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Biomedical subjects

L A Engel

Publications and source records attributed to L A Engel.

At least 55 records · Page 3Linked to original sources

Volume acceleration as an index of neuromuscular output.

At the transition from expiration to inspiration, when flow and volume changes are small, changes in the respiratory system driving pressure could determine the degree of volume acceleration (AI), which, in turn, could reflect the degree of respiratory center output. To test this hypothesis, we calculated AI occurring in each respiratory cycle at the transition from expiration to inspiration during CO2 rebreathing in 4 healthy supine subjects. To minimize the flow and volume change over the measurement interval, we measured AI just prior to inspiration within the limits of an expiratory flow of 0.2 L . sec -1 to zero flow using digital differentiation. We also measured mouth pressure 100 msec after the onset of inspiration (P0.1) during intermittent transient inspiratory airway occlusions. During CO2 rebreathing AI increased significantly with both increasing PCO2 and P0.1. We also compared pairs of rebreathing studies, performed without and with an alinear (16 cm H2O . L -1 . sec -1) inspiratory resistor (IR), repeated twice in the 4 subjects. IR markedly decreased delta VE/delta PCO2 and the slope of the increase in mean inspiratory flow rate with PCO2 (delta VT/TI/delta PCO2) but did not significantly alter either delta AI/delta PCO2 or the increase in P0.1 with PCO2 (delta P0.1/delta PCO2). However, the effects of IR on AI and P0.1 differed between the early and late phases of each rebreathing run; early in the rebreathing runs (PCO2 = 55 Torr) IR increased both AI and P0.1 by a similar amount, but near the end of rebreathing (PCO2 = 60 Torr) IR increased P0.1 but not AI. Our results are consistent with the possibility that AI reflects neuromuscular output under the conditions of the study. Hence this approach justifies further evaluation to determine its general applicability.

Adult↗

Pressure-time product, work rate, and endurance during resistive breathing in humans.

We examined the effect of increasing work rate, without a corresponding increase in the pressure-time product, on energy cost and inspiratory muscle endurance (Tlim) in five normal subjects during inspiratory resistive breathing. Tidal volume, mean inspiratory mouth pressure, duty cycle, and hence the pressure-time product were kept constant, whereas work rate was varied by changing the frequency of breathing. There was a linear decrease in Tlim of -2.1 +/- 0.5 s.J-1.min-1 (r = 0.87 +/- 0.06) with increasing work rate. The data satisfied a model of energy balance during fatiguing runs (Monod and Scherrer. Ergonomics 8: 329-337, 1965) and were consistent with the hypothesis that the rate of energy supply, or respiratory muscle blood flow, is fixed when the pressure-time product is constant. Our results indicate that during inspiratory resistive breathing against fatiguing loads, work rate determines endurance independently of the pressure-time product. On the basis of the model, our results lead to estimates of respiratory muscle blood flow and available energy stores under the conditions of our experiment.

Adult↗

Influence of inspiratory flow rate and frequency on O2 cost of resistive breathing in humans.

We examined the combined effect of an increase in inspiratory flow rate and frequency on the O2 cost of inspiratory resistive breathing (VO2 resp). In each of three to six pairs of runs we measured VO2 resp in six normal subjects breathing through an inspiratory resistance with a constant tidal volume (VT). One of each pair of runs was performed at an inspiratory muscle contraction frequency of approximately 10/min and the other at approximately 30/min. Inspiratory mouth pressure was 45 +/- 2% (SE) of maximum at the lower contraction frequency and 43 +/- 2% at the higher frequency. Duty cycle (the ratio of contraction time to total cycle time) was constant at 0.51 +/- 0.01. However, during the higher frequency runs, two of every three contractions were against an occluded airway. Because VT and duty cycle were kept constant, mean inspiratory flow rate increased with frequency. Careful selection of appropriate parameters allowed the pairs of runs to be matched both for work rate and pressure-time product. The VO2 resp did not increase, despite approximately threefold increases in both inspiratory flow rate and contraction frequency. On the contrary, there was a trend toward lower values for VO2 resp during the higher frequency runs. Because these were performed at a slightly lower mean lung volume, a second study was designed to measure the VO2 resp of generating the same inspiratory pressure (45% maximum static inspiratory mouth pressure at functional residual capacity) at the same frequency but at two different lung volumes. This was achieved with a negligibly small work rate.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

O2 cost of inspiratory and expiratory resistive breathing in humans.

