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Effect of alveolar pressure on single-breath CO diffusing capacity at mid-lung volume
Respiration Physiology. 81 (1990) 313-320
3 13
Elsevier
RESP 01691
Effect of alveolar pressure on single-breath CO diffusing capacity at mid-lung volume Shunsuke Suzuki, Hiroyuki Numata and Takao Okubo First Department of Internal Medicine, Yokohama CiO' UniversiO, School of Medicine, Yokohama. Japan (Accepted 6 May 1990) Abstract. The present study examines whether changes in the alveolar pressure (PA) affect the single breath diffusing capacity for carbon monoxide ( D e c o ) more strongly at mid-lung volume than at total lung capacity (TLC) in normal subjects. DLco was measured at 60°{,, 80°o and 100% of TLC, while PA was kept at + 30, 0, or 30 cm H 2 0 by the subject's effort during the measurement of DLco at each lung volume. The capillary blood volume (Vc) and the membrane diffusing capacity (Dm) were also determined. DLco at zero PA was found to be higher at 100~o TLC than at lower lung volumes. At PA = + 30 cm H 2 0 , Dr,co at 100°o, 803g, and 60 % TLC decreased by 8 ~o, 1 3 3 , and 13 ~'~o,respectively, and the decreases in Vc were 2 o/, 10 e'o, and 21 ~,, respectively. However, negative PA did not cause any significant changes in DLco or Vc at any lung volume. Also, D m did not change at any PA. We conclude that DLco is more affected by a positive PA at mid-lung volume than at a high lung volume, probably due to a greater decrease in Vc.
Alveolar pressure, and long diffusing capacity; Animal, man; Capillary blood volume; Diffusing capacity; of the lung, for CO, effects of alveolar pressure; Lung volume, and diffusing capacity
In patients with chronic obstructive pulmonary disease (COPD), the pleural pressure (Ppl) swing during resting ventilation is usually greater than in normal subjects. The Ppl in such patients is often positive on expiration and more negative on inspiration. Further, the pulmonary diffusing capacity is decreased in COPD. On the other hand, the pulmonary capillary bed is known to be compliant. Thus, it is possible that such large Ppl swings affect the diffusing capacity through a change in the capillary blood volume. Karp e l M . (1968) reported that an increase in the left atrial pressure caused an increase in the diffusing capacity. Furthermore, positive-pressure breathing was found to decrease not only the capillary blood volume but also the diffusing capacity (Cassidy et al., 1979; Daly el al., 1963). Similarly, Smith and Rankin (1969) showed that during the Valsalva maneuver the breath-holding diffusing capacity (DL) decreased substan-
Correspondence to: S. Suzuki, First Department of Internal Medicine, Yokohama City University School of Medicine, 3-46 Urafune-cho, Minami-Ku, Yokohama 232, Japan. 0034-5687/90/$03.50 © 1990 Elsevier Science Publishers B.V. (Biomedical Division)
314
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tially, but that the MOiler maneuver did not cause any change in DL. In contrast, Steiner etal. (1965) reported an increase in DL by the MOiler maneuver. These authors measured, however, DL at high lung volume, near total lung capacity (TLC). Morphomerry suggests the capillary lumen to be narrowed at high lung volume but maintained at low lung volume (Mazzone et al., 1978). Thus, at lower lung volume, the capillary blood volume may be more influenced by the alveolar pressure than at TLC. In order to investigate whether a change in the alveolar pressure affects the diffusing capacity more strongly at mid-lung volume than at TLC, we have measured in normal subjects the single breath diffusing capacity for CO (DLco) under the conditions of a negative and positive alveolar pressure applied during breath-holding at lung volumes near functional residual capacity (FRC) and at TLC. We furthermore have determined the membrane diffusing capacity (Din) and the capillary blood volume (Vc).
Methods Subjects. We studied nine healthy subjects, medical staff members who were familiar with respiratory maneuvers. All were male and their average age was 27 + 2 (SD) years. All, except one subject, were lifetime nonsmokers. Their average height was 171 + 5 cm (ranged from 165 to 180 cm) and the body weight 62 _+ 4 kg (ranged from 51 to 67 kg). None had a history of chronic respiratory or cardiopulmonary disease, and informed consent was obtained from all participants prior to the start of testing. Spirometry was performed by using a dry-seal spirometer (OST-85, Chest Co., Tokyo, Japan) and the lung volume was measured by a flow-type body plethysmograph (Model 2800, Gould, Dayton, OH). Vital capacity and forced expiratory volume in one second of all subjects were greater than 80°/0 of the predicted values (Cotes, 1979).
The subjects were studied in seated position after resting for at least 5 rain. DLco was determined by a modification of the Krogh breath-holding technique (Krogh, 1915 ; Forster et al., 1954; Ogilvie et al., 1957). Briefly, a gas mixture containing 0.3'/'o CO and 3°~,JoNe in air was inspired from a bag in box connected to a spirometer, so that the inspired volume and breath-holding time were recorded on the spirometer tracing. After rapidly inspiring the test gas from residual volume (RV) to a predetermined lung volume, which was controlled by a stopper of the spirometer, a valve was switched to stop inspiration, and each subject held his breath with open glottis for 10 sec and then exhaled as fast as possible. Approximately 1 L of the expired gas was sampled, after discarding the initially expired 750 ml, and analyzed by a gas chromatograph (Model 164, Hitachi, Tokyo, Japan). The breath holding time was taken from the beginning of inspiration from RV to the beginning of the sample collection. DLco was calculated by the following conventional formula, which takes into account the CO back pressure in the blood. DL measurement.
