Recent evidence has shown that systemic administration of N-acetylcysteine (NAC), a compound structurally similar to the intracellular antioxidant glutathione, inhibits skeletal muscle fatigue. To further elucidate the actions of NAC, we studied its effects on in vitro rat diaphragm contractile function. Rat diaphragm strips were incubated in tissue baths containing physiological salt solution (n = 29) or physiological salt solution containing 4 mg/ml of NAC (n = 29). Strips were stimulated by either indirect or direct means. After determination of baseline contractile characteristics, strips were fatigued for 4 min at 20 Hz (1 train/s, 0.33 ms train duration). Force-frequency relationships were then studied over a 60-min recovery period. We found that 1) NAC had significant effects on the baseline force-frequency relationship; treated strips had increased peak tension but diminished twitch tension and accelerated twitch kinetics; 2) NAC had significant fatigue-sparing effects that were magnified at 37 degrees C; and 3) NAC treatment did not improve postfatigue recovery. The effects of NAC were generally independent of the stimulation method. We conclude that NAC has direct temperature-dependent effects on diaphragm function. These effects are consistent with the properties of NAC as an antioxidant and suggest important but complex effects of oxidant stress on skeletal muscle.
There is increasing evidence that oxygen-derived free radicals produced during strenuous work by the diaphragm may contribute to diaphragm fatigue and/or injury. However, the precise identity of these oxygen radicals remains unknown, inasmuch as oxygen free radicals are extremely short lived and their detection in biologic systems is quite difficult. There is recent evidence that the salicylate-trapping method may be a useful means of monitoring tissue production of hydroxyl radical (.OH). This method is predicated on the fact that salicylate's phenolic ring can be attacked by .OH at the 3 or 5 position to yield 2,3- or 2,5-dihydroxybenzoic acid (DHB). These metabolites are stable and can be identified by high-performance liquid chromatography (HPLC) coupled with electrochemical or ultraviolet detection. To test the hypothesis that hydroxylated salicylates are produced during diaphragm fatigue, we exposed in vitro rat diaphragm strips to a physiological saline solution containing 2.0 mM sodium salicylate for approximately 15 min. The solution was then removed, and the strips were fatigued (20 Hz, 200-ms train duration, 1 train/s) via phrenic nerve stimulation for 30 s-10 min. The diaphragm strips were subsequently homogenized, and the homogenate was analyzed by HPLC coupled with ultraviolet detection. Levels of 2,3-DHB were significantly higher in fatigued than in control nonfatigued strips. There was also a significant correlation between the amount of 2,3-DHB in the fatigued muscle and the accumulated tension-time product developed during fatigue. 2,5-DHB was not consistently identified in control or experimental strips.(ABSTRACT TRUNCATED AT 250 WORDS)
To assess bronchiectasis depicted with computed tomography (CT) in patients with alpha 1-antitrypsin deficiency and to examine associated clinical correlates.CT scans in 14 patients with alpha 1-antitrypsin deficiency were evaluated by two thoracic radiologists for the presence and extent of bronchiectasis and emphysema. The findings were correlated with numeric infection scores on the basis of symptoms of sputum production and respiratory infection and with a history of conditions that may predispose to development of bronchiectasis.Six (43%) of 14 patients had CT evidence of bronchiectasis. Patients with bronchiectasis had significantly higher infection scores than did patients without bronchiectasis (P < .005). Two patients had diffuse cystic bronchiectasis, and neither reported a history of illness that may have predisposed them to this condition.Bronchiectasis may be more common in patients with alpha 1-antitrypsin deficiency than has been previously recognized. The diagnosis of alpha 1-antitrypsin deficiency should be considered in patients with emphysema and diffuse cystic bronchiectasis.
In Brief The primary care provider (PCP) has a critical role in the detection and treatment of chronic obstructive pulmonary disease (COPD). Recently, the National Lung Health Education Program evaluated surveillance and progression of COPD and recommended educating the PCP in the use of office spirometry.
Chronic Obstructive Pulmonary Disease (COPD) is a progressive disease. Frequent pneumonias and exacerbations are known to accelerate its progression. We present a case of severe emphysema whose lung function paradoxically improved following recurrent pneumonia, without lung volume reduction surgery (LVRS). A 54-year-old female with severe COPD presented for LVRS evaluation. She was not a candidate for the surgery because of the unsuitable anatomic distribution of her emphysema. The patient experienced recurrent pneumonia over the years but her lung function and oxygen requirement showed marked improvement. Follow-up imaging studies showed decreased lung volumes and focal fibrotic changes. We believe that the improvement in her lung function overtime is the reflection of lung volume reduction as a result of parenchymal remodeling due to repeated lung infection. These findings seen in our patient contribute important information for the continued effort in developing nonsurgical lung volume reduction techniques.
