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PubMed1995

Contrasting geographical distribution of mortality from pneumoconiosis and chronic bronchitis and emphysema in British coal miners.

To explore whether the characteristics of coal mine dust that predispose to chronic airways obstruction are the same as those associated with pneumoconiosis, mortality from the two disease was compared in coal miners in 22 counties of England and Wales during 1979-80 and 1982-90. The proportional mortality ratios (PMRs) for coal workers' pneumoconiosis varied from 135 (95% confidence interval (95% CI) 16-488) in Leicestershire to 3825 (95% CI 1538-7881) in South Glamorgan. The PMRs for chronic bronchitis and emphysema were consistently higher than those in other occupations, but showed much less geographical variation and did not correlate geographically with those for pneumoconiosis. These findings indicate that the pathogenetic mechanisms by which coal mine dust causes chronic bronchitis and emphysema depend on different features of the dust from those producing pneumoconiosis. Also, they suggest that current social security regulations in Britain, which require evidence of pneumoconiosis as a condition of compensation for chronic bronchitis and emphysema in coal miners, may discriminate unfairly against claimants from some regions.

Adult↗
PubMed1977

Further observations on luminal deformity and stenosis of nonrespiratory bronchioles in pulmonary emphysema.

In an endeavour to elucidate the anatomical basis for the increased resistance to airflow which characterises the most peripheral conducting air passages in pulmonary emphysema, lumina of nonrespiratory bronchioles of lungs with mainly centrilobular disease were assessed for two- and three-dimensional features by: (1) determination of percentage conformity of the lumina of individual bronchioles in histological sections to hypothetical planes through cylinders (ie, ellipses with the same areas and circumferences), and (2) comparison of luminal areas at regular intervals along bronchiolar longitudinal axes. The lumina of most nonrespiratory bronchioles from normal lungs conformed closely to their respective ellipses, thus corroborating previous observations that they are normally cylindroid. In contrast, there was a substantial excess of plane section deformities in the lumina of nonrespiratory bronchioles from the emphysematous specimens. The incidence of stenotic bronchioles (by both diameter and area determinations) was also greatly increased in emphysema. Since there was a strong positive association between such stenotic lesions and bronchiolar deformity, the latter was concluded to be a major factor in bronchiolar restriction. Furthermore, these characteristics seemed to have three-dimensional expression, for the lumina of stenotic bronchioles in emphysema were irregular in a longitudinal fashion.

Bronchi↗
PubMed1984

Airway disease in upper and lower lobes in lungs of patients with and without emphysema.

To determine whether pathological changes in the small airways are evenly distributed throughout the lung and whether there is an association of small airway disease with emphysema, pathological abnormalities of the small airways were graded in the upper and lower lobes of 13 surgical lung specimens. Except for slightly increased degrees of respiratory bronchiolar inflammation in the lower lobe, no differences were found between the two sites, nor was there any relationship between the presence of pathological abnormalities in the small airways and the presence of centrilobular emphysema. It is concluded that the predilection of centrilobular emphysema for the upper lung zone is not associated with a difference in intensity of airway disease between upper and lower lobes.

Bronchi↗
PubMed1990

Trends in lung cancer, chronic obstructive lung disease, and emphysema death rates for England and Wales 1941-85 and their relation to trends in cigarette smoking.

Trends in smoking associated respiratory diseases in England and Wales during 1941-85 have been studied, with careful attention to problems caused by changes in classification of cause of death. Three diseases were selected for analysis: lung cancer, emphysema, and chronic obstructive lung disease. During 1971-85 deaths that would previously have been certified under chronic bronchitis have increasingly tended to be classified under chronic airways obstruction. The definition of chronic obstructive lung disease that was used includes both terms to avoid the artificial decline caused by consideration of chronic bronchitis in isolation. Age specific rates for all three diseases show a pronounced cohort (period of birth) pattern, rates for men rising up to the rates for those born shortly after the turn of the century and then declining, and rates for women peaking in the cohort born 20-25 years later. For chronic obstructive lung disease, but not for lung cancer and emphysema, the cohort peak is superimposed on a sharply declining downward trend. In both sexes cohort patterns of cumulative cigarette consumption peak at a time broadly similar to those seen for the three diseases. Trends in cigarette consumption, however, cannot explain the underlying steeply declining rate of chronic obstructive lung disease. Nor can they fully explain the declining trends in lung cancer and emphysema rates in younger men and women.

Adolescent↗
PubMed1995

Single lung transplantation for end stage emphysema.