In six normal male subjects we compared the O2 cost of resistive breathing (VO2 resp) between equivalent external inspiratory (IRL) and expiratory loads (ERL) studied separately. Each subject performed four pairs of runs matched for tidal volume, breathing frequency, flow rates, lung volume, pressure-time product, and work rate. Basal O2 uptake, measured before and after pairs of loaded runs, was subtracted from that measured during resistive breathing to obtain VO2 resp. For an equivalent load, the VO2 resp during ERL (184 +/- 17 ml O2/min) was nearly twice that obtained during IRL (97 +/- 9 ml O2/min). This twofold difference in efficiency between inspiratory and expiratory resistive breathing may reflect the relatively lower mechanical advantage of the expiratory muscles in overcoming respiratory loads. Variable recruitment of expiratory muscles may explain the large variation of results obtained in studies of respiratory muscle efficiency in normal subjects.

Adult↗

Effect of expiratory glottic constriction on lung volume and pattern of breathing in adult dogs.

We examined the effect of laryngeal constriction on the pattern of breathing in 4 anaesthetized adult mongrel dogs. By means of a T-shaped tracheostomy tube the larynx could be repeatedly excluded or included in the breathing circuit. Marked expiratory activity of the thyroarytenoid muscle (TA), the main glottic constrictor, was induced by injection of 100-400 ml of air into the pleural space or by inhalation of histamine aerosol (2 dogs) which resulted in rapid shallow breathing. In 21 pairs of runs in the 4 dogs switching from tracheostomy breathing to oral breathing decreased mid-expiratory flow and frequency by 85 +/- 2% (P less than 0.001) and 48 +/- 4% (P less than 0.001), respectively. Although expiratory duration (TE) increased, end-expiratory lung volume also increased by 40 +/- 8 ml or 21 +/- 4% of the tidal volume (VT) during tracheostomy breathing (P less than 0.001). In contrast, VT remained unchanged (P = 0.9). Instantaneous ventilation decreased due to both the prolongation of TE and an increase in inspiratory duration. Our results indicate that laryngeal braking can be recruited in adult dogs and interacts with reflex mechanisms that modulate respiratory timing, thereby significantly influencing end-expiratory lung volume, ventilation and the pattern of breathing. Simulation of the laryngeal mechanism by expiratory resistive loading at the tracheostomy below the larynx points to a non-reflex mechanical effect of the larynx as a resistance in series.

Aerosols↗

Effect of cardiogenic gas mixing on arterial O2 and CO2 tensions during breath holding.

To examine the effect of cardiogenic gas mixing on gas exchange we measured arterial tension of O2 (PaO2) and arterial tension of CO2 (PaCO2) during 3- to 5-min breath holds (BH) before and after infusing 50 ml of saline into the pericardial space (PCF) of seven anesthetized, paralyzed, mechanically ventilated dogs. During BH the ventilator was disconnected and a bias flow of 50% O2 at 4-5 l/min was delivered through the side ports of a small catheter whose tip was positioned 1 cm cephalad of the carina. Paired runs, alternately with and without PCF, were performed in triplicate in each dog. Initial PaO2 was similar for control runs [81 +/- 3 mmHg (SE)] and PCF runs (78 +/- 3 mmHg; P greater than 0.1). After 3-min BH, PaO2 in PCF runs (33 +/- 3 mmHg) was less than that in control runs (58 +/- 4 mmHg) (P less than 0.001). In contrast, the pattern of PaCO2 during BH did not differ with PCF. After 3-min BH, PaCO2 was 49 +/- 3 mmHg with PCF and 49 +/- 2 mmHg in the control runs (P greater than 0.7). In two dogs, repeated 50-ml reductions in lung volume, produced by rib cage compression, did not alter the time course of PaO2 during BH. Although cardiac output decreased slightly with PCF, hemodynamic changes due to PCF were unlikely to account for the observed fall in PaO2. Our results indicate a substantial effect of cardiogenic gas mixing on O2 uptake when tracheal gas is O2 enriched during breath holding.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Effect of bronchomotor tone on static mechanical properties of lung and ventilation distribution.

