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Biomedical subjects

I Nagahiro

Publications and source records attributed to I Nagahiro.

29 records · Page 2Linked to original sources

[Five cases of pulmonary thromboembolism after chest surgery].

The incidence of pulmonary thromboembolism after chest surgery is increasing. Five cases of it in recent two years were described. Four cases were lung cancer, and the other was myasthenia gravis. All lung cancer cases were after left lobectomy, and the findings of thromboembolism were mainly detected in right lung. Though hypocapnia is characteristic of pulmonary thromboembolism, arterial blood gas tests did not show it in all cases. Slight hypoxemia and arrhythmia are noteworthy signs of pulmonary thromboembolism after chest surgery. As thrombolytic and anticoagulation therapy, urokinase and heparin were very useful in four of five cases. Four patients made a rapid recovery from pulmonary thromboembolism, but one died of cerebral hemorrhagic infarction. The other patient did not recover in spite of intense medication, extracorporeal membrane oxygenation, and pulmonary embolectomy. To prevent pulmonary thromboembolism after chest surgery, appropriate countermeasures should be considered.

Aged↗

[First successful bilateral living-donor lobar lung transplantation in Japan].

No successful lung transplantation has been reported in Japan until recently when we performed the first successful bilateral living-donor lobar lung transplantation. A 24-year-old woman with primary ciliary dyskinesia began experiencing severe respiratory insufficiency and required mechanical ventilation. On October 28, 1998, she underwent bilateral living-donor lobar transplantation, receiving her sister's lower right lobe and her mother's left lower lobe under cardiopulmonary bypass. The patient was discharged from the hospital 61 days after transplantation. Six months postoperatively, she has returned to normal life and is able to carry out daily activities. She is in good physical condition with a vital capacity of 1.77 L.

Adult↗

Recombinant Kunitz protease inhibitor ameliorates reperfusion injury in rat lung transplantation.

BACKGROUND: Recombinant Kunitz protease inhibitor (rKPI-BG022) is more homologous to human Kunitz protease inhibitor than is aprotinin. Because aprotinin has been reported to inhibit free radicals, we hypothesized that rKPI would ameliorate reperfusion injury caused by free radicals. We examined its effect and the timing of administration in an in vivo rat lung transplantation model. METHODS: All lungs were flushed with low-potassium dextran-1% glucose solution and stored for 24 hours at 4 degrees C, then orthotopic left lung transplantations were performed. Rats were divided into 4 groups (n=6) as follows: group 1 served as control; in Group 2, rKPI was added to the flush solution (10 micromol/L); in group 3, rKPI (5 mg/kg) was administered intravenously to the recipient just after reperfusion; and in group 4, rKPI was added to the flush solution (10 micromol/L) and rKPI (5 mg/kg) was administered intravenously to the recipient just after reperfusion. Twenty-four hours after transplantation, the right main pulmonary artery and right main bronchus were ligated, and the rats were ventilated with 100% O2 for 5 minutes. Peak airway pressure, blood gas analysis, serum lipid peroxide level, tissue myeloperoxidase activity, and wet-dry weight ratio were measured. RESULTS: The partial oxygen tension values of group 2 were higher than those of groups 1 and 4 (groups 1, 2, and 4: 104.8+/-15.8, 245.1+/-49.0, 101.4+/-4.5 mm Hg, respectively; p < 0.01). The partial carbon dioxide tension values of groups 3 and 4 were lower than those of group 1 (groups 1, 3, and 4: 74.5+/-5.7, 42.0+/-11.0, 46.0+/-8.4 mm Hg, respectively; p < 0.05). Peak airway pressures were lower in groups 2 and 3 than in groups 1 and 4 (groups 1, 2, 3, and 4: 22.5+/-0.5, 18.2+/-0.5, 19.2+/-0.8, 22.5+/-1.1 mm Hg; p < 0.01). Serum lipid peroxide levels in groups 2 and 3 were lower than those of groups 1 and 4 (groups 1, 2, 3, and 4: 0.793+/-0.037, 0.577+/-0.069, 0.560+/-0.029, and 0.785+/-0.053 nmol/mL, respectively; groups 2 and 3 vs group 1, and group 3 vs group 4: p < 0.01; group 2 vs group 4: p < 0.05). There were no differences in wet-dry weight ratio and tissue myeloperoxidase activity between the groups. CONCLUSION: Recombinant Kunitz protease inhibitor ameliorates reperfusion injury caused by free radicals in an in vivo rat lung transplantation model. Administration of rKPI through the flush solution and intravenous injection after reperfusion were effective separately, but the combination of the two administrations was not effective.

