JOURNAL
OF
APPLIED
PHYSIOLOGY
Vol. 41, No. 3, September
1976.
Printed
in U.S.A.
Localization of airway constriction of varying density and viscosity
using
gases
JEFFREY M. DRAZEN, STEPHEN H. LORING, AND ROLAND H. INGRAM, JR. Department of Physiology, Harvard School of Public Health, and Departments of Medicine, Peter Bent Brigham Hospital and Harvard Medical School, Boston, Massachusetts 02115
DRAZEN, JEFFREY M., STEPHEN H. LORING, AND ROLAND H. INGRAM, JR. Localization of airway constriction using gases of varying density and viscosity. J. Appl. Physiol. 41(3): 396399. 1976. -The relationship between the major site of airway constriction and change in total pulmonary resistance while breathing gases of varying density and viscosity was studied in five anesthetized dogs pretreated with atropine. Using an airway catheter, central and peripheral components of pulmonary resistance were measured by forced oscillation. Total pulmonary resistance was measured at 0.5 l/s with lungs air-filled, at 0.25 l/s with the lungs filled with 80% helium-20% oxygen (RL-He), and at 1.0 l/s with 80% sulfur hexafluoride20% oxygen (Rs-SF,). Intravenous histamine infusion resulted in a predominantly peripheral resistance increase as determined by the airway catheter and a much larger percentage increase in RL-He than in RL-SF,. Tracheal banding produced a purely central resistance increase and a greater change in RL-SF, than in RL-He. These results support theoretical predictions that the predominant site of airways constriction can be determined without an airway catheter by comparing relative changes in total pulmonary resistance using different flow regimes.
use on a chronic basis. Tantalum bronchography provides direct visualization of changes in airway size but requires complex radiographic equipment for visualization of small airways. In addition, although airway constriction can be directly measured, its effect on local pulmonary mechanics may only be inferred. Comparisons of changes in pulmonary compliance and resistance have been used by a number of investigators to localize airway responses, but this technique may be insensitive to changes which occur in the small airways in the absence of alveolar duct constriction. MEF-elastic recoil curves may be used to determine “upstream resistance,” but since the equal pressure point location may vary from large to small airways, it is not a useful technique to localize the site of airway constriction. The MEF maneuver has been used in human subjects breathing gases of differing densities and similar viscosities in order to infer the anatomic site of airway obstruction as predominantly central or peripheral (5, 8). This approach is based on the idea that high in the lung volume most of the pressure losses in the upstream segment are helium; sulfur hexafluoride; central resistance; peripheral redue to convective acceleration and turbulent flow and sistance will therefore be density sensitive, while low in the lung volume a greater portion of the upstream pressure losses will be due to laminar flow and therefore will be IT HAS BEEN DEMONSTRATED that the pulmonary re- viscosity sensitive. Since it is technically difficult to sponse to experimental intervention may involve pre- perform repeated MEF maneuvers in unanesthetized dominantly peripheral airways or central airways (2, 6, dogs, we felt that inspiratory pulmonary resistance de89, l&19). It is important to note that different investitermined while breathing gases of varying physical gators have used varying definitions of central and pe- properties might be a useful technique in the localizaripheral resistance. Different animals of the same spe- tion of the response to intervention in experimental cies may react to the same stimulus with either central animals. or peripheral airway constriction (10, 18, 19). Because In the preceding paper (‘7), we demonstrated that the the pattern of response may vary from animal to animal distribution of pulmonary resistance (RL) was altered in it is of physiological importance to identify the airways the dog by changing the pulmonary flow regime without involved in a given response. A number of techniques altering airway dimensions. In a turbulent regime (traare currently used to assessthe anatomical location of cheal Reynolds’ number --30,000) more than 80% of RL the physiological response to intervention. These in- was in airways 4.5 mm in diameter and greater, while clude use of retrograde catheters (9, 12, 18, 19), tan- by lowering tracheal Reynolds’ number to approxitalum bronchograms (2, 16), maximum expiratory flow mately 400, these same airways contributed only 40% of (MEF)-elastic recoil curves (9, 13, 15), and MEF curves RL. We have reasoned that a distribution of RL with performed while breathing gases of varying physical minimal losses in the large airways should be more properties (5, 8). Retrograde catheters give a direct sensitive to peripheral airway constriction than a remeasure of resistance partitioning but are usually used gime where large airway pressure losses are more subin open-chested animals making them a difficult tool to stantial. Conversely, a more turbulent flow regime with 396 Downloaded from www.physiology.org/journal/jappl by ${individualUser.givenNames} ${individualUser.surname} (129.186.138.035) on January 18, 2019.
