Influence of noble metals alloying additions on the corrosion behaviour of titanium in a fluoride-containing environment.

Titanium alloys exhibit excellent corrosion resistance in most aqueous media due to the formation of a stable oxide film, and some of these alloys (particularly Ti-6Al-7Nb) have been chosen for surgical and odontological implants for their resistance and biocompatibility. Treatment with fluorides (F(-)) is known to be the main method for preventing plaque formation and dental caries. Toothpastes, mouthwashes, and prophylactic gels can contain from 200 to 20,000 ppm F(-) and can affect the corrosion behaviour of titanium alloy devices present in the oral cavity. In this work, the electrochemical corrosion behaviour of Ti-1M alloys (M = Ag, Au, Pd, Pt) was assessed in artificial saliva of pH = 3.0 containing 910 ppm F(-) (0.05 M NaF) through open circuit potential, E(OC), and electrochemical impedance spectroscopy (EIS) measurements. The corrosion behaviour of the Ti-6Al-7Nb commercial alloy was also evaluated for comparison. E (OC) measurements show an active behaviour for all the titanium alloys in fluoridated acidified saliva due to the presence of significant concentrations of HF and HF(2) (-) species that dissolve the spontaneous air-formed oxide film giving rise to surface activation. However, an increase in stability of the passive oxide layer and consequently a decrease in surface activation is observed for the Ti-1M alloys. This behaviour is confirmed by EIS measurements. In fact, the Ti-6Al-7Nb alloy exhibits lower impedance values as compared with Ti-1M alloys, the highest values being measured for the Ti-1Au alloy. The experimental results show that the corrosion resistance of the studied Ti-1M alloys is similar to or better than that of Ti-6Al-7Nb alloy currently used as biomaterial, suggesting their potential for dental applications.

[Limitations of the technique to determine hydrogen peroxide levels in exhaled breath condensate from patients with adult respiratory distress syndrome]. / Limitaciones de la técnica de determinación de peróxido de hidrógeno en el condensado del aire espirado de pacientes con síndrome de distrés respiratorio del adulto.

OBJECTIVE: Exhaled breath condensate represents an alternative to bronchoalveolar lavage for the analysis of markers of inflammation and oxidative stress in patients with adult respiratory distress syndrome (ARDS). However, analysis of hydrogen peroxide (H2O2) yields variable results that do not correlate with severity of the clinical presentation. In an attempt to explain this variability, the aim of the present study was to assess the possible limitations of the most commonly used technique for analyzing H2O2 in breath condensate. PATIENTS AND METHODS: H2O2 levels were analyzed using the Gallati technique (linear range between 0.3 and 10 microM, r=0.99; P<.05) in serial samples of condensate taken from the expiratory tube of a mechanical ventilator in 6 patients with ARDS. RESULTS: The volume of condensate obtained correlated to minute ventilation (r=0.96; P<.05). In 11 out of 23 samples, a spectrophotometer reading was obtained at 450 nm despite the absence of the characteristic color of the reaction and in some of these samples a spontaneous reading was obtained that was indicative of contamination. The absorbance spectrum of these samples did not contain the characteristic peak for H2O2 at 450 nm and pretreatment of some samples with catalase did not affect the absorbance at 450 nm. CONCLUSIONS: The spectrophotometric method commonly used to measure H2O2 levels in breath condensate lacks specificity in ARDS due to the presence of variable levels of contaminants in the samples, which lead to false positives.

