Biomedical subjects

Kenji Tsushima

Publications and source records attributed to Kenji Tsushima.

At least 19 recordsLinked to original sources

PubMed2006

IgG4-associated multifocal systemic fibrosis complicating sclerosing sialadenitis, hypophysitis, and retroperitoneal fibrosis, but lacking pancreatic involvement.

A 71-year-old man was admitted with malaise, mild fever, anorexia, body weight loss, lower back pain, thirst, and polydipsia. He showed bilateral swelling of the submandibular glands. Examinations showed panhypopituitarism and a high serum IgG4 concentration. Fluorodeoxyglucose positron emission tomography (FDG-PET) revealed uptake in the pituitary gland, bilateral submandibular gland, bilateral hilar and mediastinal lymph nodes, and a mass consistent with retroperitoneal fibrosis, but not in the pancreas. Biopsy specimens from the submandibular gland and retroperitoneal mass indicated sialadenitis and retroperitoneal fibrosis respectively, and showed severe fibrosis and inflammation with marked lymphoplasmacytic infiltration and IgG4-positive plasma cell infiltration. Hormone replacement therapy with hydrocortisone resulted in marked clinical improvement. Systemic involvement found in this patient possibly corresponded to the new concept of IgG4-associated multifocal systemic fibrosis.

Aged↗

PubMed2006

Relationship between sleep-disordered breathing and lifestyle-related illnesses in subjects who have undergone health-screening.

OBJECTIVE: Simplified sleep polysomnography was performed in 207 adult men to examine the relationship between the frequency of sleep-disordered breathing (SDB) and lifestyle-related illness. METHODS: Each subject was checked for SDB using a simplified sleep polysomnograph (Auto-Set Portable; Teijin Limited, Tokyo, Japan). Apnea and hypopnea were detected with a nasal cannula type airflow sensor. Hypoxemia was checked with a percutaneous oxygen saturation (SpO2) monitor. We analyzed the relationships between SDB and body mass index (BMI) and hypertension, hyperlipidemia, liver dysfunction, fatty liver, and abnormal glucose metabolism. RESULTS: Fifty-nine subjects (29%) showed SDB with apnea hypopnea index (AHI) over 15 times/h. The frequency of obesity (BMI > or = 25), hypertension, hypercholesterolemia, fasting blood glucose level, and HbA1c were significantly higher in patients with SDB than in normal individuals (AHI < 5 times/h). The frequencies of hypertension, hyperlipidemia, and abnormal glucose metabolism were compared between the obesity-free normal AHI group and the SDB group, and only that of hypertension was significantly different between the two groups. CONCLUSIONS: The present study revealed a high frequency of SDB among Japanese individuals. The results also suggest that as SDB becomes severe, it becomes more closely linked to the onset of lifestyle-related illnesses, such as hypertension, hypercholesterolemia and abnormal glucose metabolism.

Adult↗

PubMed2006

Angiosarcoma with sacral origin metastasizing to the lung.

A 73-year-old man with fever, lumbago and hemosputum showed ground-glass opacity around multiple lung nodules on chest computed tomography. Examination of the man revealed anemia. Specimens obtained by video-assisted thoracic surgery revealed angiosarcoma, but the primary site of angiosarcoma could not be detected before autopsy. Angiosarcoma is a rare malignant neoplasm with rapid proliferation and they can arise at any region of the body. It can originate in the skin, soft tissue, liver or heart. Their multicentric and local recurrence easily leads us to misdiagnosis, and we have struggled to reach diagnosis and its origin. Angiosarcoma should be included in the different diagnosis of diffuse pulmonary hemorrhage with multiple lung nodules.

Aged↗

PubMed2006

Hypersensitivity pneumonitis induced by spores of Penicillium citrinum in a worker cultivating Enoki mushroom.

