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Biomedical subjects

L A Engel

Publications and source records attributed to L A Engel.

At least 91 records · Page 5Linked to original sources

Vertical distribution of perfusion and inspired gas in supine man.

In order to specify if a closing volume greater than expiratory reserve volume could influence the distribution of perfusion (Qr), we measured vertical Qr in 6 supine subjects before and after inhalation of an oxygen enriched gas mixture. In addition, we studied Qr and inhaled gas (V alv.) at different lung volumes. We observed a preferential perfusion of non-dependent zones of the supine lung during tidal breathing from FRC correlated to the amount of airway closure represented by the difference between FRC and closing capacity. After oxygen breathing, the distribution of perfusion is reversed and flow is preferentially distributed in the dependent zones of the supine lung. This O2 sensitive effect was time and/or volume history dependent since Qr distribution at FRC after a breath to total lung capacity was similar to that after 3 min of tidal breathing with oxygen mixture. At FRC, the ventilation was preferentially distributed to the non-dependent lung zones. The vertical gradient of both Qr and V alv. increased progressively at higher lung volumes and Va/Q ratios were usually greater in non-dependent zones.

Adult↗

Inspiratory muscle activity during induced hyperinflation.

We studied the relationship between inspiratory muscle activity and lung volume in 5 normal subjects in whom hyperinflation to 78-83% VC was induced with exgernal expiratory resistances. While breathing at this high lung volume the most negative pleural pressure (Ppl) during inspiration was -23.4 +/- 2.3 cm H2O (mean +/- 1 SE), whereas the maximum expiratory Ppl was -4.2 +/- 1.6 in four and +31 cm H2O in one subject. Using relaxation pressure-volume curves of the chest wall, we reasoned that in the 4 subjects inspiratory muscles showed a substantial persistence of activity throughout expiration. The minimum inspiratory muscle force (Pmus) during expiration was 35.9 +/- 8.4% of the peak inspiratory Pmus. Similarly, the work of the inspiratory muscles in expiration was 57.8 +/- 9.5% of the work during inspiration. In all 5 subjects the diaphragm relaxed almost completely in expiration, as evidenced by the transdiaphragmatic pressure (Pdi), which fell during expiration to 10.0 +/- 4.1% of the peak inspiratory Pdi. Inspiratory intercostal and scalene electromyographic recordings, obtained in 3 subjects, demonstrated substantial activity in expiration. We conclude that during external, resistive, expiratory loading the volume of hyperinflation is influenced by persistent activity of inspiratory muscles in expiration, and that this is due largely to the inspiratory intercostal and accessory muscles rather than the diaphragm.

Diaphragm↗

Intraregional basis for sequential filling and emptying of the lung.

We studied the sequential pattern of lung filing by measuring the slope of the alveolar plateau in single breath helium washouts after inhaling a bolus at a lung volume (VI) equivalent to 20. 40, 60 and 80% of vital capacity (VC). In seated subjects, prone dogs, both with the chest intact and wide open, and individual canine lobes, slopes at VI = 20% VC were more positive than those at VI = 80% VC, indicating a "first in - last out' pattern. Furthermore the range of slopes, which reflects the magnitude of sequencing, was comparable in the four situations. We conclude that sequential filing and emptying of the lung has predominantly an intraregional basis. A two compartment optimization analysis using single exponential pressure-volume curves suggests that only a small proportion of the lung needs to behave differently to produce the sequencing observed in individual lobes.

Adult↗

Shrinkage of dog lobes during air-drying fixation.

Air-drying of canine lung lobes, distended at a constant pressure corresponding to 50% of lobar total lung capacity, resulted in a volume shrinkage of 35.8%. To examine associated changes in shape of the lobes, the shrinkage of three orthogonal directions (x, y, and z) was quantitated by measuring the change in length per unit length (strain; epsilon) of straight lines between pleural markers. Epsilon x = 0.14, epsilon y = 0.22, and epsilon z = 0.12. This inequality of strains indicated that moderate shape changes occurred. The direction of the largest strain component (epsilon y) corresponded to a direction normal to the largest projected surface area of the lobe.

Animals↗

The role of respiratory muscles in the hyperinflation of bronchial asthma.