Limitaciones de la técnica de determinación de peróxido de hidrógeno en el condensado del aire espirado de pacientes con síndrome de distrés respiratorio del adulto / Limitations of the technique to determine hydrogen peroxide levels in exhaled breath condensate from patients with adult respiratory distress syndrome

Objetivo: El condensado del aire espirado es una alternativa al lavado broncoalveolar para estudiar marcadores de inflamación y estrés oxidativo en pacientes con síndrome de distrés respiratorio del adulto (SDRA). Sin embargo, el estudio del peróxido de hidrógeno (H2O2) ofrece resultados variables que no se relacionan con la gravedad del cuadro clínico. El objetivo del presente estudio ha sido identificar las posibles limitaciones de la técnica más utilizada para medir el H2O2 en condensado que expliquen esta variabilidad. Pacientes y métodos: Se analizaron muestras seriadas de condensado de la vía espiratoria del ventilador de 6 pacientes con SDRA mediante la técnica de Gallati (lineal entre 0,3-10 mM, r = 0,99; p < 0,05) para H2O2. Resultados: El volumen de condensado se relacionó con la ventilación minuto (r = 0,96; p < 0,05). En 11 de 23 muestras se obtuvo lectura a 450 nm sin el color característico de la reacción y en algunas se obtuvo también lectura espontánea indicativa de contaminantes. El espectro de absorción de estas muestras no mostró el pico característico del H2O2 a 450 nm y el pretratamiento de algunas muestras con catalasa no modificó la absorbancia a 450 nm. Conclusiones: El método espectrofotométrico frecuentemente empleado para medir el H2O2 en condensado es inespecífico en el SDRA por la presencia en las muestras de cantidades variables de contaminantes que determinan falsos positivos

Objective: Exhaled breath condensate represents an alternative to bronchoalveolar lavage for the analysis of markers of inflammation and oxidative stress in patients with adult respiratory distress syndrome (ARDS). However, analysis of hydrogen peroxide (H2O2) yields variable results that do not correlate with severity of the clinical presentation. In an attempt to explain this variability, the aim of the present study was to assess the possible limitations of the most commonly used technique for analyzing H2O2 in breath condensate. Patients and methods: H2O2 levels were analyzed using the Gallati technique (linear range between 0.3 and 10 mM, r=0.99; P<.05) in serial samples of condensate taken from the expiratory tube of a mechanical ventilator in 6 patients with ARDS. Results: The volume of condensate obtained correlated to minute ventilation (r=0.96; P<.05). In 11 out of 23 samples, a spectrophotometer reading was obtained at 450 nm despite the absence of the characteristic color of the reaction and in some of these samples a spontaneous reading was obtained that was indicative of contamination. The absorbance spectrum of these samples did not contain the characteristic peak for H2O2 at 450 nm and pretreatment of some samples with catalase did not affect the absorbance at 450 nm. Conclusions: The spectrophotometric method commonly used to measure H2O2 levels in breath condensate lacks specificity in ARDS due to the presence of variable levels of contaminants in the samples, which lead to false positives

Breathing pattern and gas exchange at peak exercise in COPD patients with and without tidal flow limitation at rest.

Expiratory flow limitation (FL) at rest is frequently present in chronic obstructive pulmonary disease (COPD) patients. It promotes dynamic hyperinflation with a consequent decrease in inspiratory capacity (IC). Since in COPD resting IC is strongly correlated with exercise tolerance, this study hypothesized that this is due to limitation of the maximal tidal volume (VT,max) during exercise by the reduced IC. The present study investigated the role of tidal FL at rest on: 1) the relationship of resting IC to VT,max; and 2) on gas exchange during peak exercise in COPD patients. Fifty-two stable COPD patients were studied at rest, using the negative expiratory pressure technique to assess the presence of FL, and during incremental symptom-limited cycling exercise to evaluate exercise performance. At rest, FL was present in 29 patients. In the 52 patients, a close relationship of VT,max to IC was found using non-normalized values (r=0.77; p < 0.0001), and stepwise regression analysis selected IC as the only significant predictor of VT,max. Subgroup analysis showed that this was also the case for patients both with and without FL (r=0.70 and 0.76, respectively). In addition, in FL patients there was an increase (p < 0.002) in arterial carbon dioxide partial pressure at peak exercise, mainly due to a relatively low VT,max and consequent increase in the physiological dead space (VD)/VT ratio. The arterial oxygen partial pressure also decreased at peak exercise in the FL patients (p < 0.05). In conclusion, in chronic obstructive pulmonary disease patients the maximal tidal volume, and hence maximal oxygen consumption, are closely related to the reduced inspiratory capacity. The flow limited patients also exhibit a significant increase in arterial carbon dioxide partial pressure and a decrease in arterial oxygen partial pressure during peak exercise.