Dt, c o = VA/[t(PB - 47)] X In (FAco¢o)/FAco¢t))
(1)
Dl.co AND ALVEOLAR PRESSURE
315
in which VA is the alveolar volume in ml S T P D ; t is the breath-holding time in rain; PB is the barometric pressure plus alveolar pressure in m m H g ; FAco(o ) is the initial alveolar CO concentration, calculated by multiplying the inspired CO concentration by the ratio of the late expired to inspired Ne concentrations at the end of the breath-holding period, as measured in the alveolar sample. At least two determinations of DLco that were within 5 ~o of each other were obtained, and a period of at least 10 min was allowed between the measurements. The capillary blood volume (Vc) and the membrane diffusing capacity (Dm) were determined from two D L c o measurements at low and high alveolar oxygen tensions (FIo~ = 0.188 and 0.897) by the method of Roughton and Forster (1957): 1/DE = 1/Dm + 1/(0Vc)
(2)
Vc and Dm were measured in 8 of the 9 subjects. Protocol. Each subject was instructed to make an expiratory or inspiratory effort with open glottis against the closed valve during the breath-holding time of the DLco measurement. DLco was measured at 100, 80, and 60~o of total lung capacity (TLC). The alveolar pressure ( P A ) w a s measured at the mouth during the expiratory or inspiratory effort of the breath-holding by means of a differential pressure transducer (MP-45, Validyne, Northridge, CA). PA was displayed on an oscilloscope (Model SS-5802, Iwatsu Electric Co., Tokyo, Japan), and each subject was asked to maintain PA at + 30, 0, or - 30 cm H 2 0 during the breath-holding. Before measurement of DLco the subject repeated the Mtiller and Valsalva maneuvers without inhalation of test gas, until a reproducible value of PA was obtained. PA was adjusted to + 30, 0, and - 30 cm H 2 0 at each lung volume except at TLC at which + 30 and 0 c m H 2 0 were applied. When the mouth pressure was not kept within 5 ~o of a predetermined PA during the breathholding, the DLco value was discarded. All studies were done at the same time of day and were completed within 2 weeks. Ppl measurement. To assess efficiency of both the Miiller and Valsalva maneuvers, pleural pressure (Ppl) during the maneuvers was monitored at 60 and 80~, TLC in 4 subjects. The esophageal balloon (length 10 cm; perimeter 3.5 cm) connected to a polyethylene catheter (PE-200) was positioned at the lower third of the esophagus. Ppl was measured with a differential pressure transducer (MP-45, Validyne) connected to the balloon catheter. During each maneuver, both the Ppl and mouth pressure (Pro) were recorded and Ppl was compared with that at PA = 0. During the M~iller maneuver, changes in Ppl and Pm at 80~o TLC were not different (Ppl and Pm, 29 + 2 and 29 + 1 c m H 2 0 , respectively); those at 60~o TLC were also not different (Ppl and Pm, 27 + 3 and 30 + 1 cm H20, respectively). During the Valsalva maneuver, changes in Ppl and Pm at 80~0 TLC were not different (Ppl and Pm, 30 + 1 and 29 + 2 c m H 2 0 , respectively); those at 60~o T L C were not different either (Ppl and Pro, 27 _+ 2 and 29 _+ 0.2 cm H20, respectively).
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et al.
All values are expressed as mean _+ SD. Statistical analysis was done by a paired t-test and a one-way analysis of variance ( A N O V A ) for a c o m p a r i s o n of two and three groups, respectively.
Results
A t zero PA, D L c o was lower at a lower lung volume than at T L C (P < 0.01). At 100~o T L C , D L c o at zero PA was 106 _+ 9°~o (mean _+ S D ) of the predicted value (Cotes, 1979). By the Valsalva maneuver of + 3 0 cm H 2 0 at TLC, D L c o decreased significantly, by 8 + 6'~o from zero PA ( P < 0.01)(fig. 1). The breath-holding times at PA = 0 and + 30 cm H 2 0 were 10.5 + 0.5 and 10.5 + 0.5 sec, respectively. At 80"o TLC, DLc. o at zero PA was 90 _+ 9~, o f that at 100°o TLC. By the Valsalva maneuver, D L c o decreased by 13 + 6~o from zero PA (P < 0.01) and the decrease was significantly greater than that at 1001j!i; T L C (P < 0.03)(fig. 1). By the M a l l e t maneuver o f - 30 cm H 2 0 , however, DLc. o was not changed. The breath-holding times at PA = 0, + 30 and - 30 cm H 2 0 were 10.3 + 0.5, 10.2 + 0.5 and 10.3 +_ 0.6 sec, respectively, and there were no differences among the three PA conditions. At 607o TLC, D L c o at zero PA was 83 + 11 °/o of that at 100~,o TLC. By the Valsalva maneuver D L c o decreased by 13 + 6'~o from zero PA ( P < 0.001); however, the decrease was not significantly different from that at 100')o T L C (P = 0.13). D L c o during the Mtiller maneuver showed no difference from that at zero PA. There were no differences in the breath-holding time between PA = 0, + 30 and - 3 0 cm H 2 0 (10.3 + 0.4, 10.5 + 0.5 and 10.4 _+ 0.5 sec, respectively). 35 PA=O
30
E E v
25
VaLsaLva
20
8
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15
L,
rnean+SE I
I
60 LUNG
80 VOLUME
n=9 I
100
(% OF INDIVIDUAL T L C )
Fig. 1. A plot o f D L c o a g a i n s t lung v o l u m e at PA = 0, + 30, a n d - 30 c m H 2 0 . C l o s e d circles s h o w c o n t r o l D I . c o (PA = 0), a n d c l o s e d a n d o p e n triangles r e p r e s e n t the V a l s a l v a (PA -- + 30 c m H 2 0 ) a n d Mtiller (PA = -- 30 c m H 2 0 ) m a n e u v e r , respectively. B a r s i n d i c a t e SE. * P < 0.01, * p < 0.001, c o m p a r e d to the value at PA = 0 c m H 2 0 .