A 47-year-old Japanese woman was admitted to our hospital with a 2-week history of dry cough and shortness of breath. She had been engaged in Enoki mushroom production for 22 years. Chest X-ray and chest computed tomography (CT) scan showed bilateral fine-nodular shadows and ground glass opacity. Bronchoalveolar lavage fluid demonstrated an increase of total cell counts with predominant lymphocytosis. Pathological specimens obtained by video-assisted thoracoscopic surgery revealed alveolitis and noncaseating granuloma with giant cells. Lymphocyte stimulation test showed positive responses with Enoki mushroom, culture medium, and Penicillium citrinum. On double immunodiffusion test, a precipitation line was observed between patient's serum and Penicillium citrinum antigen. She was found to have hypersensitivity pneumonitis caused by Penicillium citrinum. This is the first report of mushroom worker's lung caused by Penicillium citrinum.

Agaricales↗

PubMed2006

Usefulness of preoperative endobronchial ultrasound for airway invasion around the trachea: esophageal cancer and thyroid cancer.

BACKGROUND: It is important to confirm preoperative tracheobronchial invasion to enable the selection of the most appropriate treatment. OBJECTIVE: This study was performed to compare the usefulness of computed tomography (CT), magnetic resonance image (MRI) and bronchoscopy by endobronchial ultrasonography (EBUS) for the assessment of invasion of thyroid or esophageal cancer in cases with suspected tracheobronchial invasion. METHODS: In cases with suspected contact between the tumor and tracheobronchial wall, CT, MRI and EBUS indicated deformity of the tracheobronchial wall due to the adjacent mass. The final diagnosis was based on surgical and histological results, and/or clinical follow-up. RESULTS: Fifty-four patients were included in this study. Based on the findings of CT, MRI and EBUS, invasion was suspected in 29, 28 and 25 patients, respectively. Seventeen patients did not undergo surgery based on the results of CT, MRI and bronchoscopy with EBUS. Final diagnosis was intact trachea or bronchial adventitia in 26 patients and invasion in 28 patients. The sensitivity and specificity of CT, MRI and EBUS for invasion were 59 and 56, 75 and 73, and 92 and 83%, respectively. The accuracy of EBUS was significantly greater than that of CT in the present study (p = 0.0011). The accuracy of EBUS was significantly different from that of CT and MRI in the surgically treated patients (p = 0.005 and p = 0.032, respectively). CONCLUSION: EBUS is the most useful technique for determining the depth and extent of tumor invasion into the airway wall. The combination of MRI and EBUS will contribute to surgical planning in patients with esophageal and thyroid cancer.

Adult↗

PubMed2006

Polymyxin B immobilized column is effective for hydrochloric acid-induced lung injury in rats.

The purpose of this study was to examine whether hemoperfusion using polymyxin B (PMX) immobilized column improves hydrochloric acid (HCl)-induced lung injury. Rats weighing 350 g underwent hemoperfusion for 30 min at a flow rate of 120 ml/h after the intratracheal instillation of hydrochloric acid or water. Rats were divided into those that underwent hemoperfusion, with or without polymyxin B column, 30 min after HCl instillation ("HCl+PMX" and "HCl"), and hemoperfusion with or without polymyxin B column 30 min after water instillation ("Aqua+PMX" and "Aqua"). Systolic blood pressure, arterial blood gas analysis and white blood cell count and neutrophils were measured before, 1 and 3h after hemoperfusion. Plasma and bronchoalveolar lavage fluid concentrations of growth-related oncogene/cytokine-induced neutrophils chemoattractant-1 (GRO/CINC-1) were measured at 1 and 3h after hemoperfusion. Arterial oxygen concentrations were higher in the "HCl+PMX" group than in the "HCl" group. The total numbers of cells and neutrophils in the bronchoalveolar lavage fluid were significantly higher in the "HCl" group than in the others. The GRO/CINC-1 concentrations in the plasma and bronchoalveolar lavage fluid and the albumin ratio in the "HCl+PMX" group were significantly lower than in the "HCl" group. Direct hemoperfusion using polymyxin B immobilized column treatment affects the recruitment of circulating neutrophils to the lungs due to the decrease in mediators for non-endotoxic lung injury.