BACKGROUND: The first successful single lung transplantation was carried out in 1983 for pulmonary fibrosis. Because of the inherent advantages of single lung transplantation, a transplantation programme has been started for patients with end stage lung disease due to emphysema. METHODS: Between October 1990 and August 1993 25 patients with severe emphysema (15 men, mean age 51 years) received a single lung transplant at our institution. All patients were severely disabled with a mean (SD) 12 minute walking distance of 281 (165) metres. There were five deaths in the series, four in the first 20 days and one on day 503. Two patients suffered graft compression by air trapping in the native lung. Bronchial narrowing requiring insertion of endobronchial stenting occurred in four patients. RESULTS: Mean (SD) FEV1 improved from a preoperative value of 17.8(13%) predicted to a six month value of 53.6(13)%, and FEV1/FVC from 23.8(12)% to 68.6(15)%. After the transplant 12 patients are in New York Heart Association (NYHA) class I and the rest of the survivors are in NYHA II. Actuarial survival was 82% at one year and 74% at three years. CONCLUSIONS: Single lung transplantation is an effective treatment for end stage lung disease due to emphysema and carries an acceptable mortality and morbidity.

Adult↗
PubMed1998

Preferential binding of lysozyme to elastic fibres in pulmonary emphysema.

BACKGROUND: Lysozyme is increased in inflammatory reactions and is a component of the extracellular matrix, but its possible role in lung diseases such as emphysema and interstitial fibrosis has not been investigated. METHODS: To characterise differences in lysozyme content among normal, emphysematous, and fibrotic human lungs, tissue sections obtained from necropsy specimens were immunostained with rabbit polyclonal anti-human lysozyme antibody using the labelled streptavidin-biotin peroxidase method. The immunostained sections were evaluated semi-quantitatively (grading the degree of immunostaining on a scale of 0-4). To determine if degradation of the extracellular matrix affects lysozyme binding, hyaluronidase-treated normal lung tissues were incubated with egg white lysozyme, immunostained with the lysozyme antibody, which crossreacts with egg white lysozyme, and evaluated for degree of staining. RESULTS: Lysozyme immunostaining was significantly increased in lungs with pulmonary emphysema compared with normal or fibrotic tissues (3.4 versus 1.6 and 1.9, respectively; p < 0.05) and was preferentially associated with interstitial elastic fibres. Hyaluronidase-treated lung tissues incubated with lysozyme showed increased immunostaining for this protein compared with untreated controls (1.9 versus 1.2; p < 0.05). CONCLUSIONS: The results suggest that damage to elastic fibres and/or the surrounding extracellular matrix increases lysozyme binding. It is hypothesised that attachment of lysozyme to elastic fibres may interfere with their repair and possibly enhance the progression of pulmonary emphysema.

Elastic Tissue↗
PubMed1999

Lung volume reduction surgery (LVRS) for chronic obstructive pulmonary disease (COPD) with underlying severe emphysema.

BACKGROUND: Lung volume reduction surgery (LVRS) has recently re-emerged as a surgical option for the treatment of end stage chronic obstructive pulmonary disease (COPD) due to underlying severe emphysema. Advocates of LVRS claim that it represents a significant breakthrough in the management of this challenging group of patients while sceptics point to uncertainty about the effectiveness of the operation. METHODS: A systematic review was conducted of the evidence on the effects of LVRS in patients with end stage COPD secondary to severe emphysema. RESULTS: The most rigorous evidence on the effectiveness of LVRS came from case series. Seventy five potentially relevant studies were identified and 19 individual series met the methodological criteria for inclusion. The pattern of results was consistent across individual studies despite a significant degree of clinical heterogeneity. Significant short term benefits occurred across a range of outcomes which appeared to continue into the longer term. Physiological improvements were matched by functional and subjective improvements. Early mortality rates were low and late mortality rates compared favourably with those of the general COPD population. However, the entire research base for the intervention is subject to the limitations of study designs without parallel control groups. CONCLUSIONS: LVRS appears to represent a promising option in the management of patients with severe end stage emphysema. However, until the results of ongoing clinical trials are available, the considerable uncertainty that exists around the effectiveness and cost effectiveness of the procedure will remain.

Dyspnea↗
PubMed2006

Pulmonary emphysema: objective quantification at multi-detector row CT--comparison with macroscopic and microscopic morphometry.

