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Biomedical subjects

L A Engel

Publications and source records attributed to L A Engel.

At least 73 records · Page 4Linked to original sources

Model analysis of gas distribution within human lung acinus.

Alveolar gas concentrations were simulated in an asymmetrically branching model of a human lung acinus based on morphometric measurements. The structure was expansile so that convective flow into and out of every part was proportional to its volume. Despite the homogeneous volume change solution of a differential equation for simultaneous convection and molecular diffusion following a 1-liter breath of O2 at 0.5 l/s predicted substantial inhomogeneity of O2 concentrations. This was reflected in a twofold range of inspired gas per unit volume computed from O2 concentrations averaged throughout expiration. Even a 10-s breath hold at end inspiration did not result in uniform concentrations. Larger breaths, corresponding to a ventilation of 60 l/min, increased the degree of inhomogeneity 50%. Diffusive pendelluft at intra-acinar branch points during expiration produced a sloping alveolar plateau of 0.53% N2/l, i.e., much smaller than that measured from the whole lung in vivo. Similarly, an estimate of single-breath mixing efficiency also indicated a much smaller degree of inhomogeneity than inferred from measurements of expired gases at the mouth. The model analysis suggests that if anatomical data used are representative of a normal lung, then the intra-acinar gas inhomogeneity, although substantial, constitutes a small fraction of the overall impairment in gas mixing.

Biological Transport↗

Respiratory activity of posterior cricoarytenoid muscle and vocal cords in humans.

We examined the respiratory activity of the posterior cricoarytenoid muscle (PCA) simultaneously with the movements of the vocal cords during tidal breathing and panting in four normal seated subjects. A bipolar electrode was constructed to record the surface electromyogram (EMG) of the PCA. The glottis was visualized with a fiberoptic bronchoscope, and the glottic image was recorded simultaneously with tidal volume and a digital time marker on video tape. During quiet breathing the integrated EMG signal (EPCA) showed consistent phasic variations in each subject. The inspiratory onset of EPCA in the four subjects preceded inspiratory flow by 170 +/- 80, 650 +/- 310, 130 +/- 80, and 130 +/- 90 ms (mean +/- SD), respectively. This lead time of the PCA was similar to that between the onset of glottic widening and inspiration in each subject. The proportion of each cycle during which EPCA increased (the duty cycle) was 31 +/- 3% (mean +/- SE), whereas the inspiratory portion of the respiratory cycle constituted 37 +/- 2% (mean +/- SE), respectively. The duty cycle of the PCA remained relatively constant in the same subject on different days. During panting at functional residual capacity, the EPCA increased to 142 +/- 11% of the peak activity recorded during the preceding control breaths. This was accompanied by a sustained increase in the glottic width to 91 +/- 9% of the peak value in the preceding breaths. These results confirm the role of the PCA as a principal abductor of the vocal cords and indicate a temporal relationship between PCA activation and the inspiratory phase of the respiratory cycle during tidal breathing in humans.

Electrodes↗

Chest wall mechanics during exercise in patients with severe chronic air-flow obstruction.

We studied the dynamic mechanical properties of the chest wall in 7 patients with severe chronic air-flow obstruction (CAO). Measurements were made during quiet breathing at rest and during exercise on a bicycle ergometer at work rates equivalent to 50 and 100% of their maximal work rate (Wmax). The peak inspiratory pleural pressure relative to the chest wall relaxation curve (Pmus) increased from 13.5 +/- 1.5 cm H2O at rest to 22.4 +/- 1.7 cm H2O at Wmax, while the coincident transdiaphragmatic pressure increased from 9.7 +/- 2.1 cm H2O at rest to 16.5 +/- 2.3 cm H2O at Wmax. Consequently, the coincident gastric pressure relative to its value during relaxation (Pab) was negative at rest (-4.5 +/- 1.7 cm H2O) and became even more negative (-6.3 +/- 2.3 cm H2O) at Wmax. Yet the increase in ventilation with increasing exercise was associated with an increase in the passive outward displacement of the abdomen (delta Vab) relative to the total volume change (delta Vab + delta Vrc), such that the ration delta Vab/(delta Vab + delta Vrc) increased from 0.37 +/- 0.08 at rest to 0.52 +/- 0.05 at Wmax. There was no respiratory paradox. From the analysis of volume-pressure tracings of the chest wall compartments we inferred that expiratory intercostal and abdominal muscles contracted forcefully during expiration on exercise, resulting in a marked increase in pleural pressure and a change in thoraco-abdominal configuration. This represented the storage of elastic and gravitational energy, which was released during inspiration, contributing to inspiratory pleural pressures and the enhanced inspiratory flow.(ABSTRACT TRUNCATED AT 250 WORDS)

Abdominal Muscles↗

Changes in rib cage shape during quiet breathing, hyperventilation and single inspirations.