LOCALIZATION
OF
AIRWAY
397
CONSTRICTION
more substantial large airway losses should be more sensitive to changes in the large airways. In this communication we test the hypothesis that the airways response to intervention can be localized by comparing changes in RL before and after intervention while breathing gases of varying density and viscosity at different flow rates. METHODS
Five mongrel dogs (lo-15 kg body weight) were anesthetized with sodium pentobarbital, treated with 2.0 mg of atropine sulfate, and prepared for measurement of RL, peripheral lung resistance (Rp), and central airway resistance (Rc) as previously described (7). In brief, animals were intubated with a tight-fitting tracheal cannula with a manifold of side taps for measuring airway opening pressure. Pleural pressure was estimated from an esophageal balloon and airway pressure was determined with an airway catheter. Volume and its first two time derivates (flow and acceleration) were determined from a 200-liter volume displacement pressure-compensated plethysmograph (14). Inspiratory resistance was measured by forced oscillation using the technique of electrical subtraction with volume and accelerative corrections. As previously described the airway catheter was placed such that approximately 60% of RL was in the central airways at a volume 200-300 ml above the functional residual capacity (FRC). With the catheter so positioned the following protocols were instituted. While breathing air, and at the end of a normal expiration, the airway valve was closed and the animal inflated to a volume 500 ml above FRC three times in rapid successsion. The animal was then returned to FRC and thoracic gas volume (TGV) determined as previously described (7). After 60 s of spontaneous respiration the animal was inflated 200-300 ml above FRC and resistance (Rp and Rc) at 0.5 l/s was measured by forced oscillation at 4 Hz. Then the bias flow was changed to a mixture of 80% helium-20% oxygen (helium) and the protocol repeated except that resistance was measured at an inspiratory flow of 0.25 l/s. The bias flow was then changed to a mixture of 80% sulfur hexafluoride-20% oxygen (SF,) and the protocol repeated except that resistance was measured at an inspiratory flow of 1.0 l/s. The bias flow was then returned to air and the protocol repeated as originally described. If the TGV and resistance measured the second time on air were not different from the original determinations by more than the variability noted within a single determination (approximately lo%), a constriction was begun. If the resistance on air or TGV varied by more than lo%, another control run was initiated until the first and last air resistances varied by less than 10%. The entire three-gas protocol was then repeated during constriction until the initial and final air resistances and TGV’s agreed within 10%. Peripheral constriction was produced by intravenous histamine infusion (lo-30 ,ccg histamine base/kg per min), while central airway constriction was produced by mechanical tracheal banding.
RESULTS
During the control period prior to histamine infusion, RL measured while breathing air, helium, and SF, was 0.69 t 0.26 (mean t SD) cmH,O/l/s, 0.51 t 0.08 cmH,O/ l/s, and 2.50 t 1.04 cmH,O/l/s, respectively. During the histamine infusion, RL increased on all three flow regimes. The mean values of RL during the infusion measured while breathing air, helium, or SF, were 1.53 (range 0.64-2.31) cmH,O/l/s, 1.35 (range 0.64-2.15) cmH,O/l/s, and 3.25 (range 2.20-4.90) cmH,O/l/s, respectively. In Fig. 1, Rp and Rc before and during histamine infusion while breathing air are shown for each dog. In each case there was a large increase in Rp while the change in Rc was small and inconsistent. In each case (shown in the upper left-hand corner of each inset), the percent change in total pulmonary resistance resulting from histamine infusion was greater while breathing helium than it was while breathing SF,. The absolute lung volume at which resistance was determined varied by less than 70 ml between control and histamine infusion. The mean change in volume was -2.6 t 40.1 (mean t SD) ml. During the control period prior to tracheal banding RL measured while breathing air, helium, and SF, was 0.83 t 0.13 cmH,O/l/s, 0.52 t 0.16 cmH,O/l/s, and 2.61 t 0.54 cmH,O/l/s, respectively. After tracheal banding RL increased on all three flow regimes. The mean values for RL after banding measured while breathing air, helium, or SF, were 4.88 (range 1.25-10.0) cmH,O/l/s, 1.85 (range 0.52-3.40) cmH,O/l/s, and 18.61 (range 5.149.7) cmH,O/l/s, respectively. In Fig. 2, Rp and Rc before and during tracheal constriction while breathing air are shown for each dog. In each case Rc increased markedly while the change in Rp was small and inconsistent. As shown in the upper left-hand corner of each inset the percent change in RL resulting from tracheal
2.0.