To examine the mechanism of hyperinflation in bronchial asthma we studied lung and chest wall mechanics in 7 asymptomatic patients in whom progressive bronchoconstriction was induced by doubling the amount of inhaled aerosolized histamine. An increase in pulmonary resistance (RL) from 2.5 +/- 0.3 cmH2O . 1-1 . s (mean, +/- 1 SE) to 12.3 +/- 0.9 cmH2 was associated with a linear increase in functional residual capacity (FRC) up to 74.7 +/- 1.7% of control total lung capacity (TLCc). The mean regression coefficient was 2.3% TLCc . cmH2O-1 . 1 . s-1. At each level of hyperinflation the most positive expiratory pleural pressures measured during spontaneous breathing were generally less than the predicted chest wall relaxation pressures, indicating persistent inspiratory muscle contraction throughout expiration. This was predominantly due to inspiratory intercostal and accessory muscle activity, because measurements of transdiaphragmatic pressure indicated complete diaphragmatic relaxation early in expiration. Recruitment of abdominal muscles during expiration, inferred from measurements of gastric pressure (Pg) and abdominal antero-posterior (A-P) diameter, was progressively more apparent with increasing bronchoconstriction. We concluded that the increase in FRC in induced asthma is substantially influenced by persistent inspiratory intercostal and accessory muscle activity during expiration. Concomitant abdominal muscle recruitment results in a chest wall configuration that tends to optimize diaphragmatic function.

Abdomen↗

Dual tracer single breath studies of gas transport in the lung.

We studied the ratio of the expired He and SF6 concentrations (He/SF6) after 1 litre inspirations of a gas mixture containing 5% of He and SF6. Five subjects aged 49 to 60 yrs. performed the maneuvers with both inspiration and expiration at 0.2--0.41/s or 1.5--2.01/s. In all subjects separation of the tracer gases was observed, the He/SF6 falling early to a minimum of 0.80 +/- 0.01 (mean +/- 1 SE), and increasing gradually during expiration to a maximum of 1.08 +/- 0.01. The slope of the SF6 alveolar plateau was 1.45 +/- 0.09 times that for He. Computer simulations of simultaneous convection and diffusion in an axisymmetrical series lung model predicted a pattern of He/SF6 early in expiration which corresponded qualitatively to that observed experimentally. However, the model did not predict a rising He/SF6 ratio late in expiration. This was simulated only by incorporation of parallel inhomogeneity with sequential emptying into the model analysis. Consideration of Taylor type dispersion and airway asymmetry did not influence the simulations significantly. The results suggest that differing slopes of the alveolar plateau of two tracer gases may be due to diffusion dependent concentration differences among lung units ventilated in parallel rather than due to stratification alone.

Computers↗

Voluntary changes in ventilation distribution in the lateral posture.

To determine whether voluntary changes in the pattern of inspiratory muscle contraction influence topographical distribution of ventilation in the lateral decubitus posture during tidal breathing, we studied 4 normal subjects who breathed either naturally (N) or preferentially with intercostal and accessory muscles (IC), or with enhanced motion of the diaphragm and abdomen (Ab). We performed N2 as well as 133Xe washouts (after equilibration) which were measured at the mouth while recording regional count rates by external scintillation detectors. Ventilation per unit volume (delta V/Vo) in the nondependent lung regions was 0.55 +/- 0.05 (mean +/- 1 SD) and 0.42 +/- 0.02 of that in the dependent regions during natural and sustained Ab breathing, respectively. In contrast, during IC breathing this ratio was 0.99 +/- 0.17. Although N2 washout curves obtained during IC breathing more closely approached a monoexponential than did those from N and Ab runs, a two compartment analysis of washouts at the mouth did not demonstrate significant differences between breathing patterns. We conclude that in the lateral posture voluntary relaxation of the diaphragm during tidal breathing distributes the gas preferentially to the nondependent lung regions. Conversely, during N and Ab breathing the preferential ventilation of dependent regions is due to contraction of the diaphragm.

Diaphragm↗

On the boundary conditions used in calculations of gas mixing in alveolar lungs.

The lung boundaries exhibit a tight barrier for any insoluble gas; hence boundary conditions for lung gas mixing have to account for the absence of both diffusive and convective fluxes across the lung walls. Scrimshire et al. (1978) have, in contrast, used the less rigid boundary condition that only the net flux be zero. As we believe this boundary condition to be inappropriate for the study of insoluble gases, the results derived appear to have no physiological significance.

Humans↗

Effect of pentobarbital anesthesia on rheology and transport of canine tracheal mucus.