We measured the relative changes in upper and lower rib cage volume (delta RCU and delta RCL, respectively) using an induction coil plethysmograph (Respitrace) in seven normal seated subjects during relaxed passive expiration from total lung capacity, during quiet breathing, rapid breathing at 60 breaths/min (RB), during exercise-induced hyperventilation (EH) and during single fast inspirations. The plot of the RCU vs RCL was slightly curvilinear during relaxation from total lung capacity in all subjects. However, the inferred changes in rib cage shape were similar during RB and EH to those observed during quiet breathing and the relaxation manoeuvres. In contrast, single rapid inspirations were associated with marked and variable changes in rib cage shape, being most prominent in the first part of the breath. Our results suggest that during cyclic breathing respiratory muscle activity is so co-ordinated that the pattern of rib cage shape change is similar to that observed during relaxation. In contrast, single rapid inspirations are associated with markedly different and variable shape changes of the rib cage, presumably due to different patterns of inspiratory muscle recruitment. The results are consistent with the observation that during tidal breathing regional ventilation distribution is flow independent.

Adult↗

Gas mixing within the acinus of the lung.

The subject is reviewed with an emphasis on recent developments in model analyses. Application of computer technology has facilitated the study of simultaneous convection and diffusion within a complex geometry approximating the airways and air spaces of the lung. During an inspiration of fresh gas the diffusion front separating inspired from "alveolar" gas is stationed within a portion of the acinus where the magnitudes of gas transport by convection and diffusion are similar. This constitutes the peripheral boundary of the Fowler dead space. Asymmetry of intra-acinar branching results in an inequality of gas concentrations within alveolar gas, despite homogeneous volume expansion. This is due to an interaction between diffusion and convection at branch points subtending units of unequal lengths. During a respiratory cycle a "diffusive Pendelluft" between these units results in a "first in-first out" pattern and a sloping alveolar plateau on the expired tracing, despite synchronous and homogeneous volume changes. Experimental results suggest that incomplete alveolar gas mixing constitutes a measurable limitation to gas exchange in the normal lung.

Animals↗

Respiratory movements of the vocal cords.

We examined the movements of the vocal cords during tidal breathing, panting, and large changes in lung volume in 12 normal subjects. The glottis was observed with a fiber-optic bronchoscope, and the glottic image was recorded together with flow, volume, and a time marker onto videotape. Phasic respiratory swings in glottic width (dg) and glottic area (Ag) were reproducible in all subjects but differed substantially between subjects. In the group as a whole dg and Ag increased during inspiration to 10.1 +/- 5.6 mm and 126 +/- 8 mm2 (mean +/- SE), respectively, whereas during expiration the lowest values were 5.7 +/- 0.5 mm and 70 +/- 7 mm2, respectively. These extreme dimensions corresponded closely to the midtidal volume points in the respiratory cycle. Glottic width during vital capacity (VC) expirations was nearly 30% greater at a flow of 1.2 l/s than at 0.5 l/s, but the relationship between dg and lung volume differed between subjects. When swings in dg were minimized by panting, there was no difference in dg between functional residual capacity (FRC) and a volume corresponding to midinspiratory capacity. However, tidal breathing at this lung volume was associated with a 20% decrease in dg compared with breathing at FRC. Our observations indicate a tight coupling between the pattern of glottic movement and the respiratory volume cycle. The results suggest that during voluntary respiratory maneuvers both intrinsic laryngeal and respiratory muscles are recruited, participating as effector organs in ventilatory and respiratory control.

Adult↗

Effect of a hydrostatic pleural pressure gradient on mechanical behavior of lung lobes.

Using 133Xe, the vertical distribution of regional volume (Vr) was measured in three regions of excised canine lobes both in air and when completely submerged in saline at 40, 60, 70, and 80% lobar vital capacity (VC). The estimated pleural pressure gradient, derived from values of Vr, distance between regions, and the lobar pressure-volume (PV) curve, underestimated the true gradient by 45%. Conversely, the gradient of Vr was substantially less than predicted. From the mean depth of each region below the waterline, pleural, and hence transpulmonary, pressure (PL) was computed. The values of Vr-PL for each region at 40, 60, and 80% lung volume (VL) were related to the lobar PV curve. Slopes of lines joining initial VL-PL points on the lobar PV curve to corresponding Vr-PL points in submerged lobes represent an effective regional compliance of a lobe undergoing deformation. With one exception this was less than the corresponding homogeneous compliance, indicating a stiffening of the lobe during deformation. Slopes of lines joining Vr-PL points of each region at the three lobar volumes represent effective regional compliance of a deformed lobe undergoing volume change. This was not significantly different from the homogeneous compliance. However, effective compliance can only be an approximate indicator of the forces required for a given volume change due to the inadequacy of PL to represent the unequal stress components induced by lobe deformation.

