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The scaling of maximal oxygen consumption and pulmonary dimensions in small mammals.

This report has reexamined the relationship between standard and maximal rates of oxygen consumption (VO2std and VO2max) and pulmonary surface area in mammals whose weights extend over the lower half of the total log weight range in mammals. For combined groups of wild and laboratory animals with body weights of 2--3700 g, the following equations pertain: VO2std (ml . min-1) = 0.0602 . W0.727; VO2std, or the factorial aerobic scope, is nearly constant over this weight range at approximately 6.6 (range 5.8--7.1). In view of this finding, earlier studies relating SA or pulmonary diffusion capacity to VO2std are still appropriate models for pulmonary constraints on metabolic rate. The data summarized here suggest that, at least for wild species of mammals, pulmonary diffusion capacity may limit VO2max.

Animals↗

Antibodies to collagen in scleroderma.

Using the enzyme-linked immunosorbent assay (ELISA), we detected antibodies to interstitial (type I) and basement membrane (type IV) collagens in the sera of patients with scleroderma (systemic sclerosis). Antibodies against type IV collagen were found in significant levels in these patients and correlated with the presence of abnormal pulmonary diffusion capacity. Levels of antibodies to type I collagens also correlated significantly with pulmonary diffusion capacity. Absorption of sera with type I or type IV collagens before analysis in the ELISA eliminated reactivity in an antigen-specific pattern, indicating that these antibodies reacted with determinants specific for either type I or type IV collagens. The removal of immune complexes by ultracentrifugation had no effect on serum antibody levels. Autoantibodies to basement membrane and interstitial collagens may participate in the pathogenesis of scleroderma.

Adolescent↗

[Argon replacing helium in measurement of pulmonary carbon monoxide diffusing capacity, its normal value and clinical application].

Measuring DL COSB of 120 normal subjects by using a gas mixture, in which helium was replaced by argon, we determined the DL COSB mean value, standard deviation and the predicted value formula for both sexes. The lower limit value of DL COSB for normal subjects was defined and the positive diagnostic value investigated. A ratio of actual value to predicted value below 80% was defined as abnormal. With this diagnostic criterion 43 cases of silicosis and diffuse pulmonary interstitial fibrosis were investigated, the positive rate of the cases being 90.70%, with a false positive rate of below 10% for normal subjects, which indicates that this gas mixture and the criterion are applicable for clinical practice.

Adolescent↗

High rate of O2 consumption in exercising foxes: large PO2 difference drives diffusion across the lung.

The fox has one of the highest mass specific rates of maximal oxygen consumption (VO2max/Mb) that has been measured, yet its specific pulmonary diffusing capacity (DLO2/Mb, measured morphometrically) is similar to that of most mammalian species. It achieves a high O2 flux per unit DLO2 with a large partial pressure difference driving O2 diffusion from alveolar gas to capillary blood (PAO2-PbO2). This paper explores the mechanisms that the fox utilizes to achieve this large pressure difference and the extent to which it exploits its structural diffusing capacity. Foxes were exercised on a treadmill at maximal rates of O2 uptake. The following parameters were measured or calculated: arterial and mixed venous PO2, PCO2, pH and O2 concentration of the blood, cardiac output, hemoglobin concentration and O2 equilibrium curve of the blood, and morphometric estimates of pulmonary capillary volume and pulmonary diffusing capacity for O2. These data were used to calculate pulmonary capillary transit time and the time course of the change in O2 concentration and PO2 of the blood as it transits the lung. The fox has a morphometric pulmonary diffusing capacity of 0.098 ml O2.sec-1.mm Hg-1.kg-1. At VO2 max (3.6 ml O2.sec-1.kg-1) the fox hyperventilates, resulting in a high PAO2 (124 mm Hg); it also maintains a low PbO2 (88 mm Hg) by having a short transit time (0.13 sec) due to a high specific cardiac output (25 ml.sec-1.kg-1). Our calculations indicate that at VO2max the fox uses almost all of the pulmonary capillary transit time for O2 equilibration, in contrast to other species.

Animals↗

Interrelationship between bronchoalveolar lavage cellular constituents and pulmonary functions in sarcoidosis.

