RESUMEN
Diaphragmatic fatigue has been associated with increased production of reactive oxygen species. Among the defenses against reactive oxygen species is the glutathione redox system. The selenium-dependent enzyme glutathione peroxidase is an important component of this system. Thus, we hypothesized that selenium deficiency would lower glutathione peroxidase activity and render the diaphragm more susceptible to a mild exertional protocol. Sprague-Dawley rats were fed a selenium-deficient or control diet for 12 weeks then divided into four experimental groups: (1) unloaded, basic diet with selenium supplementation (control); (2) unloaded, selenium-deficient diet; (3) loaded, basic diet with selenium supplementation; and (4) loaded, selenium-deficient diet. Diaphragmatic in vitro contractile properties, glutathione peroxidase activity and glutathione content were measured. During inspiratory resistive loading, the animals breathed against an inspiratory resistor at 70% of maximal airway pressure until the target pressure was not achieved for five consecutive breaths. Selenium deficiency resulted in a significant decrease in diaphragmatic glutathione peroxidase activity, without changes in total glutathione content. Neither selenium deficiency nor inspiratory resistive loading alone impaired diaphragmatic contractility. Selenium deficiency in conjunction with inspiratory resistive loading resulted in a significant decrease in diaphragmatic twitch and tetanic force, with a downward shift in the force/frequency curve. These data suggest that selenium deficiency lowers diaphragmatic glutathione peroxidase activity, and when these animals are subjected to the oxidative stress of resistive loading, there is an impairment in muscle function. We conclude that a functional glutathione peroxidase is necessary to protect the diaphragm against the effects of resistive loading.
Asunto(s)
Diafragma/fisiología , Fatiga Muscular/fisiología , Selenio/deficiencia , Animales , Glutatión/metabolismo , Glutatión Peroxidasa/metabolismo , Inhalación/fisiología , Contracción Isométrica/fisiología , Masculino , Fibras Musculares Esqueléticas/enzimología , Ratas , Ratas Sprague-Dawley , Especies Reactivas de Oxígeno/metabolismoRESUMEN
We studied the effect of a nitric oxide synthase inhibitor, Nomega-Nitro-L-arginine-methyl-ester (L-NAME), on in vitro diphragmatic function both at rest (control) or after inspiratory resistive loading (IRL). Sprague-Dawley rats were anesthetized, instrumented, and then the following experimental groups: (1) controls; (2) L-NAME (100 mg/kg/body weight intravenously alone); (3) IRL alone; and (4) L-NAME + IRL. The IRL protocol consisted of applying a variable resistor to the inspiratory limb of a two-way valve at 70% of maximal airway pressure until apnea. After the experiment, the animals were sacrificed and diaphragmatic strips were obtained for activity of constitutive nitric oxide synthase (cNOS) and measurements of in vitro contractile properties: tetanic (Po) and twitch tensions (Pt). cNOS activity was significantly decreased in the L-NAME and L-NAME + IRL groups (P < or = 0.05) as compared with control and IRL groups. L-NAME alone did not affect Po or Pt. However, in both IRL groups, with and without was a significant decrease in Po and Pt. This reduction was comparable in both groups. In summary, our data showed that L-NAME resulted in a significant decrease cNOS activity, but in vitro contractility was impaired.
