 6-8 days in the untreated controls, maximum survival was prolonged to 60 days. The major adverse effects of this therapy were reduction of feeding, loss of body weight, and diarrhea. One of the 7 rats died on the 21st postoperative day due to anorexia. The effects of this therapy were investigated by histopathological examination and flow cytometric analysis using monoclonal antibodies against rat lymphocytes: OX-39 (anti-interleukin 2 receptor (IL-2R)) and OX-6 (anti-class II MHC). Histopathologically, the lung allografts showed mild perivascular and peribronchiolar cuffs of mononuclear cells, while marked reduction of the thymic medulla with FK506 treatment was also observed. Flow cytometric analysis of the transplanted lung showed no significant changes. Regarding the thymus, the percentages of positive cells labeled with OX-39 and OX-6 were significantly suppressed after this treatment. In the spleen, the number of OX-6-positive cells significantly decreased. The results using this therapy thus suggest that the suppression of IL-2R and MHC class II expression was systemically maintained for a long time.
Animals↗
Hyperinflation of canine lung allografts during storage increases reperfusion pulmonary edema.
The optimal state of inflation for lung allografts during preservation is not known. We previously showed that hyperinflation of canine lung allografts during storage improved posttransplant graft function as measured during 10 minutes of contralateral pulmonary artery occlusion. However, we have also shown that hyperinflation during storage increases pulmonary capillary permeability. It is possible that short-term total cardiac perfusion through the transplanted left lung (for assessment) may not adequately reproduce the clinical situation. The purpose of this study was to assess the effects of hyperinflation during storage in a canine left single-lung transplantation model in which all perfusion was continuously directed to the graft after implantation. Twenty canine left single-lung transplants were done. The lungs of donor animals were ventilated at a tidal volume of 750 ml and an inspired oxygen fraction of 100%. Donor lungs were flushed with modified Euro-Collins solution and the trachea occluded at end inspiration. For donors in groups I and III, the trachea was sealed at that postinflation volume. In groups II and IV, 200 cc of air was withdrawn from the endotracheal tube under positive pressure and the trachea sealed at the lower tidal volume. Lungs were then extracted and stored at 1 degree C for 12 hours. After the preservation period, left lung transplants were performed. After implantation in all groups, the right pulmonary artery was ligated. In groups I and II, the right bronchus was ligated and in groups III and IV the right bronchus was kept open. Subsequent allograft gas exchange and hemodynamics were assessed during a 6-hour period of reperfusion. After assessment, both lungs were excised, wet/dry lung weight ratio was calculated, and histologic examination was done. During the 6-hour assessment, lungs stored in a state of hyperinflation (groups I and III) showed rapid deterioration of gas exchange. At the final assessment, arterial oxygen tension and alveolar-arterial oxygen gradient of groups I and III were significantly worse than those of groups II and IV (group I versus group II: arterial oxygen tension 87.5 +/- 15.0 versus 373.8 +/- 65.5 mm Hg, alveolar-arterial oxygen gradient 564.4 +/- 13.2 versus 298.6 +/- 69.3 mm Hg, p < 0.05; group III versus group IV: arterial oxygen tension 245.4 +/- 33.0 versus 543.6 +/- 41.8 mm Hg, alveolar-arterial oxygen gradient 392.5 +/- 35.6 versus 120.5 +/- 34.7 mm Hg, p < 0.01). We conclude that donor lung hyperinflation during storage does not provide better posttransplant allograft function when perfusion is limited only to the allograft.
Animals↗
Inhaled nitric oxide improves lung allograft function after prolonged storage.
Morbidity caused by early allograft dysfunction, manifested by a progressive increase in pulmonary vascular resistance and a decrease in oxygenation, remains a serious problem in lung transplantation. Inhalation of nitric oxide, an essential homeostatic molecule, has been shown to have beneficial effects on a variety of acute lung injuries. The purpose of the present study was to investigate the effect of inhaled nitric oxide on posttransplant function of canine left lung allografts. Fourteen dogs underwent left lung allotransplantation. Donors received systemic heparin and prostaglandin E1 followed by pulmonary artery flush with modified Euro-Collins solution. Donor left lungs were stored for 18 hours at 1 degree C and subsequently implanted. Immediately after reperfusion, the contralateral right main pulmonary artery and bronchus were ligated. The chest was closed and recipients turned to the supine position for the 6-hour assessment period. Hemodynamic and arterial and venous blood gas analyses were made at 15-minute intervals at an inspired oxygen fraction of 1.0 and 5 cm of water positive end-expiratory pressure. Animals were killed at the end of the assessment. Allograft myeloperoxidase activity assays and wet/dry weight ratios were done. In group I (n = 5), nitric oxide gas was administered continuously at concentrations of 60 to 70 ppm before reperfusion and throughout the 6-hour assessment period. In group II (n = 5), nitric oxide administration was initiated at the same concentration after reperfusion injury had developed. Group III animals (n = 4) received no nitric oxide. Significant improvement in gas exchange was apparent in group I. At the end of the 6-hour assessment period, mean arterial oxygen tension was 253.8 +/- 44.7 mm Hg and 114.9 +/- 25.5 mm Hg in groups I and III, respectively (p < 0.05). Group II animals had no improvement in oxygenation with nitric oxide. Systemic hemodynamics were unaffected by nitric oxide. However, an immediate decrease in pulmonary vascular resistance was noted. Group I myeloperoxidase activity was significantly lower than that in control group III (0.24 +/- 0.06 versus 0.36 +/- 0.04 units, respectively; p < 0.05).