Bronchoalveolar lavage (BAL) using a fiberoptic bronchoscope was done in 36 patients with sarcoidosis on 45 occasions and in 19 control subjects over a period of seven years. Total cell, polymorphonuclear cell and eosinophil cell counts of bronchoalveolar lavage fluid (BALF) in patients with sarcoidosis were not significantly different from control subjects. However, lymphocyte count (% total cells) in BALF was significantly higher (P less than 0.001) in patients with sarcoidosis as compared to control subjects. Alveolar macrophage was the predominant cell type in BALF in control subjects. A significant positive correlation (r = 0.46; P less than 0.01) between vital capacity (VC) and pulmonary diffusing capacity (DLCO) and a negative correlation (r = -0.52; P less than 0.001) between BAL fluid lymphocytes (%) and DLCO (per cent predicted) was found in patients with sarcoidosis. An increase in lymphocytes in BALF is considered to be one of the parameters indicating activity of sarcoidosis. In view of the relationship between this parameter and the reduction in DLCO, the latter may also be an indicator of disease activity.

Adolescent↗

The large lungs of elite swimmers: an increased alveolar number?

In order to obtain further insight into the mechanisms relating to the large lung volumes of swimmers, tests of mechanical lung function, including lung distensibility (K) and elastic recoil, pulmonary diffusion capacity, and respiratory mouth pressures, together with anthropometric data (height, weight, body surface area, chest width, depth and surface area), were compared in eight elite male swimmers, eight elite male long distance athletes and eight control subjects. The differences in training profiles of each group were also examined. There was no significant difference in height between the subjects, but the swimmers were younger than both the runners and controls, and both the swimmers and controls were heavier than the runners. Of all the training variables, only the mean total distance in kilometers covered per week was significantly greater in the runners. Whether based on: (a) adolescent predicted values; or (b) adult male predicted values, swimmers had significantly increased total lung capacity ((a) 145 +/- 22%, (mean +/- SD) (b) 128 +/- 15%); vital capacity ((a) 146 +/- 24%, (b) 124 +/- 15%); and inspiratory capacity ((a) 155 +/- 33%, (b) 138 +/- 29%), but this was not found in the other two groups. Swimmers also had the largest chest surface area and chest width. Forced expiratory volume in one second (FEV1) was largest in the swimmers ((b) 122 +/- 17%) and FEV1 as a percentage of forced vital capacity (FEV1/FVC)% was similar for the three groups. Pulmonary diffusing capacity (DLCO) was also highest in the swimmers (117 +/- 18%). All of the other indices of lung function, including pulmonary distensibility (K), elastic recoil and diffusion coefficient (KCO), were similar. These findings suggest that swimmers may have achieved greater lung volumes than either runners or control subjects, not because of greater inspiratory muscle strength, or differences in height, fat free mass, alveolar distensibility, age at start of training or sternal length or chest depth, but by developing physically wider chests, containing an increased number of alveoli, rather than alveoli of increased size. However, in this cross-sectional study, hereditary factors cannot be ruled out, although we believe them to be less likely.

Adult↗

DLCO/Q and diffusion limitation at rest and on exercise in patients with interstitial fibrosis.

Pulmonary diffusing capacity for carbon monoxide (DLCO) and pulmonary capillary blood flow (Qp) were measured on exercise in patients with a low DLCO with the aim of predicting, from the overall DL/Qp ratio, diffusion limitation for oxygen and relating it to the fall in arterial oxygen saturation actually observed. Five patients with cryptogenic fibrosing alveolitis (DLCO ranging from 20-54% predicted normal) exercised for 5 min at a work load equal to 60% of their maximum (45 to 90 watts). At 5 min (and previously at rest) they rebreathed rapidly for 15 sec from a 1.0 L bag containing helium (He), sulphur hexafluoride (SF6) and freon-22, 30% oxygen in argon and less than 1 ppm 11C-labelled carbon monoxide. Pulmonary capillary blood flow (Qp) and diffusing capacity (DLCO) were measured from flow-weighted breath-by-breath concentrations of freon-22 and 11CO, after correction for gas mixing delays (using He and SF6). Oxygen saturation (SaO2) (ear oximetry), MO2 and MCO2 and cardiac frequency were measured. PAO2 (ideal) was derived and mixed venous O2 saturation and content were calculated (Fick); PaO2 and PVO2 were derived from standard dissociation curves. For comparison, DLCO and Qp were measured in a similar fashion in five normal subjects exercising at 60 watts. Mean DLCO in patients with fibrosis was 9.62 (SD 2.88) ml.min-1, mm Hg-1 on exercise and mean Qp was 10.48 (SD 1.79) L.min-1 giving mean DLCO/Q ratios of 0.92 (SD 0.28). At 60 watts mean DLCO/Qp in normal subjects was 2.54 (SD 0.3), 2.76-times greater than in patients. SaO2% fell in patients by 3-15% on exercise. Predictions of alveolar-end capillary PO2 gradients from these overall DL/Q gradients showed that diffusion limitation accounted for 99% of the alveolar-arterial PO2 gradient on exercise in fibrosing alveolitis. Hughes (1991 Respir. Physiol. 83:167-178) [corrected] suggests that this simple approach overestimates the contribution of diffusion limitation by about 30%.