317
D L c o AND ALVEOLAR PRESSURE
NS 0 II
120
110
NS
l
1 p,~ = +30cml'-IzO
I f
I 1
o -3o
NS
<
¢ LL 0
p:.06
-p< . 0 2
9O 8O
I
100%
,
80%
LUNG VOLUME
i
MEAN±SE
60%
(%TLC)
Fig. 2. Changes in the capillary blood volume (Vc) by a positive or negative PA. Hatched, open and stippled columns indicate values at PA of + 30, 0, and - 30 cm H20, respectively. Bars indicate SE. P values, compared to the value at PA = 0 cm H20.
o/ / or Vc values at 100/o, 80 o.... and 60/o TLC at zero PA were 74 _+ 13, 74 + 21, and 81 + 25ml, respectively, and Dm values were 100 + 25, 101 + 53, and 62 + 21 ml/min/mm Hg, respectively. At 100% TLC, the Valsalva maneuver changed neither Vc nor Dm (fig. 2). At 80~, TLC, the Valsalva maneuver caused Vc to decrease in all subjects, except for subject 9, and the average change in Vc was 10 + 12~o of Vc at zero PA (P = 0.06). The Mtfller maneuver caused Vc to increase by 20 + 48~o but this was not statistically significant. At 60~o TLC, the Valsalva maneuver caused Vc to decrease by 21 + 15~o (P < 0.02), but no change occurred from the Maller maneuver. Finally, no significant changes were noted in Dm at any lung volume by either the Valsalva maneuver or by the Mailer maneuver.
Discussion The present study demonstrated that the Valsalva maneuver of + 30 cm H 2 0 caused a greater decrease in DLco at mid-lung volume compared to that at TLC, but the Maller maneuver of - 30 cm H 2 0 did not change DLco at any lung volume. Also, the pulmonary capillary blood volume was decreased by the Valsalva maneuver and this decrease was greater at the lower lung volume. However, the Maller maneuver did not change the pulmonary capillary blood volume at any lung volume. These results suggest that at mid-lung volume, a positive alveolar pressure affects the capillary blood volume more effectively than at TLC, presumably due to the vessels being more compliant at mid-lung volume compared to TLC, resulting in a greater decrease in the pulmonary diffusing capacity with positive PA at mid-lung volume.
318
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Critique of methods. In the present study the breath holding time was calculated from the beginning of inspiration from RV to the beginning of sample collection. The time to reach a predetermined lung volume from RV may have been different among the three lung volumes and this time difference would affect the DLco values. However, such error is not expected to influence evaluation of relative changes in DLco at given lung volume by the MOiler and Valsalva maneuvers. It might be difficult to maintain positive or negative pressure with open glottis. The mouth pressure (Pm) was monitored during DLco measurement and the true PA may have been different. In a supplemental series with measurement of Ppl, however, the changes in Pm during Mtiller or Valsalva maneuver were not different from those in Ppl. Thus it is probable that during DLco measurement, Pm was a good indicator of PA. EJ]ects of lung volume. The Valsalva maneuver decreased DLco at 80 ~, and 60 o/,, TLC more than at 100 "j / o TLC. The effect of positive alveolar pressure on DLco has been studied at TLC by the single breath method, but during positive end-expiratory pressure ventilation (PEEP), DLco by the rebreathing method was measured at slightly higher lung volume than functional residual capacity (FRC) (Cassidy et al., 1979; Daly et al., 1963). Howell et al. (1961) have suggested that the vascular bed of the small vessels decreases as the lung volume increases, whereas that of larger vessels decreases. Sasaki et al. (1984) have demonstrated that the alveolar vessel volume reaches a maximum at mid-lung volume, while the pulmonary arterial and venous vascular volume is higher at higher lung volume. Also, they have shown that the alveolar vessel compliance is greatest at mid to low lung volume. On the other hand, by means of lung morphometry, Glazier et al. (1969) have shown that in a frozen dog lung, both the capillary blood volume and the capillary width are larger at PL 10 cm H 2 0 than at PL 25 cm H20. Mazzone et al. (1978) also have observed a marked stretching of the alveolar septa with a severe deformation of the capillaries at higher lung volumes. Thus, change in alveolar pressure may have a greater effect on the capillary blood volume at the lower lung volume than at TLC. Positive alveolar pressure. Positive PA during DLco measurement has been reported to decrease DLco. In a study of Smith and Rankin (1969), the Valsalva maneuver of + 86 cm H 2 0 decreased DLco by approximately 13 ~o- Further, in studies using a PEEP of approximately 10 cm H 2 0 (Cassidy et al., 1979; Daly et al., 1963), DLco was seen to fall by 11-25°J/o. In these studies, different levels of positive pressure were applied, but even a low positive PA was able to change both DLco and Vc, presumably because a longer duration of low, positive pressure breathing was able to decrease the pulmonary vascular volume effectively. In the present study, the decrease in DLco at 100%0 TLC by positive PA of + 30 cm H 2 0 amounted to 8%. The decreases in DLco due to positive PA at 803o and at 60 of, of TLC were greater than that at 100~o TLC. The capillary blood volume (Vc) at 60'~'o and 80 .... of TLC decreased by 20~o and 10~/o from positive PA, respectively, though the decrease in Vc at 100~o TLC was only 2%. It follows from these results that the decrease in DLco produced by positive PA is greater at mid-lung volume than at TLC and that this decrease is caused mainly by a decrease in Vc.