Animals↗

Vasoactive intestinal peptide ameliorates reperfusion injury in rat lung transplantation.

BACKGROUND: Vasoactive intestinal peptide (VIP) has been reported to have some properties that provide protection from lung injury. Furthermore, its protective effect in cold storage of donor lungs has been confirmed. We examined its effect and the timing of administration in an in vivo rat lung transplantation model. METHODS: All lungs were flushed with low-potassium dextran-1% glucose solution, and orthotopic left lung transplantations were performed. Rats were divided into four groups (n = 6). Group I received no preservation or storage. Groups II, III, and IV grafts were stored for 18 hours at 4 degrees C. Group II received no VIP. Group III received VIP (0.1 g/ml) via the flush solution. Group IV recipients received VIP (3 microg/kg) intravenously just after reperfusion. Twenty-four hours after transplantation, the right main pulmonary artery and right main bronchus were ligated, and the rats were ventilated with 100% O2 for 5 minutes. Mean pulmonary arterial pressure, peak airway pressure, blood gas analysis, serum lipid peroxide level, tissue myeloperoxidase activity, and wet-dry weight ratio were measured. RESULTS: The partial O2 tension values of groups III and IV were better than group II (groups II, III, and IV: 147.4 +/- 71.4, 402.1 +/- 64.8, 373.4 +/- 81.0 mm Hg; p < 0.05). Peak airway pressure was lower in groups III and IV than in group II (groups II, III, and IV: 19.7 +/- 0.8, 16.7 +/- 0.9. and 16.3 +/- 1.0 mm Hg; p < 0.05). Mean pulmonary arterial pressure in group III was lower than group II (groups II and III: 36.3 +/- 3.0 and 22.1 +/- 2.2 mm Hg; p < 0.01). Wet-dry weight ratio in group III was lower than in groups II and IV (group II, III, and IV: 5.2 +/- 0.2, 4.4 +/- 0.2, and 5.2 +/- 0.3; II vs III; p < 0.05, III vs IV; p < 0.01). Serum lipid peroxide levels in groups III and IV were significantly lower (groups II, III, and IV: 2.643 +/- 0.913, 0.455 +/- 0.147, and 0.325 +/- 0.124 nmol/ml; p < 0.01). CONCLUSION: VIP ameliorates reperfusion injury in an in vivo rat lung transplantation model. Either administration of VIP via the flush solution or systemically just after reperfusion was associated with improved pulmonary function.

Airway Resistance↗

Heat shock pretreatment protects pulmonary isografts from subsequent ischemia-reperfusion injury.

BACKGROUND: Heat shock has been associated with the acquisition of tolerance to a wide variety of stressful conditions, including ischemia. This is partly mediated by the production of various heat shock proteins (HSP), including HSP70. One novel approach to the reduction of ischemia-reperfusion injury after lung transplantation is the induction of HSP70 by heat pretreatment of the donor. The purpose of this study was to investigate the feasibility of this approach in an animal model of lung transplantation. METHODS: Animals were divided into six main groups, with groups I to III representing transplanted animals: In groups I and II, donor animals were anesthetized and then underwent heat stress 6 and 12 hours before organ harvest, respectively. Control animals underwent general anesthesia but no heat stress. After harvest, left lungs from groups I to III were preserved for 18 hours at 40 degrees C and then implanted into isogeneic recipients, which were killed 24 hours after reperfusion to assess graft function. Group IV and V animals underwent heat stress followed by a recovery period of 6 and 12 hours, respectively. Lungs were collected both at the time of harvest (right lungs) and after 18 hours of cold preservation (left lungs). Group VI served as nontransplanted controls. Groups IV to VI did not undergo lung transplantation. RESULTS: At the time of harvest but before implantation, HSP70 was significantly increased in heat-shocked nontransplanted donor lungs (groups IV and V) compared with group VI controls. After 18 hours of cold preservation, HSP70 levels were higher in group IV compared with group V and group VI controls. At 24 hours after reperfusion, mean arterial oxygenation was significantly higher in group I compared with group II and group III controls (290.25+/-24.5 vs 154.5+/-23.9 and 119.6+/-11.3 mm Hg, respectively; P < .001). Myeloperoxidase activity was improved in group I compared with group III controls (0.048+/-0.018 vs 0.137+/-0.036 deltaOD/mg/min, respectively; P < .05). The wet/dry weight ratio was also improved in group I compared with group III controls (6.2+/-0.3 vs. 7.8+/-0.4, respectively; P < .05). CONCLUSIONS: Heat pretreatment of the donor 6 hours before harvest results in increased synthesis of HSP70, which offers a dramatic protective effect against subsequent ischemia-reperfusion injury in the lung isograft.

