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Biomedical subjects

Itaru Nagahiro

Publications and source records attributed to Itaru Nagahiro.

At least 19 recordsLinked to original sources

Optimal time for post-mortem heparinization in canine lung transplantation with non-heart-beating donors.

BACKGROUND: We previously reported that post-mortem heparinization by closed-chest cardiac massage is beneficial in lung transplantation from non-heart-beating donors by preventing formation of microthrombi. In this study, we evaluated the optimal time for post-mortem heparinization in canine lung transplantation from non-heart-beating donors. METHODS: Left lung transplantation was performed in 25 weight-matched pairs of mongrel dogs. Donors were killed with an intravenous injection of potassium chloride and left at room temperature for 2 hours. The cadaver donors were assigned randomly to one of five study groups. In Group H0, heparin sodium (1,000 U/kg) was given intravenously before cardiac arrest. In Groups H10, H30, H45 and H60, heparin sodium (1,000 U/kg) was given intravenously 10, 30, 45 and 60 minutes after cardiac arrest, respectively, followed by closed-chest cardiac massage for 2 minutes. After 2 hours of cardiac arrest, donor lungs were flushed with low-potassium dextran glucose solution and preserved for 60 minutes. After left lung allotransplantation, the right pulmonary artery was ligated, and recipient animals were followed up for 3 hours. Uni- and multivariate repeat analyses were utilized for statistical assessment. RESULTS: After transplantation, gas exchange was significantly worse in Groups H45 and H60 than in Groups H0, H10 and H30. Thrombin/anti-thrombin III complex concentration during warm ischemia was significantly higher in Groups H30, H45 and H60 than in Groups H0 and H10. CONCLUSIONS: The optimal time for post-mortem heparinization in lung transplantation from non-heart-beating donors is approximately 30 minutes after cardiac arrest.

Animals↗

Transintestinal systemic oxygenation using perfluorocarbon.

PURPOSE: Perfluorocarbons have an excellent oxygen- and carbon dioxide-carrying capacity. This prompted us to investigate the feasibility of transintestinal systemic oxygenation using perfluorocarbon. METHODS: A rat hypoventilation model (room air, 20 breaths/min and a tidal volume of 10 ml/kg) was thus established, and FC-77 (Sumitomo-3M, Osaka, Japan) was used as a perfusate. Oxygenated FC-77 was perfused through the small intestine for 4 h. The rats were allocated into three groups as follows. Group 1 (n = 6): hypoventilation only; Group 2 (n = 6): saline was perfused instead of FC-77; Group 3 (n = 6): FC-77 was perfused. Arterial blood samples were drawn from the common iliac artery every 30 min until the end of perfusion. A standard blood gas analysis was performed. RESULTS: The PaO2 level in Group 3 was significantly higher than in Groups 1 or 2 (P = 0.006: at the end of perfusion, Group 1 = 58.6 +/- 14.5 mmHg, Group 2 = 65.2 +/- 29.4 mmHg, Group 3 = 84.0 +/- 35.5 mmHg). The PaCO2 level in Group 3 was significantly lower than that in Groups 1 or 2 (P = 0.014: at the end of perfusion, Group 1 = 56.8 +/- 8.5 mmHg, Group 2 = 52.6 +/- 5.7 mmHg, Group 3 = 44.4 +/- 11.1 mmHg). CONCLUSION: Our findings indicate that transintestinal systemic oxygenation is indeed possible and could therefore become a useful new modality for respiratory assist.

Animals↗

[Flail chest rescued by mechanicalventilation with early tracheotomy and physiotherapy; report of a case].

A 73-year-old man hit his fore-chest accidentally when he rode his motorcycle. A huge flail chest was observed on his central fore-chest, and multiple fractures of costal cartilage were suspected. He developed pneumonia on the 4th hospital day, and he was intubated and mechanical ventilation was initiated. Because frequent sputum aspiration was necessary and aggressive physiotherapy was desirable, a tracheotomy was performed on the same day of intubation. He recovered from respiratory failure with conservative therapy and the mechanical ventilation was disconnected 13 days later. Tracheotomy in the early phase of respiratory failure with flail chest was very effective and the surgical fixation of flail segment would not be necessary even in the case of 'stove-in chest' like the present case.

Accidents, Traffic↗

A subacute hypoxic model using a pig.