Animals↗

Factors influencing glottic dimensions during forced expiration.

To examine the relationship between expiratory effort, expiratory flow, and glottic aperture, we compared the effects of actively and passively produced changes in flow in six normal subjects. During flow transients of 1.08 +/- 0.08 l/s produced by voluntary expiratory effort, glottic width (dg) increased by 54 +/- 13% (mean +/- SE). In contrast transient increases in expiratory flow, produced passively by chest compression, were not accompanied by increases in glottic dimensions. Similarly, when subjects expired through a resistance, transient passive increases in mouth pressure of 8.1 +/- 0.8 cmH2O failed to increase glottic width. However, when similar positive-pressure transients were produced actively, dg increased by 97 +/- 36% even though the expiratory efforts were accompanied by relatively small increases in flow (0.20 +/- 0.05 l/s). During tidal breathing glottic widening commenced 160 +/- 60 ms before the onset of inspiratory flow, whereas the widening associated with active flow and pressure transients did not measurably precede the onset of the change in flow or pressure. Our results indicate that transient expulsive efforts are associated with synchronous increases in dg, regardless of whether expiratory flow increases. The findings are most readily explained by a centrally determined synchronous recruitment of intrinsic laryngeal and expiratory muscles that facilitates lung emptying by minimizing airway resistance during forced exhalation.

Adult↗

Spasmodic croup in the adult.

Recurrent inspiratory stridor, for which there appears to be no organic basis, can present a serious medical problem. We measured the changes in cross-sectional area of the glottic aperture during the respiratory cycle in a patient with recurrent inspiratory stridor when she was well, during a spontaneous attack, and during one induced with histamine aerosol. The glottis was visualized using a fiberoptic bronchoscope passed transnasally and attached to a video camera and tape recorder. During stridor there was marked constriction of the glottis on inspiration and phase reversal of the normal movements of the vocal cords with respect to respiration. Intermittent positive pressure ventilation (IPPV) and continuous positive airway pressure (CPAP) applied during stridor, in the absence of inspiratory effort, reversed the glottic narrowing. Pulmonary resistance (RL) on inspiration was elevated during stridor and returned to normal during IPPV and CPAP. Expiratory RL was normal throughout. Our results show that stridor in this patient was due to dynamic inspiratory constriction of the vocal cords. Glottic constriction could be induced by histamine aerosol and reversed when lung inflation was unaccompanied by inspiratory effort during IPPV and CPAP. Recognition and appropriate management of this condition may avoid potentially dangerous therapeutic interventions.

Adult↗

Mechanical load and inspiratory muscle action during induced asthma.

To examine the relationship between inspiratory mechanical load in asthma and the pattern of respiratory muscle recruitment, we studied lung and chest wall mechanics in 7 asymptomatic asthmatics in whom progressive bronchoconstriction was induced with inhaled aerosolized histamine. A fall in the FEV1 to 49.5 +/- 3.9% of the control value (mean +/- 1 SE) was associated with a 10.7-fold increase in the inspiratory work rate of the inspiratory muscles from 6.7 +/- 1.6 to 71.4 +/- 11.4 Joules/min. Elastic work accounted for 69% of the total work during the control period and 57% at the maximal level of bronchoconstriction studied. The net pressure-time product for the inspiratory muscles, measured over 1 min, rose fivefold from 245 +/- 33 cmH2O.s to a maximum of 1,211 +/- 107 cmH2O.s, indicating a relatively greater increase in the recruitment of the intercostal/accessory muscles of inspiration. The abdominal muscles, which were recruited during bronchoconstriction, relaxed during inspiration, and permitted outward movement of the abdominal wall with progressively smaller net increases in Pga. We concluded that during induced asthma (1) the increase in inspiratory muscle work was largely the result of hyperinflation, (2) the recruitment of the intercostal/accessory muscles exceeded that of the diaphragm, and (3) the combined action of the intercostal/accessory and abdominal muscles favored the diaphragm.

Abdominal Muscles↗

Changes in the glottic aperture during bronchial asthma.