Asunto(s)
Diafragma/efectos de los fármacos , Diafragma/fisiología , Inhibidores Enzimáticos/farmacología , NG-Nitroarginina Metil Éster/farmacología , Óxido Nítrico Sintasa/antagonistas & inhibidores , Trabajo Respiratorio , Animales , Presión Sanguínea/efectos de los fármacos , Diafragma/enzimología , Técnicas In Vitro , Masculino , Contracción Muscular/efectos de los fármacos , Óxido Nítrico Sintasa/metabolismo , Ratas , Ratas Sprague-DawleyRESUMEN
Disulfiram (Antabuse) (DSF) has been reported to protect rats and other animals from the effects of hyperbaric hyperoxia at 4 to 6 ATA (atmospheres). In contrast, DSF and diethyldithiocarbamate (DDC), its metabolite, accelerate the toxic effects in rats of 100% oxygen at 1 to 2 ATA. We have examined the effects of DSF and DDC on glutathione (GSH) levels in bovine pulmonary artery endothelial cells and Chinese hamster ovary cells. Increases in intracellular GSH occurred 8 to 24 h after addition of DSF to the culture media. These increases in intracellular GSH were associated with increases in the rate of uptake of cystine into the cells. DDC was a less effective inducer of cystine uptake and increased intracellular GSH levels than was DSF. At the concentrations used, neither DDC nor DSF caused significant decreases in intracellular superoxide dismutase levels. Exogenous sulfhydryl compounds including GSH and cysteine partially blocked the induction of cystine transport by DSF or DDC, suggesting that the induction might be mediated through a sulfhydryl reaction between DSF and some cellular components. The increases in GSH in the cultured cells were not significant by 4 h of exposure. In contrast, other stress proteins including heme oxygenase are induced by 2 to 4 h after DSF addition. In previously reported in vivo studies, DSF treatment protected against hyperbaric oxygen damage after as little as 1 to 4 h pre-exposure. This suggests that effects of DSF exposure other than GSH augmentation may be responsible for the protective effects seen in vivo.
Asunto(s)
Cistina/metabolismo , Disulfiram/farmacología , Endotelio Vascular/efectos de los fármacos , Glutatión/metabolismo , Proteínas de Choque Térmico/metabolismo , Animales , Transporte Biológico , Células CHO , Bovinos , Células Cultivadas , Cricetinae , Endotelio Vascular/enzimología , Endotelio Vascular/metabolismo , Superóxido Dismutasa/metabolismoRESUMEN
Type II lung epithelial cells are different from other lung cell types in their means of processing and regulating intracellular glutathione (GSH) levels. In lung cell types, including endothelial cells, fibroblasts, smooth muscle cells, and macrophages, oxidants, sulfhydryl reagents, and electrophilic agents have been shown to induce cystine uptake and concomitantly increase GSH levels, suggesting that cysteine, formed by intracellular reduction of cystine, is a rate-limiting substrate for GSH synthesis. The cystine transport increase was reportedly due to increase in activity of a sodium-independent transport system designated xc-. We have now examined cultures of rat lung type II cells exposed to diethylmaleic acid and arsenite. Although a rise in cellular GSH occurred, cystine transport was not induced. Cystine transport in type II cells was found to differ from the xc- system previously described. Type II cell cystine transport is primarily sodium dependent and is inhibitable by aspartate as well as glutamate and homocysteate. We conclude that the type II cell differs from other lung cell types in both its cystine transport mechanism and method of GSH regulation.
Asunto(s)
Cistina/metabolismo , Alveolos Pulmonares/metabolismo , Animales , Arsenitos/farmacología , Transporte Biológico , Bovinos , Endotelio Vascular/citología , Endotelio Vascular/metabolismo , Células Epiteliales , Epitelio/metabolismo , Maleatos/farmacología , Alveolos Pulmonares/citología , Arteria Pulmonar/citología , Arteria Pulmonar/metabolismo , Ratas , Ratas Sprague-DawleyRESUMEN
OBJECTIVE: To evaluate the safety and potential efficacy of aerosolized surfactant in intubated patients with adult respiratory distress syndrome (ARDS). DESIGN: A prospective, double-blind, placebo-controlled, randomized, parallel, multicenter pilot clinical trial. PATIENTS: A total of 51 patients with sepsis-induced ARDS were entered into the study within 18 hours of developing sepsis or sepsis syndrome. INTERVENTION: Patients were randomized into four treatment groups in a 2:1:2:1 ratio, as follows: 12 hours of surfactant per day, 12 hours of 0.6% saline per day, 24 hours of surfactant per day, and 24 hours of 0.6% saline per day. Surfactant or saline was aerosolized continuously for up to 5 days using an in-line nebulizer that aerosolized only during inspiration. MAIN OUTCOME MEASURES: Ventilatory data, arterial blood gases, and hemodynamic parameters were measured at baseline, every 4 or 8 hours during the 5 days of treatment, 24 hours after treatment, and 30 days after treatment, at which time mortality was also assessed. Safety was evaluated throughout the 30 days of the study. RESULTS: Surfactant was administered safely in ventilated patients when given continuously throughout the 5 days using the nebulizer system. Although there were no differences in any physiological parameters between the treatment groups, there was a dose-dependent trend in reduction of mortality from 47% in the combined placebo group to 41% and 35% in the groups treated with 12 hours and 24 hours of surfactant per day, respectively. CONCLUSIONS: Aerosolized surfactant was well tolerated when administered on a continuous basis for up to 5 days; however, at the doses given, it did not result in significant improvements in patients with sepsis-induced ARDS.