DLco AND ALVEOLAR PRESSURE
319
In the present study the negative PA during DLco measurement increased neither DLco nor Vc at any lung volume. Controversy still persists as to how a negative alveolar pressure may affect DL¢o. Cotes et al. (1960) found variable effects of the Mtiller maneuver on DLco and Vc in two subjects. Steiner et al. (1965) showed that negative pressure breathing for 4 or 7 min caused an increase in the single breath DLco by more than 30~o. Smith and Rankin (1969) reported that the Mtlller maneuver during the DLco measurement did not cause any substantial change in DLco but did increase Vc by 20~o. Further, Cotton et al. (1983) reported that DL¢o, when measured during slow inspiration from residual volume (RV) to TLC through a resistance, caused an increase when compared to slow inspiration without a resistance. It is thought that a negative PA increases the effective transmural pressure across the pulmonary capillary bed, resulting in distention and/or recruitment of pulmonary capillaries (Glazier et al., 1969; Maseri et al., 1972). In 9 out of 16 measurements of Vc at 60~o and at 80~o of TLC in the present study, the Mtiller maneuver increased Vc by approximately 31 ~o, but caused no change in DLco. In the study of Steiner et al. (1965) negative pressure was applied for 4 or 7 min before the DLco measurement. Cotton et al. (1983) applied negative PA of - 4 8 cm H20 during the DLco measurement. Further, Keens et al. (1979) observed that DLco was increased by negative PA of less than - 50 cm H20. In the present study the magnitude of negative pressure was less than in those studies and negative pressure was applied only for 10 sec during the DLco measurement. A given level of negative PA, namely less than - 48 cm H20, may be critical to affect the capillary blood volume in 10 sec of the breath-holding time. Thus a higher magnitude and/or longer application of negative pressure may be required to cause an increase in the capillary blood volume by the Mtiller maneuver, resulting an increase in DLco. In summary, DLco was found to be greatly influenced by positive alveolar pressure at mid-lung volume, due to a decrease in the capillary blood volume. Therefore, in chronic obstructive pulmonary disease in which the pleural pressure often becomes positive, the gas exchange during resting ventilation may be more disturbed than indicated by measurement of DLco at TLC.
Negative alveolar pressure.
References Cassidy, S.S., W. L. Eschenbacher, C.H. Robertson, Jr., J.V. Nixon, G. Blomqvist and R.L. Johnson, Jr. (1979). Cardiovascular effects of positive-pressure ventilation in normal subjects. J. Appl. Physiol. 47: 453-461. Cotes, J. E., D. P. Snidal and R. H. Shepard (1960). Effect of negative intra-alveolar pressure on pulmonary diffusing capacity. J. Appl. Physiol. 15: 372-376. Cotes, J.E. (1979). Lung Function; assessment and application in medicine, 4th ed. Oxford: Blackwell, pp. 329-387. Cotton, D.J., J.T. Mink and B.L. Graham (1983). Effect of high negative inspiratory pressure on single breath CO diffusing capacity. Respir. Physiol. 54: 19-29. Daly, W.J., J.C. Ross and R.H. Behnke (1963). The effect of changes in the pulmonary vascular bed
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produced by atropine, pulmonary engorgement, and positive-pressure breathing on diffusing and mechanical properties of the lung. J. Clin. Invest. 42: 1083-1094. Forster, R. E., W. S. Fowler, D.V. Bates and B. Van Lingen (1954). The absorption of carbon monoxide by the lungs during breathholding. J. Clin. Invest. 33:1135-1145. Glazier, J. B., J. M. B. Hughes, J. E. Maloney and J.B. West (1969). Measurements of capillary dimensions and blood volume in rapidly frozen lungs. J. Appl. Physiol. 26: 65-76. Howell, J. B. L., S. Permutt, D. F. Proctor and R. L. Riley (1961). Effect of inflation of the lung on different parts of pulmonary vascular bed. J. Appl. Physiol. 16: 71-76. Karp, R. B., P. D. Grafand J. A. Nadel (1968). Regulation of pulmonary capillary blood volume by pulmonary arterial and left atrial pressures. Circ. Res. 22: 1-10. Keens, T.G., A. Mansell, I.R.B. Krastins, H. Levison, A.C. Bryan, R.H. Hyland and N. Zamel (1979). Evaluation of the single-breath diffusing capacity in asthma and cystic fibrosis. Chest 76: 41-44. Krogh, M. (1915). The diffusion of gases through the lungs of man. J. Physiol. (London) 49: 271-300. Mazzone, R.W., C.M. Durand and J.B. West (1978). Electron microscopy of lung rapidly frozen under controlled physiological conditions. J. Appl. Physiol. 45: 325-333. Maseri, A., P. Caldini, P. Haward, R.C. Joshi, S. Permutt and K.L. Zierler (1972). Determinants of pulmonary vascular volume; recruitment versus distensibility. Circ. Res. 31: 218-227. Ogilvie, C.M., R.E. Forster, W.S. Blakemore and J.W. Morton (1957). A standardized breath holding technique for the clinical measurement of the diffusing capacity of the lung for carbon monoxide. J. Clin. Invest. 36: 1-17. Roughton, F.J.W. and R.E. Forster (1957). Relative importance of diffusion and chemical reaction rates in determining rate of exchange of gases in the human lung, with special reference to true diffusing capacity of pulmonary membrane and w~lume of blood in the lung capillaries. J. Appl. Physiol. 11: 290-302. Sasaki, H., H. Inoue, S. Suzuki, M. Nakamura and T. Takishima (1984). Effect of lung surface tension on pulmonary vascular mechanics in excised dog lungs. Respir. Physiol. 56: 21-35. Smith, T. C. and J. Rankin (1969). Puhnonary diffusing capacity and the capillary bed during Valsalva and Mfiller maneuvers. J. Appl. Physiol. 27: 826-833. Stciner, S. H., R. Frayser and J. C. Ross (1965). Alterations in pulmonary diffusing capacity and pulmonary capillary blood volume with negative pressure breathing. J. Clin. blvest. 44: 1623-1630.
