| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
RESPIRATORY |
1 Laboratoire de Physiologie, Université Victor Segalen Bordeaux II, CHU de Bordeaux, 33760, Bordeaux Cedex, France
2
Laboratoire des Adaptations Physiologiques aux Activités Physiques, Faculté des Sciences du Sport Poitiers, UPRES-EA 3813, France
3
Service de réanimation médical, CHU de Bordeaux, France
 |
Abstract |
|---|
 Top Abstract IntroductionMethodsResultsDiscussionAppendixReferences |
|---|
(Received 26 March 2007;
accepted after revision 30 April 2007;
first published online 10 May 2007)
Corresponding author H. Guénard: Laboratoire de Physiologie, Université Victor Segalen, 146 Rue Léo Saignat, 33076 Bordeaux Cedex, France. Email: herve.guenard{at}labphysio.u-bordeaux2.fr
|
Introduction |
|---|
|
TopAbstractIntroductionMethodsResultsDiscussionAppendixReferences |
|---|
) and pulmonary capillary volume (Vc). Dm is considered to be an independent variable to Vc.
In order to calculate Dm and Vc the NO/CO transfer method (TLNO/TLCO) was introduced in the lung function testing of humans in 1987 (Guénard et al. 1987). As the in vivo conductance of NO in blood is very high, the only limitation to its transfer through the barrier is the membrane. CO transfer (TLCO) depends on Dm, Vc and haemoglobin concentration. TLCO also varies with pulmonary capillary oxygen tension since CO is inversely proportional to this pressure. The ratio of NO to CO transfer (TLNO/TLCO) should therefore provide some insight into the relative properties of the membrane and capillaries.
The surface area of the alveolar membrane and capillary are identical or closely related and by consequence, Dm and Vc should be directly correlated. The hypothesis of this study is based on the assumption that Vc and Dm are dependent parameters.
Under this assumption, this study is designed to identify the significance of the TLNO/TLCO ratio through both theoretical and experimental approaches with the expectations that the new model would be relevant for physiological or clinical purposes. Specifically, we have shown that the TLNO/TLCO ratio is independent of membrane surface area and inversely proportional to the product of alveolar membrane and capillary blood layer thicknesses.
|
Methods |
|---|
|
TopAbstractIntroductionMethodsResultsDiscussionAppendixReferences |
|---|
The model generally used to describe lung transfer was established by Roughton and Forster (Forster et al. 1957):
|
| (1) |
x.Vc, where x, the conductance of the gas with the red cell, is determined in vitro using rapid reaction apparatus and Vc is the volume of blood in the lung capillaries.
In this study, the pulmonary capillary is assumed to be a rectangular box with a single side representing the membrane; Vc is the product of membrane surface area S and thickness of the capillary blood sheet K, i.e. Vc = KS. Defining µ as the membrane thickness and introducing a new variable 
as the product of membrane and blood sheet thickness in cm2, i.e. = Kµ it can be shown (see Appendix) as:
|
| (2) |
Blood sheet thickness (K) as a function of membrane thickness (µ) with different values of TLNO/TLCO is illustrated in Fig. 1. The TLNO/TLCO ratio is inversely proportional to the thickness of the membrane and pulmonary capillary sheet.
|
As 
and hence TLNO/TLCO are independent of membrane and pulmonary capillary sheet surface area, the effect of altering membrane or blood sheet thickness in normal subjects was investigated by varying lung volume, applying positive and negative pressure, and inducing haemodilution.
We made three assumptions: (1) the reduction in alveolar volume would either increase the alveolar membrane thickness (balloon behaviour) or remain constant if the membrane folds (bellow behaviour); (2) positive or negative continuous pressure breathing would change the capillary sheet thickness by compression (positive pressure) or distension (negative pressure) without altering the alveolar membrane thickness; and (3) haemodilution would increase the thickness of the capillary blood sheet.