Asunto(s)
Alcoholes Grasos/uso terapéutico , Fosforilcolina , Polietilenglicoles/uso terapéutico , Surfactantes Pulmonares/uso terapéutico , Síndrome de Dificultad Respiratoria/tratamiento farmacológico , APACHE , Adulto , Aerosoles , Anciano , Método Doble Ciego , Esquema de Medicación , Combinación de Medicamentos , Alcoholes Grasos/administración & dosificación , Femenino , Hemodinámica , Humanos , Intubación , Masculino , Persona de Mediana Edad , Proyectos Piloto , Polietilenglicoles/administración & dosificación , Estudios Prospectivos , Surfactantes Pulmonares/administración & dosificación , Respiración Artificial , Síndrome de Dificultad Respiratoria/etiología , Síndrome de Dificultad Respiratoria/fisiopatología , Síndrome de Dificultad Respiratoria/terapia , Pruebas de Función Respiratoria , Sepsis/fisiopatología , Análisis de SupervivenciaRESUMEN
Development of tuberculomas on adequate tuberculosis therapy is an uncommon event. This case report describes a patient who developed multiple intracranial tuberculomas while receiving adequate supervised outpatient therapy for sensitive pulmonary tuberculosis who was documented to have no intracranial lesions prior to initiation of treatment.
Asunto(s)
Antituberculosos/administración & dosificación , Fibrosis Pulmonar/etiología , Tuberculoma Intracraneal/complicaciones , Tuberculosis Pulmonar/tratamiento farmacológico , Quimioterapia Combinada , Humanos , Masculino , Persona de Mediana Edad , Tomografía Computarizada por Rayos X , Tuberculoma Intracraneal/diagnóstico por imagen , Tuberculosis Pulmonar/complicacionesRESUMEN
Controversy has surrounded the use of single-lung transplantation (SLT) for the treatment of endstage obstructive lung disease. In recent years, several transplant centers have performed SLT for such indications. In this report, we describe functional results in patients undergoing SLT for obstructive lung disease, twenty-two followed over one year and 10 over two years. Data include pulmonary function testing, gas exchange, quantitative ventilation and perfusion to the lung graft, and results of symptom-limited graded cycle exercise testing after SLT. Our results show improvement in obstructive dysfunction FEV1 0.49 +/- 0.13 L (16 +/- 4% predicted) pre-SLT to 1.71 +/- 0.43 L (57 +/- 12% predicted) 3 mo after SLT, FEV1/FVC 0.30 +/- 0.07 pre-SLT to 0.75 +/- 0.09 3 mo after SLT, and improvement in arterial oxygenation, PaO2 58 +/- 10 mm Hg pre SLT to PaO2 86 +/- 13 mm Hg 3 mo post-SLT. In addition, these improvements were sustained up to 1 to 2 yr post-SLT. The majority of ventilation and perfusion go to the new lung graft. After SLT, patients have reduced maximum oxygen consumption (VO2max 40 to 60% predicted) but do not have ventilatory limitation to exercise and can carry out daily activities without compromise. We conclude that SLT is a viable medium-term therapeutic option for endstage obstructive lung disease. The long-term future of this technique remains to be determined.