3 13
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RESP 01691
Effect of alveolar pressure on single-breath CO diffusing capacity at mid-lung volume Shunsuke Suzuki, Hiroyuki Numata and Takao Okubo First Department of Internal Medicine, Yokohama CiO' UniversiO, School of Medicine, Yokohama. Japan (Accepted 6 May 1990) Abstract. The present study examines whether changes in the alveolar pressure (PA) affect the single breath diffusing capacity for carbon monoxide ( D e c o ) more strongly at mid-lung volume than at total lung capacity (TLC) in normal subjects. DLco was measured at 60°{,, 80°o and 100% of TLC, while PA was kept at + 30, 0, or 30 cm H 2 0 by the subject's effort during the measurement of DLco at each lung volume. The capillary blood volume (Vc) and the membrane diffusing capacity (Dm) were also determined. DLco at zero PA was found to be higher at 100~o TLC than at lower lung volumes. At PA = + 30 cm H 2 0 , Dr,co at 100°o, 803g, and 60 % TLC decreased by 8 ~o, 1 3 3 , and 13 ~'~o,respectively, and the decreases in Vc were 2 o/, 10 e'o, and 21 ~,, respectively. However, negative PA did not cause any significant changes in DLco or Vc at any lung volume. Also, D m did not change at any PA. We conclude that DLco is more affected by a positive PA at mid-lung volume than at a high lung volume, probably due to a greater decrease in Vc.
Alveolar pressure, and long diffusing capacity; Animal, man; Capillary blood volume; Diffusing capacity; of the lung, for CO, effects of alveolar pressure; Lung volume, and diffusing capacity
In patients with chronic obstructive pulmonary disease (COPD), the pleural pressure (Ppl) swing during resting ventilation is usually greater than in normal subjects. The Ppl in such patients is often positive on expiration and more negative on inspiration. Further, the pulmonary diffusing capacity is decreased in COPD. On the other hand, the pulmonary capillary bed is known to be compliant. Thus, it is possible that such large Ppl swings affect the diffusing capacity through a change in the capillary blood volume. Karp e l M . (1968) reported that an increase in the left atrial pressure caused an increase in the diffusing capacity. Furthermore, positive-pressure breathing was found to decrease not only the capillary blood volume but also the diffusing capacity (Cassidy et al., 1979; Daly el al., 1963). Similarly, Smith and Rankin (1969) showed that during the Valsalva maneuver the breath-holding diffusing capacity (DL) decreased substan-
Correspondence to: S. Suzuki, First Department of Internal Medicine, Yokohama City University School of Medicine, 3-46 Urafune-cho, Minami-Ku, Yokohama 232, Japan. 0034-5687/90/$03.50 © 1990 Elsevier Science Publishers B.V. (Biomedical Division)
314
s. SUZUKI et al.
tially, but that the MOiler maneuver did not cause any change in DL. In contrast, Steiner etal. (1965) reported an increase in DL by the MOiler maneuver. These authors measured, however, DL at high lung volume, near total lung capacity (TLC). Morphomerry suggests the capillary lumen to be narrowed at high lung volume but maintained at low lung volume (Mazzone et al., 1978). Thus, at lower lung volume, the capillary blood volume may be more influenced by the alveolar pressure than at TLC. In order to investigate whether a change in the alveolar pressure affects the diffusing capacity more strongly at mid-lung volume than at TLC, we have measured in normal subjects the single breath diffusing capacity for CO (DLco) under the conditions of a negative and positive alveolar pressure applied during breath-holding at lung volumes near functional residual capacity (FRC) and at TLC. We furthermore have determined the membrane diffusing capacity (Din) and the capillary blood volume (Vc).
Methods Subjects. We studied nine healthy subjects, medical staff members who were familiar with respiratory maneuvers. All were male and their average age was 27 + 2 (SD) years. All, except one subject, were lifetime nonsmokers. Their average height was 171 + 5 cm (ranged from 165 to 180 cm) and the body weight 62 _+ 4 kg (ranged from 51 to 67 kg). None had a history of chronic respiratory or cardiopulmonary disease, and informed consent was obtained from all participants prior to the start of testing. Spirometry was performed by using a dry-seal spirometer (OST-85, Chest Co., Tokyo, Japan) and the lung volume was measured by a flow-type body plethysmograph (Model 2800, Gould, Dayton, OH). Vital capacity and forced expiratory volume in one second of all subjects were greater than 80°/0 of the predicted values (Cotes, 1979).
The subjects were studied in seated position after resting for at least 5 rain. DLco was determined by a modification of the Krogh breath-holding technique (Krogh, 1915 ; Forster et al., 1954; Ogilvie et al., 1957). Briefly, a gas mixture containing 0.3'/'o CO and 3°~,JoNe in air was inspired from a bag in box connected to a spirometer, so that the inspired volume and breath-holding time were recorded on the spirometer tracing. After rapidly inspiring the test gas from residual volume (RV) to a predetermined lung volume, which was controlled by a stopper of the spirometer, a valve was switched to stop inspiration, and each subject held his breath with open glottis for 10 sec and then exhaled as fast as possible. Approximately 1 L of the expired gas was sampled, after discarding the initially expired 750 ml, and analyzed by a gas chromatograph (Model 164, Hitachi, Tokyo, Japan). The breath holding time was taken from the beginning of inspiration from RV to the beginning of the sample collection. DLco was calculated by the following conventional formula, which takes into account the CO back pressure in the blood. DL measurement.
