Autosomal dominant myopathy with proximal weakness and early respiratory muscle involvement maps to chromosome 2q.
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Two Swedish families with autosomal dominant myopathy, who also had proximal weakness, early respiratory failure, and characteristic cytoplasmic bodies in the affected muscle biopsies, were screened for linkage by means of the human genome screening set (Cooperative Human Linkage Center Human Screening Set/Weber version 6). Most chromosome regions were completely excluded by linkage analysis (LOD score <-2). Linkage to the chromosomal region 2q24-q31 was established. A maximum combined two-point LOD score of 4.87 at a recombination fraction of 0 was obtained with marker D2S1245. Haplotype analysis indicated that the gene responsible for the disease is likely to be located in the 17-cM region between markers D2S2384 and D2S364. The affected individuals from these two families share an identical haplotype, which suggests a common origin. (+info)
Subcellular adaptation of the human diaphragm in chronic obstructive pulmonary disease.
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Pulmonary hyperinflation impairs the function of the diaphragm in patients with chronic obstructive pulmonary disease (COPD). However, it has been recently demonstrated that the muscle can counterbalance this deleterious effect, remodelling its structure (i.e. changing the proportion of different types of fibres). The aim of this study was to investigate whether the functional impairment present in COPD patients can be associated with structural subcellular changes of the diaphragm. Twenty individuals (60+/-9 yrs, 11 COPD patients and 9 subjects with normal spirometry) undergoing thoracotomy were included. Nutritional status and respiratory function were evaluated prior to surgery. Then, small samples of the costal diaphragm were obtained and processed for electron microscopy analysis. COPD patients showed a mean forced expiratory volume in one second (FEV1) of 60+/-9% predicted, a higher concentration of mitochondria (n(mit)) in their diaphragm than controls (0.62+/-0.16 versus 0.46+/-0.16 mitochondrial transections (mt) x microm(-2), p<0.05). On the other hand, subjects with air trapping (residual volume (RV)/total lung capacity (TLC) >37%) disclosed not only a higher n(mit) (0.63+/-0.17 versus 0.43+/-0.07 mt x microm(-2), p<0.05) but shorter sarcomeres (L(sar)) than subjects without this functional abnormality (2.08+/-0.16 to 2.27+/-0.15 microm, p<0.05). Glycogen stores were similar in COPD and controls. The severity of airways obstruction (i.e. FEV1) was associated with n(mit) (r=-0.555, p=0.01), while the amount of air trapping (i.e. RV/TLC) was found to correlate with both n(mit) (r=0.631, p=0.005) and L(sar) (r=-0.526, p<0.05). Finally, maximal inspiratory pressure (PI,max) inversely correlated with n(mit) (r=-0.547, p=0.01). In conclusion, impairment in lung function occurring in patients with chronic obstructive pulmonary disease is associated with subcellular changes in their diaphragm, namely a shortening in the length of sarcomeres and an increase in the concentration of mitochondria. These changes form a part of muscle remodelling, probably contributing to a better functional muscle behaviour. (+info)
Long-term recovery of diaphragm strength in neuralgic amyotrophy.
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Diaphragm paralysis is a recognized complication of neuralgic amyotrophy that causes severe dyspnoea. Although recovery of strength in the arm muscles, when affected, is common, there are little data on recovery of diaphragm function. This study, therefore, re-assessed diaphragm strength in cases of bilateral diaphragm paralysis due to neuralgic amyotrophy that had previously been diagnosed at the authors institutions. Fourteen patients were recalled between 2 and 11 yrs after the original diagnosis. Respiratory muscle and diaphragm strength were measured by volitional manoeuvres as maximal inspiratory pressure and sniff transdiaphragmatic pressure. Cervical magnetic phrenic nerve stimulation was used to give a nonvolitional measure of diaphragm strength: twitch transdiaphragmatic pressure. Only two patients remained severely breathless. Ten of the 14 patients had evidence of some recovery of diaphragm strength, in seven cases to within 50% of the lower limit of normal. The rate of recovery was variable: one patient had some recovery after 2 yrs, and the rest took 3 yrs or more. In conclusion, in most patients with diaphragm paralysis due to neuralgic amyotrophy, some recovery of the diaphragm strength occurs, but the rate of recovery may be slow. (+info)
Respiratory muscle involvement in multiple sclerosis.
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Respiratory complications are common in the terminal stages of multiple sclerosis and contribute to mortality in these patients. When respiratory motor pathways are involved, respiratory muscle weakness frequently occurs. Although it is well established that weakness of the respiratory muscles produces a restrictive ventilatory defect, the degree of muscle weakness and pulmonary function are poorly related. Respiratory muscle weakness was observed in patients with normal or near normal pulmonary function. Expiratory muscle weakness is more prominent than inspiratory muscle weakness and may impair performance of coughing. Subsequently, in addition to bulbar dysfunction, respiratory muscle weakness may contribute to ineffective coughing, pneumonia, and sometimes even acute ventilatory failure may ensue. Respiratory muscle weakness may also occur early in the course of the disease. Recent studies suggest that the respiratory muscles can be trained for both strength and endurance in multiple sclerosis patients. Whether respiratory muscle training delays the development of respiratory dysfunction and subsequently improves exercise capacity and cough efficacy, prevents pulmonary complications or prolongs survival in the long-term remains to be determined. (+info)
Breathing responses to small inspiratory threshold loads in humans.