Asunto(s)
Enfermedades Pulmonares Obstructivas/cirugía , Trasplante de Pulmón , Mecánica Respiratoria , Adulto , Dióxido de Carbono/sangre , Prueba de Esfuerzo , Femenino , Estudios de Seguimiento , Volumen Espiratorio Forzado , Humanos , Enfermedades Pulmonares Obstructivas/sangre , Enfermedades Pulmonares Obstructivas/fisiopatología , Trasplante de Pulmón/mortalidad , Masculino , Persona de Mediana Edad , Oxígeno/sangre , Capacidad de Difusión Pulmonar , Tasa de Supervivencia , Capacidad Pulmonar Total , Capacidad VitalRESUMEN
The association of oxygen radical generation with impaired diaphragm performance has previously been reported after inspiratory resistive loading (IRL). We hypothesized that exposure of rats to normobaric hyperoxia (O2) could produce impaired diaphragm function because of free radical production. Sprague-Dawley rats were divided into four groups: 1) room air (control), 2) > 95% O2 for 24 h, 3) > 95% O2 for 48 h, and 4) > 95% O2 for 60 h. Each group was studied at rest after the O2 exposure and then after IRL. During IRL, the animals breathed through an inspiratory resistor until they were unable to sustain > 70% of the maximum airway pressure. Diaphragm samples were obtained for analysis of glutathione (GSH) and glutathione disulfide (GSSG) concentrations. In vitro isometric contractile properties were also determined, including maximal tetanic tension (Po) and maximal twitch tension (Pt), in GSSG content and in GSSG-to-GSH ratios. Hyperoxia for > 48 h resulted in significant decreases in Po and Pt and an increase in GSSG content and in GSSG-to-GSH ratios compared with other groups. Those same animals subjected to IRL showed a further decrease in Po and Pt. These data suggest that free radical generation may occur in the diaphragm during a hyperoxia exposure associated with activation of the GSH redox cycle and impairment of diaphragm function.
Asunto(s)
Diafragma/fisiopatología , Hiperoxia/fisiopatología , Resistencia de las Vías Respiratorias/fisiología , Animales , Diafragma/metabolismo , Radicales Libres/metabolismo , Glutatión/metabolismo , Hiperoxia/metabolismo , Masculino , Contracción Muscular/fisiología , Fatiga Muscular/fisiología , Tamaño de los Órganos/fisiología , Consumo de Oxígeno/fisiología , Ratas , Ratas Sprague-DawleyAsunto(s)
Diafragma/metabolismo , Especies Reactivas de Oxígeno/metabolismo , Enfermedades Respiratorias/etiología , Animales , Fatiga/etiología , Fatiga/metabolismo , Depuradores de Radicales Libres , Radicales Libres/metabolismo , Peroxidación de Lípido , Consumo de Oxígeno , Enfermedades Respiratorias/metabolismoRESUMEN
Activation of the glutathione (GSH) redox cycle with production of glutathione disulfide (GSSG) has been shown to occur in the diaphragm during inspiratory resistive loading (RB). Buthionine sulfoximine (BSO) lowers tissue GSH by irreversibly inhibiting the rate-limiting synthesis enzyme gamma-glutamylcysteine synthetase. We investigated the effects of BSO on rat diaphragm function, both at rest and after a period of RB. Rats in the RB groups underwent inspiratory RB until they were unable to sustain 70% of their maximal airway pressure. A portion of the diaphragm was analyzed for GSH and GSSG levels, and measurements of in vitro contractile properties included contraction times, maximal tetanic tension (Po), maximal twitch tension (Pt), and force frequency curves. BSO treatment produced a profound depletion of diaphragmatic GSH. Neither BSO nor RB alone significantly altered diaphragm contractile properties at this load of RB. But, in BSO-RB rats, there was a significant decrease in Pt, Po, and tetanic tension at all frequencies of stimulation compared with those in other groups. These data reveal that animals treated with BSO followed by inspiratory resistive loading exhibit marked diaphragm impairment, suggesting that GSH may play an important role in protecting the diaphragm from the stress induced by this resistive breathing protocol.