Dog 1. He 66801~ 4 SF6 7990
,?
1.6.
1
Dog 2. 2.0 He 166~x4 SF6 44x4
Dog 3. 2.0 He 240~~4 26%d 1 SF6
1.6-j
1.64
1.2.
.a
I
I’
.4
dj
/
Hlstamlne
Control
0 1
Hlstamtne
Control
-0 -
Histamine
Rp Rc
.50 .25
0’
Control
Histamine
0-I
Control
Histamine
in Rc and Rp measured at 0.5 l/s in atropinized dogs breathing air before and after intravenous histamine infusion. In the upper left-hand corner of each inset the percent change in RL resulting from histamine infusion measured while breathing helium or while breathing SF, is given. FIG.
1. Alterations
Downloaded from www.physiology.org/journal/jappl by ${individualUser.givenNames} ${individualUser.surname} (129.186.138.035) on January 18, 2019.
398
i0
DRAZEN,
’ :i
c~~{~-~~~Z$heCd
I1
Control
Constrlctlon
Tracheal
3
co~~~~~~hea~
Constrlctlon
Constnctlon
z!! :
.-7l ii
Aw +J 0.5 LPS e ._.____ ---a Rp
a
-
d
0 ---
0
Control
-- _- _ -0 Tracheal Constrictbon
,A
~------. Control
Rc
Tracheal Constrictlon
FIG. 2. Alterations in Rc and Rp measured at breathing air before and after tracheal banding. In hand corner of each inset the percent change in RL tracheal banding measured while breathing helium
0.5 l/s in dogs the upper leftresulting from or SF, is given.
banding was greater while breathing SF, than it was while breathing helium. The absolute lung volume at which resistance was determined varied by less than 50 ml between control periods and tracheal constriction. The mean change in lung volume was -13.2 t 30.7 (SD) ml. DISCUSSION
By comparing the change in inspiratory resistance measured while breathing gases of varying physical properties at different flow rates before and after experimental intervention, the predominant anatomical site of constriction was predictably related to that determined by using an airway catheter. In each case of peripheral airway constriction, the change in RL measured while breathing helium (ARL-He) was greater than the change in RL measured while breathing SF, (ARL-SF,). Co nversely, in each case of central airway constriction the ARL-SF, was greater than the ARL-He. This suggests that by comparing the ART,-He to the ARLSF, the predominant site of response to an intervention
LORING,
AND
INGRAM
can be localized. If the percent ARL-He was greater than the percent ARL-SF,, the reaction was predominantly peripheral and if the percent ARL-SF, was greater than the percent ARL-He , the reaction was predominantly central. Although th .ese experimen ts were performed in dogs, previous calculations of the distribution of lower airway resistance in human lungs (7) suggest that a similar technique might be useful in localizing the predominant site of pulmonary reaction to intervention. However, the variations caused by the glottis and upper airway (11) may contribute substantial noise and prevent reliable partitioning. The interpretation of these results depends on using an airway catheter to partition resistance while breathing air at 0.5 l/s. The errors and assumptions involved in using such a catheter were discussed in the previous paper (7). Intravenous histamine has been shown to provide primarily a peripheral constriction (3) which should be more marked in the presence of atropine. These experiments confirm and extend the work of Barnett (1). He demonstrated that helium breathing minimally affected the increased nonelastic work of breathing resulting from histamine infusion, while helium breathing did decrease the nonelastic work increase produced by tracheal banding. Our experiments give essentially similar results over a wider range of tracheal Reynolds’ numbers (loo-fold versus sevenfold) and have provided direct confirmation of the anatomical location of airway constriction with an airway catheter. Thus by using gases of varying physical properties and measuring RL at different flow rates the predominant site of pulmonary reaction to intervention may be inferred. The physical basis for this technique is that by altering gas density and flow rate, the proportion of pressure losses due to turbulence may be modified (7, 17). In a sense, therefore, the technique is similar to that used in analyzing MEF curves performed by human subjects breathing gases with differing densities and viscosities. The authors thank Jere Mead for helpful advice support and Ms. Wendy Schneider for invaluable ante. This work was supported by National Institutes
and enthusiastic technical assistof Health
Grant
14580* Received
for publication
2 February
1976.
