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Biomedical subjects

S Verbanck

Publications and source records attributed to S Verbanck.

At least 19 recordsLinked to original sources

Multiple-breath washin of helium and sulfur hexafluoride in sustained microgravity.

We performed multiple-breath washouts of N2 and simultaneous washins of He and SF6 with fixed tidal volume (approximately 1,250 ml) and preinspiratory lung volume (approximately the subject's functional residual capacity in the standing position) in four normal subjects (mean age 40 yr) standing and supine in normal gravity (1 G) and during exposure to sustained microgravity (microG). The primary objective was to examine the influence of diffusive processes on the residual, nongravitational ventilatory inhomogeneity in the lung in microG. We calculated several indexes of convective ventilatory inhomogeneity from each gas species. A normal degree of ventilatory inhomogeneity was seen in the standing position at 1 G that was largely unaltered in the supine position. When we compared the standing position in 1 G with microG, there were reductions in phase III slope in all gases, consistent with a reduction in convection-dependent inhomogeneity in the lung in microG, although considerable convective inhomogeneity persisted in microG. The reductions in the indexes of convection-dependent inhomogeneity were greater for He than for SF6, suggesting that the distances between remaining nonuniformly ventilated compartments in microG were short enough for diffusion of He to be an effective mechanism to reduce gas concentration differences between them.

Adult

Chest wall mechanics in sustained microgravity.

We assessed the effects of sustained weightlessness on chest wall mechanics in five astronauts who were studied before, during, and after the 10-day Spacelab D-2 mission (n = 3) and the 180-day Euromir-95 mission (n = 2). We measured flow and pressure at the mouth and rib cage and abdominal volumes during resting breathing and during a relaxation maneuver from midinspiratory capacity to functional residual capacity. Microgravity produced marked and consistent changes (Delta) in the contribution of the abdomen to tidal volume [DeltaVab/(DeltaVab + DeltaVrc), where Vab is abdominal volume and Vrc is rib cage volume], which increased from 30.7 +/- 3. 5 (SE)% at 1 G head-to-foot acceleration to 58.3 +/- 5.7% at 0 G head-to-foot acceleration (P < 0.005). Values of DeltaVab/(DeltaVab + DeltaVrc) did not change significantly during the 180 days of the Euromir mission, but in the two subjects DeltaVab/(DeltaVab + DeltaVrc) was greater on postflight day 1 than on subsequent postflight days or preflight. In the two subjects who produced satisfactory relaxation maneuvers, the slope of the Konno-Mead plot decreased in microgravity; this decrease was entirely accounted for by an increase in abdominal compliance because rib cage compliance did not change. These alterations are similar to those previously reported during short periods of weightlessness inside aircrafts flying parabolic trajectories. They are also qualitatively similar to those observed on going from upright to supine posture; however, in contrast to microgravity, such postural change reduces rib cage compliance.

Abdomen

Intrapulmonary gas mixing in panacinar- and centriacinar-induced emphysema in rats.

We studied ventilation distribution using the single-breath washout technique in rats with two types of induced emphysema: panacinar-like (by instilled elastase) and centriacinar-like (by inhaled CdCl2 combined with oral intake of beta-aminopropionitrile). Morphologically, panacinar and centriacinar groups presented a similar degree of airspace enlargement, which was irregularly distributed and also accompanied by fibrosis only in the centriacinar group. In terms of mechanical properties, the centriacinar group presented lower end-expiratory flows and lower compliance than the panacinar group. The ventilation distribution patterns were also different between both groups. Single-breath washout phase III slopes, reflecting mainly diffusion-convection-dependent inhomogeneities in rat lungs, were largest in the centriacinar group. The SF6-He slope difference, which was reversed in both emphysema groups with respect to the control group, could be attributed mainly to He slope changes in the panacinar group and to SF6 slope changes in the centriacinar group. In addition, the respective He and SF6 slope decrease as a function of end-inspiratory breath-hold time, was only different from the control group in the centriacinar group. The observed ventilation distribution patterns can be explained by interacinar elastic changes in the panacinar group and severe interacinar structural alterations in the centriacinar group.