Asunto(s)
Diafragma/efectos de los fármacos , Glutamato-Cisteína Ligasa/antagonistas & inhibidores , Metionina Sulfoximina/análogos & derivados , Análisis de Varianza , Animales , Butionina Sulfoximina , Diafragma/química , Diafragma/fisiología , Glutatión/análogos & derivados , Glutatión/análisis , Glutatión/efectos de los fármacos , Glutatión/metabolismo , Disulfuro de Glutatión , Masculino , Metionina Sulfoximina/farmacología , Contracción Muscular/efectos de los fármacos , Ratas , Ratas Sprague-Dawley , Pruebas de Función Respiratoria/estadística & datos numéricosRESUMEN
OBJECTIVE: To report functional results and survival in patients undergoing single lung transplantation (SLT) for pulmonary involvement associated with systemic disease or prior malignancy, criteria traditionally considered contraindications to SLT. DESIGN: Case series. SETTING: The University of Texas Health Science Center at San Antonio. PATIENTS: Nine patients who have undergone SLT for end-stage lung disease: four patients with sarcoidosis; two patients with limited scleroderma; and three patients with prior malignancies (two with prior lymphoma and bleomycin-induced pulmonary fibrosis and one who received two bone marrow transplants for acute lymphocytic leukemia and subsequently developed chemotherapy-induced pulmonary fibrosis). MEASUREMENTS: Pulmonary function testing, exercise oximetry, quantitative ventilation-perfusion lung scanning. Actuarial survival. RESULTS: All patients had marked improvement in pulmonary function, exercise oximetry, and quantitative ventilation perfusion to the SLT. One patient with scleroderma died 90 days postoperatively from Pseudomonas pneumonia with a sepsis syndrome. One patient with sarcoidosis died 150 days postoperatively from disseminated aspergillosis. At autopsy, there was no evidence of recurrent fibrosis or sarcoidosis in the transplanted lungs in either of these two patients. The seven surviving patients have returned to work or school and are conducting all activities of daily living without pulmonary disability. The 1- and 2-year actuarial survival rates in these nine patients is 68.6 percent as compared with the 1- and 2-year actuarial survival rates of 66.3 percent and 55.8 percent in the remainder of our SLT group as a whole (n = 49). Despite pharmacologic immunosuppression, there is no evidence of recurrent malignancy in the 3 patients with prior malignancies. CONCLUSIONS: We conclude that carefully selected patients with end-stage lung involvement related to systemic disease or chemotherapy-induced fibrosis may benefit from SLT.
