Ventilation distribution during histamine provocation

Verbanck, S., D. Schuermans, A. Van Muylem, M. Paiva, M. Noppen, and W. Vincken. Ventilation distribution during histamine provocation. J. Appl. Physiol. 83(6):1907-1916, 1997.We investigated ventilation inhomogeneity duringprovocation with inhaled histamine in 20 asymptomatic nonsmokingsubjects. We used N₂multiple-breath washout (MBW) to deriveparameters S_condand S_acin as ameasurement of ventilation inhomogeneity in conductive and acinar zonesof the lungs, respectively. A 20% decrease of forced expiratory volume in 1 s (FEV₁) was used todistinguish responders from nonresponders. In the responder group,average FEV₁ decreased by 26%,whereas S_condincreased by 390% with no significant change inS_acin. In thenonresponder group, FEV₁ decreasedby 11%, whereasS_cond increased by 198% with no significantS_acin change.Despite the absence of change inS_acin duringprovocation, baselineS_acin wassignificantly larger in the responder vs. the nonresponder group. Themain findings of our study are that during provocation largeventilation inhomogeneities occur, that the small airways affected bythe provocation process are situated proximal to the acinar zone wherethe diffusion front stands, and that, in addition to overall decreasein airway caliber, there is inhomogeneous narrowing of parallelairways.

     

Mechanical implications of in vivo human diaphragm shape.

Using magnetic resonance imaging, we measured the three-dimensional form of the diaphragm in vivo in four supine relaxed subjects at functional residual capacity and calculated its total surface area, the right and left surface areas in the zone of apposition, and the principal radii of curvature as a function of height. The area of apposition comprised 45 +/- 1.5% (SE) of the total surface area of the diaphragm. Available data on the area of the central tendon indicate that a considerable part of the muscular part of the diaphragm is lung apposed. The curvature was linearly related to height over 7 cm of the posterior half of each hemidiaphragm. From the linear portion of this graph and assuming a vertical gradient of transdiaphragmatic pressure of 0.75 cmH2O/cm, we applied the Laplace law and calculated tensions of 54 and 32 g/cm for right and left sides, respectively. We conclude that the shape of at least part of the posterior half of the relaxed human diaphragm in the supine position at functional residual capacity can be explained by the Laplace law, suggesting that both the lung and abdominal contents behave sufficiently as fluids so that they do not impose their shape on the diaphragm. Because diaphragm muscle is partly lung apposed, it is unlikely that the diaphragm functions simply as a piston.     

Interference with withdrawal signs of naloxone-induced opiate withdrawal under anesthesia is anesthetic-specific in opiate-dependent rats.

We hypothesized that interference of opiate antagonist-precipitated withdrawal signs under anesthesia is anesthetic-specific. Three groups of morphine-dependent rats were compared in different experimental conditions using a protocol of rapid withdrawal induction by an antagonist under anesthesia. We observed that ketamine and midazolam have different effects on the expression of withdrawal. This brings specific insights into the pharmacological basis of therapy with induction of opiate antagonist.     

Relationships between the lung clearance index and conductive and acinar ventilation heterogeneity

The lung clearance index (LCI) derived from a multiple breath washout test has regained considerable popularity in recent years, alternatively being promoted as an early detection tool or a marker of small airways function. In this study, we systematically investigated the link between LCI and indexes of acinar and conductive airways ventilation heterogeneity (Sacin, Scond) to assess potential contributions from both lung zones. Relationships were examined in 55 normal subjects after provocation, where only Scond is known to be markedly increased, and in 55 asthma patients after bronchodilation, in whom both Scond and Sacin ranged between normal and abnormal. LCI was correlated to Scond in both groups (R = 0.37-0.43; P < 0.01 for both); in the asthma group, LCI was also tightly correlated to Sacin (R = 0.70; P < 0.001). Potential mechanisms operational at various levels of the bronchial tree were identified by considering washout curvilinearity in addition to LCI to distinguish specific ventilation and dead space effects (also illustrated by simple 2-compartment model simulations). Although the asthma data clearly demonstrate that LCI can reflect very peripheral ventilation heterogeneities, the normal provocation data also convincingly show that LCI increases may be the exclusive result of far more proximal ventilation heterogeneities. Because LCI potentially includes heterogeneities at all length scales, it is suggested that ventilation imaging in combination with LCI measurement at the mouth could identify the scale of relevant ventilation heterogeneities. In the meantime, interpretations of LCI results in the clinic based on washout curves collected at the mouth should be handled with caution.     