Administration, Inhalation

Conductive and acinar lung-zone contributions to ventilation inhomogeneity in COPD.

We investigated ventilation inhomogeneity in patients with chronic obstructive pulmonary disease (COPD) through use of the multiple breath N2 washout test (MBW). From an alveolar slope analysis throughout the MBW, we derived two indices, S(cond) and S(acin), as a measure of ventilation inhomogeneity in conductive and acinar zones of the lungs, respectively (J. Appl. Physiol. 1997;83:1807-1816). We evaluated the relationship of S(cond) and S(acin) to standard lung-function indices by means of a principal-components factor analysis, which linked correlated indices to independent factors accounting for 81% of the total variance within the COPD group. S(acin) was linked to the so-called acinar lung-zone factor, which also comprises diffusion capacity measurements. S(cond) was linked to the so-called conductive lung-zone factor, which also comprises specific airway conductance (S(Gaw)) and forced expiratory flows. FEV1 divided by FVC (FEV1/FVC) was the only variable linked to both the conductive and the acinar lung-zone factors. The fact that S(cond) and S(acin) were linked to independent factors provides statistical confirmation of the hypothesis that S(cond) and S(acin) reflect independent lung alterations, whereas FEV1/FVC behavior indicates a combined conductive and acinar contribution to airways obstruction.

Airway Resistance

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

During single-breath washouts in normal gravity (1 G), the phase III slope of sulfur hexafluoride (SF6) is steeper than that of helium (He). Two mechanisms can account for this: 1) the higher diffusivity of He enhances its homogeneous distribution; and 2) the lower diffusivity of SF6 results in a more peripheral location of the diffusion front, where airway asymmetry is larger. These mechanisms were thought to be gravity independent. However, we showed during the Spacelab Life Sciences-2 spaceflight that in sustained microgravity (microG) the SF6-to-He slope difference is abolished. We repeated the protocol during short periods (27 s) of microG (parabolic flights). The subjects performed a vital-capacity inspiration and expiration of a gas containing 5% He-1.25% SF6-balance O2. As in sustained microG, the phase III slopes of He and SF6 decreased. However, during short-term microG, the SF6-to-He slope difference increased from 0.17 +/- 0.03%/l in 1 G to 0.29 +/- 0.06%/l in microG, respectively. This is contrary to sustained microG, in which the SF6-to-He slope difference decreased from 0.25 +/- 0.03%/l in 1 G to -0.01 +/- 0.06%/l in microG. The increase in phase III slope difference in short-term microG was caused by a larger decrease of He phase III slope compared with that in sustained microG. This suggests that changes in peripheral gas mixing seen in sustained microG are mainly due to alterations in the diffusive-convective inhomogeneity of He that require > 27 s of microG to occur. Changes in pulmonary blood volume distribution or cardiogenic mixing may explain the differences between the results found in short-term and sustained microG.

Adult

Pulmonary tissue volume, cardiac output, and diffusing capacity in sustained microgravity.

In microgravity (microG) humans have marked changes in body fluids, with a combination of an overall fluid loss and a redistribution of fluids in the cranial direction. We investigated whether interstitial pulmonary edema develops as a result of a headward fluid shift or whether pulmonary tissue fluid volume is reduced as a result of the overall loss of body fluid. We measured pulmonary tissue volume (Vti), capillary blood flow, and diffusing capacity in four subjects before, during, and after 10 days of exposure to microG during spaceflight. Measurements were made by rebreathing a gas mixture containing small amounts of acetylene, carbon monoxide, and argon. Measurements made early in flight in two subjects showed no change in Vti despite large increases in stroke volume (40%) and diffusing capacity (13%) consistent with increased pulmonary capillary blood volume. Late in-flight measurements in four subjects showed a 25% reduction in Vti compared with preflight controls (P < 0.001). There was a concomittant reduction in stroke volume, to the extent that it was no longer significantly different from preflight control. Diffusing capacity remained elevated (11%; P < 0.05) late in flight. These findings suggest that, despite increased pulmonary perfusion and pulmonary capillary blood volume, interstitial pulmonary edema does not result from exposure to microG.