To study the relationship between bronchomotor tone, static mechanical properties of the lung, and ventilation distribution, we measured the pressure-volume (P-V) curve of the lung and several ventilatory indexes before and after intravenous atropine in eight normal subjects. The indexes of ventilation distribution were derived from multiple breath N2 washouts by a recently developed analysis (7,8). The latter not only provides a sensitive measure of overall ventilation inhomogeneity but distinguishes between the convection-dependent inhomogeneity (CDI) among larger lung units and that due to the interaction of convection and diffusion (DCDI) within the lung periphery. Atropine decreased lung elastic recoil but distensibility, as defined by the exponent (K) in the monoexponential analysis of the P-V data, was unchanged. The overall ventilation inhomogeneity increased by 37% after atropine (P less than 0.02) due to an increase in the CDI component. More importantly, there was a significant correlation between the loss of lung recoil (but not K) and each of the indexes of CDI among the subjects. There was no correlation between the changes in lung recoil and in DCDI. Our findings indicate that normal bronchomotor tone contributes to the elastic recoil of the lung. Furthermore, the tone is distributed in a way that enhances the uniformity of ventilation distribution among diffusion-independent lung units. Presumably this is achieved by minimizing interacinar intrinsic inequalities in static mechanical properties.

Adult↗

Responses of the posterior cricoarytenoid and alae nasi muscles to increased chemical drive in man.

We examined the electromyographic activity of the posterior cricoarytenoid (PCA) simultaneously with the alae nasi (AN) in response to increasing chemical drive in 5 normal, awake human subjects. During progressive isocapnic hypoxia the peak of the integrated PCA activity (EPCA) increased as a function of tidal volume (VT), and in 3 of the 5 subjects the residual variance of an exponential fit (of the form EPCA = A - Be-KVT, where A, B and K are constants) was significantly less than that of a linear regression. In the other 2 subjects the data were too noisy to detect a difference although a positive relationship was present. In contrast, during progressive hyperoxic hypercapnia we found a linear relationship between EPCA and VT (r = 0.84 +/- 0.14) in all subjects over a comparable ventilatory range. The peak of the integrated AN activity (EAN) increased linearly with increasing VT during both hypoxia (r = 0.90 +/- 0.08) and hypercapnia (r = 0.89 +/- 0.12). Tonic EPCA also increased as a function of VT during both hypoxia and hypercapnia and at a VT of 1.6 L constituted 26 +/- 6% and 24 +/- 8% of the respective maximal peak EPCA. During hypoxia the relative increase in tonic EPCA occurred at a lower VT than during hypercapnia. Our results suggest that there are qualitative differences in the response of the PCA to increased chemical drive between hypoxia and hypercapnia. This is consistent with differing inputs to some upper airway motoneurones from central and peripheral chemoreceptors.

Adult↗

Effect of tidal volume on ventilation maldistribution.

To examine the effect of changing tidal volume (VT) on ventilation distribution, we studied multiple breath nitrogen washouts in 4 normal subjects breathing with a VT of 0.6, 1.0 or 1.5 L. We used a recently developed technique of analysis (Crawford et al., 1985) that distinguishes inhomogeneity of gas concentrations due to the interaction of convection and diffusion in the lung periphery (DCDI) from ventilation maldistribution among larger units determined at more proximal branchpoints (CDI). The results indicate that increases in VT reduce the inhomogeneity due to DCDI but increase that due to CDI. In view of the VT dependence of physiological dead space, derived from arterial PCO2, we speculate that the increase in CDI has a dominant effect on gas exchange.