Dt, c o = VA/[t(PB - 47)] X In (FAco¢o)/FAco¢t))
(1)
Dl.co AND ALVEOLAR PRESSURE
315
in which VA is the alveolar volume in ml S T P D ; t is the breath-holding time in rain; PB is the barometric pressure plus alveolar pressure in m m H g ; FAco(o ) is the initial alveolar CO concentration, calculated by multiplying the inspired CO concentration by the ratio of the late expired to inspired Ne concentrations at the end of the breath-holding period, as measured in the alveolar sample. At least two determinations of DLco that were within 5 ~o of each other were obtained, and a period of at least 10 min was allowed between the measurements. The capillary blood volume (Vc) and the membrane diffusing capacity (Dm) were determined from two D L c o measurements at low and high alveolar oxygen tensions (FIo~ = 0.188 and 0.897) by the method of Roughton and Forster (1957): 1/DE = 1/Dm + 1/(0Vc)
(2)
Vc and Dm were measured in 8 of the 9 subjects. Protocol. Each subject was instructed to make an expiratory or inspiratory effort with open glottis against the closed valve during the breath-holding time of the DLco measurement. DLco was measured at 100, 80, and 60~o of total lung capacity (TLC). The alveolar pressure ( P A ) w a s measured at the mouth during the expiratory or inspiratory effort of the breath-holding by means of a differential pressure transducer (MP-45, Validyne, Northridge, CA). PA was displayed on an oscilloscope (Model SS-5802, Iwatsu Electric Co., Tokyo, Japan), and each subject was asked to maintain PA at + 30, 0, or - 30 cm H 2 0 during the breath-holding. Before measurement of DLco the subject repeated the Mtiller and Valsalva maneuvers without inhalation of test gas, until a reproducible value of PA was obtained. PA was adjusted to + 30, 0, and - 30 cm H 2 0 at each lung volume except at TLC at which + 30 and 0 c m H 2 0 were applied. When the mouth pressure was not kept within 5 ~o of a predetermined PA during the breathholding, the DLco value was discarded. All studies were done at the same time of day and were completed within 2 weeks. Ppl measurement. To assess efficiency of both the Miiller and Valsalva maneuvers, pleural pressure (Ppl) during the maneuvers was monitored at 60 and 80~, TLC in 4 subjects. The esophageal balloon (length 10 cm; perimeter 3.5 cm) connected to a polyethylene catheter (PE-200) was positioned at the lower third of the esophagus. Ppl was measured with a differential pressure transducer (MP-45, Validyne) connected to the balloon catheter. During each maneuver, both the Ppl and mouth pressure (Pro) were recorded and Ppl was compared with that at PA = 0. During the M~iller maneuver, changes in Ppl and Pm at 80~o TLC were not different (Ppl and Pm, 29 + 2 and 29 + 1 c m H 2 0 , respectively); those at 60~o TLC were also not different (Ppl and Pm, 27 + 3 and 30 + 1 cm H20, respectively). During the Valsalva maneuver, changes in Ppl and Pm at 80~0 TLC were not different (Ppl and Pm, 30 + 1 and 29 + 2 c m H 2 0 , respectively); those at 60~o T L C were not different either (Ppl and Pro, 27 _+ 2 and 29 _+ 0.2 cm H20, respectively).
316
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et al.
All values are expressed as mean _+ SD. Statistical analysis was done by a paired t-test and a one-way analysis of variance ( A N O V A ) for a c o m p a r i s o n of two and three groups, respectively.
Results
A t zero PA, D L c o was lower at a lower lung volume than at T L C (P < 0.01). At 100~o T L C , D L c o at zero PA was 106 _+ 9°~o (mean _+ S D ) of the predicted value (Cotes, 1979). By the Valsalva maneuver of + 3 0 cm H 2 0 at TLC, D L c o decreased significantly, by 8 + 6'~o from zero PA ( P < 0.01)(fig. 1). The breath-holding times at PA = 0 and + 30 cm H 2 0 were 10.5 + 0.5 and 10.5 + 0.5 sec, respectively. At 80"o TLC, DLc. o at zero PA was 90 _+ 9~, o f that at 100°o TLC. By the Valsalva maneuver, D L c o decreased by 13 + 6~o from zero PA (P < 0.01) and the decrease was significantly greater than that at 1001j!i; T L C (P < 0.03)(fig. 1). By the M a l l e t maneuver o f - 30 cm H 2 0 , however, DLc. o was not changed. The breath-holding times at PA = 0, + 30 and - 30 cm H 2 0 were 10.3 + 0.5, 10.2 + 0.5 and 10.3 +_ 0.6 sec, respectively, and there were no differences among the three PA conditions. At 607o TLC, D L c o at zero PA was 83 + 11 °/o of that at 100~,o TLC. By the Valsalva maneuver D L c o decreased by 13 + 6'~o from zero PA ( P < 0.001); however, the decrease was not significantly different from that at 100')o T L C (P = 0.13). D L c o during the Mtiller maneuver showed no difference from that at zero PA. There were no differences in the breath-holding time between PA = 0, + 30 and - 3 0 cm H 2 0 (10.3 + 0.4, 10.5 + 0.5 and 10.4 _+ 0.5 sec, respectively). 35 PA=O
30
E E v
25
VaLsaLva
20
8
-J r-',
15
L,
rnean+SE I
I
60 LUNG
80 VOLUME
n=9 I
100
(% OF INDIVIDUAL T L C )
Fig. 1. A plot o f D L c o a g a i n s t lung v o l u m e at PA = 0, + 30, a n d - 30 c m H 2 0 . C l o s e d circles s h o w c o n t r o l D I . c o (PA = 0), a n d c l o s e d a n d o p e n triangles r e p r e s e n t the V a l s a l v a (PA -- + 30 c m H 2 0 ) a n d Mtiller (PA = -- 30 c m H 2 0 ) m a n e u v e r , respectively. B a r s i n d i c a t e SE. * P < 0.01, * p < 0.001, c o m p a r e d to the value at PA = 0 c m H 2 0 .