Animals↗

PubMed2006

Relationship between calcium-activated chloride channel 1 and MUC5AC in goblet cell hyperplasia induced by interleukin-13 in human bronchial epithelial cells.

BACKGROUND: Interleukin (IL)-13 has recently been reported as the major T-helper 2 cytokine involved in mucus overproduction and oversecretion in allergic airways. However, the relationship between human calcium-activated chloride channel-1 (hCLCA1) and MUC5AC induced by IL-13 in vitro has not been fully investigated. OBJECTIVES: The present study examines whether IL-13 induces the expression of hCLCA1 in normal human bronchial epithelial (NHBE) cells. We also investigated the relationship between hCLCA1 and MUC5AC expression and the development of goblet cell hyperplasia (GCH). METHODS: NHBE cells were isolated from human bronchi, and cultured with an air-liquid interface. hCLCA1 and MUC5AC gene and protein expression, as well as GCH were examined in the cells after exposure to IL-13. RESULTS: Incubation with IL-13 for 14 and 21 days increased the total number of epithelial cells, the number of periodic acid-Schiff (PAS)-stained epithelial cells, the number of goblet cells, as well as expression of mRNA and protein of hCLCA1 and MUC5AC. The number of goblet cells with secretory granules also increased after 21 days of incubation with IL-13. Niflumic acid, a chloride channel inhibitor, reduced mRNA expression of hCLCA1 and MUC5AC, and reduced the number of PAS-positive cells after incubation with IL-13. NHBE cells exposed or not to IL-13 expressed IL-13 receptor alpha(1) (IL-13Ralpha(1)), and an antibody to IL-13 Ralpha(1) also reduced the number of PAS-positive cells after exposure to IL-13. CONCLUSIONS: IL-13 might induce the expression of MUC5AC and hCLCA1 gene and protein in well-differentiated NHBE cells. These cells might also differentiate into goblet cells and become hyperplastic.

Adult↗

PubMed2006

Clinical differences in the Global Initiative for Chronic Obstructive Lung Disease Stage 0.

This study was to examine the clinical differences between Stage 0 and normal subjects, using low-dose chest computed tomography (CT) and pulmonary function tests. Enrolled subjects performed as a health check for lung cancer screening including low-dose CT and pulmonary function tests. Subjects were divided into Stage 0, chronic obstructive pulmonary disease according to pulmonary function tests, and normal subjects. The severity of emphysema (visual score) was calculated on three low-dose CT slices. Low-dose CT and pulmonary function tests were performed in 1359 men and 888 women. The numbers and percentages of men and women smokers were 1076 (79.2%), and 107 (12.0%), respectively. A total of 722 individuals had one or more respiratory symptoms, such as cough (69.8%), sputum (75.8%), or shortness of breathing (0.83%). Of the 722 subjects, 71 (9.8%) individuals satisfied the criteria of chronic respiratory symptoms. Among the normal subjects, smoking caused differences in airflow limitation as a result of pulmonary function tests. The proportion of smokers and the visual score were significantly higher in Stage 0 than those in the normal subjects. The percentages of the maximal mid-expiratory flow (%MMF) and of the peak expiratory flow rate were significantly lower in Stage 0 than in the normal subjects. %MMF and the proportion of visual score were significantly lower in the smoking Stage 0 than in the nonsmoking Stage 0 subjects. Smoking would indicate early signs of emphysematous change between Stage 0 and normal subjects in comparison of pulmonary function tests and visual score of low-dose CT.

Female↗

PubMed2006

Therapeutic effects for hypersensitivity pneumonitis induced by Japanese mushroom (Bunashimeji).