Breath Tests↗

Influence of lung volume on oxygen cost of resistive breathing.

We examined the relationship between the O2 cost of breathing (VO2 resp) and lung volume at constant load, ventilation, work rate, and pressure-time product in five trained normal subjects breathing through an inspiratory resistance at functional residual capacity (FRC) and when lung volume (VL) was increased to 37 +/- 2% (mean +/- SE) of inspiratory capacity (high VL). High VL was maintained using continuous positive airway pressure of 9 +/- 2 cmH2O and with the subjects coached to relax during expiration to minimize respiratory muscle activity. Six paired runs were performed in each subject at constant tidal volume (0.62 +/- 0.2 liters), frequency (23 +/- 1 breaths/min), inspiratory flow rate (0.45 +/- 0.1 l/s), and inspiratory muscle pressure (45 +/- 2% of maximum static pressure at FRC). VO2 resp increased from 109 +/- 15 ml/min at FRC by 41 +/- 11% at high VL (P less than 0.05). Thus the efficiency of breathing at high VL (3.9 +/- 0.2%) was less than that at FRC (5.2 +/- 0.3%, P less than 0.01). The decrease in inspiratory muscle efficiency at high VL may be due to changes in mechanical coupling, in the pattern of recruitment of the respiratory muscles, or in the intrinsic properties of the inspiratory muscles at shorter length. When the work of breathing at high VL was normalized for the decrease in maximum inspiratory muscle pressure with VL, efficiency at high VL (5.2 +/- 0.3%) did not differ from that at FRC (P less than 0.7), suggesting that the fall in efficiency may have been related to the fall in inspiratory muscle strength. During acute hyperinflation the decreased efficiency contributes to the increased O2 cost of breathing and may contribute to the diminished inspiratory muscle endurance.

Adult↗

Effect of breath holding on ventilation maldistribution during tidal breathing in normal subjects.

To test the hypothesis that during the course of a multiple-breath N2 washout (MBNW) diffusion-dependent ventilation maldistribution is more apparent in the early breaths, whereas convection-dependent maldistribution predominates in the later breaths, we performed MBNW with 0-, 1-, and 4-s end-inspiratory breath holds (BH0, BH1, BH4, respectively) in five normal subjects. Each subject breathed with a constant tidal volume of 1 liter, at 10-12 breaths/min and at constant flow rates. For each breath we computed the slope of the alveolar plateau normalized by the mean expired N2 concentration (Sn), the Bohr dead space (VDB), and an index analogous to the Fowler dead space (V50). In all five subjects, Sn, VDB, and V50 decreased with breath holding, indicating diffusion dependence of these indexes. Over the first five breaths the rate of increase of Sn as a function of cumulative expired volume (delta Sn/delta sigma VE) decreased by 29 and 54% during BH1 and BH4, respectively, compared with BH0. In contrast, from breath 5 to the end of the washout there was no significant change in delta Sn/delta sigma VE during BH1 and BH4 compared with BH0. Our results provide further experimental support for the hypothesis that the increase of Sn as a function of cumulative expired volume after the fifth breath constitutes a diffusion-independent index of ventilation inhomogeneity. It therefore reflects alveolar gas inequalities among larger units.(ABSTRACT TRUNCATED AT 250 WORDS)

Humans↗

Upper airway dimensions and movements in bronchial asthma.