Subjects
Twenty-five non-smoking subjects were recruited for testing alterations in TLNO and TLCO following changes in alveolar volume (Va). The same group of subjects was also tested for the positive or negative pressure breathing protocols on different days. Twelve additional non-smoking volunteers participated in the dilution testing. All subjects underwent two measurements of total lung capacity (TLC) and forced expiratory manoeuvers in a plethysmograph (Medi-Soft, Dinant, Belgium) prior to the experiments to ensure their respiratory functionality was in the normal range.
The study was approved by the ethics committee of the University Hospital. All subjects were provided with a written description of the study and gave their consent before the experiments started.
TLCO and TLNO measurements
The single breath technique for the transfer of NO and CO has been described elsewhere (Guénard et al. 1987; Glenet et al. 2006). In brief, the subject breathed quietly through a filter in a screen flow-meter for 15 s and was then asked to make a single breath manoeuvre. After a forced slow expiration, the subject inspired rapidly as deep as possible or to a predetermined level and maintained apnoea for 4 s. A fast expiration was then performed during which 0.5 l of alveolar gas was sampled after discarding the first 0.8 l of expired gas to wash out the experimental and anatomical dead space. The inhaled mixture was composed of NO (40 p.p.m.), He (8%), CO (1600 p.p.m.), O2 (19%) in nitrogen. NO was added to the gas mixture just before the test to avoid any reaction of this gas with oxygen. This procedure was automated. NO at 450 p.p.m. was stored in one tank with nitrogen, the other gases were stored in another tank (Air Liquide). Calibrations of NO, CO and He were automated and performed each day. The linearity of the analysers was checked by the factory (Hypercompact +, Dinant). TLCO and TLNO and the derived variables Dm, Vc and Va (alveolar volume during the apnoea), were then calculated as described in previous studies (Guénard et al. 1987). The total breath-holding time was taken as the sum of inspired time, the true breath-holding time and the expired time up to the time of the sampling period. It has been shown that this procedure produced reproducible values regardless of the durations of individual sequence (Moinard & Guénard, 1990; Cotton et al. 1992).
The value of NO was estimated to be very high and its inverse was negligible. Therefore there was no difference between TLNO and DmNO. The coefficient relating DmNO to DmCO was set at 1.97. The CO value used in the equation was cited from Forster with a pH value of 7.4 and a mean oxygen capillary pressure of 100 mmHg (Forster, 1987). Vc values were standardized with a haemoglobin concentration of 140 g l–1, when no haemoglobin concentration was measured. It took 5 min to prepare the inhaled gas mixture. For each sample, triple measurements were performed if two measurements did not produce consistent results. NO and CO transfer measurements were validated if the difference between the two measurements was within 10%.
TLNO and TLCO versus Va measurement
Twenty-five subjects were trained to rapidly interrupt their breath during inspiration at 65, 80 or 100% of TLC. Single-breath NO and CO transfer measurements (TLNO and TLCO, respectively) at 10 min intervals were performed in the sitting position. The tests were performed successively in random order at the preset value of Va. After a deep expiration, the subject was asked to interrupt the next deep inspiration of testing gas mixture at a predefined level. The investigator provided vocal assistance when necessary.
Continuous negative or positive pressure breathing (CNP and CPP, respectively)
The gas transfer rates of the subjects were measured in the sitting position breathing under either positive or negative pressure through the mouth. To perform CNP, a Venturi device was connected to the flow-meter, and when needed, a continuous negative pressure through the mouth of the subject. The Venturi was supplied with compressed air (7 bars) at a maximum flowrate of 3 l s–1 giving a stable CNP of –9 cmH2O. The CNP was applied 30 s before and throughout the manoeuver except during deep inspiration when the subject inhaled the test gas mixture. CPP was performed by reversing the Venturi device. A stable positive pressure of +12 cmH2O was created. The pressure was interrupted at the end of the breath-hold, at the start of expiration. The subjects were trained to keep their thorax fully inflated during the apnoea without relaxation to avoid glottis closure.
