Respiratory muscle pharmacology.
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Adrenal Cortex Hormones↗
Biomedical subjects
M Decramer
Publications and source records attributed to M Decramer.
Corticosteroid treatment and nutritional deprivation cause a different pattern of atrophy in rat diaphragm.
Triamcinolone (TR) causes type IIb fiber atrophy in the rat diaphragm, which is associated with changes in contractile properties. We investigated whether this is a direct effect of TR or the result of an accompanying loss of body and diaphragm weights. For 6 wk, adult rats received saline intramuscularly, TR (0.5 mg/kg im), or nutritional depletion (ND) that resulted in a similar (approximately 40%) reduction in body weight as TR. In these animals, the half-relaxation time of the diaphragm bundles increased, the force-frequency relationship shifted leftward, and the resistance to fatigue was increased. No histological changes were found in the ND diaphragm, in contrast to severe myogenic alterations in the TR diaphragm. Type IIb fiber cross-sectional area (CSA) in the TR diaphragm was reduced by 51%, whereas type I and IIa CSAs were unaffected. In the ND animals, the CSAs of type I, IIa, and IIb fibers were reduced by 31, 33, and 52%, respectively. Similar changes occurred in the deep part of the m. gastrocnemius. In conclusion, myogenic changes and selective type IIb fiber atrophy were caused by TR, whereas ND induced generalized fiber type atrophy without histological changes.
Adrenal Cortex Hormones↗
Theophylline increases oxygen consumption during inspiratory resistive loading.
The effect of theophylline on diaphragmatic blood flow (Qdi) and oxygen consumption (VO2di) was studied in eight lightly anesthetized dogs during quiet breathing and inspiratory resistive loading. Qdi was determined with the radioactive microsphere tracer technique, and VO2di was calculated as the product of Qdi and the diaphragmatic arterio-venous oxygen difference. During quiet breathing, theophylline increased minute ventilation (9.3 +/- 1.7 versus 5.1 +/- 0.4 L/min), mean inspiratory flow (547 +/- 60 versus 378 +/- 56 ml/s), and duty cycle (0.270 +/- 0.042 versus 0.192 +/- 0.024) but did not significantly alter Qdi or VO2di. Conversely, Qdi increased significantly during loaded breathing compared with quiet breathing (37 +/- 4 versus 27 +/- 3 ml/100 g/min) and was further increased by theophylline (45 +/- 7 ml/100 g/min). Theophylline did not alter the tension-time index of the diaphragm (TTdi) during inspiratory resistive loading (0.054 +/- 0.006 versus 0.056 +/- 0.004, p NS) but resulted in a disproportionate and significant increase in VO2di (2.66 +/- 0.53 versus 1.78 +/- 0.26 ml/100 g/min). Similarly, total-body oxygen consumption (VO2TB) during inspiratory loading increased significantly after theophylline (24%), but the tension-time index of the inspiratory muscles (TTi), a measure of the total respiratory load, was unchanged. We conclude that theophylline significantly increases VO2di and VO2TB at the same TTdi and TTi during resistive loading. This enhanced energy expenditure needs consideration in the clinical management of pulmonary disorders that increase the work of breathing.
Animals↗
Optimal assessment and management of chronic obstructive pulmonary disease (COPD). The European Respiratory Society Task Force.
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Humans↗
Mechanism of theophylline-induced inotropic effects on foreshortened canine diaphragm.
The mechanisms of theophylline-induced inotropic effects at shorter diaphragm length have not yet been explored. We wondered whether the greater inotropic effects of the drug at shorter diaphragm length might result from an effect on intracellular calcium level. Forty pairs of diaphragm bundles were stimulated at 70% of optimal length in the presence of either verapamil (10(-5)M), calcium-free Krebs solution (buffered or not with 2 mM ethylene glycol tetra-acetic acid (EGTA)) or ryanodine (10(-6) M). Theophylline (1 mM) was subsequently added to one muscle bundle and, after 15 min, twitches were repeated. The twitch potentiation induced by theophylline (37 +/- 21%) was unaffected by verapamil (43 +/- 26%), or zero calcium (39 +/- 18%) and virtually unchanged when the latter was buffered with EGTA. By contrast, theophylline failed to increase twitch tension after pretreatment with ryanodine, a blocker of the calcium release by the sarcoplasmic reticulum. This decreased twitch tension in control (-5 +/- 11%) and experimental (-14 +/- 12%) bundles and prolonged half-relaxation time as a result of impaired sarcoplasmic reticulum calcium reuptake. We conclude that the inotropic effects of theophylline on twitch tension in foreshortened canine diaphragm bundles were not related to sarcoplasmic reticulum. This is consistent with an action of theophylline on the sarcoplasmic reticulum.