[Quality of life in patients with chronic obstructive pulmonary disease and the impact of physical training]. / Calidad de vida en pacientes con enfermedad pulmonar obstructiva crónica e impacto del entrenamiento físico.

BACKGROUND: Health related quality of life (QoL) is severely impaired in COPD patients as a consequence of dyspnea and limited exercise tolerance, which lead to physical deconditioning and muscle atrophy resulting in weakness and fatigue. Psychosocial factors such as depression and anxiety also contribute to this impairment. AIM: To evaluate: a) the impact of COPD on quality of life, and b) the effect of 10 weeks of exercise training on exercise performance and on QoL. PATIENTS AND METHODS: The Spanish version of the Chronic Respiratory Questionnaire (CRQ) was applied to 55 COPD patients (FEV1 37 +/- 13% pred) for the assessment of QoL and in 30 of them submitted to exercise training for 10 weeks. Exercise performance was evaluated by measuring: six-minute walking distance, maximal workload (Wmax), maximal O2 consumption (VO2max) as well as endurance time, blood lactic acid, dyspnea and leg fatigue during a submaximal exercise. Trained patients were evaluated before and after training. RESULTS: COPD patients showed a reduction (mean +/- SD) in the four domains of the CRQ: dyspnea (3.1 +/- 0.9); fatigue (4.3 +/- 1.3); mastery (4.65 +/- 1.3), emotional function (4.1 +/- 0.97), and in Wmax and VO2max (52 +/- 16 Watt and 970 +/- 301 ml/min). No significant relationship between the impairment in exercise tolerance and in QoL was observed. Exercise training significantly improved the four domains of QoL (p < 0.0001), Wmax (p < 0.05), VO2max (p < 0.02) and endurance time (p < 0.001). Isotime exercise measurements of dyspnea, leg fatigue and lactic acid decreased after training (p < 0.001, each). No significant relation between changes in QoL and changes in exercise performance were observed. CONCLUSIONS: Our results demonstrate that QoL is seriously impaired in patients with COPD and confirm: (a) the lack of relationship of QoL to the usually measured physiological parameters, and (b) the beneficial effect of exercise training on QoL through the reduction of symptoms. These findings stresses the need of measuring quality of life in our patients if we want to evaluate the impact of therapeutic procedures on well-being from the patients' perspective.

Bleomycin-induced chronic lung damage does not resemble human idiopathic pulmonary fibrosis.

Administration of bleomycin into the lungs of experimental animals has been utilized as a model to understand human pulmonary fibrosis. Most of the studies, however, have focused on early stages of the lung reaction. We hypothesized that chronic stages of the model may not mimic idiopathic pulmonary fibrosis, since in preliminary studies, lung volume and compliance were not decreased. Eight male Sprague-Dawley rats receiving intratracheal bleomycin (0.5 U/100 g body weight) underwent measurement of FRC, inspiratory capacity, and lung compliance 120 d later. Lung histologic changes were evaluated using light microscopy. Eight rats without intervention served as controls. Results show that our model, in early stages, has histologic changes no different from those previously described elsewhere. In chronic stages, however, the model does not behave as a restrictive syndrome: FRC is normal or increased, whereas lung compliance is normal. Focal peribronchiolar inflammation and fibrosis associated with paracicatricial emphysematous changes are the main histologic features of long-term lung remodeling after bleomycin. We conclude that while the chronic stages of the model may be informative in understanding mechanisms of fibrosis, care should be taken not to extrapolate to human idiopathic pulmonary fibrosis. We speculate that the model might resemble a particular subgroup of human interstitial lung disease, namely, those involving peribronchiolar structures.