REFERENCES 1. BARNETT, T. B. Effects of helium-oxygen mixtures on pulmonary mechanics during airway constriction. J. AppZ. PhysioZ. 22: 707713, 1967. 2. CLARKE, S. W., P. D. GRAF, AND J. A. NADEL. In vivo visualization of small-airway constriction after pulmonary microembolism in cats and dogs. J. AppZ. PhysioZ. 29: 646-650, 1970. 3. COLEBATCH, H. J. H., C. R. OLSZEN, AND J. A. NADEL. Effect of histamine, serotonin, and acetylcholine on the peripheral airways. J. AppZ. Physiol. 21: 217-226, 1966. 4. COLEBATCH, H. J. H. The humoral regulation of alveolar ducts. In: Airway Dynamics: Physiology and PharmacoZogy , edited by A. Bouhuys. Springfield, Ill.: Thomas, 1970, p. 169-189. 5. DESPAS, P. J., M. LEROUS, AND P. T. MACKLEM. Site of airway obstruction in asthma as determined by measuring maximal expiratory flow breathing air and a helium-oxygen mixture. J. CZin. Invest. 51: 3235-3243, 1972.
6. DRAZEN, J. M., AND K. F. AUSTEN. Effects of intravenous administration of slow-reacting substance of anaphylaxis, histamine, bradykinin, and prostaglandin FZa on pulmonary mechanics in the guinea pig. J. CZin. Invest. 53: 1679-1685, 1974. 7. DRAZEN, J. M., S. H. LORING, AND R. H. INGRAM. Distribution of pulmonary resistance: effects of gas density, gas viscosity, and flow rate. J. AppZ. PhysioZ. 41: 388-395, 1976. 8. FRIDY, W. W., JR., R. H. INGRAM, JR., J. C. HIERHOLZER, AND M. T. COLEMAN. Airways function during mild viral respiratory illnesses. Ann. InternaL Med. 80: 150-155, 1974. 9. GARDINER, A. J., L. WOOD, P. GAYRARD, H. L. MENKES, AND P. T. MACKLEM. Influence of constriction in central or peripheral airways on maximal expiratory flow rates in dogs. J. AppZ. Physiol. 36: 554-560, 1974. 10. INGRAM, R. H., JR., Effects of airway versus arterial CO, changes on lung mechanics in dogs. J. AppZ. Physiol. 38: 603-
Downloaded from www.physiology.org/journal/jappl by ${individualUser.givenNames} ${individualUser.surname} (129.186.138.035) on January 18, 2019.
LOCALIZATION
OF
AIRWAY
CONSTRICTION
607, 1975. 11. JAEGER, M. J., AND H. MATTHYS. The pressure flow characteristics of the human airways. In: Airway Dynamics, Physiology and Pharmacology, edited by A. Bouhuys. Springfield, Ill.: Thomas, 1970, p. 21-32. 12. MACKLEM, P. T., AND J. MEAD. Resistance of central and peripheral airways measured by a retrograde catheter. J. AppZ. PhysioZ. 22: 395-401, 1967. 13. MACKLEM, P. T., AND J. MEAD. Factors determining maximal expiratory flow in dogs. J. AppZ. Physiol. 25: 159-169, 1968. 14. MEAD, J. Volume displacement body plethysmograph for respiratory measurements in human subjects. J. AppZ. PhysioZ. 15: 736-640, 1960. 15. MEAD, J., J. M. TURNER, P. T. MACKLEM, AND J. B. LITTLE. Significance of the relationship between lung recoil and maxi-
399 mum expiratory flow. J. AppZ. Physiol. 22: 95-108, 1967. 16. NADEL, J. A. New technique for studying structural changes of airways in vivo using powdered tantalum. In: Airway Dynamics: Physiology and Pharmacology, edited by A. Bouhuys. Springfield, Ill.: Thomas, 1970, p. 73-84. 17. WOOD, L. D. H., L. A. ENGEL, P. GRIFFIN, P. DESPAS, AND P. T. MACKLEM. Effect of gas physical properties and flow on lower pulmonary resistance. J. AppZ. Physiol. 41: 234-244, 1976. 18. WOOLCOCK, A. J., P. T. MACKLEM, J. HOGG, N. J. WILSON, J. A. NADEL, N. R. FRANK, AND J. BRAIN. Effect of vagal stimulation on central and peripheral airways in dogs. J. AppZ. PhysioZ. 26: 806-813, 1969. 19. WOOLCOCK, A. J., P. T. MACKLEM, J. C. HOGG, AND N. J. WILSON. Influences of autonomic nervous system on airway resistance and elastic recoil. J. AppZ. PhysioZ. 26: 814-818, 1969.