Asunto(s)
Enfermedades Pulmonares/cirugía , Trasplante de Pulmón , Fibrosis Pulmonar/cirugía , Sarcoidosis Pulmonar/cirugía , Adulto , Aspergilosis/complicaciones , Bleomicina/efectos adversos , Femenino , Estudios de Seguimiento , Humanos , Enfermedades Pulmonares/etiología , Trasplante de Pulmón/mortalidad , Trasplante de Pulmón/fisiología , Masculino , Persona de Mediana Edad , Fibrosis Pulmonar/inducido químicamente , Esclerodermia Sistémica/complicaciones , Tasa de Supervivencia , Factores de TiempoRESUMEN
Glutathione (GSH) administered intraperitoneally significantly prolongs the time to initial seizure and survival time of rats exposed to hyperbaric hyperoxia (HBO). Acivicin is an antitumor antibiotic that is an inhibitor of gamma-glutamyl transpeptidase (GGT), an enzyme necessary for the breakdown and transport across cell membranes of GSH. To determine whether acivicin treatment alters GSH-induced protection from HBO, rats were dosed with 25 mg/kg of acivicin or vehicle 1 h before O2 exposure at an inspired O2 fraction of 1.0 at 4 ATA. Immediately before exposure, rats received GSH (1 mmol/kg) or vehicle. Time to seizure and time to death were recorded during exposure by direct observation. In separate groups of rats on the same dosing schedule, plasma GSH, renal GGT, and brain GGT were measured 15 min after the GSH injection without HBO exposure and 100 min after the beginning of HBO exposure. Renal GGT was decreased to 2.5% of control and brain GGT to 37% of control in the acivicin-dosed rats. Plasma GSH increased 3-fold in rats given acivicin alone, 52-fold in rats given GSH alone, and 84-fold in rats receiving both acivicin and GSH. Rats dosed with GSH alone had significantly prolonged times to seizure and death compared with all other groups. Rats dosed with GSH after receiving acivicin were not protected from HBO despite the large increase in plasma GSH that occurred in these animals. GSH treatment did not increase tissue GSH in lung, liver, or brain at 160 or 200 min of exposure.(ABSTRACT TRUNCATED AT 250 WORDS)
Asunto(s)
Glutatión/antagonistas & inhibidores , Oxigenoterapia Hiperbárica/efectos adversos , Isoxazoles/farmacología , Oxígeno/antagonistas & inhibidores , Animales , Encéfalo/enzimología , Química Encefálica/efectos de los fármacos , Glutatión/metabolismo , Glutatión/farmacología , Riñón/enzimología , Riñón/metabolismo , Pulmón/enzimología , Pulmón/metabolismo , Masculino , Oxígeno/toxicidad , Ratas , Ratas Sprague-Dawley , Convulsiones/inducido químicamente , Convulsiones/prevención & control , gamma-Glutamiltransferasa/antagonistas & inhibidores , gamma-Glutamiltransferasa/metabolismoRESUMEN
N,N'-bis(2-chloroethyl)-N-nitro-sourea (BCNU) is a potent inhibitor of glutathione reductase (GSSG-Red) activity in both tissues and cells. We examined the effects of treating alveolar type II cells with BCNU and found that a marked decrease in cellular GSSG-Red activity occurred in these cells associated with a time-dependent increase in cellular glutathione (GSH) concentrations. The increase in GSH was not found to be related to changes in cellular gamma-glutamyl transpeptidase activity, gamma-glutamylcysteine synthetase activity, nor increased intracellular transport of cystine. When the BCNU-exposed cells were incubated with hydrogen peroxide to produce oxidant stress, the cells exhibited increased susceptibility to oxidant damage when compared with controls, despite the fact that cellular concentrations of GSH were markedly elevated.
Asunto(s)
Carmustina/farmacología , Glutatión/metabolismo , Membranas Intracelulares/metabolismo , Alveolos Pulmonares/metabolismo , Animales , Supervivencia Celular , Glutamato-Cisteína Ligasa/metabolismo , Glutatión Reductasa/antagonistas & inhibidores , Peróxido de Hidrógeno/farmacología , Masculino , Alveolos Pulmonares/citología , Alveolos Pulmonares/efectos de los fármacos , Ratas , Ratas Sprague-Dawley , gamma-Glutamiltransferasa/metabolismoRESUMEN
Solid-organ transplantation has flourished during the last decade, with transplantation of heart and lungs becoming available to patients with end-stage cardiac or pulmonary diseases. The first lung transplant was performed in 1963 on a 58-year-old man with bronchogenic carcinoma. He survived for 18 days. During the next two decades, approximately 40 lung transplant procedures were attempted without success. These early attempts at lung transplantation were unsuccessful because of the development of lung rejection, anastomotic complications, or infection in the transplant recipients. In the early 1980s, human heart-lung transplantation was successfully performed for the treatment of pulmonary vascular disease. After this procedure, single-lung transplantation for the treatment of end-stage interstitial lung disease and obstructive lung disease was developed. More recently, the technique of double-lung transplantation has come into existence. This article reviews various aspects of lung transplantation, including immunosuppression, lung graft preservation, the various surgical techniques and types of lung transplant procedures available, recipient and donor selection criteria, and postoperative care of the transplant recipient. In addition, infectious and noninfectious complications seen in this particular patient population, including acute and chronic rejection, will be discussed.