Factores sistémicos con potencial acción sobre la función muscular periférica en pacientes con EPOC / Systemic factors that can affect peripheral muscle function in COPD patients

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[Strength of inspiratory muscles in chronic heart failure and chronic pulmonary obstructive disease]. / Potencia de los músculos inspiratorios en insuficiencia cardíaca crónica y en enfermedad pulmonar obstructiva crónica.

BACKGROUND: The maximal pressure generated by inspiratory muscles (PIMax) is an index of their strength which is diminished in both chronic obstructive pulmonary disease (COPD) and chronic heart failure (CHF). Although inspiratory muscle power output (IMPO), which includes both strength and velocity of shortening, has been shown to be reduced in COPD, there is no information regarding IMPO in CHF. AIM: To measure IMPO in patients with CHF and COPD. PATIENTS AND METHODS: We studied 9 CHF patients with functional capacity II and III and 9 patients with severe COPD. Eight normal subjects of similar ages were included as controls. Power output was measured using the incremental threshold loading test. RESULTS: Maximal IMPO was significantly reduced in both groups of patients. Power output developed with each increasing load was also diminished, basically as a consequence of a reduction in Vinsp. The degree of dyspnea at the end of the test was greater in COPD than in CHF patients and normal subjects. For a given level of power, dyspnea was also greater in patients than in normals subjects. There was no decrease in SpO2 during the test. CONCLUSIONS: IMPO is equally reduced in COPD and CHF patients. Power output is better related to dyspnea than PIMax, probably because of the inclusion of shortening velocity.

Role of inspiratory capacity on exercise tolerance in COPD patients with and without tidal expiratory flow limitation at rest.

Expiratory flow limitation promotes dynamic hyperinflation during exercise in chronic obstructive pulmonary disease (COPD) patients with a consequent reduction in inspiratory capacity (IC), limiting their exercise tolerance. Therefore, the exercise capacity of patients with tidal expiratory flow limitation (FL) at rest should depend on the magnitude of IC. The presented study was designed to evaluate the role of FL on the relationship between resting IC, other respiratory function variables and exercise performance in COPD patients. Fifty-two patients were included in the study. Negative expiratory pressure (NEP) uptake (VO2,max) were measured during an incremental symptom-limited cycle exercise. Twenty-nine patients were FL at rest. The IC was normal in all non-FL patients, while in most FL subjects it was decreased. Both WRmax and VO2,max were lower in FL patients (p<0.001, each). A close relationship of WRmax and O2,max to IC was found (r=0.73 and 0.75, respectively; p<0.0001, each). In the whole group, stepwise regression analysis selected IC and forced expiratory volume in one second (FEV1)/forced vital capacity (FVC) (% predicted) as the only significant contributors to exercise tolerance. Subgroup analysis showed that IC was the sole predictor in FL patients, and FEV1/FVC in non-FL patients. Detection of flow limitation provides useful information on the factors that influence exercise capacity in chronic obstructive pulmonary disease patients. Accordingly, in patients with flow limitation, inspiratory capacity appears as the best predictor of exercise tolerance, reflecting the presence of dynamic hyperinflation.

[Peroxide metabolism on respiratory muscles: effect of growth, maturation and aging]. / Metabolismo de peróxidos en músculos respiratorios: efecto del crecimiento, desarrollo y envejecimiento.

BACKGROUND: Glutathione peroxidase (GSHPx) and catalase are two important cellular antioxidant enzymes involved in H2O2 and lipid-peroxide metabolism. AIM: To study the effects of growth, maturation and aging on the activity of these enzymes. MATERIAL AND METHODS: GSHPx and catalase specific activities were measured in samples of diaphragm and intercostal muscle of male Sprague-Dawley rats of different ages (21, 50, 70, 180 and 365 days), anesthetised with chloral hydrate (45 mg/100 g i.p.). RESULTS: The diaphragm and intercostal muscles did not differ in GSHPx activity at 21 days. After that, GSHPx activity increased progressively with age, but following a different pattern, in each muscle, suggesting an increase in enzyme substrates with age. In one year old animals, GSHPx activity was 5 times higher for the diaphragm and 3 times higher for the intercostal muscles, when compared with values observed at 21 days of age. Catalase activity also increased with age in the diaphragm but not in the intercostal muscles. CONCLUSIONS: GSHPx activity increases progressively with age in rat respiratory muscles, with a time course that is specific of each muscle. Catalase activity increases with age only in the diaphragm. These results support the hypothesis that antioxidants in respiratory muscles undergo specific regulatory changes with age.