Animals↗

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↗

Inhaled nitric oxide at the time of harvest improves early lung allograft function.

BACKGROUND: Inhalation of nitric oxide (NO) has been shown to have beneficial effects on a variety of acute lung injuries, including lung allograft reperfusion injury. The purpose of the present study was to investigate the effects of inhaled NO at the time of harvest on function of canine left lung allografts after transplantation. METHODS: Ten dogs underwent left lung allotransplantation. Donor lungs were flushed with modified Euro-Collins solution and stored for 21 hours at 1 degree C. Immediately after transplantation, the contralateral main pulmonary artery and bronchus were ligated to assess isolated allograft function. Hemodynamics and arterial blood gases (inspired oxygen fraction, 1.0) were assessed intermittently for 6 hours prior to sacrifice. Allograft myeloperoxidase activity and wet to dry weight ratio were assessed. Donor animals were divided into two groups. Group I animals (n = 5) received no NO. In group II (n = 5), donors received inhaled NO (60 ppm) at the time of harvest. RESULTS: Pulmonary vascular resistance decreased to 79.6% of baseline because of inhalation of 60 ppm NO in group II donor animals. Thiobarbituric acid-reactive materials were reduced during the storage period in group II, a finding suggesting less oxidant injury during storage in donor lungs treated with NO. Throughout the 6-hour assessment, oxygenation in group II was superior to that in group I (p < 0.05). At 360 minutes of assessment, mean arterial oxygen tension in groups I and II was 88.9 +/- 11.4 mm Hg and 169.1 +/- 33.0 mm Hg, respectively. Myeloperoxidase activity was significantly decreased in group II (p < 0.05), data indicating reduced neutrophil sequestration. Wet to dry weight ratio was significantly lower in group II. CONCLUSIONS: These data suggest that inhaled NO at the time of harvest improves early function of preserved lung allografts by attenuating oxidant injury during storage and subsequent neutrophil sequestration.

Administration, Inhalation↗

Ex vivo adenoviral-mediated gene transfer to lung isografts during cold preservation.

BACKGROUND: Although whole-organ gene transfer has been reported in heart and liver transplant models, it has not been well characterized in lung grafts. The aim of this study was to determine the feasibility of ex vivo gene transfer to rat lung isografts during cold preservation using an adenoviral vector. METHODS: F344 rats, divided into four groups, underwent orthotopic left lung transplantation. In group I, lung grafts were flushed with adenovirus carrying the beta-galactosidase gene. After storage at 10 degrees C, grafts were implanted in recipient animals. Group II underwent the same procedure but graft storage was at 4 degrees C. Groups III (10 degrees C) and IV (4 degrees C) served as controls. On postoperative day 5, recipients were sacrificed, and native and transplanted lungs were examined. RESULTS: In group I, all animals showed successful, albeit patchy, gene expression. This occurred in 2 of 4 animals in group II, the other 2 showing no expression. Transduced cells were consistent morphologically with endothelial cells and pneumocytes. A minimal mononuclear inflammatory infiltrate was present. Control groups showed no transduction. CONCLUSIONS: It is feasible to perform ex vivo adenoviral-mediated gene transfer to rat lung isografts during cold preservation.