Contribution of upper airway geometry to convective mixing

We investigated the axial dispersive effect of the upper airway structure (comprising mouth cavity, oropharynx, and trachea) on a traversing aerosol bolus. This was done by means of aerosol bolus experiments on a hollow cast of a realistic upper airway model (UAM) and three-dimensional computational fluid dynamics (CFD) simulations in the same UAM geometry. The experiments showed that 50-ml boluses injected into the UAM dispersed to boluses with a half-width ranging from 80 to 90 ml at the UAM exit, across both flow rates (250, 500 ml/s) and both flow directions (inspiration, expiration). These experimental results imply that the net half-width induced by the UAM typically was 69 ml. Comparison of experimental bolus traces with a one-dimensional Gaussian-derived analytical solution resulted in an axial dispersion coefficient of 200-250 cm(2)/s, depending on whether the bolus peak and its half-width or the bolus tail needed to be fully accounted for. CFD simulations agreed well with experimental results for inspiratory boluses and were compatible with an axial dispersion of 200 cm(2)/s. However, for expiratory boluses the CFD simulations showed a very tight bolus peak followed by an elongated tail, in sharp contrast to the expiratory bolus experiments. This indicates that CFD methods that are widely used to predict the fate of aerosols in the human upper airway, where flow is transitional, need to be critically assessed, possibly via aerosol bolus simulations. We conclude that, with all its geometric complexity, the upper airway introduces a relatively mild dispersion on a traversing aerosol bolus for normal breathing flow rates in inspiratory and expiratory flow directions.     

Paradoxical helium and sulfur hexafluoride single-breath washouts in short-term vs. sustained microgravity

Lauzon, Anne-Marie, G. Kim Prisk, Ann R. Elliott, SylviaVerbanck, Manuel Paiva, and John B. West. Paradoxical helium andsulfur hexafluoride single-breath washouts in short-term vs. sustainedmicrogravity. J. Appl. Physiol. 82(3):859-865, 1997.During single-breath washouts in normal gravity (1 G), the phase III slope of sulfur hexafluoride(SF₆) is steeper than that ofhelium (He). Two mechanisms can account for this:1) the higher diffusivity of Heenhances its homogeneous distribution; and2) the lower diffusivity ofSF₆ results in a more peripherallocation of the diffusion front, where airway asymmetry is larger.These mechanisms were thought to be gravity independent. However, weshowed during the Spacelab Life Sciences-2 spaceflight that insustained microgravity (µG) theSF₆-to-He slope difference isabolished. We repeated the protocol during short periods (27 s) of µG(parabolic flights). The subjects performed a vital-capacityinspiration and expiration of a gas containing 5% He-1.25%SF₆-balanceO₂. As in sustained µG, thephase III slopes of He and SF₆decreased. However, during short-term µG, theSF₆-to-He slope differenceincreased from 0.17 ± 0.03%/l in 1 G to 0.29 ± 0.06%/l inµG, respectively. This is contrary to sustained µG, in which theSF₆-to-He slope difference decreased from 0.25 ± 0.03%/l in 1 G to 0.01 ± 0.06%/lin µG. The increase in phase III slope difference in short-term µGwas caused by a larger decrease of He phase III slope compared with that in sustained µG. This suggests that changes in peripheral gasmixing seen in sustained µG are mainly due to alterations in thediffusive-convective inhomogeneity of He that require >27 s of µGto occur. Changes in pulmonary blood volume distribution or cardiogenicmixing may explain the differences between the results found inshort-term and sustained µG.

     

Single-breath washout experiments in rat lungs.

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.     

Similar ventilation distribution in normal subjects prone and supine during tidal breathing.

Multiple-breath washout (MBW) tests, with end-expiratory lung volume at functional residual capacity (FRC) and 90% O(2), 5% He, and 5% SF(6) as an inspired gas mixture, were performed in healthy volunteers in supine and prone postures. The semilog plot of MBW N(2) concentrations was evaluated in terms of its curvilinearity. The MBW N(2) normalized slope analysis yielded indexes of acinar and conductive ventilation heterogeneity (Verbanck S, Schuermans D, Van Muylem A, Paiva M, Noppen M, and Vincken W. J App Physiol 83: 1907-1916, 1997). Also, the difference between SF(6) and He normalized phase III slopes was computed in the first MBW expiration. Only MBW tests with similar FRC in the prone and supine postures (P > 0.1; n = 8) were considered. Prone and supine postures did not reveal any significant differences in curvilinearity, N(2) normalized slope-derived indexes of conductive or acinar ventilation heterogeneity, nor SF(6)-He normalized phase III slope difference in the first MBW expiration (P > 0.1 for all). The absence of significant changes in any of the MBW indexes suggests that ventilation heterogeneity is similar in the supine and prone postures of normal subjects breathing near FRC.