After 10 min of rest in the sitting position, the transfer rate was measured under three conditions: breathing under ambient, negative and positive pressure. The tests were performed successively in random order to obtain two ambient pressures, two CNP and two CPP validated measures. Means of the values of validated measures were calculated. A 5 min recovery period was given between tests.
Haemodilution
Haemodilution measurements were conducted with 12 additional subjects. Before haemodilution, their transfer rates were firstly measured while the subjects were seated and then in a supine position. The subject was then asked to drink 1.5 l of warm water (32°C) over 15 min. The water was warmed to avoid any thermal discomfort. Measurements of transfers were taken 20, 30 and 40 min after the subject finished drinking.
For each subject, one ear lobe was heated with an infrared bulb and Rubefiant cream (Finalgon Boerhinger Inghelheim, Germany) applied to obtain maximum vasodilatation. Capillary blood samples were collected both before and 35 min after water intake. The haemoglobin concentration and the carboxyhaemoglobin (HbCO) percentage were measured immediately (Bayer Chiron Rapid'lab 840) after the samples were obtained.
Statistical analysis
Means and standard deviation (S.D.) for each variable in each condition were calculated. For the haemodilution experiment, a non-parametric analysis of variance was used to test changes in the dependent variables. All other experimental conditions were studied using a parametric analysis of variance.
|
Results |
|---|
|
TopAbstractIntroductionMethodsResultsDiscussionAppendixReferences |
|---|
|
The slope of the linear regression equation between TLNO/TLCO ratio and age in all of the 37 subjects was close to 0 (TLNO/TLCO = 0.003 x Age + 4.7, r2 = 0.02) indicating that the TLNO/TLCO ratio was independent of age.
Correlation between Vc and Dm
For the 37 subjects in the sitting position at maximal lung volume, there was a linear relationship between Vc versus Dm: Vc = 1.18 Dm + 1.9 (P < 0.01; r2 = 0.84). In this equation the constant value was not different from zero (Fig. 2).
|
As indicated in Table 2, a decrease in Va from 7.4 ± 1.1 to 4.8 ± 0.8 l induced a greater decrease in TLNO (31%) than in TLCO (18%). The TLNO/TLCO ratio decreased in all subjects (Fig. 3). The average TLNO/TLCO ratio decreased significantly from 4.91 ± 0.25 to 4.2 ± 0.34. The decrease in Vc with Va was small but significant (7%) which was smaller than the decrease in DmCO. When Va decreased from 100 to 65%, increased from 0.55 ± 0.05 to 0.74 ± 0.13 µm2.
|
|
Va was not altered by CNP while it decreased slightly during CPP. Breathing during CNP increased TLCO, TLNO and Vc significantly. TLNO/TLCO decreased and increased significantly between CPP and CNP conditions (Table 3).
|
The greatest changes in TLCO and Vc corrected for haemoglobin concentration (Vccor) were measured 40 min after the end of haemodilution (Fig. 4). TLNO and TLCO corrected for haemoglobin concentration (TLCOcor) were not significantly altered by haemodilution. However, the TLNO/TLCOcor ratio decreased significantly from 4.85 ± 0.27 to 4.52 ± 0.25 (P < 0.05). 
increased by 13%.
|
|
Reproducibility
Means, S.D.s and coefficients of variation were calculated in six subjects who performed on four different days the TLNO/TLCO measurement with and without a CNP of 10 mmHg at rest. TLNO/TLCO ratios were about 4.83 ± 0.15 to 4.61 ± 0.16 from control condition to a CNP level of 10 mmHg. Coefficients of variation were low, about 1.5% in each condition.
|
Discussion |
|---|
|
TopAbstractIntroductionMethodsResultsDiscussionAppendixReferences |
|---|
|
We also assumed that the value of NO is infinity in vivo (Guénard et al. 1987). This has been accepted by most research groups; however, in vitro estimation of NO provided a finite value of about 4 ml min–1 Torr–1 ml–1 (Borland et al. 2006). The most plausible explanation for this discrepancy is that the lack of boundary layer reduced intra-erythrocyte diffusion resistance which increases NO in practice to infinite in vivo
(Chakraborty et al. 2004).