[Effects of inspiratory muscle training on the oxygen cost of breathing in patients with chronic obstructive pulmonary disease]. / Efecto del entrenamiento muscular inspiratorio en el costo de oxígeno de la ventilación en pacientes con enfermedad pulmonar obstructiva crónica.

BACKGROUND: Patients with chronic obstructive pulmonary disease have an increased inspiratory work, since they must overcome high loads due to increased airway resistance. AIM: To determine if the reduction in the metabolic cost of exercise observed in patients with chronic obstructive pulmonary disease (COPD) after inspiratory muscle training, was due to a reduction in the oxygen cost of breathing. PATIENTS AND METHODS: Nine patients with COPD (FEV1 39 +/- 13%) subjected to inspiratory muscle training, using a training load of 30% of maximal inspiratory pressure, during 10 weeks; 5 patients with COPD (FEV1 44 +/- 18%) not subjected to training, and 7 healthy controls (FEV1 110 +/- 10%) were studied. The cost of breathing was calculated as the difference in VO2 measured at rest and after breathing a gas mixture containing air and 5% CO2. Exercise VO2 was measured at submaximal exercise. RESULTS: Oxygen cost of breathing was increased in patients with COPD and it was inversely correlated with FEV1 (r = -0.86 p < 0.001). Inspiratory muscle training increased maximal inspiratory pressure and decreased exercise VO2. Oxygen cost of breathing increased in six and decreased in three trained patients. Changes in this parameter after training did not correlate with the reduction in exercise VO2 or the increment in maximal inspiratory pressure. CONCLUSIONS: The reduction in exercise VO2 after inspiratory muscle training is not due to a reduction in the oxygen cost of breathing.

[Inspiratory muscle training in patients with chronic obstructive pulmonary disease]. / Entrenamiento muscular inspiratorio en pacientes con enfermedad pulmonar obstructiva crónica.

We analyze the effect of inspiratory muscle training (IMT) in patients with chronic obstructive pulmonary disease (COPD), with special emphasis on its effects on inspiratory muscle function and clinical outcomes. We reviewed only randomized, controlled studies that have either controlled both the load and the breathing pattern when using resistive training or have employed a threshold trainer in which the load is independent of the pattern of breathing, since methodological aspects may explain inconsistent results in the literature. In these circumstances, most of the studies demonstrated positive effects on inspiratory muscle function. Clinical effects were seldom evaluated; limited available data showed a reduction in dyspnea that was related to an increase in maximal inspiratory pressures (PIMax). When exercise capacity was evaluated through the distance the patients were able to walk in 6 or 12 minutes, most studies demonstrated a significant increase. Other reported positive effects were improvement in nocturnal SaO2, inspiratory muscle power output and maximal inspiratory flow rate. Based in this review, a recommended training regime appears to be an intermediate load (30-40% PIMax) using a threshold device for 30 minutes daily for at least 5 weeks. Although in the literature the criteria for selecting patients are not always well defined, we consider IMT as a helpful procedure for pulmonar rehabilitation in those patients with a moderately severe inspiratory muscle dysfunction presenting dyspnea during daily living activities despite optimal therapy.

Effect of inspiratory muscle training with an intermediate load on inspiratory power output in COPD.