PURPOSE: To prospectively compare pulmonary function tests and helical computed tomographic (CT) indexes for quantifying pulmonary emphysema with macroscopic and microscopic morphometry. MATERIALS AND METHODS: The investigation was approved by the local ethics committee, and written informed consent was obtained from patients. Multi-detector row CT of the thorax was performed with simultaneous acquisition of four 1-mm sections in 80 patients (57 men, 23 women; age range, 38-79 years) referred for surgical resection of lung cancer. From the raw data, 1.25-mm-thick sections were reconstructed at 10-mm intervals. Relative areas of lung with attenuation coefficients lower than nine thresholds and eight percentiles of the distribution of attenuation coefficients were calculated. Relative areas and percentiles were compared with areas found macroscopically to have emphysema and with two microscopic indexes assessed on resected specimens. Pulmonary function tests were measured 24-48 hours before surgery. Spearman correlation coefficients were calculated between each set of CT data obtained with the nine tested thresholds and eight percentiles with macroscopic and microscopic measurements. RESULTS: For relative lung areas, the strongest correlation with macroscopy was observed with a threshold of -970 HU (r = 0.543, P < .001) and that with microscopy was observed at -960 and -970 HU, depending on the index considered (r = 0.592, P < .001 and r = -0.546, P < .001, respectively). For percentiles, 1st percentile showed the strongest correlation with both macroscopy (r = -0.463, P < .001) and microscopy (r = -0.573, P < .001; and r = 0.523, P < .001 for each microscopic measurement). Forced expiratory volume in 1 second and vital capacity ratio, diffusing capacity of lung for carbon monoxide, and each of the three CT indexes were complementary to predict microscopic indexes. CONCLUSION: Relative lung areas with attenuation coefficients lower than -960 or -970 HU and 1st percentile are valid indexes to quantify pulmonary emphysema on multi-detector row CT scans.

Adult↗
PubMed2006

Elastase-induced pulmonary emphysema in rats: comparison of computed density and microscopic morphometry.

PURPOSE: To prospectively compare computed tomographic (CT) quantification of pulmonary emphysema in elastase-treated rats with morphometry and to evaluate the information yielded by CT quantification and pulmonary function tests. MATERIALS AND METHODS: This study was approved by the local committee on care and use of animals in research. Thirty-six animals were used. Emphysema was produced by means of one or two tracheal injections of 300 IU of elastase, 8 weeks apart, in seven and 12 rats, respectively. As a control group, 10 rats received an injection of normal saline. The dynamic resistance, dynamic compliance, and static compliance were measured. CT was performed with 1-mm section thickness and 3-mm intervals. Relative areas of lung with attenuation coefficients lower than nine chosen thresholds (from -900 to -980 HU) and eight percentiles (from 1st to 18th percentiles) of the distribution of attenuation coefficients were compared with measurements of alveoli size--that is, mean interwall distance (MIWD) and mean perimeter per field (MP). Correlations between data obtained with thresholds and percentiles and MIWD and MP were investigated by means of Spearman coefficients (r(s)). Values of pulmonary function tests, most appropriate relative area threshold, and percentile were investigated by means of stepwise multiple regressions. RESULTS: For thresholds, relative surface area with attenuation coefficients less than -940 HU (RA(940)) showed the strongest correlations with findings at microscopy (r(s) = 0.676, P < .001 for MIWD; r(s) = -0.720, P < .001 for MP). For percentiles, the 3rd percentile showed the strongest correlations (r(s) = -0.647, P < .001 for MIWD; r(s) = 0.701, P < .001 for MP). Dynamic compliance and RA(940) or 3rd percentile were complementary for predicting microscopic measurements. CONCLUSION: In rats, RA(940) and the 3rd percentile reflect the extent of elastase-induced pulmonary emphysema and are complementary to dynamic compliance to predict microscopic extent.

Animals↗
PubMed1997

Patients with emphysema: quantitative CT analysis before and after lung volume reduction surgery. Work in progress.