Downloaded from www.physiology.org/journal/jappl by ${individualUser.givenNames} ${individualUser.surname} (129.186.138.035) on January 18, 2019.
OF
APPLIED
PHYSIOLOGY
Vol. 41, No. 3, September
1976.
Printed
in U.S.A.
Localization of airway constriction of varying density and viscosity
using
gases
JEFFREY M. DRAZEN, STEPHEN H. LORING, AND ROLAND H. INGRAM, JR. Department of Physiology, Harvard School of Public Health, and Departments of Medicine, Peter Bent Brigham Hospital and Harvard Medical School, Boston, Massachusetts 02115
DRAZEN, JEFFREY M., STEPHEN H. LORING, AND ROLAND H. INGRAM, JR. Localization of airway constriction using gases of varying density and viscosity. J. Appl. Physiol. 41(3): 396399. 1976. -The relationship between the major site of airway constriction and change in total pulmonary resistance while breathing gases of varying density and viscosity was studied in five anesthetized dogs pretreated with atropine. Using an airway catheter, central and peripheral components of pulmonary resistance were measured by forced oscillation. Total pulmonary resistance was measured at 0.5 l/s with lungs air-filled, at 0.25 l/s with the lungs filled with 80% helium-20% oxygen (RL-He), and at 1.0 l/s with 80% sulfur hexafluoride20% oxygen (Rs-SF,). Intravenous histamine infusion resulted in a predominantly peripheral resistance increase as determined by the airway catheter and a much larger percentage increase in RL-He than in RL-SF,. Tracheal banding produced a purely central resistance increase and a greater change in RL-SF, than in RL-He. These results support theoretical predictions that the predominant site of airways constriction can be determined without an airway catheter by comparing relative changes in total pulmonary resistance using different flow regimes.
use on a chronic basis. Tantalum bronchography provides direct visualization of changes in airway size but requires complex radiographic equipment for visualization of small airways. In addition, although airway constriction can be directly measured, its effect on local pulmonary mechanics may only be inferred. Comparisons of changes in pulmonary compliance and resistance have been used by a number of investigators to localize airway responses, but this technique may be insensitive to changes which occur in the small airways in the absence of alveolar duct constriction. MEF-elastic recoil curves may be used to determine “upstream resistance,” but since the equal pressure point location may vary from large to small airways, it is not a useful technique to localize the site of airway constriction. The MEF maneuver has been used in human subjects breathing gases of differing densities and similar viscosities in order to infer the anatomic site of airway obstruction as predominantly central or peripheral (5, 8). This approach is based on the idea that high in the lung volume most of the pressure losses in the upstream segment are helium; sulfur hexafluoride; central resistance; peripheral redue to convective acceleration and turbulent flow and sistance will therefore be density sensitive, while low in the lung volume a greater portion of the upstream pressure losses will be due to laminar flow and therefore will be IT HAS BEEN DEMONSTRATED that the pulmonary re- viscosity sensitive. Since it is technically difficult to sponse to experimental intervention may involve pre- perform repeated MEF maneuvers in unanesthetized dominantly peripheral airways or central airways (2, 6, dogs, we felt that inspiratory pulmonary resistance de89, l&19). It is important to note that different investitermined while breathing gases of varying physical gators have used varying definitions of central and pe- properties might be a useful technique in the localizaripheral resistance. Different animals of the same spe- tion of the response to intervention in experimental cies may react to the same stimulus with either central animals. or peripheral airway constriction (10, 18, 19). Because In the preceding paper (‘7), we demonstrated that the the pattern of response may vary from animal to animal distribution of pulmonary resistance (RL) was altered in it is of physiological importance to identify the airways the dog by changing the pulmonary flow regime without involved in a given response. A number of techniques altering airway dimensions. In a turbulent regime (traare currently used to assessthe anatomical location of cheal Reynolds’ number --30,000) more than 80% of RL the physiological response to intervention. These in- was in airways 4.5 mm in diameter and greater, while clude use of retrograde catheters (9, 12, 18, 19), tan- by lowering tracheal Reynolds’ number to approxitalum bronchograms (2, 16), maximum expiratory flow mately 400, these same airways contributed only 40% of (MEF)-elastic recoil curves (9, 13, 15), and MEF curves RL. We have reasoned that a distribution of RL with performed while breathing gases of varying physical minimal losses in the large airways should be more properties (5, 8). Retrograde catheters give a direct sensitive to peripheral airway constriction than a remeasure of resistance partitioning but are usually used gime where large airway pressure losses are more subin open-chested animals making them a difficult tool to stantial. Conversely, a more turbulent flow regime with 396 Downloaded from www.physiology.org/journal/jappl by ${individualUser.givenNames} ${individualUser.surname} (129.186.138.035) on January 18, 2019.