There is very little information about the effect of inspiratory muscle training on inspiratory flow (V'I) and thus on power output (PO) in patients with chronic obstructive pulmonary disease (COPD). In this study we aimed to evaluate the changes induced by training on the determinants of PO. Thirty one patients with severe COPD were randomly divided into: Group 1, trained with 30% maximal inspiratory pressure (PI,max); Group 2, with 10% PI,max; and Group 3 also trained with 30% PI,max, but the breathing pattern was evaluated while performing the training manoeuvres along inspiratory muscle training (IMT). All groups used a threshold device for 10 weeks. The PO for each of the loads during an incremental threshold test was evaluated prior to and after training. Maximal PO (POmax) increased in all groups, but the increment was higher in groups trained with 30% PI,max (p<0.005), mainly due to an increase in V'I. Group 3 showed a progressive increase in V'I (p<0.001) during the training manoeuvres in spite of an increase in load along IMT. In addition, the load after IMT was overcome with a shorter inspiratory time (tI) (p<0.02), a smaller tI/total duration of the respiratory cycle (t(tot)), (p<0.001) with no change in tidal volume or t(tot). The increment in POmax in this group correlated with the V'I generated while training (r=0.85; p<0.0001). We conclude that in patients with chronic obstructive pulmonary disease, the use of an intermediate threshold load for training improves power output mainly by increasing inspiratory flow, an effect consistent with an increase in shortening velocity of inspiratory muscles.

[Experimental pulmonary emphysema in rats. Inflammatory phenomena and progression of lung damage]. / Enfisema pulmonar experimental en la rata: fenómenos inflamatorios y progresión del daño pulmonar.

BACKGROUND: Although the hamster model of elastase induced emphysema is well characterized, the rat model has received less attention. AIM: To evaluate the effect of a single intratracheal elastase dose on lung pathological changes of Sprague-Dawley rats. MATERIAL AND METHODS: Rats were injected with a single intratracheal elastase dose of 28 U/100 g body weight or saline and studied 7, 15, 30 and 365 days after injection. RESULTS: Forty percent of rats died in the first 48 hours after injection, six were sacrificed at 7 days, 6 at 15 days, 7 at 30 days and 12 at 365 days. Progressive centroacinar emphysema was found from day 7 after elastase, with a persistent inflammatory reaction in the vicinity of emphysematous areas. CONCLUSIONS: Present findings differ from the panacinar emphysema described in the hamster using a similar elastase dose.

Inspiratory muscle training in chronic airflow limitation: effect on exercise performance.

The effect of inspiratory muscle training (IMT) on exercise capacity in patients with chronic airflow limitation (CAL) has been debated. The present study was planned to further investigate the effects of IMT on exercise performance. Twenty patients (aged 62+/-1 yrs; forced expiratory volume in one second/forced vital capacity (FEV1/FVC) 36+/-2%) were trained 30 min daily for 6 days a week during 10 weeks, with either 30% (Group 1) or 10% (Group 2) of peak maximal inspiratory pressure (PI,max) as a training load. Exercise performance was evaluated by the distance walked in 6 min (6MWD) and by changes in oxygen consumption (V'O2) and minute ventilation (V'E) during a progressive exercise test. Changes in PI,max and dyspnoea were also measured. Results showed a significant increment in peak PI,max in both groups, whereas dyspnoea and 6MWD improved only in Group 1 (p<0.05 and p<0.01, respectively). No increment in maximal workload or in peak V'O2 was observed in either group. Patients in Group 1, however, showed a reduction in V'E and V'O2 for the same exercise. A correlation between changes in V'E and V'O2 during a workload of 75 kpm x min(-1) was observed in Group 1 (r=0.92; p<0.001). We conclude that inspiratory muscle training using a load of 30% peak maximal inspiratory pressure, improves dyspnoea, increases walking capacity and reduces the metabolic cost of exercise.

Detection of free radicals in blood by electron spin resonance in a model of respiratory failure in the rat.