Administration, Inhalation↗
[Thoracoscopic extended thymectomy in conjunction with a collar incision of the neck for cases of myasthenia gravis].
Extended thymectomy in conjunction with a collar incision of the neck was performed thoracoscopically for a 64-year-old women with myasthenia gravis. Although this patient had Osserman type II B myasthenia gravis not associated with a thymoma, the clinical symptoms were alleviated after the surgery. Although this surgical procedure has the disadvantage such as of being time-consuming, it also has various advantages such as: 1) extended thymectomy can be performed without a midsternotomy, 2) the wound is small and not prominent, 3) surgical invasiveness is slight, and 4) postoperative pain is mild. This method was considered to be an extremely useful surgical method which should be used in future for cases of myastenia gravis not associated with a thymoma.
Endoscopy↗
[A case of thymoma in an elderly patient associated with myasthenia gravis].
A case of thymoma in an elderly patient associated with myasthenia gravis (MG) was reported. A 81-year-old female with growing dim of eye was diagnosed as MG, and treated with Mestinon. Two months later, she was detected to have an anterior mediastinal tumor on chest rentogenography and CT. She was diagnosed as MG (Osserman type IIA) with thymoma by Tensilon test and high anti-acetylcholine-receptor antibody level. Extended thymothymectomy was performed and the tumor was encapsulated and not invasive (stage I, lymphocyte predominant type). Postoperative course was good and subjective symptoms were improved without medication.
Age of Onset↗
[A case of catamenial hemoptysis (pulmonary endometriosis) cured by VATS lobectomy].
We report here a case in which for hemoptysis during menstruation (catamenial hemoptysis) right middle lobectomy was performed thoracoscopically under a preoperative diagnosis of pulmonary endometriosis with a successful outcome. The patient was a 27-year-old housewife who from the age of 24 years experienced hemoptysis during menstruation, and was diagnosed as having pulmonary endometriosis on the basis of detailed examinations including bronchoscopy and chest CT. From the age of 26 years hormone therapy was administered, but the hemoptysis recurred with the menstruation following its cessation. After admission to this department bronchoscopy performed at the time of menstruation revealed bleeding from right B4 while chest CT showed an abnormal shadow in right S4 b. Right middle lobectomy was then performed thoracoscopically under a diagnosis of right middle lobe endometriosis. In the resected specimen findings of pulmonary hemosiderosis, granulomatous phlebitis and micrometastases from a thyroid cancer were noted. The postoperative course was favorable with no further episodes of hemoptysis occurring. In this case histological proof of endometriosis could not be obtained, but the diagnosis of pulmonary endometriosis was strongly suggested by the clinical course and objective findings such as pulmonary hemosiderosis.
Adult↗
[Thoracoscopic surgery of lung tumors].
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Endoscopy↗
[A clinicopathological study of adenosquamous carcinoma of the lung].
We studied, clinicopathologically, 34 cases of adenosquamous carcinoma (ASC) treated in our institution over the last 30 years. Its incidence was 2.3% of all primary lung cancers. Following findings were characteristics to this type of lung cancer, male dominant, old age, heavy smoker, comparatively large diameter, peripheral location, and normal level of tumor makers. The 5-year survival rates were 35.0% for ASC, 38.1% for squamous cell carcinoma (SCC), and 50.2% for adenocarcinoma (AC). The component of SCC was predominant or equal to that of AC in 27 (79.4%) ASC cases. The degree of cell differentiation was moderate and both SCC and AC components showed the same degree of cell differentiation in most cases. Lymph node metastasis was seen in 15 (48.4%) cases.
Aged↗
Improved lung function by urokinase infusion in canine lung transplantation using non-heart-beating donors.
We evaluated the effect of urokinase on pulmonary microthrombi formation of the donor lung using a canine cadaver left lung allotransplantation model. Donor animals were sacrificed with an intravenous injection of potassium chloride without heparinization and were divided into three groups. In group 1 (n = 6), cadavers were left at room temperature for 1 hour, and lung retrieval was then performed after flushing the lung block with low potassium-dextran-glucose solution. Donor lungs were stored for 3 hours at 8 degrees C. In group 2 (n = 6), donor lungs were treated as in group 1 except that the cadavers were left at room temperature for 2 hours instead of 1 hour before lung retrieval. In group 3 (n = 6), donor lungs were treated as in group 2 except that high-dose urokinase (120,000 IU) was injected into the main pulmonary artery after flushing with low-potassium-dextrose-glucose solution. In all groups after left lung transplantation, the right pulmonary artery was ligated, and recipient animals were followed up for 6 hours after reperfusion. The fibrin degradation product level in the donor lung tissue was also measured. All recipient animals in group 1 survived the 6-hour observation period with excellent gas exchange and stable hemodynamics. Group 3 had significantly better gas exchange than group 2 and similar cardiopulmonary function as group 1. The fibrin degradation product level in the donor lungs before transplantation was significantly higher in group 3 than in group 2.(ABSTRACT TRUNCATED AT 250 WORDS)
Animals↗