Single-breath washout experiments in rat lungs

1991 ◽  
Vol 71 (3) ◽  
pp. 855-862 ◽  
Author(s):  
N. Gonzalez Mangado ◽  
G. Peces-Barba ◽  
S. Verbanck ◽  
M. Paiva

Single-breath washouts were performed on 30 Wistar rats postmortem in studies in which breaths of 90% O2–5% He-5% SF6 were given. We investigated the effects of variations in preinspiratory lung volume, inspired volume, end-inspiratory breath-hold time, and inspiratory and expiratory flows on the alveolar plateau slopes for N2, He, and SF6. The main result is that the slope for He was always larger than the slope for SF6, except for large breath-hold times (approximately 15 s), contrary to previous findings in other species. Slopes for the three gases decreased with increasing inspiratory and expiratory flows when flows were greater than 1 ml/s. There was a strong correlation between the magnitude of a slope and its curvilinearity, suggesting that the concentration heterogeneity in the lung that causes the slope is due to interaction between diffusion and convection. The results seem incompatible with heterogeneities of parenchymal elasticity, which have been said to contribute to alveolar slopes in dog lungs but appear to be completely explainable as the result of diffusion-convection interaction in an asymmetric lung structure that has acini widely spread along the tracheobronchial tree.

1993 ◽  
Vol 75 (2) ◽  
pp. 927-932 ◽  
Author(s):  
D. J. Cotton ◽  
M. B. Prabhu ◽  
J. T. Mink ◽  
B. L. Graham

In normal seated subjects we increased single-breath ventilation inhomogeneity by changing both the preinspiratory lung volume and breath-hold time and examined the ensuing effects on two different techniques of measuring the diffusing capacity of the lung for carbon monoxide (DLCO). We measured the mean single-breath DLCO using the three-equation method (DLCOSB-3EQ) and also measured DLCO over discrete intervals during exhalation by the "intrabreath" method (DLCOexhaled). We assessed the distribution of ventilation using the normalized phase III slope for helium (SN). DLCOSB-3EQ was unaffected by preinspiratory lung volume and breath-hold time. DLCOexhaled increased with increasing preinspiratory lung volume and decreased with increasing breath-hold time. These changes correlated with the simultaneously observed changes in ventilation inhomogeneity as measured by SN (P < 0.01). We conclude that measurements of DLCOexhaled do not accurately reflect the mean DLCO. Intrabreath methods of measuring DLCO are based on the slope of the exhaled CO concentration curve, which is affected by both ventilation and diffusion inhomogeneities. Although DLCOexhaled may theoretically provide information about the distribution of CO uptake, the concomitant effects of ventilation nonuniformity on DLCOexhaled may mimic or mask the effects of diffusion nonuniformity.


1992 ◽  
Vol 73 (6) ◽  
pp. 2623-2630 ◽  
Author(s):  
D. J. Cotton ◽  
M. B. Prabhu ◽  
J. T. Mink ◽  
B. L. Graham

In patients with airflow obstruction, we found that ventilation inhomogeneity during vital capacity single-breath maneuvers was associated with decreases in the three-equation single-breath CO diffusing capacity of the lung (DLcoSB-3EQ) when breath-hold time (tBH) decreased. We postulated that this was due to a significant resistance to diffusive gas mixing within the gas phase of the lung. In this study, we hypothesized that this phenomenon might also occur in normal subjects if the breathing cycle were altered from traditional vital capacity maneuvers to those that increase ventilation inhomogeneity. In 10 normal subjects, we examined the tBH dependence of both DLcoSB-3EQ and the distribution of ventilation, measured by the mixing efficiency and the normalized phase III slope for helium. Preinspiratory lung volume (V0) was increased by keeping the maximum end-inspiratory lung volume (Vmax) constant or by increasing V0 and Vmax. When V0 increased while Vmax was kept constant, we found that the tBH-independent and the tBH-dependent components of ventilation inhomogeneity increased, but DLcoSB-3EQ was independent of V0 and tBH. Increasing V0 and Vmax did not change ventilation inhomogeneity at a tBH of 0 s, but the tBH-dependent component decreased. DLcoSB-3EQ, although independent of tBH, increased slightly with increases in Vmax. We conclude that in normal subjects increases in ventilation inhomogeneity with increases in V0 do not result in DLcoSB-3EQ becoming tBH dependent.


1987 ◽  
Vol 62 (5) ◽  
pp. 1962-1969 ◽  
Author(s):  
W. A. Whitelaw ◽  
B. McBride ◽  
G. T. Ford

The mechanism by which large lung volume lessens the discomfort of breath holding and prolongs breath-hold time was studied by analyzing the pressure waves made by diaphragm contractions during breath holds at various lung volumes. Subjects rebreathed a mixture of 8% CO2–92% O2 and commenced breath holding after reaching an alveolar plateau. At all volumes, regular rhythmic contractions of inspiratory muscles, followed by means of gastric and pleural pressures, increased in amplitude and frequency until the breakpoint. Expiratory muscle activity was more prominent in some subjects than others, and increased through each breath hold. Increasing lung volume caused a delay in onset and a decrease in frequency of contractions with no consistent change in duty cycle and a decline in magnitude of esophageal pressure swings that could be accounted for by force-length and geometric properties. The effect of lung volume on the timing of contractions most resembled that of a chest wall reflex and is consistent with the hypothesis that the contractions are a major source of dyspnea in breath holding.