We measured the cross-sectional area of the glottis in 12 asymptomatic asthmatic subjects before and after bronchoconstriction (BC) induced by histamine or ultrasonically nebulized water aerosol. The glottis was visualized using a fiberoptic bronchoscope attached to a video camera and tape recorder onto which flow and volume were simultaneously recorded. During induced asthma, measurements of forced expiratory flow fell to 36 +/- 3% (mean +/- SE) of control. Glottic area at mid-expiration (Age) fell from 75 +/- 14 mm2 by 45 +/- 8% (p less than 0.005). In some subjects, expiratory constriction of the supraglottic portion of the larynx and pharynx was also noted. Five subjects showed mild constriction (13 to 32%) of the glottis during inspiration. The administration of 10 cm H2O of continuous positive airway pressure (CPAP) during the induced asthma temporarily abolished expiratory constriction of the glottis and supraglottic structures; Age increased from 45 +/- 15 to 79 +/- 11 mm2 (p less than 0.01). The constriction returned when CPAP was stopped. After reversal of BC by salbutamol Age returned to values similar to those before BC. Although the mechanism for the expiratory glottic constriction is not known, it may be related to the different pattern of respiratory muscle activity seen in asthma. We speculate that the glottic constriction may contribute to hyperinflation by slowing expiratory flow and/or allowing a reduction in the persistent inspiratory muscle activity during expiration.

Adult↗

Gas mixing in the lungs of dogs and pigs.

We performed single breath washouts in 14 dogs and 4 pigs using a gas mixture containing 5% helium (He) and 5% sulphur hexafluoride (SF6) with, and without, an end inspiratory breathhold. In dogs, the slope of the alveolar plateau was steeper for SF6 than for He, the difference decreasing after 20 sec of breathholding. In contrast, in pigs there was no difference between the two slopes although both were steeper than in dogs. Following a 15-sec breathhold, both slopes decreased, that of the He plateau becoming significantly flatter than that for SF6. Furthermore, the expirate became relatively SF6 enriched. The results indicate that in pigs the mechanism responsible for the sloping alveolar plateau is not diffusion dependent, and hence cannot be due to 'stratification'. Neither do the results support diffusive interaction within an asymmetrical acinus as a basis for the slope. Our findings suggest that the latter is due to sequential emptying of relatively large units subtended by a branch point in which gas transport is entirely convective.

Animals↗

Influence of bronchial asymmetry on cardiogenic gas mixing in the lung.

To examine whether diffusive interaction in an asymmetrical bronchial tree contributes to cardiogenic mixing, we simulated the changes in nitrogen concentration (FN2) in an asymmetrical two-trumpet model of the lung based on canine anatomy during an inspiration of 100% oxygen and a subsequent breathhold. Results were obtained by solving a second-order differential gas-transport equation for simultaneous convection and diffusion with the assumption that velocity profiles were blunt. Cardiogenic flow pulses were simulated by periodic flow oscillations superimposed on constant respiratory flows. Both during inspiration and breath-holding the simulated pattern of FN2 within conducting airways was qualitatively similar to that observed in open-chested dogs. Despite the assumption of blunt velocity profiles, the apparent enhancement of gas mixing by oscillatory flows was comparable to that attributed to cardiogenic mixing in experimental studies. The results suggest that cardiogenic flow pulses in an asymmetrical bronchial tree may enhance gas mixing within the conducting airways by causing phasic displacements of diffusion fronts toward branchpoints subtending lung units of unequal volume. Diffusion of gas from the smaller units accelerates the decrease in inspired gas concentration within conducting airways.

Animals↗

Effects of inspiratory loading on respiratory muscle activity during expiration.

We studied respiratory muscle activity during expiration in four normal subjects during inspiratory resistive and elastic loading, with and without positive and expiratory pressure. Net inspiratory muscle activity (Pmus) was measured by relating esophageal pressure to the chest wall relaxation pressure-volume (P-V) curve. Abdominal muscle activity (Pabd) was quantitated by relating gastric pressure to the relaxation P-V curve of the abdomen. The decay rates of Pmus and of transdiaphragmatic pressure (Pdi) were increased during loading, and end-expiratory lung volume decreased. The decay rates of Pmus and Pdi were inversely related to expiratory duration. Inspiratory intercostal/accessory activity during expiration was frequently observed together with Pabd, especially during elastic loading. We conclude that external mechanical loads, acting during inspiration, influence respiratory muscle behavior during expiration. Inspiratory loads diminish expiratory braking by the inspiratory muscles and recruit expiratory muscles. The rate of expiration is enhanced and its duration shortened. Simultaneous persistent action of the inspiratory intercostal and accessory muscles throughout expiration may serve to optimize diaphragmatic length.