LOCALIZATION
OF
AIRWAY
397
CONSTRICTION
more substantial large airway losses should be more sensitive to changes in the large airways. In this communication we test the hypothesis that the airways response to intervention can be localized by comparing changes in RL before and after intervention while breathing gases of varying density and viscosity at different flow rates. METHODS
Five mongrel dogs (lo-15 kg body weight) were anesthetized with sodium pentobarbital, treated with 2.0 mg of atropine sulfate, and prepared for measurement of RL, peripheral lung resistance (Rp), and central airway resistance (Rc) as previously described (7). In brief, animals were intubated with a tight-fitting tracheal cannula with a manifold of side taps for measuring airway opening pressure. Pleural pressure was estimated from an esophageal balloon and airway pressure was determined with an airway catheter. Volume and its first two time derivates (flow and acceleration) were determined from a 200-liter volume displacement pressure-compensated plethysmograph (14). Inspiratory resistance was measured by forced oscillation using the technique of electrical subtraction with volume and accelerative corrections. As previously described the airway catheter was placed such that approximately 60% of RL was in the central airways at a volume 200-300 ml above the functional residual capacity (FRC). With the catheter so positioned the following protocols were instituted. While breathing air, and at the end of a normal expiration, the airway valve was closed and the animal inflated to a volume 500 ml above FRC three times in rapid successsion. The animal was then returned to FRC and thoracic gas volume (TGV) determined as previously described (7). After 60 s of spontaneous respiration the animal was inflated 200-300 ml above FRC and resistance (Rp and Rc) at 0.5 l/s was measured by forced oscillation at 4 Hz. Then the bias flow was changed to a mixture of 80% helium-20% oxygen (helium) and the protocol repeated except that resistance was measured at an inspiratory flow of 0.25 l/s. The bias flow was then changed to a mixture of 80% sulfur hexafluoride-20% oxygen (SF,) and the protocol repeated except that resistance was measured at an inspiratory flow of 1.0 l/s. The bias flow was then returned to air and the protocol repeated as originally described. If the TGV and resistance measured the second time on air were not different from the original determinations by more than the variability noted within a single determination (approximately lo%), a constriction was begun. If the resistance on air or TGV varied by more than lo%, another control run was initiated until the first and last air resistances varied by less than 10%. The entire three-gas protocol was then repeated during constriction until the initial and final air resistances and TGV’s agreed within 10%. Peripheral constriction was produced by intravenous histamine infusion (lo-30 ,ccg histamine base/kg per min), while central airway constriction was produced by mechanical tracheal banding.
RESULTS
During the control period prior to histamine infusion, RL measured while breathing air, helium, and SF, was 0.69 t 0.26 (mean t SD) cmH,O/l/s, 0.51 t 0.08 cmH,O/ l/s, and 2.50 t 1.04 cmH,O/l/s, respectively. During the histamine infusion, RL increased on all three flow regimes. The mean values of RL during the infusion measured while breathing air, helium, or SF, were 1.53 (range 0.64-2.31) cmH,O/l/s, 1.35 (range 0.64-2.15) cmH,O/l/s, and 3.25 (range 2.20-4.90) cmH,O/l/s, respectively. In Fig. 1, Rp and Rc before and during histamine infusion while breathing air are shown for each dog. In each case there was a large increase in Rp while the change in Rc was small and inconsistent. In each case (shown in the upper left-hand corner of each inset), the percent change in total pulmonary resistance resulting from histamine infusion was greater while breathing helium than it was while breathing SF,. The absolute lung volume at which resistance was determined varied by less than 70 ml between control and histamine infusion. The mean change in volume was -2.6 t 40.1 (mean t SD) ml. During the control period prior to tracheal banding RL measured while breathing air, helium, and SF, was 0.83 t 0.13 cmH,O/l/s, 0.52 t 0.16 cmH,O/l/s, and 2.61 t 0.54 cmH,O/l/s, respectively. After tracheal banding RL increased on all three flow regimes. The mean values for RL after banding measured while breathing air, helium, or SF, were 4.88 (range 1.25-10.0) cmH,O/l/s, 1.85 (range 0.52-3.40) cmH,O/l/s, and 18.61 (range 5.149.7) cmH,O/l/s, respectively. In Fig. 2, Rp and Rc before and during tracheal constriction while breathing air are shown for each dog. In each case Rc increased markedly while the change in Rp was small and inconsistent. As shown in the upper left-hand corner of each inset the percent change in RL resulting from tracheal
2.0.