1994 ◽  
Vol 76 (4) ◽  
pp. 1494-1501 ◽  
Author(s):  
G. R. Soparkar ◽  
J. T. Mink ◽  
B. L. Graham ◽  
D. J. Cotton

The dynamic changes in CO concentration [CO] during a single breath could be influenced by topographic inhomogeneity in the lung or by peripheral inhomogeneity due to a gas mixing resistance in the gas phase of the lung or to serial gradients in gas diffusion. Ten healthy subjects performed single-breath maneuvers by slowly inhaling test gas from functional residual capacity to one-half inspiratory capacity and slowly exhaling to residual volume with target breath-hold times of 0, 1.5, 3, 6, and 9 s. We calculated the three-equation single-breath diffusing capacity of the lung for CO (DLSBCO-3EQ) from the mean [CO] in both the entire alveolar gas sample and in four successive equal alveolar gas samples. DLSBCO-3EQ from the entire alveolar gas sample was independent of breath-hold time. However, with 0 s of breath holding, from early alveolar gas samples DLSBCO-3EQ was reduced and from late alveolar gas samples it was increased. With increasing breath-hold time, DLSBCO-3EQ from the earliest alveolar gas sample rapidly increased, whereas from the last alveolar gas sample it rapidly decreased such that all values from the small alveolar gas samples approached DLSBCO-3EQ from the entire alveolar sample. These changes correlated with ventilation inhomogeneity, as measured by the phase III He concentration slope and the mixing efficiency, and were larger for maneuvers with inspired volumes to one-half inspiratory capacity vs. total lung capacity.(ABSTRACT TRUNCATED AT 250 WORDS)


1989 ◽  
Vol 76 (6) ◽  
pp. 673-676 ◽  
Author(s):  
A. H. Kendrick ◽  
A. Rozkovec ◽  
M. Papouchado ◽  
J. West ◽  
G. Laszlo

1. Resting pulmonary blood flow (Q.), using the uptake of the soluble inert gas Freon-22 and an indirect estimate of lung tissue volume, has been estimated during breath-holding (Q.c) and compared with direct Fick cardiac output (Q.f) in 16 patients with various cardiac disorders. 2. The effect of breath-hold time was investigated by comparing Q.c estimated using 6 and 10 s of breath-holding in 17 patients. Repeatability was assessed by duplicate measurements of Q.c in the patients and in six normal subjects. 3. Q.c tended to overestimate Q.f, the bias and error being 0.09 l/min and 0.59, respectively. The coefficient of repeatability for Q.c in the patients was 0.75 l/min and in the normal subjects was 0.66 1/min. For Q.f it was 0.72 l/min. There was no significant difference in Q.c measured at the two breath-hold times. 4. The technique is simple to perform, and provides a rapid estimate of Q., monitoring acute and chronic changes in cardiac output in normal subjects and patients with cardiac disease.


1991 ◽  
Vol 71 (3) ◽  
pp. 847-854 ◽  
Author(s):  
S. Verbanck ◽  
N. Gonzalez Mangado ◽  
G. Peces-Barba ◽  
M. Paiva

Multiple-breath washouts were performed on 30 Wistar rats postmortem in a study in which breaths of 90% O2–5% He-5% SF6 were given. Preliminary comparison of alveolar plateau slopes obtained from anesthetized rats in vivo and postmortem showed that ventilation distribution remains the same within 1 h after the animals were killed. For maneuvers with different preinspiratory lung volumes and end-inspiratory breathholding, we computed the normalized N2 slope (Sn) and Fowler and Bohr dead spaces [VDF(n) and VDB(n), respectively] as a function of breath number (n). For all maneuvers analyzed, Sn of all gases increased in the first two or three breaths and reached a horizontal asymptote thereafter. The value of Sn decreased, both with increasing preinspiratory lung volume and breath hold of 4 s. The fact that the horizontal Sn asymptote is reached after only two or three breaths suggests the absence of convection-dependent inhomogeneities (CDI) in rat lungs. This contrasts with multiple-breath washout experiments in humans, where interregional (gravity-dependent CDI) and intraregional CDI generate a marked increase in Sn throughout the entire washout. Also, in contrast with results in humans, VDF and VDB were independent of n. The present work suggests that rats may be used to study diffusion- and convection-dependent inhomogeneities without the influence of CDI or gas exchange.


2018 ◽  
Vol 52 (1) ◽  
pp. 1500677 ◽  
Author(s):  
Mathias Munkholm ◽  
Jacob Louis Marott ◽  
Lars Bjerre-Kristensen ◽  
Flemming Madsen ◽  
Ole Find Pedersen ◽  
...  