We measured the diameter and vertical displacement of the laryngeal and oropharyngeal airways in 8 seated asymptomatic asthmatic subjects (31 to 60 yr of age) before and after bronchoconstriction (BC) induced by histamine phosphate aerosol. An image of the airways was obtained in 2 planes using an X-ray fluoroscope attached to a videotape recorder, onto which signals of flow and volume at the mouth were recorded simultaneously. We calculated real dimensions from the video image using size markers included in the picture. During BC, when FEV1 fell to 35 +/- 4% (mean +/- SE) of control, the lateral diameter (DLAT) of the larynx at mid-expiration narrowed over approximately 10 mm vertical height above the glottis. Lateral diameter of the glottis during mid-expiration fell from 6.5 +/- 1.5 mm by 46 +/- 12% (p less than 0.05), but that during inspiration was unchanged. In the 3 subjects with the greatest glottic narrowing, anteroposterior diameter (DAP) and DLAT of the larynx at the level of the corniculate cartilages narrowed by 28 and 27%, respectively. There was inspiratory dilatation of the oropharynx during BC. The DAP during inspiration at the level of the hyoid increased from 15.0 +/- 1.5 to 17.5 +/- 1.5 mm (p less than 0.05), while that at the level of the third cervical vertebra (C3) increased from 12.5 +/- 1.5 to 17.0 +/- 2.0 mm (p less than 0.05). The diameters during mid-expiration were unchanged so that the difference between inspiration and mid-expiration increased at both levels. Higher in the oropharynx (20 mm above C3), expiratory DAP decreased in 6 of 8 subjects.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Model analysis of intra-acinar gas exchange.

A previously described multibranch-point model, incorporating branching asymmetry within an acinus, has been extended to include gas exchange at the alveolar surface. Using a transport equation for simultaneous convection and diffusion within the gas phase and independent perfusion of all nodes, we obtained steady-state solutions for the temporal and spatial distributions of O2 and CO2 tensions within an acinus during a respiratory cycle. Results for conditions corresponding to both rest and moderate exercise indicated a significant inhomogeneity of gas concentrations within a single acinus. The coefficient of variation of PACO2 at end-inspiration during exercise reached 11.3%. Despite this non-uniformity the computation of a negligible PAO2 - PAO2 difference indicated no impairment in gas exchange. The simulations are consistent with the hypothesis that in the normal lung the whole acinus acts functionally as a gas exchanging unit and ventilation-perfusion inequality has an interacinar basis.

Carbon Dioxide↗

Effect of expiratory loading on glottic dimensions in humans.

We examined the effects of external mechanical loading on glottic dimensions in 13 normal subjects. When flow-resistive loads of 7, 27, and 48 cmH2O X l-1 X s, measured at 0.2 l/s, were applied during expiration, glottic width at the mid-tidal volume point in expiration (dge) was 2.3 +/- 12, 37.9 +/- 7.5, and 38.3 +/- 8.9% (means +/- SE) less than the control dge, respectively. Simultaneously, mouth pressure (Pm) increased by 2.5 +/- 4, 3.0 +/- 0.4, and 4.6 +/- 0.6 cmH2O, respectively. When subjects were switched from a resistance to a positive end-expiratory pressure at comparable values of Pm, both dge and expiratory flow returned to control values, whereas the level of hyperinflation remained constant. Glottic width during inspiration (unloaded) did not change on any of the resistive loads. There was a slight inverse relationship between the ratio of expiratory to inspiratory glottic width and the ratio of expiratory to inspiratory duration. Our results show noncompensatory glottic narrowing when subjects breathe against an expiratory resistance and suggest that the glottic dimensions are influenced by the time course of lung emptying during expiration. We speculate that the glottic constriction is related to the increased activity of expiratory medullary neurons during loaded expiration and, by increasing the internal impedance of the respiratory system, may have a stabilizing function.

Adult↗

Pressure-time product, flow, and oxygen cost of resistive breathing in humans.