317
D L c o AND ALVEOLAR PRESSURE
NS 0 II
120
110
NS
l
1 p,~ = +30cml'-IzO
I f
I 1
o -3o
NS
<
¢ LL 0
p:.06
-p< . 0 2
9O 8O
I
100%
,
80%
LUNG VOLUME
i
MEAN±SE
60%
(%TLC)
Fig. 2. Changes in the capillary blood volume (Vc) by a positive or negative PA. Hatched, open and stippled columns indicate values at PA of + 30, 0, and - 30 cm H20, respectively. Bars indicate SE. P values, compared to the value at PA = 0 cm H20.
o/ / or Vc values at 100/o, 80 o.... and 60/o TLC at zero PA were 74 _+ 13, 74 + 21, and 81 + 25ml, respectively, and Dm values were 100 + 25, 101 + 53, and 62 + 21 ml/min/mm Hg, respectively. At 100% TLC, the Valsalva maneuver changed neither Vc nor Dm (fig. 2). At 80~, TLC, the Valsalva maneuver caused Vc to decrease in all subjects, except for subject 9, and the average change in Vc was 10 + 12~o of Vc at zero PA (P = 0.06). The Mtfller maneuver caused Vc to increase by 20 + 48~o but this was not statistically significant. At 60~o TLC, the Valsalva maneuver caused Vc to decrease by 21 + 15~o (P < 0.02), but no change occurred from the Maller maneuver. Finally, no significant changes were noted in Dm at any lung volume by either the Valsalva maneuver or by the Mailer maneuver.
Discussion The present study demonstrated that the Valsalva maneuver of + 30 cm H 2 0 caused a greater decrease in DLco at mid-lung volume compared to that at TLC, but the Maller maneuver of - 30 cm H 2 0 did not change DLco at any lung volume. Also, the pulmonary capillary blood volume was decreased by the Valsalva maneuver and this decrease was greater at the lower lung volume. However, the Maller maneuver did not change the pulmonary capillary blood volume at any lung volume. These results suggest that at mid-lung volume, a positive alveolar pressure affects the capillary blood volume more effectively than at TLC, presumably due to the vessels being more compliant at mid-lung volume compared to TLC, resulting in a greater decrease in the pulmonary diffusing capacity with positive PA at mid-lung volume.
318
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Critique of methods. In the present study the breath holding time was calculated from the beginning of inspiration from RV to the beginning of sample collection. The time to reach a predetermined lung volume from RV may have been different among the three lung volumes and this time difference would affect the DLco values. However, such error is not expected to influence evaluation of relative changes in DLco at given lung volume by the MOiler and Valsalva maneuvers. It might be difficult to maintain positive or negative pressure with open glottis. The mouth pressure (Pm) was monitored during DLco measurement and the true PA may have been different. In a supplemental series with measurement of Ppl, however, the changes in Pm during Mtiller or Valsalva maneuver were not different from those in Ppl. Thus it is probable that during DLco measurement, Pm was a good indicator of PA. EJ]ects of lung volume. The Valsalva maneuver decreased DLco at 80 ~, and 60 o/,, TLC more than at 100 "j / o TLC. The effect of positive alveolar pressure on DLco has been studied at TLC by the single breath method, but during positive end-expiratory pressure ventilation (PEEP), DLco by the rebreathing method was measured at slightly higher lung volume than functional residual capacity (FRC) (Cassidy et al., 1979; Daly et al., 1963). Howell et al. (1961) have suggested that the vascular bed of the small vessels decreases as the lung volume increases, whereas that of larger vessels decreases. Sasaki et al. (1984) have demonstrated that the alveolar vessel volume reaches a maximum at mid-lung volume, while the pulmonary arterial and venous vascular volume is higher at higher lung volume. Also, they have shown that the alveolar vessel compliance is greatest at mid to low lung volume. On the other hand, by means of lung morphometry, Glazier et al. (1969) have shown that in a frozen dog lung, both the capillary blood volume and the capillary width are larger at PL 10 cm H 2 0 than at PL 25 cm H20. Mazzone et al. (1978) also have observed a marked stretching of the alveolar septa with a severe deformation of the capillaries at higher lung volumes. Thus, change in alveolar pressure may have a greater effect on the capillary blood volume at the lower lung volume than at TLC. Positive alveolar pressure. Positive PA during DLco measurement has been reported to decrease DLco. In a study of Smith and Rankin (1969), the Valsalva maneuver of + 86 cm H 2 0 decreased DLco by approximately 13 ~o- Further, in studies using a PEEP of approximately 10 cm H 2 0 (Cassidy et al., 1979; Daly et al., 1963), DLco was seen to fall by 11-25°J/o. In these studies, different levels of positive pressure were applied, but even a low positive PA was able to change both DLco and Vc, presumably because a longer duration of low, positive pressure breathing was able to decrease the pulmonary vascular volume effectively. In the present study, the decrease in DLco at 100%0 TLC by positive PA of + 30 cm H 2 0 amounted to 8%. The decreases in DLco due to positive PA at 803o and at 60 of, of TLC were greater than that at 100~o TLC. The capillary blood volume (Vc) at 60'~'o and 80 .... of TLC decreased by 20~o and 10~/o from positive PA, respectively, though the decrease in Vc at 100~o TLC was only 2%. It follows from these results that the decrease in DLco produced by positive PA is greater at mid-lung volume than at TLC and that this decrease is caused mainly by a decrease in Vc.