Adenoviridae↗

Preharvest nitroprusside flush improves posttransplantation lung function.

BACKGROUND: Morbidity as a result of early allograft dysfunction remains a significant problem in clinical lung transplantation. We previously demonstrated that nitroprusside (NP), a potent nitric oxide donor, administered before storage and again during reperfusion, reduced lung reperfusion injury. The purpose of the present study was to determine whether these observations were storage effects, reperfusion effects, or both. MATERIALS AND METHODS: Fifteen dogs underwent left lung allotransplant. Donor lungs were flushed with modified Euro-Collins solution and stored for 21 hours at 1 degree C. Immediately after transplantation, the contralateral right main pulmonary artery and bronchus were ligated to assess isolated allograft function. Hemodynamics and arterial blood gas analysis (FIO2 1.0) were assessed for 6 hours before sacrifice. Allograft myeloperoxidase (MPO) activity and wet to dry weight (W/D) ratio were assessed. Animals were divided into three groups for timing of NP administration. Group I (n = 5) animals received no NP. In group II (n = 5), donor lungs received NP (10 mg/L) in the flush solution only. In group III (n = 5), recipient animals received NP (0.2 mg/kg) just before reperfusion, as well as a continuous infusion (0.1 mg/kg/hr) during the assessment period. RESULTS: Significant improvement in gas exchange was apparent in groups II and III compared with group I, but there was no significant difference between groups II and III. After 6-hour reperfusion, mean PaO2 values were 85.46 +/- 13.32 mm Hg in group I, 298.74 +/- 61.25 mm Hg in group II (p < 0.05), and 311.12 +/- 43.39 mm Hg in group III (p < 0.05). Systemic vascular resistance was significantly lower in group III than in group I (p < 0.05). MPO activities decreased in groups II (p < 0.05) and III (p < 0.05), indicating reduced neutrophil sequestration. W/D ratio was significantly lower in groups II and III. CONCLUSION: Both methods of NP administration are effective, but NP administration in the recipient is accompanied by a decrease in systemic vascular resistance. From a clinical point of view, NP administration in the flush solution is a sufficiently effective and practical method to reduce lung allograft reperfusion injury.

Analysis of Variance↗

[Treatment of 11 cases of pulmonary arteriovenous fistula].

We have experienced a total of 11 patients operated for pulmonary arteriovernous fistula (PAVF) from 1976 to 1993 consisting of three males and eight females with the average age of 35 years. To reserve the pulmonary function, limited resections were applied for all cases (partial resection in 8, fistula excision in 2, and segmentectomy in one case). The most recent case, a 36-year-old female who had two abnormal shadows on her routine chest X-ray, was diagnosed as PAVF by pulmonary arteriogram. She was treated by fistula excision in the right S8 lesion and embolization in the left S1 + 2 lesion. Because of its unsatisfactory natural course, PAVF should be treated aggressively by surgery and/or by embolization according to the size, shape and localization.

Adolescent↗

[Extended resection for lung cancer].

Of the 740 patients with primary lung cancer operated on at our department between January, 1982 and December, 1991, 108 (14.6%) underwent extended operation involving combined resection of adjacent organs. The 5-year survival rates in patients who underwent resection of the parietal pleura (n = 62), thoracic wall (n = 25), diaphragm (n = 11), left atrium (n = 7), superior vena cava (n = 6), and aorta (n = 5) were 13.8%, 20.5%, 14.9%, 0%, 51.4%, 0%, and 20.0%, respectively. Surgical treatment for stage III advanced lung cancer is controversial, but the 5-year survival rates in those who underwent combined resection of the parietal pleura, thoracic wall including the ribs, left atrium, and aorta were not lower than that in all patients with stage III lung cancer. Especially, long-term survivals of 5 years and 11 months and 10 years and 6 months were obtained in patients who underwent resection of the left atrium, and 6-year survival was observed in a patient who underwent resection of the aorta, suggesting that extended resection is effective in some cases. The outcome of combined resection of the diaphragm and the superior vena cava was poor, with no patients surviving for 5 years.

Adult↗