Analysis of Variance↗
Rat diaphragm contractility and histopathology are affected differently by low dose treatment with methylprednisolone and deflazacort.
The extent to which treatment with low doses of the nonfluorinated steroid methylprednisolone affects diaphragm contractility and morphology is unknown. In the present study, we compared the effects of equipotent doses of methylprednisolone and deflazacort, an oxazoline derivate of prednisolone with less systemic side-effects on bone structure and carbohydrate metabolism. Twenty six male adult rats were randomized to receive daily saline (control), methylprednisolone 0.4 mg.kg-1 or deflazacort 0.5 mg.kg-1 i.m. Contractile properties and histopathology were measured after a 6 week treatment period. During treatment, body weight increased in control and methylprednisolone-treated animals, but decreased by 4.2 +/- 1.1% (mean +/- SD) in the deflazacort group. Similarly, diaphragm mass in the deflazacort group was decreased compared to control and methylprednisolone groups. Twitch tension and twitch characteristics of isolated diaphragm bundles were similar in the three groups. Maximal tetanic tension was decreased in the deflazacort group. The force-frequency curve of the deflazacort bundles shifted downwards compared to control. Fatigue occurring during this protocol was greatest in the methylprednisolone- and deflazacort-treated animals. Microscopic examination revealed no gross abnormalities in the three groups. Histochemical analysis after staining for myosin adenosine triphosphatase (ATP-ase) showed that in the deflazacort group cross-sectional area of type I, IIa and IIb fibres were decreased. We conclude that low doses of methylprednisolone caused subtle and negligible changes in rat diaphragm contractile properties without affecting fibre dimensions, while deflazacort at an equipotent dose induced generalized fibre atrophy and changes in diaphragm contractility.
Animals↗
Contribution of the parasternal intercostals to inspiratory rib elevation in dogs.
To estimate the contribution of the parasternal intercostals to rib elevation during quiet breathing, parasternal intramuscular pressure, Pim, in the fourth interspace and displacement of the rib just below were measured in eight supine anesthetized dogs during: (1) bilateral stimulation of the parasternals, (2) quiet breathing before, after phrenicotomy, and subsequent vagotomy. During quiet breathing, the parasternal contribution averaged 66 +/- 12% of the rib elevation caused by inspiratory rib cage muscles. This contribution decreased in relative terms after phrenicotomy (37 +/- 14%) and subsequent vagotomy (26 +/- 14%) while it tended to increase in absolute terms (from 1.9 +/- 2.4 to 2.1 +/- 2.5 NS, and 2.4 +/- 2.4 mm P < 0.01, respectively). Rib elevation caused by inspiratory rib cage muscles increased after phrenicotomy (116 +/- 63%, P < 0.001) and subsequent vagotomy (279 +/- 60%, P < 0.001) as did Pim (19 +/- 10% NS and 41 +/- 36% P < 0.01, respectively). Moreover, the mechanical interaction of the parasternals among different interspaces measured in three other dogs, was likely to be limited during quiet breathing. We conclude that after diaphragm paralysis, the parasternals played a progressively smaller role while other rib cage muscles were increasingly recruited.
Animals↗
Value of computed tomography and mediastinoscopy in preoperative evaluation of mediastinal nodes in non-small cell lung cancer. A study of 569 patients.
The efficacy of computed tomography (CT) and mediastinoscopy as staging modalities to assess mediastinal lymph node status was evaluated in 569 patients with a presumed resectable non-small cell lung cancer (NSCLC). Computed tomography scan was performed in every patient and followed by mediastinoscopy in 331 and by thoracotomy in 477 patients. Mediastinal lymph nodes on CT larger than 1.5 cm were considered pathological. Overall, CT had a sensitivity of 69%, a specificity of 71% and an accuracy of 71% in identifying mediastinal lymph node metastases. For mediastinoscopy these figures were 72%, 100% and 89%, respectively. Computed tomography accuracy was distinctly lower in squamous cell carcinomas and in central tumors, as CT sensitivity was significantly lower in left-sided tumors. The positive predictive value (PPV) of CT in T1 lesions (29%) and PPV and negative predictive value (NPV) of CT in T2 squamous cell carcinomas (30% and 83%, respectively) were low, so questioning its use in those instances. We perform a mediastinoscopy in every situation except for squamous cell carcinomas or small (less than 3 cm) peripheral tumors in the absence of enlarged mediastinal lymph nodes. This selective attitude is rewarding since a) the number of pN2 in the straight thoracotomy group was only 16% versus 41% in the mediastinoscopy group, b) the exploratory thoracotomy rate in the straight thoracotomy group was low (4.6%).