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To investiage the effect of inspiratory threshold load (ITL) on breathing, all previous work studied loads that were much greater than would be encountered under pathophysiological conditions. We hypothesized that mild ITL from 2.5 to 20 cmH2O is sufficient to modify control and sensation of breathing. The study was performed in healthy subjects. The results demonstrated that with mild ITL 1) inspiratory difficulty sensation could be perceived at an ITL of 2.5 cmH2O; 2) tidal volume increased without change in breathing frequency, resulting in hyperpnea; and 3) although additional time was required for inspiratory pressure to attain the threshold before inspiratory flow was initiated, the total inspiratory muscle contraction time remained constant. This resulted in shortening of the available time for inspiratory flow, so that the tidal volume was maintained or increased by significant increase in mean inspiratory flow. On the basis of computer simulation, we conclude that the mild ITL is sufficient to increase breathing sensation and alter breathing control, presumably aiming at maintaining a certain level of ventilation but minimizing the energy consumption of the inspiratory muscles. (+info)
Influence of central antitussive drugs on the cough motor pattern.
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The present study was conducted to determine the effects of administration of centrally active antitussive drugs on the cough motor pattern. Electromyograms of diaphragm and rectus abdominis muscles were recorded in anesthetized, spontaneously breathing cats. Cough was produced by mechanical stimulation of the intrathoracic trachea. Centrally acting drugs administered included codeine, morphine, dextromethorphan, baclofen, CP-99,994, and SR-48,968. Intravertebral artery administration of all drugs reduced cough number (number of coughs per stimulus trial) and rectus abdominis burst amplitude in a dose-dependent manner. Codeine, dextromethorphan, CP-99,994, SR-48,968, and baclofen had no effect on cough cycle timing (CTtot) or diaphragm amplitude during cough, even at doses that inhibited cough number by 80-90%. Morphine lengthened CTtot and inhibited diaphragm amplitude during cough, but these effects were not dose dependent. Only CP-99,994 altered the eupneic respiratory pattern. Central antitussive drugs primarily suppress cough by inhibition of expiratory motor drive and cough number. CTtot and inspiratory motor drive are relatively insensitive to the effects of these drugs. CTtot can be controlled independently from cough number. (+info)
Early occurrence of respiratory muscle deoxygenation assessed by near-infrared spectroscopy during leg exercise in patients with chronic heart failure.
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The mechanisms of respiratory muscle deoxygenation during incremental leg exercise with expired gas analysis were investigated in 29 patients with chronic heart failure and 21 normal subjects. The deoxygenation and blood volume of the respiratory muscle and exercising leg muscle were assessed by near-infrared spectroscopy (NIRS). To evaluate the influence of the leg exercise on the blood volume of the respiratory muscle, 10 normal subjects also underwent a hyperventilation test with NIRS. The respiratory muscle deoxygenation point (RDP), at which oxygenated hemoglobin starts to decrease, was observed in both groups during exercise. The oxygen consumption (VO2) and the minute ventilation at the RDP in the patients was lower (p<0.01). At the same VO2, the respiratory rate was higher in patients (p<0.01). During exercise, the blood volume of the leg muscle increased, while that of the respiratory muscle decreased. During a hyperventilation test, the minute ventilation was higher than that of the RDP during exercise, the blood volume of the respiratory muscle did not decrease, and the RDP was not detectable. In conclusion, a limited ability to increase perfusion of respiratory muscles during exercise combined with the greater work of breathing results in early respiratory muscle deoxygenation in patients with chronic heart failure. (+info)
Contribution of lung function to exercise capacity in patients with chronic heart failure.
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BACKGROUND: The importance of exercise capacity as an indicator of prognosis in patients with heart disease is well recognized. However, factors contributing to exercise limitation in such patients have not been fully characterized and in particular, the role of lung function in determining exercise capacity has not been extensively investigated. OBJECTIVE: To examine the extent to which pulmonary function and respiratory muscle strength indices predict exercise performance in patients with moderate to severe heart failure. METHODS: Fifty stable heart failure patients underwent a maximal symptom-limited cardiopulmonary exercise test on a treadmill to determine maximum oxygen consumption (VO2max), pulmonary function tests and maximum inspiratory (PImax) and expiratory (PEmax) pressure measurement. RESULTS: In univariate analysis, VO2max correlated with forced vital capacity (r = 0.35, p = 0.01), forced expiratory volume in 1 s (r = 0.45, p = 0.001), FEV1/FVC ratio (r = 0.37, p = 0.009), maximal midexpiratory flow rate (FEF25-75, r = 0. 47, p < 0.001), and PImax (r = 0.46, p = 0.001), but not with total lung capacity, diffusion capacity or PEmax. In stepwise linear regression analysis, FEF25-75 and PImax were shown to be independently related to VO2max, with a combined r and r2 value of 0. 56 and 0.32, respectively. CONCLUSIONS: Lung function indices overall accounted for only approximately 30% of the variance in maximum exercise capacity observed in heart failure patients. The mechanism(s) by which these variables could set exercise limitation in heart failure awaits further investigation. (+info)