BACKGROUND: Bunashimeji-related hypersensitivity pneumonitis is found among workers who cultivate the mushroom in indoor facilities. An evaluation of protective measures was initiated using the outcomes of clinical, immunological, and radiological findings. METHODS: Twenty-two patients presented with symptoms of HP; all were employed cultivating Bunashimeji mushrooms in indoor facilities. After hospitalization, 6 of 22 patients quit their job to avoid exposure to spores (Avoidance group). Sixteen patients continued to work used a mask for 3 months, and were then divided into two subgroups: Mask alone (seven patients) and mask plus oral prednisolone (Mask + PSL) (nine patients). The erythrocyte sedimentation rate (ESR), serum Krebs von der Lungen-6 (KL-6), surfactant protein-D (SP-D), lymphocyte stimulation test (LST), ground-glass scores in chest high-resolution computed tomography (HRCT), and bronchoalveolar lavage (BAL) were assessed before and after treatment. RESULTS: Complete avoidance resulted in a significant decrease in LST. There was a significant decrease after PSL treatment in serum KL-6, SP-D, and total cell counts in the BAL fluid in the Mask + PSL group. In the Mask alone group, serum KL-6, SP-D, ground-glass scores in chest HRCT and total cell counts in BAL fluid showed high levels compared with the other two groups. CONCLUSIONS: Complete cessation was the best treatment for hypersensitivity pneumonitis. The use of a mask was ineffective for patients with a high serum KL-6 and SP-D concentration and severe ground-glass opacity on chest HRCT. Initial treatment with PSL is recommended for these patients with high levels of total cell counts in BAL fluid.

Agaricales↗

PubMed2006

Endobronchial argon plasma coagulation for the management of post-intubation tracheal stenosis.

Post-intubation tracheal stenosis is usually caused by pressure necrosis at the cuff. Despite the fact that this phenomenon is well known and both large volume and low pressure cuffs have been developed, this lesion nevertheless continues to occur. Although the best results for tracheal reconstruction are obtained by an experienced surgeon, not all patients are able to undergo this operation for either medical or personal reasons. Argon plasma coagulation (APC) using flexible bronchoscopy has been successfully employed in the treatment of post-intubation tracheal stenosis in two of the surgery-refused and inoperable patients. The patients immediately experienced a relief of symptoms after APC. APC was thus performed 3-4 times every 1-2 weeks for each patient. In addition, there were no complications related to this procedure. The number of published clinical reports describing APC in benign airway stenosis are increasing. APC has also been reported to have several advantages over other interventional endobronchial techniques in the management of tracheo-bronchial stenosis. We report two patients, and to our knowledge this is the first description of APC being used in the treatment of endobronchial dilatation for post-intubation tracheal stenosis.

Aged↗

PubMed2006

[Successful treatment of intrapericardial administration of carboplatin following systemic chemotherapy in a case of advanced thymic cancer with cardiac tamponade].

A 72-year-old woman developed cardiac tamponade due to direct invasion of thymic cancer. Carboplatin was administered into the pericardial cavity two times with a total dose of 600 mg. Pericardial effusion disappeared without any toxicities. Following four cycles of systemic chemotherapy by carboplatin, doxorubicin, vincristine, cyclophosphamide (ADOC), partial response was obtained. She is alive 10 month after being given a diagnosis of cardiac tamponade. Intrapericardial administration of carboplatin is a useful therapy for control of pericardial effusion and chemosensitive cases should de identified among patients with thymic cancer.

Aged↗

PubMed2005

Comparison of bronchoscopic diagnosis for peripheral pulmonary nodule under fluoroscopic guidance with CT guidance.