TLNO/TLCO ratio and lung deflation
TLNO decreased by 31% when the alveolar volume decreased from 7.4 to 4.8 l. This could either be due to a reduction in surface area or an increase in the thickness of the alveolar membrane. TLCO decreased to a lesser extent relative to TLNO (or DmCO) indicating that the capillary lung volume was altered less than DmCO. Indeed, Vc only decreased by 7%. To simplify the interpretation, this decrease would be considered negligible compared with the 31% decrease in Dm. The mean ratio of TLNO/TLCO decreased from 4.9 to 4.2 and, increased by 32%. If the 31% decrease in Dm was only due to a 31% decrease in the lung surface without any change in the thickness of the membrane, the blood sheet thickness (K) would increase by 31% (since K = Vc/S), which is in agreement with the 32% observed increase in the value. The lack of increase in the thickness of the membrane could be due to its folding; however, it seems that folding occurs only at low lung volumes, according to the morphometric data (Gil et al. 1979). Moreover, the occurrence of folding could be due to the manner in which the in vitro preparation of the tissue was performed (Oldmixon & Hoppin, 1991). A more likely explanation is that the thin membrane limiting many capillaries, at least in part, bulges outside the thick part of the alveolar septa (Fig. 5). Therefore the thin part of capillaries is not stretched like the thick part of the septa (West et al. 2007). Moreover the increase in capillary diameter at low lung volume would distend their walls (Weibel et al. 1973; Gil et al. 1979; Tschumperlin & Margulies, 1999). Gehr et al. measured the harmonic mean thickness µh of the membrane (0.65 µm) which takes its thinner part into account more than the arithmetic mean (Gehr et al. 1978). The relationship between µh and lung volume seems not to have been studied. Indeed, the images of lung sections obtained at different lung volumes showed an increase in blood sheet thickness without a clear change in membrane thickness (Gil et al. 1979; Tschumperlin & Margulies, 1999).
|
NO and CO transfers during CNP and CPP
CNP breathing at maximal lung volume induced a significant increase in along with a decrease in TLNO/TLCO associated with increases in both Vc and Dm as compared with CPP. These results suggest a recruitment of capillaries with CNP resulting in an increase in both the surface area of the gas exchange membrane and blood volume in the capillaries as well as the distension of capillaries, thereby, increasing K and values.
To avoid any respiratory discomfort and interstitial oedema, the negative pressure used in our study was moderate. As a result, an increase in the µ value is unlikely. This last point has been verified in two subjects by measuring NO and CO transfer rates after 10 min of CNP at –15 cmH2O. There was no decrease in Dm compared with the measurement made after 30 s of CNP suggesting that there was no induction of an interstitial oedema. Steiner et al. (1965) observed an increase in Vc and Dm after applying high CNP for either 4 or 7 min (–26 to –52 cmH2O) in five subjects.
