Subcellular adaptation of the human diaphragm in chronic obstructive pulmonary disease. (1/360)

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. (2/360)

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)

Human lung volumes and the mechanisms that set them. (3/360)

Definitions of human lung volumes and the mechanisms that set them are reviewed in the context of pulmonary function testing, with attention to the distinction between functional residual capacity (FRC) and the static relaxation volume of the respiratory system, and to the circumstances in which FRC and residual volume are set by dynamic rather than by static mechanisms. Related terms, conventions, and issues are addressed, including some common semantic and conceptual difficulties, with attention to "gas trapping", "hyperinflation", and "restriction".  (+info)

Contribution of lung function to exercise capacity in patients with chronic heart failure. (4/360)

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)

Helium and sulfur hexafluoride bolus washin in short-term microgravity. (5/360)

We performed single-breath washout (SBW) tests in which He and sulfur hexafluoride (SF6) were inspired throughout the vital capacity inspirations or were inhaled as discrete boluses at different points in the inspiration. Tests were performed in normal gravity (1 G) and in up to 27 s of microgravity (microG) during parabolic flight. The phase III slope of the SBW could be accurately reconstructed from individual bolus tests when allowance for airways closure was made. Bolus tests showed that most of the SBW phase III slope results from events during inspiration at lung volumes below closing capacity and near total lung capacity, as does the SF6-He phase III slope difference. Similarly, the difference between 1 G and microG in phase III slopes for both gases was entirely accounted for by gravity-dependent events at high and low lung volumes. Phase IV height was always larger for SF6 than for He, suggesting at least some airway closure in close proximity to airways that remain open at residual volume. These results help explain previous studies in microG, which show large changes in gas mixing in vital capacity maneuvers but only small effects in tidal volume breaths.  (+info)

Differential lung mechanics are genetically determined in inbred murine strains. (6/360)

Genetic determinants of lung structure and function have been demonstrated by differential phenotypes among inbred mice strains. For example, previous studies have reported phenotypic variation in baseline ventilatory measurements of standard inbred murine strains as well as segregant and nonsegregant offspring of C3H/HeJ (C3) and C57BL/6J (B6) progenitors. One purpose of the present study is to test the hypothesis that a genetic basis for differential baseline breathing pattern is due to variation in lung mechanical properties. Quasi-static pressure-volume curves were performed on standard and recombinant inbred strains to explore the interactive role of lung mechanics in determination of functional baseline ventilatory outcomes. At airway pressures between 0 and 30 cmH2O, lung volumes are significantly (P < 0.01) greater in C3 mice relative to the B6 and A/J strains. In addition, the B6C3F1/J offspring demonstrate lung mechanical properties significantly (P < 0.01) different from the C3 progenitor but not distinguishable from the B6 progenitor. With the use of recombinant inbred strains derived from C3 and B6 progenitors, cosegregation analysis between inspiratory timing and measurements of lung volume and compliance indicate that strain differences in baseline breathing pattern and pressure-volume relationships are not genetically associated. Although strain differences in lung volume and compliance between C3 and B6 mice are inheritable, this study supports a dissociation between differential inspiratory time at baseline, a trait linked to a putative genomic region on mouse chromosome 3, and differential lung mechanics among C3 and B6 progenitors and their progeny.  (+info)

Airway remodeling in asthma amplifies heterogeneities in smooth muscle shortening causing hyperresponsiveness. (7/360)

Although airway remodeling and inflammation in asthma can amplify the constriction response of a single airway, their influence on the structural changes in the whole airway network is unknown. We present a morphometric model of the human lung that incorporates cross-sectional wall areas corresponding to the adventitia, airway smooth muscle (ASM), and mucosa for healthy and mildly and severely asthmatic airways and the influence of parenchymal tethering. A heterogeneous ASM percent shortening stimulus is imposed, causing distinct constriction patterns for healthy and asthmatic airways. We calculate lung resistance and elastance from 0.1 to 5 Hz. We show that, for a given ASM stimulus, the distribution of wall area in asthmatic subjects will amplify not only the mean but the heterogeneity of constriction in the lung periphery. Moreover, heterogeneous ASM shortening that would produce only mild changes in the healthy lung can cause hyperresponsive changes in lung resistance and elastance at typical breathing rates in the asthmatic lung, even with relatively small increases in airway resistance. This condition arises when airway closures occur randomly in the lung periphery. We suggest that heterogeneity is a crucial determinant of hyperresponsiveness in asthma and that acute asthma is more a consequence of extensive airway wall inflammation and remodeling, predisposing the lung to produce an acute pattern of heterogeneous constriction.  (+info)

Alveolar epithelial surface area-volume relationship in isolated rat lungs. (8/360)

In vitro studies of the alveolar epithelial response to deformation require knowledge of the in situ mechanical environment of these cells. Because of the presence of tissue folding and crumpling, previous measurements of the alveolar surface area available for gas exchange are not equivalent to the epithelial surface area. To identify epithelial deformations in uniformly inflated lungs representative of the in vivo condition, we studied isolated Sprague-Dawley rat lungs (n = 31) fixed by perfusion with glutaraldehyde on deflation after cycling three times at high lung volume (10-25 cmH2O). The epithelial basement membrane in 45 electron micrographs (x12,000)/rat was traced, digitally scanned, and analyzed. Epithelial basement membrane surface area (EBMSA) was computed from a morphometric relationship. EBMSA was found to increase 5, 16, 12, and 40% relative to EBMSA at 24% total lung capacity at lung volumes of 42, 60, 82, and 100% total lung capacity, respectively. The increases in EBMSA suggest that epithelial cells undergo significant deformations with large inflations and that alveolar basement membrane deformation may contribute to lung recoil at high lung pressures.  (+info)