BACKGROUND: A new diagnostic procedure has been established for the selection of appropriate therapy for small lung lesions. We compared the sensitivity of real-time multi-slice computed tomography (MSCT) and X-ray television (TV) fluoroscopic guidance for performing bronchoscopy. METHODS: The first author performed and interpreted all bronchoscopies described in this study. The diagnosis of malignancy or benign was based on the results of histopathological examination, as well as clinical and imaging follow-up MSCT. We also compared the diagnostic yields of lesion size between MSCT and X-ray TV fluoroscopic guidance. RESULTS: Real-time MSCT and X-ray TV fluoroscopic guidance was conducted in 82 and 78 patients, respectively. The lesion size detected by real-time MSCT and X-ray TV fluoroscopic guidance was <10 mm (n=21, 14), 11-15 mm (n=24, 12), 16-20 mm (n=19,14), 21-25 mm (n=9, 12) and >26 mm (n=9, 26). The sensitivity of real-time MSCT- and X-ray TV fluoroscopic guidance was 62.2% and 52.6%, respectively. The sensitivity of real-time MSCT fluoroscopic guidance for histopathologic diagnosis of lesions less than 15 mm was higher than that of X-ray TV fluoroscopic guidance. While it was difficult to histopathologically diagnose small lung lesions less than 10mm in diameter, real-time MSCT fluoroscopic guidance offers a better chance of such diagnosis, irrespective of the size of the lesion, compared with X-ray TV fluoroscopic guidance. CONCLUSION: Real-time MSCT fluoroscopic guidance allows the bronchoscopist to accurately determine the location of the instruments in relation to the lesion in real time, thus helping to reduce the number of negative cases.

Adult↗

PubMed2005

Hypersensitivity pneumonitis due to Bunashimeji mushrooms in the mushroom industry.

BACKGROUND: Detection of hypersensitivity pneumonitis (HP) in employees involved in the Bunashimeji mushroom industry is difficult. The level of precipitating antibody is not related with the prediction of progression and resolution of HP. The aims of this study were to examine the actual prevalence of HP in the Bunashimeji industry and the clinical differences among selected employees. METHODS: One hundred and fourteen employees worked in Bunashimeji enterprises. These subjects were divided into the following subgroups: office workers, pickers/packers with mask and pickers/packers without mask. We measured serum Krebs von der Lungen-6 (KL-6), surfactant protein (SP)-A and SP-D, and examined the stimulation index (SI) due to Bunashimeji spores. Chest high-resolution computed tomography (HRCT), pulmonary function tests and bronchoalveolar lavage (BAL) were performed for select employees who showed positive SI values (>200%) to examine the clinical differences. RESULTS: The proportion of respiratory symptoms was significantly higher in the pickers/packers than that in the office workers. The picker/packer group had high serum KL-6 concentrations and SI compared with the office worker group. Thirty select employees were divided into the following three subgroups: HP, select employees without HP, and SI <400% and KL-6 <500 U/ml , using high SI levels (>400%) and positive serum KL-6 concentration (>500 U/ml). Four exhibited ground glass opacities with centrilobular fine nodules on HRCT, and 8 had high numbers of lymphocytes in the BAL fluid. The BAL findings and serum KL-6 concentrations showed significant differences among the three groups. CONCLUSIONS: Four employees were evaluated as having HP. Serum KL-6 and SP-D may be related to the resolution of HP in addition to SI and chest HRCT.

Agaricales↗

PubMed2005

Activated protein C attenuates acid-aspiration lung injury in rats.

Acid aspiration causes direct lung damage and secondary inflammatory response involving several cytokines and accumulation of neutrophils. Activated protein C (APC) exhibits antithrombotic and anti-inflammatory properties. We examined the effect and mechanism of pre-treatment APC on acid-aspirated lung injury in rats. Anesthetized rats were instilled intratracheally with normal saline (NS, 2 ml kg(-1)) or hydrochloric acid (HCl, 0.1 N, 2 ml kg(-1)). Thirty minutes before HCl instillation, APC (200 U kg(-1) h(-1)) was infused continuously into the right jugular vein. Animals were ventilated during the experiments. Five hours after HCl or NS instillation, bronchoalveolar lavage fluid (BALF) and lung tissue samples were obtained. Total and differential cell count, absorbance, albumin concentration, concentrations of tumor necrosis factor (TNF)-alpha, interleukin (IL)-6 and cytokine-induced neutrophil chemoattractant (CINC) in BALF, wet and dry weight (W/D) ratio were measured. Platelet count and fibrin degradation product (FDP) in peripheral blood were also measured. HCl instillation markedly increased these values in BALF as well as W/D ratio. APC attenuated the parameters increased by HCl-induced lung injury in rats. However, HCl instillation and APC treatment did not cause significant changes in platelet count and FDP compared with the control. We conclude that APC treatment protected the rats against HCl-induced lung injury and that this action seemed to be due to the anti-inflammatory properties of this protein rather than its anti-coagulant effects.