Dog 1. He 66801~ 4 SF6 7990
,?
1.6.
1
Dog 2. 2.0 He 166~x4 SF6 44x4
Dog 3. 2.0 He 240~~4 26%d 1 SF6
1.6-j
1.64
1.2.
.a
I
I’
.4
dj
/
Hlstamlne
Control
0 1
Hlstamtne
Control
-0 -
Histamine
Rp Rc
.50 .25
0’
Control
Histamine
0-I
Control
Histamine
in Rc and Rp measured at 0.5 l/s in atropinized dogs breathing air before and after intravenous histamine infusion. In the upper left-hand corner of each inset the percent change in RL resulting from histamine infusion measured while breathing helium or while breathing SF, is given. FIG.
1. Alterations
Downloaded from www.physiology.org/journal/jappl by ${individualUser.givenNames} ${individualUser.surname} (129.186.138.035) on January 18, 2019.
398
i0
DRAZEN,
’ :i
c~~{~-~~~Z$heCd
I1
Control
Constrlctlon
Tracheal
3
co~~~~~~hea~
Constrlctlon
Constnctlon
z!! :
.-7l ii
Aw +J 0.5 LPS e ._.____ ---a Rp
a
-
d
0 ---
0
Control
-- _- _ -0 Tracheal Constrictbon
,A
~------. Control
Rc
Tracheal Constrictlon
FIG. 2. Alterations in Rc and Rp measured at breathing air before and after tracheal banding. In hand corner of each inset the percent change in RL tracheal banding measured while breathing helium
0.5 l/s in dogs the upper leftresulting from or SF, is given.
banding was greater while breathing SF, than it was while breathing helium. The absolute lung volume at which resistance was determined varied by less than 50 ml between control periods and tracheal constriction. The mean change in lung volume was -13.2 t 30.7 (SD) ml. DISCUSSION
By comparing the change in inspiratory resistance measured while breathing gases of varying physical properties at different flow rates before and after experimental intervention, the predominant anatomical site of constriction was predictably related to that determined by using an airway catheter. In each case of peripheral airway constriction, the change in RL measured while breathing helium (ARL-He) was greater than the change in RL measured while breathing SF, (ARL-SF,). Co nversely, in each case of central airway constriction the ARL-SF, was greater than the ARL-He. This suggests that by comparing the ART,-He to the ARLSF, the predominant site of response to an intervention
LORING,
AND
INGRAM
can be localized. If the percent ARL-He was greater than the percent ARL-SF,, the reaction was predominantly peripheral and if the percent ARL-SF, was greater than the percent ARL-He , the reaction was predominantly central. Although th .ese experimen ts were performed in dogs, previous calculations of the distribution of lower airway resistance in human lungs (7) suggest that a similar technique might be useful in localizing the predominant site of pulmonary reaction to intervention. However, the variations caused by the glottis and upper airway (11) may contribute substantial noise and prevent reliable partitioning. The interpretation of these results depends on using an airway catheter to partition resistance while breathing air at 0.5 l/s. The errors and assumptions involved in using such a catheter were discussed in the previous paper (7). Intravenous histamine has been shown to provide primarily a peripheral constriction (3) which should be more marked in the presence of atropine. These experiments confirm and extend the work of Barnett (1). He demonstrated that helium breathing minimally affected the increased nonelastic work of breathing resulting from histamine infusion, while helium breathing did decrease the nonelastic work increase produced by tracheal banding. Our experiments give essentially similar results over a wider range of tracheal Reynolds’ numbers (loo-fold versus sevenfold) and have provided direct confirmation of the anatomical location of airway constriction with an airway catheter. Thus by using gases of varying physical properties and measuring RL at different flow rates the predominant site of pulmonary reaction to intervention may be inferred. The physical basis for this technique is that by altering gas density and flow rate, the proportion of pressure losses due to turbulence may be modified (7, 17). In a sense, therefore, the technique is similar to that used in analyzing MEF curves performed by human subjects breathing gases with differing densities and viscosities. The authors thank Jere Mead for helpful advice support and Ms. Wendy Schneider for invaluable ante. This work was supported by National Institutes
and enthusiastic technical assistof Health
Grant
14580* Received
for publication
2 February
1976.