Adult↗

Effect of RBC shape and deformability on pulmonary O2 diffusing capacity and resistance to flow in rabbit lungs.

Isolated rabbit lungs were perfused with washed and resuspended human red blood cells (RBCs) in the presence of drugs known to change the shape and deformability of RBCs. With sodium salicylate (0.5-2 g/l), which causes echinocytosis and increases RBC deformability, lung diffusing capacity for O2 (DLO2) increased by 21%. When chlorpromazine, which induces stomatocytosis and stiffens RBCs, was given (50 mg/l), DLO2 decreased by 18%. With sodium salicylate, the mean pulmonary artery pressure dropped by 14% from control values, whereas it increased by 18% under chlorpromazine. Comparative experiments with hemoglobin solutions did not reveal any effect of those two drugs either on DLO2 or on pulmonary arterial pressure, which indicates that the effects of sodium salicylate and chlorpromazine were due to changes in RBC shape and deformability. It is concluded that RBC shape and deformability affect pulmonary artery pressure and oxygen diffusing capacity, which may have an influence on oxygen transfer to tissue and hence be of clinical relevance.

Animals↗

Series ventilation, diffusion in airways, and stratified inhomogeneity.

Functional inhomogeneity in lungs, meaning local variance of PCO2 and PO2 in alveolar space, may be of parallel and/or series nature. The effects of both kinds of inhomogeneity are qualitatively similar (decrease of the efficiency of alveolar gas exchange) and difficult to differentiate by experimental analysis. As far as diffusive mixing is concerned, methods specifically suited for detection and quantification of stratified inhomogeneities are based on separation of multiple test gases of differing diffusivity. The results of studies by such methods indicate that for alveolar O2 exchange the resistance attributable to stratification is in most cases less than the reciprocal pulmonary diffusing capacity for O2. In the conventional analysis of alveolar gas exchange, effects of stratification would contribute to alveolar dead space ventilation or would be incorporated in the pulmonary diffusing capacity.

Animals↗

Lung diffusion capacity, oxygen uptake, cardiac output and oxygen transport during exercise before and after an himalayan expedition.

Studies were made of pulmonary diffusion capacity and oxygen transport before and after an expedition to altitudes at and above 4900 m. Maximum power (Pmax) and maximal oxygen uptake (VO2max) were measured in 11 mountaineers in an incremental cycle ergometer test (25W.min-1) before and after return from basecamp (30 days at 4900 m or higher). In a second test, cardiac output (Qc) and lung diffusion capacity of carbon monoxide (DL,cg) were measured by acetylene and CO rebreathing at rest and during exercise at low, medium and submaximal intensities. After acclimatization, VO2max and Pmax decreased by 5.1% [from 61.0 (SD 6.2) to 57.9 (SD 10.2) ml.kg-1, n.s.] and 9.9% [from 5.13 (SD 0.66) to 4.62 (SD 0.42) W.kg-1, n.s.], respectively. The maximal cardiac index and DL,cg decreased significantly by 15.6% [14.1 (SD 1.41) 1.min-1.m-2 to 11.9 (SD 1.44)1.min-1.m-2, P < 0.05] and 14.3% [85.9 (SD 4.36) ml.mmHg-1. min-1 to 73.6 (SD 15.2) ml.mmHg-1.min-1, P < 0.05], respectively. The expedition to high altitude led to a decrease in maximal Qc, oxygen uptake and DL,cg. A decrease in muscle mass and capillarity may have been responsible for the decrease in maximal Qc which may have resulted in a decrease of DL,cg and an increase in alveolar-arterial oxygen difference. The decrease in DL,cg especially at lower exercise intensities after the expedition may have been due to a ventilation-perfusion mismatch and changes in blood capacitance. At higher exercise intensities diffusion limitation due to reduced pulmonary capillary contact time may also have occurred.

Acclimatization↗

Differences in cardio-respiratory responses to exhaustive exercise between athletes and non-athletes.