Albumins↗

PubMed2005

Risk factors for hospital-acquired bacteremia.

OBJECTIVE: Bacteremia is one of the most serious health problems associated with high morbidity and mortality. The aim of this study was to identify risk factors for bacteremia in daily medical care to facilitate rapid and accurate clinical decisions about treatment. PATIENTS AND METHODS: We studied 306 inpatients retrospectively. Age, peripheral neutrophil count, C-reactive protein (CRP), platelets, serum total cholesterol, total protein, albumin and cholinesterase were compared in patients with positive- and negative-blood cultures. The associations between blood culture positivity and glucose tolerance, bedridden state, presence of a central venous catheter (CVC) or urinary catheter were examined. On October 14, 2002, strategies for prevention of catheter-related infection were altered in our hospital. We studied the impact of these changes on the risk of bacteremia. RESULTS: Sixty-seven patients had positive and 239 had negative blood cultures. Age, neutrophil, platelets, total protein, albumin, and cholinesterase were significantly different between the culture-positive patients and the culture-negative patients. Multivariate analysis showed albumin and platelets as independent predictors. The bedridden state and catheter-inserted states (central venous or urinary) conferred significantly higher positive blood culture rates. Multivariate analysis showed using urinary catheters and indwelling femoral CVCs as independent risk factors. There was no significant difference in the blood culture-positive rate before and after the change in prevention strategies; before the change, 6 of 9 catheter-inserted blood culture-positive cases yielded MRSA, while 4 of 12 cultures yielded Staphylococcus epidermidis after the change. CONCLUSION: Our study highlights the risk factors of bacteremia in vulnerable patients.

Adolescent↗

PubMed2004

JTE-607, a cytokine release blocker, attenuates acid aspiration-induced lung injury in rats.

The present study was designed to clarify the effects of (-)-ethyl N-[3,5-dichloro-2-hydroxy-4-[2-(4-methyl-piperazin-1-yl)ethoxy]benzoyl]-l-phenylalaninate dihydrochloride (JTE-607), a novel multiple cytokine inhibitor, on hydrochloric acid (HCl) aspiration lung injury in rats. HCl (0.1 N, 2 ml kg(-1)) was instilled into male Sprague-Dawley rats that were pretreated with or without JTE-607 (30 or 75 mg kg(-1) h(-1)). As a control, normal saline (2 ml kg(-1)) was instilled in rats. All the animals were anesthetized with intraperitoneally injected pentobarbital sodium (40 mg kg(-1)). Bronchoalveolar lavage was performed 5 h (h) after HCl or normal saline instillation. In bronchoalveolar lavage fluid, the increases in total nuclear cell counts, neutrophil counts, optical density at 412 nm as an indication of pulmonary hemorrhage, concentrations of albumin, tumor necrosis factor (TNF)-alpha, interleukin (IL)-6 and cytokine-induced neutrophil chemoattractant induced by HCl instillation were significantly reduced by JTE-607 pretreatment. The level of expression of tumor necrosis factor-alpha and interleukin-6 mRNA in lung tissue was analyzed. The mean expression level of tumor necrosis factor-alpha and interleukin-6 mRNA in the JTE-607 group was lower than that in the HCl and NS groups. The wet-to-dry weight ratio was also determined, and JTE-607 at the dose of 75 mg kg(-1) h(-1) significantly attenuated the increased wet-to-dry weight ratio induced by HCl. These results suggest that JTE-607 can inhibit the production of inflammatory cytokines such as tumor necrosis factor-alpha, interleukin-6 and cytokine-induced neutrophil chemoattractant and attenuate acid-induced lung injury in rats. This agent might be therapeutically useful for lung injury.