PURPOSE: A large animal model of hypoxia is necessary to develop a new therapeutic method for respiratory failure. METHODS: The experiments were performed on six pigs weighing from 15 to 19 kg. Under general anesthesia the left chest was opened and the left main bronchus was closed by a stapler. A Swan-Ganz catheter was inserted through the right jugular vein. The right carotid artery was cannulated and the mean arterial blood pressure was monitored, and arterial blood samples were drawn every 24 h until 96 h after the operation. The blood samples were submitted for a blood gas analysis. All data were expressed as the mean +/- standard deviation of the mean. RESULTS: The partial pressure of the oxygen of the arterial blood at baseline (104.8 +/- 24.3 mmHg) significantly decreased at 24 h after closure of the bronchus (76.7 +/- 9.9 mmHg, P < 0.001) and thereafter remained at the same level for 4 days. CONCLUSION: This hypoxic model using a pig was found to be very simple, effective, and reproducible. This model can be used for a variety of experiments to evaluate new therapeutic modalities for respiratory failure.

Animals↗

Transintestinal oxygenation with perfluorocarbon: investigation of perfusion rate.

OBJECTIVE: Perfluorocarbons are structurally similar to hydrocarbons but with the hydrogen atoms replaced by fluorine. In general, perfluorocarbons have an excellent oxygen and carbon dioxide carrying capacity. We studied the suitability of oxygenated perfluorocarbon as an agent for transintestinal oxygenation and measured its perfusion rates under different conditions. SUBJECTS AND METHODS: We used FC-77 (Sumitomo 3M, Tokyo, Japan) perfluorocarbon and a rat hypoventilation model (room air, 20 breaths/min, a tidal volume of 10 ml/kg). Oxygenated FC-77 was perfused through the small intestine for 4 hours. Rats were allocated to 3 experimental groups according to the perfusion rate and a control group: Group 1 (n=6), 10 ml/min; Group 2 (n=6), 2.5 ml/min; Group 3 (n=6), 0.75 ml/min; Group 4 (n=6) served as a control (hypoventilation only). Arterial blood samples were drawn every 30 minutes. Standard blood gas analysis was performed. RESULTS: After four hours of perfusion, the PaO2 levels in Groups 1 to 3 were significantly better than Group 4 (p<0.01, Group 1: 141.7 +/- 18.0 mmHg, Group 2: 145.2 +/- 25.1 mmHg, Group 3: 120.5 +/- 21.2 mmHg, Group 4: 67.4 +/- 7.2 mmHg). PaCO2 levels in Groups 1 and 2 were significantly better than Groups 3 and 4 (p<0.01, Group 1: 42.6 +/- 7.2 mmHg, Group 2: 52.1 +/- 7.7 mmHg, Group 3: 78.2 +/- 22.8 mmHg, Group 4: 75.3 +/- 10.3 mmHg). CONCLUSION: In the present settings, 8 ml/kg/min was adequate for oxygenation and CO2 clearance. This approach promises to become another modality for respiratory assistance.

Animals↗

Living-donor lobar lung transplantation for bronchiolitis obliterans after bone marrow transplantation.

We report a successful case of living-donor lobar lung transplantation (LDLLT) for severe bronchiolitis obliterans (BO) after bone marrow transplantation (BMT). The patient is a 29-year-old woman who underwent BMT because of aplastic anemia in 1995. In 1996, BO developed in the patient because of chronic graft-versus-host disease. In May 2000, a LDLLT was performed. Pulmonary function tests showed improvement of both vital capacity and forced expiratory volume in 1 second. At present, 91 months after BMT and 38 months after lung transplantation, the patient is in good health. LDLLT may offer a therapeutic option for the treatment of BO after BMT.

Adult↗

Effects of postmortem heparinization in canine lung transplantation with non-heart-beating donors.