Adenocarcinoma↗
Pulmonary histiocytosis X diagnosed by bone biopsy. Report of a case.
Histiocytosis X of the lung is associated with bone lesions in 4 to 20%. We report a case in which the diagnosis was missed in spite of repeated bronchoscopies with transbronchial lavage. The diagnosis was finally established by isotope bone scan, subsequent skeletal CT-scan and bone biopsy.
Adult↗
Inotropic effects of aminophylline on canine diaphragm are enhanced by hyperinflation.
During acute hyperinflation, patients with chronic obstructive pulmonary disease are likely to have foreshortened inspiratory muscles. Because the effects of aminophylline on contractile properties of the foreshortened diaphragm have never been studied in vivo, we compared these effects with those obtained at functional residual capacity (FRC). In 12 anesthetized dogs, bilateral phrenic nerve stimulation (1, 10, 20, and 100 Hz) was performed at FRC and near total lung capacity (TLC) before and 1 h after each injection of aminophylline, given in cumulative doses of 20, 40, and 80 mg/kg (serum levels of 18.7 +/- 6.3, 29.9 +/- 5.9, and 60.4 +/- 11.9 mg/l, respectively). Passive diaphragm shortening from FRC to TLC, measured in eight animals, averaged 30 +/- 12% of the resting length and increased to 35 +/- 12 and 34 +/- 13% after 40 and 80 mg/kg, respectively. After aminophylline, the increase in transdiaphragmatic pressure at FRC did not reach statistical significance, whereas near TLC transdiaphragmatic pressure significantly increased with 80 mg/kg at all stimulus frequencies (e.g., at 20 Hz from 4.4 +/- 2.9 to 6.7 +/- 2.9 cmH2O) and with 40 mg/kg at 10 and 20 Hz. Diaphragm length changes during stimulation were unchanged after aminophylline both at FRC and near TLC. We conclude that aminophylline has a pronounced inotropic effect on foreshortened canine diaphragm, even at concentrations close to the therapeutic range in humans.
Aminophylline↗
Inotropic effects of theophylline on foreshortened canine diaphragm.
We previously demonstrated that theophylline exerted greater inotropic effects on foreshortened canine diaphragm than on diaphragm placed at resting length in vivo (1). To ensure that these effects result from an effect on the muscle itself, they were examined in vitro. Thus, the effects of increasing doses of theophylline (20, 100, 200, and 400 mg/L) or addition of Krebs solution on twitch tension (Pt) of bundles placed at optimal length (Lo) and 70% Lo were compared. At Lo, compared with time-matched control, Pt significantly increased after theophylline (e.g., 37 +/- 32 versus -8 +/- 12% after 400 mg/L) except with 20 mg/L. At 70% Lo, Pt increased with all theophylline concentrations in a dose-related manner (e.g., 14 +/- 15 versus -6 +/- 7% and 114 +/- 57 versus -8 +/- 11% after 20 and 400 mg/L, respectively). Time to peak tension and half-relaxation time remained unchanged after theophylline both at Lo and 70% Lo. In addition, for a given concentration, twitch potentiation was significantly greater at 70% Lo than at Lo, the difference increasing with increasing concentration (e.g., 3 times greater with 400 mg/L). We conclude that theophylline-induced inotropic effects on Pt were more pronounced on foreshortened canine diaphragm bundles than on bundles placed at Lo. These observations confirm that theophylline-induced inotropic effects on foreshortened muscle previously observed in vivo are likely to result from a direct effect on muscle contractility.
Analysis of Variance↗
Corticosteroids contribute to muscle weakness in chronic airflow obstruction.
Twenty-one patients with chronic obstructive pulmonary disease (COPD) or asthma, admitted to our division because of exacerbation of their conditions and requiring intensified treatment with corticosteroids, underwent pulmonary function tests, tests of respiratory muscle function, measurement of quadricep strength, and a variety of anthropometric and biochemical measurements. All tests were performed the 10th day after admission. As expected, muscle strength and pulmonary function were interrelated. Surprisingly, the average daily dose of steroids taken in the previous 6 mo, which ranged from 1.4 to 21.3 mg (average 4.3 mg), was significantly related to inspiratory muscle strength (PImax) and a similar tendency was present for expiratory muscle strength (PEmax). Multiple regression analysis of the relationship between PImax and quadriceps force (QF) and steroid dose revealed that the average daily dose independently explained 32% of the variance in PImax and up to 51% of the variance in QF. These relationships were independent of the degree of bronchial obstruction estimated by percentage predicted FEV1. Other significant determinants were age, sex, and COPD for PImax and age, sex, and body weight for QF. The present study demonstrates that in patients with COPD or asthma, respiratory and peripheral muscle strength and steroid treatment are interrelated despite the relatively low doses administered. This observation imposes further limitations on the prolonged treatment of chronic airflow obstruction with systemic corticosteroids.