TLNO/TLCO ratio and haemodilution
The significant decrease in the TLNO/TLCOcor ratio following haemodilution suggests that the increase in plasma volume induces distension of lung capillaries. Vascular expansion was achieved using a non-invasive procedure. The induced haemodilution was moderate as the decrease in haemoglobin concentration was only 0.6 g dl–1 following water ingestion. However, this change was sufficient to induce a significant decrease in TLNO/TLCOcor. In the present protocol a slight increase in Vc was planned to avoid interstitial oedema. Vccor was indeed slightly increased (8%). Forty-five minutes after water intake, Va decreased by 0.38 l, suggesting a corresponding increase in vascular thoracic blood volume. This decrease in Va might have contributed to the decrease in the TLNO/TLCOcor ratio. Taking into account the results obtained at different Va, this decrease in TLNO/TLCOcor ratio would be considered negligible (Table 1). Farney et al. (1977) induced rapid plasma expansion in five subjects by infusing 2 l of saline solution . A twofold increase in Vc and a decrease in DmCO in some subjects were observed, suggesting the development of pulmonary interstitial oedema. Vc, corrected by haemoglobin concentration, increased by about 100%. In this condition it could be assumed that these authors would have found larger alterations in TLNO/TLCOcor ratio.
TLNO/TLCO ratio in health and lung disease
Relative alterations in this ratio in healthy subjects following physiological perturbations such as those used in this work might appear small; however, it should be noted that the range of variation of this ratio does not start at zero but at 1.97, the value of coefficient A for which coefficient is infinite. Using relative variation in this last coefficient is straighter. According to most publications, the normal range of the ratio is between 4 and 5, and is larger in patients. As suggested here, the value of the ratio in a given individual depends on the structure of the alveolo-capillary membrane, being therefore a morphological trait. However, while differing from one subject to another, this ratio in a given individual is reproducible from day to day, the mean coefficient of variation of the ratio measured being 1.5% with or without CNP.
As CO increases while the mean capillary oxygen pressure decreases, TLCO would be increased in hypoxaemic patients. The TLNO/TLCO ratio would therefore be decreased in these patients. This bias can be avoided by calculating using the proper value for CO in coefficient B (Appendix, eqn (A12).
Patients with pulmonary hypertension had a higher TLNO/TLCO ratio than control subjects, suggesting that the capillary sheet is thinner than normal (Borland et al. 1996; van der Lee et al. 2006). This change is probably due to structural alterations in the capillaries (Villaschi & Pietra, 1986). An elevated ratio (about 10) has been experimentally found in a lung model made of a membrane oxygenator which had a very thin membrane with tiny pores and a thick layer of blood only a small fraction of which partakes in gas exchange (Borland et al. 2006). This highlights the fact that this ratio is effectively sensitive to , the product of membrane and blood sheet thicknesses.
In patients with left ventricular dysfunction a significant increase in TLCO/Dm, hence a decrease in TLNO/TLCO ratio, was observed 1 h after 830 ml infusion of 0.9% saline (Puri et al. 1999). NO and CO transfers are not dependent on cardiac blood flow as shown by Borland et al. (2006) but are dependent on the often related alterations in Vc and Dm. Alterations in the capillary structure have also been described in patients with diffuse parenchymal lung diseases. Phansalkar et al. found a decrease in TLNO/TLCO ratio (3.5 versus 4.4 in healthy subjects) in patients with stages 2 and 3 of sarcoidosis (Phansalkar et al. 2004). Unselected patients with these diseases had a TLNO/TLCO ratio value close to control (van der Lee et al. 2006). Interestingly, the thickening of the membrane has been described in stages 2 and 3 of sarcoidosis (Planes et al. 1994); in other interstitial lung diseases the alterations in the alveolo-capillary structure are less constant (Panchal & Koss, 1997). This highlights the variety in the alteration in lung function in these diseases.
Patients with COPD had a similar mean TLNO/TLCO ratio relative to healthy subjects but the distribution of the data was significantly greater than that of healthy subjects (4.43 ± 0.93 and 4.32 ± 0.40, respectively) (Moinard & Guénard, 1990). This suggests that COPD alters the alveolar capillary membrane function either by thickening or thinning of one or both its components. In situations where both TLNO and TLCO are decreased and the TLNO/TLCO ratio remains normal, such as in COPD patients, this suggests a decrease in the lung surface area for gas exchange but a normal alveolar capillary thickness. The heterogeneity of the lung structure and function is not taken into account in the present model. Radioactive NO and CO molecules could allow a regional analysis of TLNO/TLCO ratio.