OBJECTIVE: Microthrombus formation appears to be one of the major detrimental factors in lung transplantation from non-heart-beating donors. The purpose of this study was to evaluate the effects of postmortem heparinization by closed-chest cardiac massage in a canine model of left single-lung allotransplantation from non-heart-beating donors. METHODS: Left lung transplantation was performed in 18 weight-matched pairs of mongrel dogs. Donors were killed with an intravenous injection of potassium chloride and left at room temperature for 2 hours. The cadaveric donors were assigned randomly to one of the three groups. In group 1 (n = 6), no heparin was given as a control. In group 2 (n = 6), heparin sodium (1000 U/kg) was administered intravenously before cardiac arrest. In group 3 (n = 6), heparin sodium (1000 U/kg) was administered intravenously 10 minutes after death, then closed-chest cardiac massage was performed for 2 minutes. After 2 hours of cardiac arrest, donor lungs were flushed with low-potassium dextran-glucose solution and preserved for 60 minutes. After left lung transplantation, the right pulmonary artery was ligated, and recipient animals were followed up for 3 hours. Univariate and multivariate repeated analyses were used for statistics. RESULTS: Both groups 2 and 3 had significantly better gas exchange and lower pulmonary vascular resistance than group 1. Changes in thrombin-antithrombin III complex concentration during the warm ischemia indicated that postmortem heparinization suppressed clotting activation in the donor. CONCLUSIONS: Postmortem heparinization by cardiac massage is beneficial in lung transplantation from non-heart beating donors by preventing microthrombus formation.

Animals↗

Relation of epidermal growth factor receptor, phosphorylated-Akt, and hypoxia-inducible factor-1alpha in non-small cell lung cancers.

The role of the epidermal growth factor receptor (EGFR)/Posphorylated-Akt (P-Akt) signaling axis in regulating hypoxia-inducible factor-1alpha (HIF-1alpha) expression in vivo is not well understood and is of potential clinical importance since the extent of hypoxia in the tumor environment is thought to be an important determination of resistance to chemotherapy and radiotherapy. We performed the immunohistochemical studies in 80 patients with non-small cell lung cancers to evaluate EGFR, P-Akt, and HIF-1alpha expression. Significant correlation between P-Akt and HIF-1alpha (P=0.0006) and marginal correlation between EGFR and P-Akt (P=0.066) were found. P-Akt was shown to be a poor prognostic factor as to patients with lymph node involvement (P=0.031).

Aged↗

Intermittent pneumatic compression is effective in preventing symptomatic pulmonary embolism after thoracic surgery.

PURPOSE: Postoperative pulmonary embolism (PE) remains a fatal complication even in thoracic surgery. We have used intermittent pneumatic compression for the prophylaxis of postoperative PE since 1998, and herein examined its effectiveness. METHODS: Seven hundred and six patients, whose medical records showed use/no use of pneumatic compression for prophylaxis of PE, underwent general thoracic surgery in our department from December 1995 to December 2000. Their clinical records were reviewed, and variables were compared between patients who experienced clinically apparent PE and patients who did not have PE. RESULTS: Three hundred and forty-four patients did not receive any prophylactic treatment, and 7 of these (2.0%) experienced postoperative PE. Three hundred and sixty-two patients received prophylactic pneumatic compression and none of these developed PE. There was a statistical correlation between the occurrence of PE and the application of pneumatic compression (Chi(2)-test, P = 0.006). Six of the seven patients with PE were operated on in the right decubitus position, and the operative position and the prevalence of PE was also significantly correlated (Chi(2)-test, P = 0.024). Other factors, such as age, sex, operative time, duration until patients became fully ambulatory, body mass index, and character of the disease, did not have significant correlation with the occurrence of PE. CONCLUSIONS: Pneumatic compression was found to effectively prevent postoperative PE. The right decubitus position is considered to be a risk factor for the development of postoperative PE in thoracic surgery.

Aged↗

Allowable warm ischemic time to tracheal extraction for allotransplantation of cryopreserved trachea.

OBJECTIVE: The allowable warm ischemic time from circulatory arrest to tracheal extraction for allotransplantation of cryopreserved tracheal grafts from cadaveric donors was examined in adult mongrel dogs. SUBJECTS AND METHODS: The animals were divided into 4 groups (n = 28) according to the warm ischemic time of less than 1 hour, 3 hours, 6 hours, and 12 hours, after transplantation, and comparisons were made. The grafts were cryopreserved for at least 2 months and were evaluated by extraction from the recipients generally 2 months after transplantation. RESULTS: All the grafts with a warm ischemic time of less than 1 hour were viable and did not show stenosis. This group did not differ significantly from the groups with a warm ischemic time of 3 and 6 hours in terms of viability. However, all of the grafts with a warm ischemic time of 12 hours showed stenosis, and there was a significantly lower viability rate. Histological examination of the grafts showed that warm ischemia caused necrosis of the tracheal cartilage. CONCLUSION: Based on these results, it was concluded that 6 hours was the maximum allowable warm ischemic time for cryopreserved tracheal transplantation, and that necrosis of the tracheal cartilage due to warm ischemia reduced the viability of the grafts.