Tracheal mucus samples were collected from six tracheostomized dogs before and after induction of pentobarbital anesthesia. The dynamic mechanical properties of the mucus were determined by the magnetic microrheometer technique. In 15 experiments, the mean value of elasticity at 1 rad/s rose from 67 dyn/cm2 before anesthesia to 212 dyn/cm2 in the period 15-90 min after induction. At the same time, mean viscosity at 1 rad/s rose from 24 to 79 P. The mucociliary transportability of some of the mucus samples was assayed by means of in vitro frog palate technique. In 10 experiments, the relative transport rate for dog tracheal mucus went from 98% of frog palate control befor anesthesia to 79% during pentobarbital anesthesia. A negative relationship between from palate transport rate and mucus elasticity was found. A negative correlation between transport and mucus viscosity at constant elasticity was also discovered. Finally, the mucus collection rate was reduced by a factor of about 8 during anesthesia, suggesting a reduction in the average depth of mucus.

Animals↗

Variability of airway responses to inhaled histamine in normal subjects.

Dose-response curves to inhaled histamine were studied in 12 normal subjects. Pulmonary resistance (RL) and dynamic compliance (Cdyn) were measured during tidal breathing, and maximum expiratory flow rates, at an absolute lung volume corresponding to 40% of control vital capacity, were obtained during forced expiration from tidal end inspiration (Vmax40p) and from total lung capacity (Vmax40c). Threshold was defined as the histamine dose at which a departure from the range of normal measurements was observed. RL and Vmax40p indicated lowest threshold values, which varied by a factor of 32 and 38, respectively. There was no correlation between reactivity, which reflects the slope of the dose-response curve beyond the threshold dose, and threshold doses, nor between the initial RL (normalized for lung volume) and either threshold or reactivity. In eight subjects, restudied on two occasions after 10 mg propranolol or after saline, injected in a double-blind manner, there was no change in the dose-response curves. These results indicate that different indices of bronchoconstriction may yield different dose-response curves and hence different sensitivities. In addition, a wide variation of airway responses to inhaled histamine exists in the normal population and beta-blockade does not influence this variability.

Adult↗

Pulmonary interdependence of gas transport.

We have examined the interaction of convection and gas-phase diffusion among parallel pathways of the human lung by solving the differential equation for gas transport in a solid geometric model. Two trumpet-shaped units with a threefold differences in volume flow were joined at a branch point that could be varied in position along the airway tree. Because diffusion dominates gas transport in peripheral airways, or when time for diffusion is large, alveolar concentrations are more homogeneous than predicted from volume flows when the branch point is peripheral to respiratory bronchioles, or when total flow rate is small. When the branch point is in the larger airways, subtending large units of lung, diffusion is less important, so that alveolar concentration of each unit depends almost completely on its volume flow. These simulations provide a possible explanation for experimental findings of partial separation of inert gases of differing diffusivities and of improved O2 exchange when dense gases are breathed.

Helium↗

Models of the pressure-volume relationship of the human lung.

The static pressure-volume (PV) curve from TLC to RV of 11 human subjects was fitted by a hyperbolic-sigmoid model: P = k1/(VM--V)+k2/(Vm--V)+k3, where VM and Vm are the upper and lower asymptotes respectively, and k1, k2, k3 are shape constants. Least-squares nonlinear regression was used to evaluate the constants for the individual and mean data. Average SD of residuals was 0.57 cm H2O and average reduction of residual variance was 99.93%. In spite of substantial differences between PV curves, the latter can be modelled accurately. For the mean PV curve, values for VM, Vm and k1, k2, k3 were 110% VC, -4.34% VC, 260 cm H2O/% VC, 50.5 cm H2O/% VC and 3.13 cm H2O respectively. Unlike previously proposed models, the above includes data below FRC. It describes the truly linear portion of the PV curve at and above FRC. The lower inflection point is accomodated at different lung volumes. When used in a compartmental analysis of a homogeneous lung exposed to a constant pleural pressure gradient, it predicts sequential emptying of dependent and nondependent lung regions consistent with that observed experimentally.

Humans↗

Effects of intravenous histamine on lung mechanics in man after beta-blockade.