In conclusion, the TLNO/TLCO ratio is inversely related to the thicknesses of the alveolar membrane and capillary sheet. This ratio can be calculated following a single NO/CO transfer manoeuver and could provide better insight into understanding diseases thought to alter the thickness of either the alveolar membrane or lung capillary blood sheet.
|
Appendix |
|---|
|
TopAbstractIntroductionMethodsResultsDiscussionAppendixReferences |
|---|
|
| (3) |
x .Vc. x is the rate of reaction of x with haemoglobin depending on its actual concentration and Vc is the amount of blood in the lung capillaries. In the present study the exchange surface S of the membrane is assumed to be related to Vc. A simple linear relationship is proposed:
|
| (4) |
Dm apart from at the surface is a function of the membrane thickness µ (cm), the coefficient of diffusion, dx (cm2 min–1), and the coefficient of solubility of the gas 
x (mmHg–1).
|
| (5) |
|
| (6) |
|
| (7) |
x and x are constants.
For NO transfer, 
can be considered negligible:
|
| (8) |
|
| (9) |
|
| (10) |
|
| (11) |
|
| (12) |
|
| (13) |
|
| (14) |
|
References |
|---|
|
TopAbstractIntroductionMethodsResultsDiscussionAppendixReferences |
|---|
Borland C, Dunningham H, Bottrill F & Vuylsteke A (2006). Can a membrane oxygenator be a model for lung NO and CO transfer? J Appl Physiol 100, 1527–1538.
Chakraborty S, Balakotaiah V & Bidani A (2004). Diffusing capacity reexamined: relative roles of diffusion and chemical reaction in red cell uptake of O2, CO, CO2, and NO. J Appl Physiol 97, 2284–2302.
Cotton DJ, Taher F, Mink JT & Graham BL (1992). Effect of volume history on changes in DLcoSB-3EQ with lung volume in normal subjects. J Appl Physiol 73, 434–439.
Farney RJ, Morris AH, Gardner RM & Armstrong JD Jr (1977). Rebreathing pulmonary capillary and tissue volume in normals after saline infusion. J Appl Physiol 43, 246–253.
Forster RE (1987). Diffusion of gases across the alveolar membrane. In Handbook of Physiology, section 3, The Respiratory System, vol. IV, Gas Exchange, ed. Farhi LE & Tenney SM, pp. 71–88. American Physiological Society, Bethesda, MD, USA.
Forster RE, Roughton FJ, Cander L, Briscoe WA & Kreuzer F (1957). Apparent pulmonary diffusing capacity for CO at varying alveolar O2 tensions. J Appl Physiol 11, 277–289.
Gehr P, Bachofen M & Weibel ER (1978). The normal human lung: ultrastructure and morphometric estimation of diffusion capacity. Respir Physiol 32, 121–140.[CrossRef][Medline]
Gil J, Bachofen H, Gehr P & Weibel ER (1979). Alveolar volume-surface area relation in air- and saline-filled lungs fixed by vascular perfusion. J Appl Physiol 47, 990–1001.
Glenet SN, de Bisschop CM, Dridi R & Guénard HJ (2006). Membrane conductance in trained and untrained subjects using either steady state or single breath measurements of NO transfer. Nitric Oxide 15, 199–208.[CrossRef][Medline]
Graham BL, Mink JT & Cotton DJ (2002). Effects of increasing carboxyhemoglobin on the single breath carbon monoxide diffusing capacity. Am J Respir Crit Care Med 165, 1504–1510.