Animals↗

How to predict forced vital capacity after living-donor lobar-lung transplantation.

BACKGROUND: Living-donor lobar-lung transplantation (LDLLT) has evolved from a rarely performed experimental procedure to an accepted therapy for selected patients who are unlikely to survive the long wait for cadaveric lungs. However, a convincing study has not been performed that shows the effects of small grafts and of pre-operative variables in predicting functional outcome of recipients after LDLLT. METHODS: From October 1998 to March 2002, 2 male and 11 female patients underwent LDLLT. Mean age was 27.3 years (range, 8-53 years). Diagnoses included primary pulmonary hypertension (n = 5), idiopathic interstitial pneumonia (n = 2), bronchiolitis obliterans (n = 2), bronchiectasis (n = 2), lymphangioleiomyomatosis (n = 1), and cystic fibrosis (n = 1). Donors included 12 men and 14 women with a mean age of 40 years. Given that the right lower lobe consists of 5 segments, the left lower lobe of 4, and the whole lung of 19, we estimated the graft forced vital capacity (FVC) based on the donor's measured FVC and compared this with the recipient's FVC measured after LDLLT. RESULTS: Currently, all patients are alive, with a mean follow-up of 22.2 months (range, 10-51 months). The recipients' FVC measured at 6 months (1,813 +/- 86 ml) correlated well with the graft FVC (1,803 +/- 70 ml), estimated based on the donors' measured FVC (r = 0.802, p = 0.00098). CONCLUSIONS: Recipient FVC after LDLLT can be predicted by measuring donor FVC before surgery regardless of the diagnosis of the recipient.

Adolescent↗

The technique of unilateral double lobar lung transplantation in a canine model.

OBJECTIVE: Bilateral living-donor lobar lung transplantation has become an accepted alternative to cadaveric lung transplantation. Because only one lobe is implanted in each chest cavity, this procedure seems to be best suited for children and small adults. The purpose of this study was to develop a technique of unilateral double lobar lung transplantation that can be applied to large adult patients. METHODS: Unilateral double lobar lung transplantation was performed in 6 weight-matched pairs of dogs. In donor animals the right middle, lower, and cardiac lobes were separated as a right graft, and the left lower lobe was separated as a left graft. In recipient animals these 2 grafts were implanted in the right hemithorax after right pneumonectomy. The left graft was implanted as a right upper lobe, having been rotated 180 degrees along the vertical axis and then 180 degrees along the horizontal axis. The right graft was implanted in the natural anatomic position. Function of the transplanted grafts was assessed for 3 hours after ligation of the left main pulmonary artery while the animals were ventilated with 100% oxygen. RESULTS: Morphologic adaptation of the 2 grafts in the right hemithorax was found to be excellent. All 6 animals survived the assessment period with excellent pulmonary function. At the end of the 3-hour assessment period, the arterial oxygen tension was 519 +/- 31 mm Hg, and the mean pulmonary artery pressure was 30.5 +/- 1.7 mm Hg. CONCLUSIONS: Unilateral double lobar lung transplantation was technically possible and associated with satisfactory early pulmonary function in a canine experimental model.

Animals↗

Improved survival after living-donor lobar lung transplantation.

OBJECTIVE: Survival after living-donor lobar lung transplantation has been reported to be similar to that after cadaveric lung transplantation. The purpose of this study was to summarize our 5-year experience of living-donor lobar lung transplantation for critically ill patients. METHODS: Between October 1998 and April 2004, we performed living-donor lobar lung transplantation in 30 critically ill patients with various lung diseases, including 5 (17%) patients on a ventilator. Mean age was 30.4 years (range, 8-55 years). Postoperative management included slow weaning from a ventilator, relatively low-dose immunosuppressants, and careful rejection monitoring on the basis of radiographic and clinical findings without transbronchial lung biopsy. RESULTS: The average duration of mechanical ventilation was 15.4 days, intensive care unit stay was 23.5 days, and hospital stay was 64.6 days. Clinically judged acute rejection occurred at an average rate of 1.5 episodes per patient, but infection occurred in only one patient during the first month. In spite of the complicated postoperative course, all patients were discharged without oxygen inhalation. Four patients had unilateral bronchiolitis obliterans syndrome, but the decrease in their forced expiratory volume in 1 second values stopped within 9 months. All 30 recipients are currently alive, with a follow-up period of 1 to 66 months. All donors have returned to their previous lifestyles. CONCLUSIONS: Living-donor lobar lung transplantation can be applied to both pediatric and adult patients with very limited life expectancies. It might provide better survival than conventional cadaveric lung transplantation.