Abdominal Muscles↗

Effect of continuous positive airway pressure on respiratory mechanics and pattern of breathing in induced asthma.

We studied the effects of continuous positive airway pressure (CPAP) in 8 asthmatic subjects in whom bronchospasm was induced by aerosolized histamine. The CPAP (12.0 +/- 0.9 cm H2O) increased functional residual capacity by only 0.27 +/- 0.12 L, raised the minimal pleural pressure (Ppl) during inspiration from -32.3 +/- 2.6 cm H2O to -22.8 +/- 2.3 cm H2O (p less than 0.01), and decreased the swings in transdiaphragmatic pressure (Pdi) from 35.1 +/- 2.4 cm H2O to 29.6 +/- 3.7 cm H2O (p less than 0.05). Although ventilation (VE) increased, the inspiratory work per liter of VE fell significantly. More importantly, the pressure-time product for the inspiratory muscles (integral of Ppl.dl) measured over 60 s, fell from 830 +/- 111 to 573 +/- 41 cm H2O.s (p less than 0.05), whereas that for the diaphragm (integral of Pdi.dt) fell from 690 +/- 91 to 497 +/- 74 cm H2O.s (p less than 0.05). We conclude that in induced asthma, CPAP reduces the load on the inspiratory muscles, improving their efficiency and decreasing the energy cost of their action. Our results justify further investigation into the role of CPAP in the treatment of respiratory failure caused by severe bronchial asthma.

Abdominal Muscles↗

Analyses of sequential filling and emptying of the lung.

We simulated sequential filling and emptying of a lung lobe (Fukuchi et al., 1980) by solving a differential equation for simultaneous convection and diffusion within a solid expansile model of an asymmetrical acinus. For a given degree of asymmetry subtended at a fixed branch point the shorter units are consistently better ventilated (by diffusion) despite homogeneous lung expansion. Thus a helium bolus inhaled at 80% of vital capacity (VC) results in a higher helium concentration (FHe) at full inflation within the shorter units. A bolus inhaled at 20% VC results in relatively greater FHe in longer units. On expiration diffusive interaction between parallel pathways at the branch point results in a range of alveolar plateaus whose slope varies inversely with the volume at which the helium bolus is inhaled. This interdependence of gas transport among parallel pathways contributes to the "first in-last out' pattern observed experimentally. Comparison of radially expansile with axial-radially expansile models does not produce qualitatively significant differences. However, equilibration of gas concentrations during breathholding in the model occurs more rapidly than under experimental conditions indicating that other mechanisms may also contribute to the observed pattern of lung filling and emptying.

Humans↗

The anatomical basis for the sloping N2 plateau.

We examined the influence of asymmetry on the interaction of convection and gas-phase diffusion within the acinus of the lung. Single breaths of O2 were simulated by solving a differential equation for gas transport in two trumpet shaped units which were joined at a branch point and whose relative lengths and volumes were made to vary. Despite synchronous bulk flow to the from the units, in proportion to their relative volumes, the shorter unit always reached a higher O2 concentration (FO2) at end inspiration. Interdependence of gas transport at the branch point resulted in a falling FO2 within the shorter unit during expiration. The FO2 at the exit of the model therefore decreased progressively throughout expiration, simulating a sloping alveolar plateau. The simulations suggest that despite the relatively short distances separating parallel intra-acinar pathways, convective-diffusive interactions in the presence of asymmetry may produce substantial inhomogeneity in alveolar gas concentrations. Furthermore, the slope of the N2 plateau in the normal mammalian lung is explicable on the basis of the asymmetrical airway anatomy and well defined physical processes.

Humans↗

Cranio-caudal distribution of inspired gas and perfusion in supine man.

We measured the cranio-caudal distribution (A/B) of slowly inspired gas (VI) and of perfusion (Q) at different lung volumes in 8 supine subjects. When supine closing capacity (CC) exceeded supine FRC, A/B of VI was greater than unity and decreased at higher lung volumes (VL). When CC less than FRC, A/B of VI less than or equal to 1.0 and showed no VL dependence. When abdominal girth/height ratio (Ag/Ht) exceeded 0.50, supine CC was greater than upright CC and A/B of VI was greater. In contrast, A/B of Q greater than 1.0 at all VL and was not related to (FRC--CC). The results suggest that cranio-caudal distribution of inspired gas is influenced by airway closure in the dependent paradiaphragmatic lung regions and that the latter is enhanced in the presence of abdominal obesity. Perfusion distribution is preferential to lung apices, relatively volume independent, and not influenced by airway closure.

Adult↗