PURPOSE: To quantitatively assess the morphologic changes in the lungs after lung volume reduction surgery and determine whether changes at quantitative computed tomography (CT) reflect changes in lung function. MATERIALS AND METHODS: In 10 patients, chest CT images were obtained at full inspiration and expiration before and after surgery. A semiautomated segmentation method was developed to isolate the lung regions and calculate the lung volumes and frequency distribution of attenuation values. The changes in lung volume and attenuation after surgery were compared with clinical findings, and an exploratory evaluation of outcome predictors was conducted. RESULTS: Semiautomated segmentation and quantitative analysis compared favorably with manual techniques, and there was good correlation between the emphysema indexes and percentage predicted forced expiratory volume in 1 second, forced expiratory volume in 1 second/forced vital capacity, and diffusing capacity. The emphysema index decreased from 60% to 38% at inspiration and from 60% to 27% at expiration after surgery. The average CT lung volume decreased from 7.5 to 5.6 L at inspiration (25%) and from 6.4 to 3.8 L (41%) at expiration after surgery and correlated well with measurements at plethysmography. CONCLUSION: Substantial decreases in the lung volumes and emphysema index, increased airflow, possible reexpansion of some remaining lung, and the relation between preoperative quantitative CT indexes and clinical outcome suggest a multifactorial mechanism for improvement seen after surgery.

Adult↗
PubMed2004

GM-CSF mediates alveolar epithelial type II cell changes, but not emphysema-like pathology, in SP-D-deficient mice.

Surfactant protein D (SP-D) is a member of the collectin subfamily of C-type lectins, pattern recognition proteins participating in the innate immune response. Gene-targeted mice deficient in SP-D develop abnormalities in surfactant homeostasis, hyperplasia of alveolar epithelial type II cells, and emphysema-like pathology. Granulocyte/macrophage colony-stimulating factor (GM-CSF) is required for terminal differentiation and subsequent activation of alveolar macrophages, including the expression of matrix metalloproteinases and reactive oxygen species, factors thought to contribute to lung remodeling. Type II cells also express the GM-CSF receptor. Thus we hypothesized GM-CSF might mediate some or all of the cellular and structural abnormalities in the lungs of SP-D-deficient mice. To test this, SP-D (D-G+) and GM-CSF (D+G-) single knockout mice as well as double knockout mice deficient for both SP-D and GM-CSF (D-G-) were analyzed by design-based stereology. Compared with wild type, D-G+ as well as D+G- mice showed decreased alveolar numbers, increased alveolar sizes, and decreased alveolar epithelial surface areas. These emphysema-like changes were present to a greater extent in D-G- mice. D-G+ mice developed type II cell hyperplasia and hypertrophy with increased intracellular surfactant pools, whereas D+G- mice had smaller type II cells with decreased intracellular surfactant pools. In contrast to the emphysematous changes, the type II cell alterations were mostly corrected in D-G- mice. These results indicate that GM-CSF-dependent macrophage activity is not necessary for emphysema development in SP-D-deficient mice, but that type II cell metabolism and proliferation are, either directly or indirectly, regulated by GM-CSF in this model.

Animals↗
PubMed2004

Abnormal mouse lung alveolarization caused by Smad3 deficiency is a developmental antecedent of centrilobular emphysema.

Transforming growth factor-beta (TGF-beta) signaling plays an important regulatory role during lung development and remodeling. Smad3 is a major downstream signal transducer in the TGF-beta pathway from the cell membrane to the nucleus. In Smad3 null mutant mice, we have observed retarded lung alveolarization from postnatal day 7 to day 28, and subsequently centrilobular emphysema starting from day 28, as determined by morphometric analysis. In addition to the morphological changes, peripheral lung cell proliferation in Smad3 knockout mice was reduced compared with the wild-type control between postnatal days 7 and 28. Expression of tropoelastin at the mRNA level was also dramatically decreased in Smad3 knockout lungs from postnatal day 28 through adulthood. Furthermore, increased matrix metalloproteinase-9 protein expression and activity were detected in the Smad3 knockout mouse lung tissue and the bronchoalveolar lavage fluid at postnatal day 28 when the centrilobular emphysema pathology was just beginning to appear. Therefore, these results indicate that Smad3 not only has a positive regulatory impact on neonatal lung alveolarization but also potentially plays a protective role against the occurrence of centrilobular emphysema later on in life.

Animals↗
PubMed2006

Differential induction of apoptosis by cigarette smoke extract in primary human lung fibroblast strains: implications for emphysema.