Asunto(s)
Trasplante de Corazón-Pulmón , Terapia de Inmunosupresión , Trasplante de Pulmón , Bronquiolitis Obliterante/etiología , Rechazo de Injerto , Humanos , Cuidados Intraoperatorios/métodos , Preservación de Órganos , Complicaciones Posoperatorias/etiología , Resultado del TratamientoRESUMEN
Formation of oxygen-derived free radicals and activation of the glutathione (GSH) redox cycle has been associated with impaired rat diaphragm performance. Diethylmaleate (DEM) given intraperitoneally irreversibly conjugates with GSH, resulting in marked decreases in tissue concentrations of GSH. We have investigated the effects of acute GSH depletion by DEM on diaphragmatic function during resistive breathing (RB) in the rat. The experimental groups were 1) control, 2) DEM alone, 3) RB, and 4) DEM with RB (DEM + RB). RB was obtained by inspiratory RB until the rats were unable to sustain 70% of maximum airway opening pressure. A portion of the diaphragm was frozen for biochemical assays, and the rest of the diaphragm was prepared for measurement of in vitro contractile properties, including maximum tetanic tension, twitch tension, force-frequency curves, and contraction times. DEM treatment produced a profound depletion of GSH in the DEM and DEM + RB groups. Neither DEM nor RB alone significantly altered diaphragm contractile properties. In DEM + RB rats, however, there was a significant decrease in maximum tetanic tension, twitch tension, and tetanic tension. These data reveal that DEM produced an acute depletion of GSH in the diaphragm without impairment of the muscle in nonstressed rats. In the presence of DEM-induced GSH depletion, RB did result in marked diaphragm impairment. The depletion of GSH and the subsequent impairment in diaphragm contractility after RB suggest that GSH may play an important role in protecting the diaphragm against oxidative stress associated with RB.
Asunto(s)
Diafragma/fisiología , Maleatos/farmacología , Mecánica Respiratoria/efectos de los fármacos , Animales , Análisis de los Gases de la Sangre , Diafragma/efectos de los fármacos , Diafragma/metabolismo , Fatiga/metabolismo , Fatiga/fisiopatología , Glutatión/metabolismo , Contracción Isométrica/efectos de los fármacos , Peroxidación de Lípido/efectos de los fármacos , Peroxidación de Lípido/fisiología , Masculino , Consumo de Oxígeno/efectos de los fármacos , Esfuerzo Físico/fisiología , Ratas , Ratas Sprague-Dawley , Sustancias Reactivas al Ácido Tiobarbitúrico/metabolismoRESUMEN
Oxygen therapy is administered to decrease tissue hypoxia and to relieve arterial hypoxemia. High concentrations of oxygen are often used in patients with adult respiratory distress syndrome. Supplying oxygen to animals has been known to produce tissue damage, with toxicity increasing with the increase of oxygen concentrations and exposure pressures. End-organ damage from hyperoxia depends on both the concentration of oxygen administered and the oxygen pressure during exposure. Prolonged exposure to hyperbaric oxygen causes central nervous system and pulmonary toxicity, which results in atelectasis, pulmonary edema, and seizures. Lung damage may occur as a result of normobaric hyperoxia. A severe retinopathy (retrolental fibroplasia) occurs in neonates during oxygen exposures. For all of these reasons, the lowest possible concentration of oxygen that relieves tissue hypoxia is recommended in patients with adult respiratory distress syndrome.