Adolescent↗

DNA methylation of multiple genes and clinicopathological relationship of non-small cell lung cancers.

Aberrant methylation of 5' CpG islands is thought to play an important role in the inactivation of tumor suppressor genes in several types of cancers. In non-small cell lung cancer (NSCLC), several genes are known to be frequently methylated and the correlation of their methylation with clinical features has been studied. We determined the methylation of p16, CDH13 and RAR-beta which were reported to be methylated frequently in NSCLCs and HPP-1 which was known to be methylated in other types of cancers. The correlation between methylation and clinicopathological features were examined. The frequencies of methylation in NSCLCs were 20% for p16, 37% for CDH13, 34% for RAR-beta, and 13% for HPP1. The methylation of p16 is correlated with smoking history and methylation of HPP1 was significantly more frequent in adenocarcinomas than in squamous cell carcinomas. This is the first description of aberrant methylation of the HPP1 gene in lung cancers and our data support the previous reports on methylation in NSCLCs and association with smoking.

Adenocarcinoma↗

[Benign mediastinal tumors].

Most of benign mediastinal tumors are asymptomatic; however, sometimes we encounter emergent cases. In this article we discuss with regard to the situation that benign mediastinal tumors with severe symptoms need to be treated emergently. Any benign mediastinal tumors can cause respiratory and cardiac failure as they grow large enough to compress surrounding structures. It is very unique that the symptoms are relieved or worsen according to the patients' position. Rupture of mature teratoma is another situation which necessitates emergent therapy. The symptoms due to rupture depends on the site, that is pericardial space, intrapulmonary, and thoracic cavity. The mechanism of rupture is suspected to autolysis, infection, and necrosis of the tumor. Anesthesia is an important issue in treating such huge mediastinal tumors, because general anesthesia using muscle relaxants can introduce acute respiratory or cardiac failure. Patient's position is again very important, for example, in the patients with orthopnea anesthesia is sometimes initiated and the patient is intubated in sitting position. Although it is rare, we must be aware of these emergent situations when we treat patients with benign mediastinal tumors.

Adult↗

Living-donor lobar lung transplantation for various lung diseases.

OBJECTIVE: We report on our early experience in living-donor lobar lung transplantation for patients with various lung diseases including restrictive, obstructive, septic, and hypertensive lung diseases. METHODS: From October 1998 to March 2002, living-donor lobar lung transplantation was performed in 14 patients with end-stage lung diseases. There were 11 female patients and 3 male patients, with ages ranging from 8 to 53 years, including 4 children and 10 adults. Diagnoses included primary pulmonary hypertension (n = 6), idiopathic interstitial pneumonia (n = 2), bronchiolitis obliterans (n = 2), bronchiectasis (n = 2), lymphangioleiomyomatosis (n = 1), and cystic fibrosis (n = 1). Bilateral living-donor lobar lung transplantation was performed in 13 patients and right single living-donor lobar lung transplantation was performed for a 10-year-old boy with primary pulmonary hypertension. RESULTS: All the 14 patients are currently alive with a follow-up period of 4 to 45 months. Although their forced vital capacity (1327 +/- 78 mL, 50.2% of predicted) was limited at discharge, arterial oxygen tension on room air (98.5 +/- 1.8 mm Hg) and systolic pulmonary artery pressure (24.8 +/- 1.6 mm Hg) were excellent. Forced vital capacity improved gradually and reached 1894 +/- 99 mL, 67.4% of predicted, at 1 year. All donors have returned to their previous lifestyles. CONCLUSIONS: Living-donor lobar lung transplantation can be applied to restrictive, obstructive, septic, and hypertensive lung diseases. This type of procedure can be an alternative to conventional cadaveric lung transplantation for both pediatric and adult patients who would die soon otherwise.

Adolescent↗