Previous work has suggested that a free radical mechanism is involved in some types of muscle fatigue and that there can be free radicals released extracellularly. Because muscle fatigue may be an important factor in respiratory failure, the authors tested the hypothesis that increased concentrations of free radicals could be detected in the blood of animals undergoing severe resistive loading to respiratory failure. An ex vivo spin trapping technique with alpha-phenyl-N-tert-butylnitrone (PBN) was used to investigate the possible formation of free radicals in systemic blood samples by electron spin resonance (ESR) spectrometry. After 2.5-3 h of severe inspiratory resistive loading with 70% supplemental inspired oxygen, free radical levels in the form of PBN-adducts were found to rise significantly over the control group breathing room air and the control group breathing 70% oxygen (p < 0.05, N = 8). There were no significant differences between control groups breathing room air and control groups breathing 70% oxygen. This study presents direct evidence that free radicals are produced ex vivo and that they can be detected in the systemic circulation due to excessive resistive loading of the respiratory muscles.

Detection of free radicals by electron spin resonance in rat diaphragm after resistive loading.

Indirect evidence supports free radical production in the diaphragm under excessive mechanical loads in both in vitro and in situ preparations. We hypothesized that free radicals are produced in the diaphragm with loads in vivo at a sufficient concentration to be detected by electron spin resonance (ESR) spectroscopy. Anesthetized rats underwent severe inspiratory resistive loading for 2.5-3 h with maintenance of blood oxygenation and arterial blood pressure by breathing 70% oxygen. The ESR spectra of four samples (freeze-clamped at liquid nitrogen temperature) from each experimental animal were compared with the spectra from a control animal breathing air and a control animal breathing 70% oxygen. We observed 1) an approximately 30% increase in intensity of free radical signal in experimental animals (n = 10) compared with control animals breathing oxygen (n = 10; P < 0.01) and control animals breathing air (n = 10; P < 0.05), 2) that oxygen alone had no effect on the ESR spectrum, and 3) the intensity of the ESR signal decreased approximately 25% in the experimental group when samples were taken 10 min postmortem, whereas no difference in signal was observed for control animals. We conclude that the diaphragm shows an increased production of free radicals associated with respiratory failure induced by resistive breathing.

Loss of diaphragm glutathione is associated with respiratory failure induced by resistive breathing.

It has been suggested that oxidant stress may contribute to dysfunction of respiratory muscles undergoing severe work loads. We examined changes in glutathione content and redox status in the diaphragm and intercostal muscles of anesthetized Sprague-Dawley rats exposed to prolonged inspiratory resistive loading while breathing 70% O2. These results were compared with those from control groups breathing air or 70% O2. Changes in liver glutathione were also examined. Freeze-clamping and an enzymatic recycling assay were used. Results show that 1) in controls, glutathione content was higher in the diaphragm than in the intercostals, 2) severe hypercapnic acidosis without hypoxemia was present with loading, 3) total diaphragm glutathione decreased approximately 35% with no increase in glutathione oxidation with resistive breathing, whereas intercostal and liver glutathione remained unchanged, and 4) the drop in diaphragm glutathione correlated significantly with the drop in minute ventilation and the increase in arterial PCO2, whereas it was not directly related to intensity of respiratory muscle activity. In conclusion, although diaphragm susceptibility to oxidant stress may be increased with resistive breathing, it is unlikely that the modest decrease in total glutathione contributed significantly to respiratory failure in this model.

The effects of beta 2-agonists and caffeine on respiratory and limb muscle performance.

The possibility that respiratory muscle function may be improved by drug therapy is of clinical importance, but remains controversial. A series of studies concerning the effects of maximally tolerated dosages of terbutaline, tulobuterol (a new beta 2-agonist) and caffeine on respiratory muscle strength and limb muscle strength and endurance were undertaken in normal subjects. Drugs were administered orally, 2 h before study. Caffeine produced a small but statistically significant increase in the stimulated contraction force at 20 Hz, and a small beneficial effect on recovery from a fatiguing protocol; maximum voluntary contraction force of the quadriceps was increased by 3.8%. Terbutaline and tulobuterol had no beneficial effects on either respiratory or limb muscle function. We conclude that conventional dosages of these bronchodilator drugs do not greatly affect skeletal muscle performance.