Adrenal Cortex Hormones↗
Theophylline alters distribution of blood flow to respiratory muscles.
This study was designed to examine the effects of theophylline on respiratory muscle blood flow in 11 lightly anesthetized and spontaneously breathing dogs using the radioactive microsphere tracer technique. During quiet breathing, blood flow to the costal diaphragm (25.1 +/- 13.9 ml/100 g/min) exceeded blood flow to the parasternal intercostals (18.0 +/- 10.2 ml/100 g/min, p < 0.05). Inspiratory resistive loading abolished these differences by increasing blood flow to the parasternal intercostals more than to the diaphragm. Aminophylline (40 mg/kg) significantly increased minute ventilation and tidal transdiaphragmatic pressure (Pdi) swing during quiet breathing but not during inspiratory resistive loading. Theophylline did not affect diaphragmatic blood flow during inspiratory resistive loading while the same Pdi swing and tension-time index (TTdi) were reached. During quiet breathing, however, theophylline significantly (p < 0.05) increased blood flow to the triangularis sterni from 7.9 +/- 5.6 to 18.1 +/- 25.6 ml/100 g/min and to the transversus abdominis from 10.8 +/- 8.4 to 14.6 +/- 10.5 ml/100 g/min and tended to increase blood flow to the costal diaphragm and the parasternals. We conclude that (1) during quiet breathing, but not during inspiratory resistive loading, blood flow to the costal diaphragm exceeded flow to the parasternal intercostals; (2) during quiet breathing, theophylline increased blood flow to the expiratory muscles as it promoted recruitment of expiratory muscles; and (3) theophylline did not affect diaphragmatic blood flow for a given TTdi.
Airway Resistance↗
Twitch potentiating effects of theophylline on rat diaphragm are enhanced by foreshortening.
In patients with chronic obstructive pulmonary disease (COPD) and acute respiratory failure, acute hyperinflation is likely to induce foreshortening of inspiratory muscles. Since no data are available on the effects of inotropic agents at lengths below the optimal length (Lo), we compared the effects of theophylline on forty rat diaphragm bundles placed at Lo and at 70% Lo. Twitches and tetanic stimulations were recorded before and after addition of theophylline, in concentrations of 20, 100, 200 or 400 mg.l-1. Compared with values obtained before theophylline, twitch tension (Pt) and maximal tetanic tension (Po) of the bundles placed at Lo slightly decreased at 20 and 100 mg.l-1 whereas a clear increase in Pt was obtained at 400 mg.l-1 (15 +/- 21% (mean +/- SD)). In contrast, Pt of the bundles placed at 70% Lo increased with all theophylline concentrations, and vastly more than at Lo (e.g. at 400 mg.l-1: 74 +/- 34%, p < 0.05); whereas Po slightly decreased, except at 400 mg.l-1. Moreover, the difference between the effects at Lo and at 70% Lo increased with increasing theophylline concentrations. We conclude that even at low, in vivo attainable serum levels, theophylline exerted greater positive inotropic effects on twitch tension (Pt) of rat diaphragm when foreshortened than when at optimal length.
Animals↗
Assessment of respiratory muscle function.
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Adult↗
Inspiratory muscle training: where are we?
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Breathing Exercises↗
Platypnoea syndrome caused by atrial septal aneurysm.
A patient with platypnoea after right pneumonectomy and radiotherapy is described. On transoesophageal contrast echocardiography and cardiac catheterization, an atrial septal aneurysm with interatrial right-to-left shunting was detected. Symptoms disappeared after surgical correction. To the best of our knowledge, this is the first report of a patient with a septal aneurysm and severe platypnoea.
Aged↗
A persistent unilateral lung infiltrate.
We describe the case of an intrabronchial aspirated foreign body that caused a persistent right lower lobe infiltrate. A first fibreoptic bronchoscopy demonstrated a mass with tumour-like appearance in the right bronchus intermedias, but the bronchial biopsies and the cytological smears of the bronchial aspirate failed to reveal any malignancy. During a control fibreoptic bronchoscopy, we found a chicken bone in this friable granulation tissue. It was subsequently removed with a flexible bronchofibrescope and a four-pronged forceps under topical anaesthesia.
Aged↗