To study the factors limiting the O2 supply in heavy exercise, O2 uptake at exhaustion was determined by progressive loading method with a bicycle ergometer in 33 well-trained male runners and 34 male sedentary adults. Pulmonary ventilation, oxygen removal, respiratory rate, tidal volume, pulmonary diffusing capacity, alveolar-capillary oxygen difference, cardiac output, arterial-venous oxygen difference, stroke volume and heart rate were measured. It was found that pulmonary diffusing capacity, cardiac output and stroke volume were correlated with the difference in O2 uptake at exhaustion between athletes and non-athletes.

Adolescent↗

Cardiopulmonary function during 10 days of head-down tilt bedrest.

Pulmonary and cardiovascular responses to simulated weightlessness, i. e. 6 degrees head-down tilt bedrest (HDT) were investigated in six healthy male volunteers (mean age 26 yrs). Pulmonary diffusing capacity, functional residual capacity, pulmonary capillary blood flow, and lung tissue volume were measured by inert gas rebreathing. Heart rate and mean arterial blood pressure were obtained from finger blood pressure readings using a plethysmographic technique (Finapres). The short-term (20 min) response to HDT consisted of a 22% increase in pulmonary blood flow, and 13% and 31% falls in blood pressure and heart rate relative to standing. Functional residual capacity fell by 33%, while lung tissue volume increased insignificantly. Subsequent measurements during 10 days of HDT and 5 days of recovery revealed no further changes in lung volume, lung tissue volume, or blood pressure. However, diffusing capacity fell gradually and remained 4%-5% below baseline values after the 7th day of bedrest and during recovery (p less than 0.05). Pulmonary blood flow decreased by 16% during head-down bedrest and recovered partially within the following 5 days (p less than 0.05). We conclude that during and after simulated weightlessness marked alterations in cardiovascular function and marginal affections of gas exchange can be demonstrated already at rest. They may be considered as contributing factors to orthostatic and exercise intolerance observed after space flight.

Adult↗

Reduced alveolar-capillary membrane diffusing capacity in chronic heart failure. Its pathophysiological relevance and relationship to exercise performance.

BACKGROUND: The pulmonary diffusing capacity for carbon monoxide (DLCO) is reduced in chronic heart failure (CHF) and is an independent predictor of peak exercise oxygen uptake. The pathophysiological basis for this remains unknown. The aim of this study was to partition DLCO into its membrane conductance (DM) and capillary blood volume components (Vc) and to assess if alveolar-capillary membrane function correlated with functional status, exercise capacity, and pulmonary vascular resistance. METHODS AND RESULTS: The classic Roughton and Forster method of measuring single-breath DLCO at varying alveolar oxygen concentrations was used to determine DM and Vc in 15 normal subjects and 50 patients with CHF. All performed symptom-limited maximal bicycle exercise tests with respiratory gas analysis; 15 CHF patients underwent right heart catheterization. DLCO was significantly reduced in CHF patients compared with normal subjects, predominantly because of a reduction in DM (7.0 +/- 2.6 versus 12.9 +/- 3.8 versus 20.0 +/- 6.1 mmol.min-1.kPa-1 in New York Heart Association class III, class II, and normal subjects, respectively, P < .0001), even when the reduction in lung volumes was accounted for by the division of DM by the effective alveolar volume. The Vc component of DLCO was not impaired. DM significantly correlated with maximal exercise oxygen uptake (r = .72, P < .0001) and inversely correlated with pulmonary vascular resistance (r = .65, P < .01) in CHF. CONCLUSIONS: Reduced alveolar-capillary membrane diffusing capacity is the major component of impaired pulmonary gas transfer in CHF, correlating with maximal exercise capacity and functional status. DM may be a useful marker for the alveolar-capillary barrier damage induced by raised pulmonary capillary pressure.

Blood-Air Barrier↗

Effect of indoor feeding season for cattle on lung function of dairy farmers.

The effect of the indoor feeding season for cattle on pulmonary function was studied in 91 randomly selected healthy, non-smoking dairy farmers who did not use personal dust respirators. All the farmers lived in the rural municipality of Pielavesi in eastern Finland. The reference group consisted of 90 healthy, non-smoking urban dwellers who were teachers randomly selected from all the teachers employed by the city of Kuopio (situated in the same administrative district as Pielavesi). Studies of pulmonary function included flow-volume spirometry and measurement of pulmonary diffusing capacity. Among farmers, even a follow-up period of only 6 months was long enough to reveal restrictive impairment in lung function; among teachers restrictive impairment was not found. No evidence of impairment of pulmonary diffusing capacity was found in either of the study groups during the follow-up. Among teachers, changes in lung function did not differ from those previously reported as physiologically normal.

Adult↗