Cigarette smoke is the principal cause of emphysema. Recent attention has focused on the loss of alveolar fibroblasts in the development of emphysema. Fibroblasts may become damaged by oxidative stress and undergo apoptosis as a result of cigarette smoke exposure. Not all smokers develop lung diseases associated with tobacco smoke, a fact that may reflect individual variation among human fibroblast strains. We hypothesize that fibroblasts from different human beings vary in their ability to undergo apoptosis after cigarette smoke exposure. This could account for emphysematous changes that occur in the lungs of some but not all smokers. Primary human lung fibroblast strains were exposed to cigarette smoke extract (CSE) and assessed for viability, morphological changes, and mitochondrial transmembrane potential as indicators of apoptosis. We also examined the generation of intracellular reactive oxygen species (ROS), 4-hydroxy-2-nonenal, and changes in glutathione (GSH) and glutathione disulfide (GSSG) levels. Each human lung fibroblast strain exhibited a differential sensitivity to CSE as judged by changes in mitochondrial membrane potential, viability, ROS generation, and glutathione production. Interestingly, the thiol antioxidants N-acetyl-L-cysteine and GSH eliminated CSE-induced changes in fibroblast morphology such as membrane blebbing, nuclear condensation, and cell size and prevented alterations in mitochondrial membrane potential and the generation of ROS. These findings support the concept that oxidative stress and apoptosis are responsible for fibroblast death associated with exposure to tobacco smoke. Variations in the sensitivity of fibroblasts to cigarette smoke may account for the fact that only some smokers develop emphysema.

Aldehydes↗
PubMed1998

Time course of neutrophil and macrophage elastinolytic activities in cigarette smoke-induced emphysema.

The aim of this study was to compare the time course of neutrophil and macrophage elastinolytic potentials in the lungs of rats exposed daily to cigarette smoke inhalation for 1-6 mo in relation to the onset and progression of cigarette smoke-induced emphysema. Normal room air-exposed rats served as controls. Morphometric data of lung histological sections showed evidence of emphysema lesions in the lungs of smoke-exposed rats at month 2 and continuing to month 6. Data of total and differential cell counts in bronchoalveolar lavage fluid and collagenase-dissociated lung showed an increased number of lung neutrophils at month 1 of smoke exposure, but this was reduced to control levels at months 2-6. In contrast, an increased number of lung macrophages was evident in the smoke-exposed rats at month 2 of exposure and continued to month 6. Data of the elastinolytic activities of the neutrophils and macrophages, determined in [3H]elastin-coated culture wells, showed that the elastinolytic activity of lung neutrophils in the smoke-exposed rats was similar to that of the control air-exposed rats at months 1-6 of exposure. In contrast, the elastinolytic activity of lung macrophages in the smoke-exposed rats was increased at month 2 of exposure and remained increased at month 6. Excessive in vivo lung elastin breakdown (judged by increased levels of elastin-derived peptides and desmosine in lavage fluid, determined immunologically) was observed in the smoke-exposed rats at months 2-6 of exposure. These data indicate that the time course of increased macrophage-directed elastinolytic activity in the lung, not that of neutrophils, is more closely associated with the evolution of cigarette smoke-induced emphysema.

Animals↗
PubMed1980

Influence of starvation on enzyme-induced emphysema.

Adult rats were exposed to an aerosol of 10% papain for 8 h twice in a 2-wk interval. The control rats were exposed to isotonic saline in the same manner. Three weeks after the final exposure rats were divided into four groups: emphysema-fed, emphysema-starved, control-fed, and control-starved. Starved animals received one-third of their measured daily food consumption and water ad libitum for 6 wk. Final body weight, dry and wet weights of lungs and postfixation lung volume (VL) were significantly lower in starved rats. Dry-to-wet weight ratios were not significantly different among the groups, but VL/body weight was significantly higher in starved animals. Elastic recoil pressure of lung tissue determined in saline-filled lungs decreased and chord compliance over mid- and high-volume ranges increased significantly in starved animals both in control and emphysema groups. Mean linear intercept of air spaces was greater and internal surface area was smaller in starved rats in each group. Therefore, it appears that starvation aggravates the preexisting emphysematous processes in rat lungs.

Animals↗
PubMed1983

Effect of beta-adrenergic blockade on hyperventilation and exercise tolerance in emphysema.