In six nonatopic normal subjects, neither intravenous histamine infusion (0.3 mg.kg-1.min-1) nor intravenous propanolol (10 mg) alone produced significant change in pulmonary mechanics. Histamine infusion after propranolol resulted in an increase in pulmonary resistance (RL) from 2.1 +/- 0.41 (mean +/- 1 SE) to 3.3 +/- 0.76 cmH2O./-1.S-1 (P greater than 0.05); maximal flow at 50% total lung capacity (Vmax 50) decreased from 3.6 +/- 0.35 to 2.7 +/- 0.44 l/s (P greater than 0.01). Similar changes in Vmax 50 were observed during partial forced expiratory maneuvers from end-tidal inspiration (PEFV). On 80:20 helium-oxygen mixture Vmax 50 during maximal expiration (MEFV) decreased from 4.9 +/- 0.61 to 3.4 +/- 0.61 l/s (P greater than 0.005) and during PEFV diminished from 4.6 +/- 0.61 to 2.8 +/- 0.46 l/s (P greater than 0.005). Density dependence (deltaVmax 50) decreased significantly (P greater than 0.05) during PEFV but not during MEFV. There were no significant changes in tidal pulmonary compliance, in closing volume and closing capacity (resident gas technique), and in inflation and deflation pressure-volume curves. We conclude that iv histamine in low doses constricts peripheral conducting airways in man but this effect is masked by histamine-induced release of catecholamines from the adrenal glands.

Adult↗

Flow dependence of gas distribution and the pattern of inspiratory muscle contraction.

We measured regional distribution of xenon-133 boli at 0.25, 0.75, and 1.5 l/s in four normal seated subjects during inspirations performed predominantly with intercostal and accessory muscles (IC) or with the diaphragm, accompanied by outward abdominal motion (Ab). In six additional subjects we inferred the topographical distribution of helium boli during similar breaths and flow rates from the slope of the alveolar plateau recorded during a slow expiration (less than 0.5 l/s). Distribution of the helium boli was studied during natural as well as IC and Ab inspirations. At each of the flow rates IC breaths distributed relatively more of the inspired bolus to upper lung regions than did Ab inspirations. Natural breaths at 0.25 l/s resulted in distributions similar to those of Ab inspirations, whereas at 1.5 l/s the distribution approached that of IC inspirations. A three-compartment model, representing upper, middle, and lower lung regions, was used to simulate bolus distribution. The experimental data showed substantial departure from predictions based on regional time constants alone. However, additional small differences in applied pressure (less than 0.50 cmH2O) between the regions satisfactorily accounted for the gas distribution.

Abdominal Muscles↗

Influence of the panting technique on the plethysmographic measurement of thoracic gas volume.

In 7 normal subjects we studied the effect of different panting techniques on the measurement of thoracic gas volume (VTG). When inspiratory efforts against the occluded airway were performed primarily with intercostal and accessory muscles, the value of VTG was significantly larger than during efforts performed primarily with the diaphragm. The difference could be as large as 900 ml during the same occlusion and was due to compression and decompression of abdominal gas. The divergence of the measured VTG from the true VTG depended on the volume of abdominal gas (Vab) and the ratio of gastrict to mouth pressure changes (deltaPg/deltaPm). In our normal subjects, Vab was 358 +/- 65 ml (mean +/- SE) and deltaPg/deltaPm ranged from 0.7 to -2.5. In 10 randomly selected patients with a variety of pulmonary disorders, the mean value of deltaPg/deltaPm was 0.32. In one subject with asthma who increased his total lung capacity by one liter after exercising, deltaPg/deltaPm did not change significantly from the control value. Our results indicated that the pattern of panting is an important determinant of the accuracy of plethysmographic measurement of VTG. However, preliminary results from studies of patients suggest that the error is small and does not account for the large changes in lung volume measured in patients with acute asthma.

Abdomen↗

Topographical ventilation and perfusion distribution during IPPB in the lateral posture.

We measured topographical ventilation and perfusion distribution in the gravity field using 133Xe in 5 normal subjects either during natural breathing or during intermittent positive pressure ventilation (IPPB) in the lateral decubitus posture. The ratio of ventilation of upper regions to that of lower regions increased from 0.61 +/- 0.10 (mean +/- SE) during natural breathing to 0.95 +/- 0.08 during IPPB. In contrast, the ratio of regional perfusion was unchanged in the 2 conditions. Consequently, distribution of regional ventilation-perfusion ratios became less homogeneous during IPPB. Whereas during natural breathing the ratio of ventilation-perfusion of upper regions to that of lower regions was 1.09 +/- 0.18, during IPPB this ratio was 1.52 +/- 0.14. Despite the differences in regional ventilation distribution between natural breathing and IPPB, analysis of multiple-breath 133Xe washouts measured at the mouth did not reveal any difference. The results are consistent with the hypothesis that the magnitude of diaphragmatic tension is the main determinant of topographical ventilation distribution in the lateral posture.

Humans↗