Asunto(s)
Terapia por Inhalación de Oxígeno/efectos adversos , Oxígeno/envenenamiento , Síndrome de Dificultad Respiratoria/terapia , Adulto , Animales , Enfermedades del Sistema Nervioso Central/inducido químicamente , Radicales Libres , Humanos , Recién Nacido , Unidades de Cuidados Intensivos , Enfermedades Pulmonares/inducido químicamente , Oxígeno/metabolismo , Intoxicación/complicaciones , Intoxicación/etiología , Intoxicación/fisiopatología , Intoxicación/prevención & control , Retinopatía de la Prematuridad/inducido químicamente , Superóxido Dismutasa/fisiología , Factores de TiempoRESUMEN
Allopurinol is a potent xanthine oxidase inhibitor that has been administered to animals to protect tissues from oxidant injury. We hypothesized that allopurinol may protect against oxidant injury by inhibiting the inflammatory response. Male Sprague-Dawley rats were injected daily with vehicle or allopurinol and compared with noninjected controls. Animals were exposed to room air or 90% oxygen for 14 days. At the end of the exposure period, all animals were lavaged and bronchoalveolar lavage fluid (BALF) was examined for cell counts, lactate dehydrogenase (LDH), and protein. BALF neutrophils were significantly increased in oxygen-exposed noninjected controls (33 +/- 7 x 10(3)/mm3) and also in the vehicle-inoculated oxygen-exposed animals (43 +/- 6 x 10(3)/mm3). Allopurinol treatment resulted in a decrease in the neutrophilic alveolar response in oxygen-exposed animals (5.3 +/- 4 x 10(3)/mm3, P < 0.001). These data reveal that oxygen exposure produces a neutrophilic alveolar response that is attenuated by allopurinol treatment. BALF protein and LDH were significantly increased in all inoculated and noninoculated oxygen-exposed animals compared with air-exposed animals. Therefore, allopurinol decreases the neutrophilic alveolar response produced by a hyperoxic exposure in the rat but does not decrease lung injury as assessed by alveolar LDH and protein release.
Asunto(s)
Alopurinol/farmacología , Líquido del Lavado Bronquioalveolar/citología , Neutrófilos/efectos de los fármacos , Oxígeno/toxicidad , Animales , Proteínas Sanguíneas/metabolismo , Líquido del Lavado Bronquioalveolar/enzimología , L-Lactato Deshidrogenasa/sangre , L-Lactato Deshidrogenasa/metabolismo , Recuento de Leucocitos/efectos de los fármacos , Pulmón/citología , Pulmón/fisiología , Macrófagos Alveolares/efectos de los fármacos , Macrófagos Alveolares/fisiología , Masculino , Ratas , Ratas Sprague-DawleyRESUMEN
Single lung transplantation (SLT) has become a therapeutic option for the treatment of end-stage obstructive lung disease. Between January 1989 and June 1990, there were 14 patients with end-stage obstructive lung disease who underwent SLT. Eleven of these patients were surviving at 1 year following transplantation. Three of the patients had received left-sided SLT, and eight had received right-sided SLT. In the patients receiving left-sided SLT, the native right lung radiographically appeared to compress the left lung graft. In the patients receiving right-sided SLT, the native left lung did not appear to compress the right lung graft. We hypothesized that right SLT may provide a functional advantage over left SLT for patients with obstructive lung disease. We compared pulmonary function test results before and after transplantation (approximately 3 and 12 months) and compared quantitative ventilation-perfusion lung scan results between the patients with left SLT and those with right SLT. Additionally, we compared graded-exercise test results at 3 and 12 months after transplant between the two groups. Our data revealed no statistical difference in pulmonary function test results or graded-exercise test results between the two groups, although patients undergoing right SLT showed greater increases in FEV1 and forced vital capacity than those undergoing left SLT. Quantitative ventilation and perfusion were greater to the graft in patients receiving right-sided SLT than in patients receiving left-sided SLT, most likely due to the larger size of the right lung. We conclude that there is no functional difference between patients undergoing left or right SLT for end-stage obstructive lung disease.