Ventilation, heart rate, and arterial blood gas tensions were measured at rest and during incremental exercise in 10 patients with emphysema after intravenous placebo or 7 mg metoprolol. Metoprolol reduced heart rate by 14% (P less than 0.001) and ventilation by 11% (P less than 0.01), but there was no significant difference in arterial O2 or CO2 tension (Pao2 and PaCO2, respectively). Metoprolol increased the time to exhaustion on a cycle ergometer (P less than 0.05) but did not improve the 12-min walking distance. A double-blind randomized crossover comparison of 4 wk treatment with atenolol (100 mg/day), metoprolol (100 mg/day), or matched placebo was performed in 12 patients with emphysema. Both beta-adrenoceptor antagonists reduced resting heart rate by 33% (P less than 0.001) and resting minute ventilation by 11% (P less than 0.025). There was no change in resting or exercise Pao2 or Paco2. During steady-state exercise on a cycle ergometer, atenolol and metoprolol reduced ventilation by 14 and 4%, respectively. This was accompanied by 11 and 5% reductions in O2 consumption (P less than 0.05) and 13 and 6% falls in CO2 production (P less than 0.05). There were no significant changes in tests of exercise tolerance, but forced expiratory volume in 1 s and forced vital capacity were reduced during beta 1-adrenergic blockade. beta 1-Blocking drugs reduce hyperventilation in emphysema by reducing pulmonary gas exchange without a change in arterial blood gas tensions. Increased airflow obstruction prevents this reduction being of therapeutic value.

Administration, Oral↗
PubMed1987

Structure of abdominal muscles in the hamster: effect of elastase-induced emphysema.

The present study examined the effects of elastase-induced emphysema on the structure of the external oblique and transverse abdominis muscles and a non-respiratory muscle, the extensor digitorum longus. Muscle structure was assessed from the cross-sectional area (CSA) and percent of individual fiber types in histochemically stained sections and from the number of sarcomeres arranged in series along the length of individual fibers. Data were obtained in eight hamsters with emphysema and nine saline-injected controls. In the normal (control) animals the external oblique was thicker but contained fewer sarcomeres than the transverse abdominis. Fiber size was similar in the two muscles. In the transverse abdominis the percents of fast-glycolytic and fast-oxidative fibers were greater and smaller, respectively, than in the external oblique. Lung volume of emphysematous hamsters was 168% of control values (P less than 0.001). In emphysematous compared with control animals, the CSA of fast-twitch fibers in the external oblique and transverse abdominis was significantly reduced. Fiber length and sarcomere number were significantly decreased in the transverse abdominis but not in the external oblique in emphysematous hamsters. In contrast, fiber size and composition of the extensor digitorum longus was similar in emphysematous and control animals. These data indicate that cellular responses of the ventilatory muscles to chronic hyperinflation and altered thoracic geometry induced by emphysema are not present in limb skeletal muscle. We speculate that changes in fiber length and CSA of fast fibers in the abdominal expiratory muscles reflect responses to chronic alterations in the mechanics of breathing that may affect muscle load, length, or the pattern of activity.

Abdominal Muscles↗
PubMed1997

Effect of pulmonary emphysema on diaphragm capillary geometry.

In emphysema, the diaphragm shortens by losing sarcomeres. We hypothesized that unless capillaries undergo a similar shortening, capillary geometry must be altered. Without quantifying this geometry, capillary length and surface area per fiber volume, which are critical measurements of the structural potential for blood-tissue exchange, cannot be resolved. Five months after intratracheal elastase (E) or saline (control; C) instillation, diaphragms from male Syrian golden hamsters were glutaraldehyde perfusion fixed in situ at reference lung positions (residual volume, functional residual capacity, total lung capacity) to provide diaphragms fixed over a range of sarcomere lengths. Subsequently, diaphragms were processed for electron microscopy and analyzed morphometrically. Emphysema increased lung volume changes from -20 to 25 cmH2O airway pressure (i.e., passive vital capacity) and excised lung volume (both P < 0.001). In each region of the costal diaphragm (i.e., ventral, medial, dorsal), sarcomere number was reduced (all P < 0.05). Capillary-to-fiber ratio increased (C = 2.2 +/- 0.1, E = 2.8 +/- 0.1; P < 0.01) and fibers hypertrophied (C = 815 +/- 35, E = 987 +/- 67 microns2; P < 0.05; both values at 2.5 microns sarcomere length). Capillary geometry was markedly altered by the loss of sarcomeres in series. Specifically, the additional capillary length derived from capillary tortuosity and branching was increased by 183% at 2.5 microns sarcomere length compared with C values (C, 359 +/- 43; E, 1,020 +/- 158 mm-2, P < 0.01). This significantly increased total capillary length (C, 3,115 +/- 173; E, 3,851 +/- 219mm-2 at 2.5 microns, P < 0.05) and surface area (C, 456 +/- 13; E, 519 +/- 24 cm-1, P < 0.05) per fiber volume. Thus emphysema substantially alters diaphragm capillary geometry and augments the capillary length and surface area available for blood-tissue exchange.

Animals↗