We examined the relationship between the pressure-time product (Pdt) of the inspiratory muscles and the O2 cost of breathing (VO2 resp) in five normal subjects breathing through an external inspiratory resistance with a tidal volume of 800 ml at a constant end-expiratory lung volume [functional residual capacity, (FRC)]. Each subject performed 30-40 runs, each of approximately 30 breaths, with inspiratory flow rates ranging from 0.26 +/- 0.01 to 0.89 +/- 0.04 l/s (means +/- SE) and inspiratory mouth pressures ranging from 10 +/- 1 to 68 +/- 4% of the maximum inspiratory pressure at FRC. In all subjects VO2 resp was linearly related to Pdt when mean inspiratory flow (VI) was constant, but the slope of this relationship increased with increasing VI. Therefore, Pdt is an accurate index of VO2 resp only when VI is constant. There was a linear relationship between the VO2 resp and the work rate across the external resistance (W) for all runs in each subject over the range of W 10 +/- 1 to 137 +/- 21 J/min. Thus, at a constant tidal volume the VO2 resp was related to the mean inspiratory pressure, independent of flow or inspiratory duration. If the VO2 resp were determined mainly during inspiration, then for a given rate of external work or O2 consumption, VI would be inversely related to mean inspiratory pressure. Efficiency (E) was 2.1 +/- 0.2% and constant over a large range of VI, pressure, work rate, or resistance and was not altered by the presence of a potentially fatiguing load. The constant E over such a wide range of conditions implies a complex integration of the recruitment, mechanical function, and energy consumption of the muscles utilized in breathing.

Adult↗

Convection- and diffusion-dependent ventilation maldistribution in normal subjects.

We performed multiple-breath N2 washouts (MBNW) with tidal volumes of 1 liter at 8-16 breaths/min and constant flow rates in six normal subjects. For each breath we computed the slope of the alveolar plateau, normalized by the mean expired N2 concentration (Sn), the Bohr dead space (VDB), an index analogous to the Fowler dead space (V50), and the normalized slope of phase II (S2). In four subjects helium (He) and sulfur hexafluoride (SF6) were washed out after equilibration with a 5% gas mixture of each tracer. The Sn for He and SF6 increased in consecutive breaths, but the difference (delta Sn) increased only over the first five breaths, remaining constant thereafter. In all six subjects Sn, VDB, and V50 increased progressively in consecutive breaths of the MBNW, the increase in Sn being the greatest, approximately 290% from the first to the 23-25th breath. In contrast, S2 was unchanged initially and decreased after the sixth breath. The results indicate that after the fifth breath the increase in Sn during a MBNW is diffusion independent and may constitute a sensitive index of convection-dependent inhomogeneity (CDI). Subtraction of this component from the first breath suggests that Sn in a single-breath washout is largely due to a diffusion-dependent mechanism. The latter may reflect an interaction of convection and diffusion within the lung periphery, whereas CDI may comprise ventilation inequality among larger units, subtended by more centrally located branch points.

Diffusion↗

Effect of abdominal strapping on chest wall mechanics during exercise in patients with severe chronic air-flow obstruction.

We studied the effect of abdominal loading on exercise performance in 7 patients with severe chronic air-flow obstruction (CAO). The patients were exercised to exhaustion on a bicycle ergometer at a work rate equivalent to 80% of their maximal work rate. Three exercise studies were completed in the same afternoon. The first and third were control studies; in the second, the abdomen was strapped with a belt that was secured after the patient had expired below FRC. Neither TLC (p greater than 0.3) nor FRC (p greater than 0.05) were altered by strapping. Exercising with the abdomen strapped resulted in a 40% increase in transdiaphragmatic pressure (Pdi) (p less than 0.005), but neither the peak inspiratory pleural pressure relative to the relaxation curve nor the minute ventilation differed from those of the control study (p greater than 0.7). Nevertheless, strapped exercise endurance (119 +/- 27 s) was significantly lower than control endurance (154 +/- 35 s; p less than 0.01). Because of the increase in Pdi, the computed tension-time index of the diaphragm increased from a control value of 0.13 +/- 0.05 to 0.20 +/- 0.06 (p less than 0.05) when strapped. However, neither the pleural pressure nor the Pdi swings decreased during the last 30 s of the runs, indicating that inspiratory muscle fatigue was not the basis for the reduced endurance when the abdomen was strapped. Strapping the abdomen may improve the length-tension relationship of the diaphragm at a given lung volume, and the increased Pdi suggests improved diaphragmatic function.(ABSTRACT TRUNCATED AT 250 WORDS)

Abdomen↗