Blood Gas Analysis

Ventilation distribution during histamine provocation.

We investigated ventilation inhomogeneity during provocation with inhaled histamine in 20 asymptomatic nonsmoking subjects. We used N2 multiple-breath washout (MBW) to derive parameters Scond and Sacin as a measurement of ventilation inhomogeneity in conductive and acinar zones of the lungs, respectively. A 20% decrease of forced expiratory volume in 1 s (FEV1) was used to distinguish responders from nonresponders. In the responder group, average FEV1 decreased by 26%, whereas Scond increased by 390% with no significant change in Sacin. In the nonresponder group, FEV1 decreased by 11%, whereas Scond increased by 198% with no significant Sacin change. Despite the absence of change in Sacin during provocation, baseline Sacin was significantly larger in the responder vs. the nonresponder group. The main findings of our study are that during provocation large ventilation inhomogeneities occur, that the small airways affected by the provocation process are situated proximal to the acinar zone where the diffusion front stands, and that, in addition to overall decrease in airway caliber, there is inhomogeneous narrowing of parallel airways.

Airway Resistance

Anomalous behavior of helium and sulfur hexafluoride during single-breath tests in sustained microgravity.

We performed single-breath wash-in tests for He and SF6 in four subjects exposed to 14 days of microgravity (microG) during the Spacelab flight Spacelab Life Sciences-2. Subjects inspired a vital capacity breath of 5% He-1.25% SF6-balance O2 and then exhaled to residual volume at 0.5l/s. The tests were also performed with a 10-s breath hold at the end of inspiration. Measurements were also made with the subjects standing and supine in 1 G. Phase III slope was measured after the dead-space washout and before the onset of airway closure. In all subjects in 1 G, whether standing or supine, phase III slope for SF6 was significantly steeper than that for He. However, in microG, the slopes became the same. Furthermore, after breath holding in microG, the SF6 slopes were significantly flatter than those for He. On return to 1 G, the changes were reversed, and there was no difference between preflight and postflight values. Because most of the phase III slope reflects events occurring in the acinar regions of the lung, the results suggest that microG causes conformational changes in the acini or changes in cardiogenic mixing in the lung periphery, but in either case the mechanism is unclear.

Adult

Specific ventilation distribution in microgravity.

We studied the contribution of inter- and intraregional inhomogeneities of specific ventilation (delta V/Vo) from the rebreathing inert gas trace in microgravity and on Earth. The rebreathing tests were carried out by four astronauts before, during, and after the 10-day Spacelab D-2 mission. Starting from functional residual capacity, the rebreathing maneuver consisted of eight reinspirations from a bag filled with 1.8-2.2 liters of test gas mixtures containing approximately 5% argon. The rate of argon equilibration in the rebreathing bag, termed RBeq, was quantified by determining the logarithm of the actual minus the equilibrated argon concentrations normalized to the inspired minus the equilibrated argon concentrations. A compartmental model of the lung (S. Verbanck and M. Paiva. J. Appl. Physiol. 76: 445-454, 1994) was used to validate the method for determining RBeq and to simulate the influence of intra- and interregional delta V/Vo inhomogeneities on the RBeq curve. The comparison between the experimental Earth-based and microgravity RBeq curves and model simulations shows that gravity-independent delta V/Vo inhomogeneity is at least as large as gravity-dependent delta V/Vo inhomogeneity.

Adult

Multiple-breath washout and washin experiments in steers.