Animals↗

PubMed2004

Effects of granulocyte colony-stimulating factor (G-CSF) and neutrophil elastase inhibitor (ONO-5046) on acid-induced lung injury in rats.

It has been suggested that neutrophils play an important role in acid-aspirated lung injury. We examined the effects of the high dose of granulocyte-colony stimulating factor (G-CSF), which is capable of increasing peripheral neutrophils, and a specific neutrophil elastase inhibitor (ONO-5046) on acid lung injury in rats. Animals were anesthetized and normal saline (NS, 2 mL kg(-1)) or hydrochloric acid (HCl, 0.1 N 2 mL kg(-1)) was then instilled into trachea. Thirty minutes before HCl instillation, G-CSF (150 microg kg(-1)) was injected subcutaneously or ONO-5046 (10 mg kg(-1) h(-1)) was infused continuously into the right jugular vein. Animals were ventilated during the experiments. Five hours after HCl or NS instillation, bronchoalveolar lavage fluid (BALF) and lung tissue samples were obtained. Total nuclear cell count, absorbance, albumin, tumor necrosis factor (TNF)-alpha, interleukin (IL)-6, cytokine-induced neutrophil chemoattractant (CINC), neutrophil elastase in BALF, wet-to-dry (W/D) ratio were measured. HCl aspiration markedly increased these values in BALF and W/D ratio. Both ONO-5046 and G-CSF attenuated the parameters increased by acid-induced lung injury in rats. The data suggests that neutrophils play an important role in acid-induced lung injury. However, high-dose G-CSF does not exacerbate acid-aspirated lung injury in rats, although this agent causes an increase in peripheral neutrophils.

Animals↗

PubMed2004

Effect of ONO1714, a specific inducible nitric oxide synthase inhibitor, on lung lymph filtration and gas exchange during endotoxemia in unanesthetized sheep.

BACKGROUND: The effect of nitric oxide synthase inhibitor on acute lung injury remains controversial. The current study was designed to examine effects of a newly synthesized and selective inducible nitric oxide synthase inhibitor, ONO1714, on endotoxin-induced lung injury in unanesthetized sheep. METHODS: Thirteen unanesthetized sheep chronically instrumented with a lung lymph fistula and vascular catheters for monitoring were prepared. Animals were randomly allocated into two experimental groups. In experiment 1, sheep (n = 6) were infused only with endotoxin (1 microg/kg) for 30 min. In experiment 2, sheep (n = 7) were pretreated with ONO1714 (0.1 mg/kg) before 30 min of endotoxin administration, and the endotoxin was infused in the same manner as in experiment 1. Mean pulmonary arterial pressure, left atrial pressure, systemic arterial pressure, and lung lymph flow were measured. Observation was continued over 5 h after endotoxin administration. RESULTS: ONO1714 did not cause any pulmonary hemodynamic changes at baseline or exert any influences on transient pulmonary hypertension and increased pulmonary vascular resistance during endotoxemia. However, inducible nitric oxide synthase inhibition with ONO1714 significantly reduced lung lymph filtration and improved abnormal oxygenation during endotoxemia. In addition, increased nitrate-nitrite in plasma and lung lymph in response to endotoxin was prevented by treatment with ONO1714. CONCLUSIONS: These findings suggest that nitric oxide release by the inducible nitric oxide synthase pathway partially contributes to the increased permeability of pulmonary edema and decreased oxygenation during endotoxemia in sheep.

Acute Disease↗