The aim of this study was to determine reference equations for the combined measurement of diffusing capacity of the lung for carbon monoxide (CO) and nitric oxide (NO) (DLCONO). In addition, we wanted to appeal for consensus regarding methodology of the measurement including calculation of diffusing capacity of the alveolo-capillary membrane (Dm) and pulmonary capillary volume (Vc).DLCONO was measured in 282 healthy individuals aged 18–97 years using the single-breath technique and a breath-hold time of 5 s (true apnoea period). The following values were used: 1) specific conductance of nitric oxide (θNO)=4.5 mLNO·mLblood−1·min−1·mmHg−1; 2) ratio of diffusing capacity of the membrane for NO and CO (DmNO/DmCO)=1.97; and 3) 1/red cell CO conductance (1/θCO)=(1.30+0.0041·mean capillary oxygen pressure)·(14.6/Hb concentration in g·dL−1).Reference equations were established for the outcomes of DLCONO, including DLCO and DLNO and the calculated values Dm and Vc. Independent variables were age, sex, height and age squared.By providing new reference equations and by appealing for consensus regarding the methodology, we hope to provide a basis for future studies and clinical use of this novel and interesting method.


1996 ◽  
Vol 3 (4) ◽  
pp. 247-257 ◽  
Author(s):  
Brian L Graham ◽  
Joseph T Mink ◽  
David J Cotton

Conventional methods of measuring the single breath diffusing capacity of the lung for carbon monoxide (DLcoSB) are based on the Krogh equation, which is valid only during breath holding. Rigid standardization is used to approximate a pure breath hold manoeuvre, but variations in performing the manoeuvre cause errors in the measurement of DLcoSB. The authors previously described a method of measuring DLcoSBusing separate equations describing carbon monoxide uptake during each phase of the manoeuvre: inhalation, breath holding and exhalation. The method is manoeuvre-independent, uses all of the exhaled alveolar gas to improve estimates of mean DLcoSBand lung volume, and is more accurate and precise than conventional methods. A slow, submaximal, more physiological single breath manoeuvre can be used to measure DLcoSBin patients who cannot achieve the flow rates and breath hold times necessary for the standardized manoeuvre. The method was initially implemented using prototype equipment but commercial systems are now available that are capable of implementing this method. The authors describe how to implement the method and discuss considerations to be made in its use.


1985 ◽  
Vol 58 (4) ◽  
pp. 1319-1325 ◽  
Author(s):  
B. L. Graham ◽  
J. T. Mink ◽  
D. J. Cotton

The single-breath diffusing capacity of the lung for CO [DLCO(SB)] is considered a measure of the conductance of CO across the alveolar-capillary membrane and its binding with hemoglobin. Although incomplete mixing of inspired gas with alveolar gas could theoretically influence overall diffusion, conventional calculations of DLCO(SB) spuriously overestimate DLCO(SB) during short breath-holding periods when incomplete mixing of gas within the lung might have the greatest effect. Using the three-equation method to calculate DLCO(SB) which analytically accounts for changes in breath-hold time, we found that DLCO(SB) did not change with breath-hold time in control subjects but increased with increasing breath-hold time in both patients with asthma and patients with emphysema. The increase in DLCO(SB) with increasing breath-hold time correlated with the phase III slope of the single-breath N2 washout curve. We suggest that in patients with ventilation maldistribution, DLCO(SB) may be decreased for the shorter breath-hold maneuvers because overall diffusion is limited by the reduced transport of CO from the inspired gas through the alveolar gas prior to alveolar-capillary gas exchange.


2017 ◽  
Vol 49 (2) ◽  
pp. 1600962 ◽  
Author(s):  
Gerald S. Zavorsky ◽  
Connie C.W. Hsia ◽  
J. Michael B. Hughes ◽  
Colin D.R. Borland ◽  
Hervé Guénard ◽  
...  

Diffusing capacity of the lung for nitric oxide (DLNO), otherwise known as the transfer factor, was first measured in 1983. This document standardises the technique and application of single-breathDLNO. This panel agrees that 1) pulmonary function systems should allow for mixing and measurement of both nitric oxide (NO) and carbon monoxide (CO) gases directly from an inspiratory reservoir just before use, with expired concentrations measured from an alveolar “collection” or continuously sampledviarapid gas analysers; 2) breath-hold time should be 10 s with chemiluminescence NO analysers, or 4–6 s to accommodate the smaller detection range of the NO electrochemical cell; 3) inspired NO and oxygen concentrations should be 40–60 ppm and close to 21%, respectively; 4) the alveolar oxygen tension (PAO2) should be measured by sampling the expired gas; 5) a finite specific conductance in the blood for NO (θNO) should be assumed as 4.5 mL·min-1·mmHg-1·mL-1of blood; 6) the equation for 1/θCO should be (0.0062·PAO2+1.16)·(ideal haemoglobin/measured haemoglobin) based on breath-holdingPAO2and adjusted to an average haemoglobin concentration (male 14.6 g·dL−1, female 13.4 g·dL−1); 7) a membrane diffusing capacity ratio (DMNO/DMCO) should be 1.97, based on tissue diffusivity.


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