Multiple-breath N2 washouts (WO) and washins (WI) were performed during regular tidal breathing in 11 unsedated healthy steers approaching pulmonary functional maturity (mean body weight = 271 kg). They inspired 20% O2 in 80% Ar during the WO and air during the WI. For each steer, we computed two indexes of ventilation inhomogeneity from the N2 WO curves: 1) the curvilinearity of the logarithm of end-tidal N2 concentrations as a function of cumulative expired volume reflected in the ratio of two slopes fitted between 100 and 50% and between 50 and 10%, respectively, of end-tidal N2 concentration of the first breath of the WO; and 2) the N2 phase III slope divided by the mean expired concentration (Sn) of each breath also plotted as a function of cumulative expired volume. Equivalent computation of both parameters was done on WI and WO curves, and similar results were obtained. The mean slope ratio was 0.812 +/- 0.119 (SD) for all the steers, which is consistent with topographic gravity-dependent specific ventilation distribution inhomogeneity. Sn was independent of the breath number both for WO and WI (mean Sn = 0.130 +/- 0.057 liters-1), suggesting that emptying between unequally ventilated units, is synchronous. This behavior resembles that observed in rats postmortem (S. Verbanck, E.R. Weibel, and M. Paiva. J. Appl Physiol. 71: 847-854, 1991) but contrasts with experiments in humans, in whom convection-dependent ventilation inhomogeneities generate a marked increase in Sn throughout the entire WO (A. B. H. Crawford, M. Makowska, M. Paiva, and L. A. Engel. J. Appl. Physiol. 59: 838-846, 1985). This is surprising because one would expect gravity-dependent sequential emptying in animals of this size.

Animals

Theoretical basis for time 0 correction in the rebreathing analysis.

The uptake of a soluble gas during rebreathing is simulated in a compartmental model. The lung is assumed to consist of two parallel units, each one divided into three compartments: a personal dead space, an alveolar space, and a tissue volume. These units are connected to the rebreathing bag via a common dead space. Gas exchange is incorporated into the model for a given cardiac output. Inert and soluble gas concentrations are computed as a function of time in the various compartments by means of differential equations. Using different initial conditions, we simulate time-dependent concentration traces "at the mouth" and estimate the errors made by traditional analysis of the end-tidal gas concentrations with respect to the "time 0" correction method as was first proposed by Sackner et al. (Am. Rev. Respir. Dis. 111:157-165, 1975). We provide a theoretical basis for this correction method and outline the conditions that need to be fulfilled for its application. We show that the tissue volume and cardiac output estimates are less affected by ventilation and perfusion inhomogeneities when the time 0 correction method is used. This is particularly relevant for the expected increase in tissue volume in microgravity where ventilation and perfusion inhomogeneities are expected to be attenuated.

Blood Gas Analysis

Three-dimensional reconstruction of the in vivo human diaphragm shape at different lung volumes.

The ability of the diaphragm to generate pressures at different lung volumes (VLs) in humans may be determined by the following factors: 1) its in vivo three-dimensional shape, radius of curvature, and tension according to Laplace law; 2) the relative degree to which it is apposed to the rib cage (i.e., zone of apposition) and lungs (i.e., diaphragm dome); and 3) its length-force properties. To gain more insight into these factors we have reconstructed from nuclear magnetic images the three-dimensional shape of the diaphragm of four normal subjects under supine relaxed conditions at four different VLs: residual volume, functional residual capacity, functional residual capacity plus one-half of the inspiratory capacity, and total lung capacity. Under our experimental conditions the shape of the diaphragm changes substantially in the anteroposterior plane but not in the coronal one. Multivariate regression analysis indicates that the zone of apposition is dependent on both diaphragm shortening and lower rib cage widening with lung inflation, although much more on the first of these two factors. Because of the changes in anteroposterior shape and expansion of the insertional origin at the costal margin with lung inflation, the data therefore suggest that the diaphragm may be more accurately modeled by a "widening piston" (Petroll's model) than a simple "piston in a cylinder" model. A significant portion of the muscular surface is lung apposed, suggesting that diaphragmatic force has radial vectors in the dome and vectors along the body axis in the zone of apposition. The muscular surface area of the diaphragm decreased linearly by approximately 41% with VL from residual volume to total lung capacity. Diaphragmatic fibers may shorten under physiological conditions more than any other skeletal muscle. The large changes in fiber length combined with limited shape changes with lung inflation suggest that the length-twitch force properties of the diaphragm may be the most important factor for the pressure-generating function of this respiratory muscle in response to bilateral phrenic shocks at different VLs.