DLco AND ALVEOLAR PRESSURE
319
In the present study the negative PA during DLco measurement increased neither DLco nor Vc at any lung volume. Controversy still persists as to how a negative alveolar pressure may affect DL¢o. Cotes et al. (1960) found variable effects of the Mtiller maneuver on DLco and Vc in two subjects. Steiner et al. (1965) showed that negative pressure breathing for 4 or 7 min caused an increase in the single breath DLco by more than 30~o. Smith and Rankin (1969) reported that the Mtlller maneuver during the DLco measurement did not cause any substantial change in DLco but did increase Vc by 20~o. Further, Cotton et al. (1983) reported that DL¢o, when measured during slow inspiration from residual volume (RV) to TLC through a resistance, caused an increase when compared to slow inspiration without a resistance. It is thought that a negative PA increases the effective transmural pressure across the pulmonary capillary bed, resulting in distention and/or recruitment of pulmonary capillaries (Glazier et al., 1969; Maseri et al., 1972). In 9 out of 16 measurements of Vc at 60~o and at 80~o of TLC in the present study, the Mtiller maneuver increased Vc by approximately 31 ~o, but caused no change in DLco. In the study of Steiner et al. (1965) negative pressure was applied for 4 or 7 min before the DLco measurement. Cotton et al. (1983) applied negative PA of - 4 8 cm H20 during the DLco measurement. Further, Keens et al. (1979) observed that DLco was increased by negative PA of less than - 50 cm H20. In the present study the magnitude of negative pressure was less than in those studies and negative pressure was applied only for 10 sec during the DLco measurement. A given level of negative PA, namely less than - 48 cm H20, may be critical to affect the capillary blood volume in 10 sec of the breath-holding time. Thus a higher magnitude and/or longer application of negative pressure may be required to cause an increase in the capillary blood volume by the Mtiller maneuver, resulting an increase in DLco. In summary, DLco was found to be greatly influenced by positive alveolar pressure at mid-lung volume, due to a decrease in the capillary blood volume. Therefore, in chronic obstructive pulmonary disease in which the pleural pressure often becomes positive, the gas exchange during resting ventilation may be more disturbed than indicated by measurement of DLco at TLC.
Negative alveolar pressure.
References Cassidy, S.S., W. L. Eschenbacher, C.H. Robertson, Jr., J.V. Nixon, G. Blomqvist and R.L. Johnson, Jr. (1979). Cardiovascular effects of positive-pressure ventilation in normal subjects. J. Appl. Physiol. 47: 453-461. Cotes, J. E., D. P. Snidal and R. H. Shepard (1960). Effect of negative intra-alveolar pressure on pulmonary diffusing capacity. J. Appl. Physiol. 15: 372-376. Cotes, J.E. (1979). Lung Function; assessment and application in medicine, 4th ed. Oxford: Blackwell, pp. 329-387. Cotton, D.J., J.T. Mink and B.L. Graham (1983). Effect of high negative inspiratory pressure on single breath CO diffusing capacity. Respir. Physiol. 54: 19-29. Daly, W.J., J.C. Ross and R.H. Behnke (1963). The effect of changes in the pulmonary vascular bed
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produced by atropine, pulmonary engorgement, and positive-pressure breathing on diffusing and mechanical properties of the lung. J. Clin. Invest. 42: 1083-1094. Forster, R. E., W. S. Fowler, D.V. Bates and B. Van Lingen (1954). The absorption of carbon monoxide by the lungs during breathholding. J. Clin. Invest. 33:1135-1145. Glazier, J. B., J. M. B. Hughes, J. E. Maloney and J.B. West (1969). Measurements of capillary dimensions and blood volume in rapidly frozen lungs. J. Appl. Physiol. 26: 65-76. Howell, J. B. L., S. Permutt, D. F. Proctor and R. L. Riley (1961). Effect of inflation of the lung on different parts of pulmonary vascular bed. J. Appl. Physiol. 16: 71-76. Karp, R. B., P. D. Grafand J. A. Nadel (1968). Regulation of pulmonary capillary blood volume by pulmonary arterial and left atrial pressures. Circ. Res. 22: 1-10. Keens, T.G., A. Mansell, I.R.B. Krastins, H. Levison, A.C. Bryan, R.H. Hyland and N. Zamel (1979). Evaluation of the single-breath diffusing capacity in asthma and cystic fibrosis. Chest 76: 41-44. Krogh, M. (1915). The diffusion of gases through the lungs of man. J. Physiol. (London) 49: 271-300. Mazzone, R.W., C.M. Durand and J.B. West (1978). Electron microscopy of lung rapidly frozen under controlled physiological conditions. J. Appl. Physiol. 45: 325-333. Maseri, A., P. Caldini, P. Haward, R.C. Joshi, S. Permutt and K.L. Zierler (1972). Determinants of pulmonary vascular volume; recruitment versus distensibility. Circ. Res. 31: 218-227. Ogilvie, C.M., R.E. Forster, W.S. Blakemore and J.W. Morton (1957). A standardized breath holding technique for the clinical measurement of the diffusing capacity of the lung for carbon monoxide. J. Clin. Invest. 36: 1-17. Roughton, F.J.W. and R.E. Forster (1957). Relative importance of diffusion and chemical reaction rates in determining rate of exchange of gases in the human lung, with special reference to true diffusing capacity of pulmonary membrane and w~lume of blood in the lung capillaries. J. Appl. Physiol. 11: 290-302. Sasaki, H., H. Inoue, S. Suzuki, M. Nakamura and T. Takishima (1984). Effect of lung surface tension on pulmonary vascular mechanics in excised dog lungs. Respir. Physiol. 56: 21-35. Smith, T. C. and J. Rankin (1969). Puhnonary diffusing capacity and the capillary bed during Valsalva and Mfiller maneuvers. J. Appl. Physiol. 27: 826-833. Stciner, S. H., R. Frayser and J. C. Ross (1965). Alterations in pulmonary diffusing capacity and pulmonary capillary blood volume with negative pressure breathing. J. Clin. blvest. 44: 1623-1630.