REFERENCES 1. BARNETT, T. B. Effects of helium-oxygen mixtures on pulmonary mechanics during airway constriction. J. AppZ. PhysioZ. 22: 707713, 1967. 2. CLARKE, S. W., P. D. GRAF, AND J. A. NADEL. In vivo visualization of small-airway constriction after pulmonary microembolism in cats and dogs. J. AppZ. PhysioZ. 29: 646-650, 1970. 3. COLEBATCH, H. J. H., C. R. OLSZEN, AND J. A. NADEL. Effect of histamine, serotonin, and acetylcholine on the peripheral airways. J. AppZ. Physiol. 21: 217-226, 1966. 4. COLEBATCH, H. J. H. The humoral regulation of alveolar ducts. In: Airway Dynamics: Physiology and PharmacoZogy , edited by A. Bouhuys. Springfield, Ill.: Thomas, 1970, p. 169-189. 5. DESPAS, P. J., M. LEROUS, AND P. T. MACKLEM. Site of airway obstruction in asthma as determined by measuring maximal expiratory flow breathing air and a helium-oxygen mixture. J. CZin. Invest. 51: 3235-3243, 1972.
6. DRAZEN, J. M., AND K. F. AUSTEN. Effects of intravenous administration of slow-reacting substance of anaphylaxis, histamine, bradykinin, and prostaglandin FZa on pulmonary mechanics in the guinea pig. J. CZin. Invest. 53: 1679-1685, 1974. 7. DRAZEN, J. M., S. H. LORING, AND R. H. INGRAM. Distribution of pulmonary resistance: effects of gas density, gas viscosity, and flow rate. J. AppZ. PhysioZ. 41: 388-395, 1976. 8. FRIDY, W. W., JR., R. H. INGRAM, JR., J. C. HIERHOLZER, AND M. T. COLEMAN. Airways function during mild viral respiratory illnesses. Ann. InternaL Med. 80: 150-155, 1974. 9. GARDINER, A. J., L. WOOD, P. GAYRARD, H. L. MENKES, AND P. T. MACKLEM. Influence of constriction in central or peripheral airways on maximal expiratory flow rates in dogs. J. AppZ. Physiol. 36: 554-560, 1974. 10. INGRAM, R. H., JR., Effects of airway versus arterial CO, changes on lung mechanics in dogs. J. AppZ. Physiol. 38: 603-
Downloaded from www.physiology.org/journal/jappl by ${individualUser.givenNames} ${individualUser.surname} (129.186.138.035) on January 18, 2019.
LOCALIZATION
OF
AIRWAY
CONSTRICTION
607, 1975. 11. JAEGER, M. J., AND H. MATTHYS. The pressure flow characteristics of the human airways. In: Airway Dynamics, Physiology and Pharmacology, edited by A. Bouhuys. Springfield, Ill.: Thomas, 1970, p. 21-32. 12. MACKLEM, P. T., AND J. MEAD. Resistance of central and peripheral airways measured by a retrograde catheter. J. AppZ. PhysioZ. 22: 395-401, 1967. 13. MACKLEM, P. T., AND J. MEAD. Factors determining maximal expiratory flow in dogs. J. AppZ. Physiol. 25: 159-169, 1968. 14. MEAD, J. Volume displacement body plethysmograph for respiratory measurements in human subjects. J. AppZ. PhysioZ. 15: 736-640, 1960. 15. MEAD, J., J. M. TURNER, P. T. MACKLEM, AND J. B. LITTLE. Significance of the relationship between lung recoil and maxi-
399 mum expiratory flow. J. AppZ. Physiol. 22: 95-108, 1967. 16. NADEL, J. A. New technique for studying structural changes of airways in vivo using powdered tantalum. In: Airway Dynamics: Physiology and Pharmacology, edited by A. Bouhuys. Springfield, Ill.: Thomas, 1970, p. 73-84. 17. WOOD, L. D. H., L. A. ENGEL, P. GRIFFIN, P. DESPAS, AND P. T. MACKLEM. Effect of gas physical properties and flow on lower pulmonary resistance. J. AppZ. Physiol. 41: 234-244, 1976. 18. WOOLCOCK, A. J., P. T. MACKLEM, J. HOGG, N. J. WILSON, J. A. NADEL, N. R. FRANK, AND J. BRAIN. Effect of vagal stimulation on central and peripheral airways in dogs. J. AppZ. PhysioZ. 26: 806-813, 1969. 19. WOOLCOCK, A. J., P. T. MACKLEM, J. C. HOGG, AND N. J. WILSON. Influences of autonomic nervous system on airway resistance and elastic recoil. J. AppZ. PhysioZ. 26: 814-818, 1969.
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