Diaphragm

Simulations of washout experiments in postmortem rat lungs.

We developed a rat lung model to simulate single-breath and multiple-breath washout experiments performed by Verbanck et al. (J. Appl. Physiol. 71: 847-854, 1991) and González Mangado et al. (J. Appl. Physiol. 71: 855-862, 1991). The multi-branch-point rat lung model is based on anatomic data of the rat airway tree as obtained by Rodriguez et al. (Am. J. Anat. 180: 143-155, 1987). We simulated single- and multiple-breath washout maneuvers and computed the slope of the alveolar plateaus and Fowler and Bohr dead spaces. In general, the comparison between experiments and simulations shows a good agreement, suggesting that the mechanism of diffusion-convection interaction in an asymmetric structure entirely accounts for the ventilation maldistribution in the rat lung. In particular, it is shown that the marked asymmetry of the rat lung structure is responsible for the fact that He slopes are larger than SF6 slopes in rat lungs, as opposed to what is observed in other species.

Animals

Effect on single-breath washout and lung function of elastase-induced emphysema in rats.

Lung volumes, diffusing capacity (DLCO), quasi-static pressure-volume curves (P-V), forced expiration (FE) and He-SF6 single-breath washout (SBW) were performed in Wistar rats with emphysema induced by different doses of pancreatic elastase in saline, instilled intratracheally 6 wk prior to the tests. Emphysema was quantitatively assessed by mean linear intercept (Lm) measurements on 5-microns lung sections. Lung volume, P-V curve, and FE dependence on Lm, as well as the nonsignificant dependence of DLCO on Lm, are generally similar to results reported by others. The most interesting observation concerns the SBW: N2 slopes of the alveolar plateau, compared for identical lung volumes, did not change with the degree of emphysema. By contrast, the He-SF6 slope difference did depend significantly on the degree of emphysema. Based on the diffusion front theory, the present work suggests that in rats with elastase-induced emphysema, the phase III slope modifications relate mainly to elastic and not to structural alterations.

Analysis of Variance

Controlled delivery of krypton-81m boli in normal subjects: results and implications.

Interregional sequential filling potentially affects lung ventilation imaging, depending on the distribution of the tracer within the inspired volume. We investigated its importance quantitatively under near tidal breathing conditions in the upright lung using a short-lived radioactive tracer. Ten normal volunteers performed two runs of 900-ml breaths (from functional residual capacity) in which 100 ml of 81mKr boli were delivered "early" or "late" in inspiration, i.e., 50 ml or 450 ml volumetric depth. Apex-to-base gradients in the vertical profile were -106 +/- 22 (s.e.) counts/cm (early) and -187 +/- 24 (s.e.) counts/cm (late). Ratios of upper-to-lower regional ventilation (U/L) were 0.88 +/- 0.01 (s.e.) (early) and 0.81 +/- 0.01 (s.e.) (late). Simulations with a compartment model show that a simple pattern of sequential filling can by itself account for the experimental results observed. Control over 81mKr delivery can be important to physiologically accurate assessment of ventilation-perfusion matching. Controlled delivery techniques could also modify effectiveness and targeting of other inhaled agents including therapeutic aerosols.

Administration, Inhalation

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.

Adult

Multiple-breath washout experiments in rat lungs.

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

Animals

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.

Animals