Guénard H, Varene N & Vaida P (1987). Determination of lung capillary blood volume and membrane diffusing capacity in man by the measurements of NO and CO transfer. Respir Physiol 70, 113–120.[CrossRef][Medline]
Hsia CC, McBrayer DG & Ramanathan M (1995). Reference values of pulmonary diffusing capacity during exercise by a rebreathing technique. Am J Respir Crit Care Med 152, 658–665.[Abstract]
Moinard J & Guénard H (1990). Determination of lung capillary blood volume and membrane diffusing capacity in patients with COLD using the NO-CO method. Eur Respir J 3, 318–322.[Abstract]
Oldmixon EH & Hoppin FG Jr (1991). Alveolar septal folding and lung inflation history. J Appl Physiol 71, 2369–2379.
Panchal A & Koss MN (1997). Role of electron microscopy in interstitial lung disease. Curr Opin Pulm Med 3, 341–347.[CrossRef][Medline]
Phansalkar AR, Hanson CM, Shakir AR, Johnson RL Jr & Hsia CC (2004). Nitric oxide diffusing capacity and alveolar microvascular recruitment in sarcoidosis. Am J Respir Crit Care Med 169, 1034–1040.
Planes C, Valeyre D, Loiseau A, Bernaudin JF & Soler P (1994). Ultrastructural alterations of the air–blood barrier in sarcoidosis and hypersensitivity pneumonitis and their relation to lung histopathology. Am J Respir Crit Care Med 150, 1067–1074.[Abstract]
Puri S, Dutka DP, Baker BL, Hughes JM & Cleland JG (1999). Acute saline infusion reduces alveolar-capillary membrane conductance and increases airflow obstruction in patients with left ventricular dysfunction. Circulation 99, 1190–1196.
Stam H, Kreuzer FJ & Versprille A (1991). Effect of lung volume and positional changes on pulmonary diffusing capacity and its components. J Appl Physiol 71, 1477–1488.
Steiner SH, Frayser R & Ross JC (1965). Alterations in pulmonary diffusing capacity and pulmonary capillary blood volume with negative pressure breathing. J Clin Invest 44, 1623–1630.[Medline]
Tschumperlin DJ & Margulies SS (1999). Alveolar epithelial surface area-volume relationship in isolated rat lungs. J Appl Physiol 86, 2026–2033.
van der Lee I, Zanen P, Grutters JC, Snijder RJ & van den Bosch JM (2006). Diffusing capacity for nitric oxide and carbon monoxide in patients with diffuse parenchymal lung disease and pulmonary arterial hypertension. Chest 129, 378–383.
Villaschi S & Pietra GG (1986). Alveolo-capillary membrane in primary pulmonary hypertension. Appl Pathol 4, 132–137.[Medline]
Weibel ER, Federspiel WJ, Fryder-Doffey F, Hsia CC, Konig M, Stalder-Navarro V & Vock R (1993). Morphometric model for pulmonary diffusing capacity. I. Membrane diffusing capacity. Respir Physiol 93, 125–149.[CrossRef][Medline]
Weibel ER, Untersee P, Gil J & Zulauf M (1973). Morphometric estimation of pulmonary diffusion capacity. VI. Effect of varying positive pressure inflation of air spaces. Respir Physiol 18, 285–308.[CrossRef][Medline]
West JB, Watson RR & Fu Z (2007). The human lung; did evolution get it wrong? Eur Respir J 29, 11–17.
|
Acknowledgements |
|---|
We thank R. Marthan for helpful comments.
This article has been cited by other articles:
|
|
 |
|
  C. Borland A place for TL,NO with TL,CO? Eur. Respir. J., May 1, 2008; 31(5): 918 - 919. [Full Text] [PDF]
|
|
|
|
 |
|
 H. Dressel, L. Filser, R. Fischer, D. de la Motte, W. Steinhaeusser, R. M. Huber, D. Nowak, and R. A. Jorres Lung Diffusing Capacity for Nitric Oxide and Carbon Monoxide: Dependence on Breath-Hold Time Chest, May 1, 2008; 133(5): 1149 - 1154. [Abstract] [Full Text] [PDF]
|
|
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
