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Biomedical subjects

S C Luijendijk

Publications and source records attributed to S C Luijendijk.

At least 37 records · Page 2Linked to original sources

Sloping alveolar plateaus of He and SF6 measured in excised cat lungs ventilated at constant volume by pressure changes.

Single-breath washout experiments with He and SF6 were performed in excised cat lungs placed in a closed, liquid-filled reservoir, where lung volume was clamped by the surrounding liquid and breathing was accomplished by hyperbaric pressure changes (pressure breathing) produced by a piston pump. Under these conditions the flow into each lung unit was assumed to be proportional to its volume, and sequential filling and emptying of lung units by convection probably did not occur. Thus, implicitly, gravity-dependent patterns of sequential filling and emptying of lung regions were also excluded. Different lung volumes (VL = 50%, 75%, 100% TLC, where TLC is total lung capacity), tidal volumes (VT = 21%, 34%, 47% TLC) and durations of post-inspiratory apnea (tA = 0,1,2,4,8 sec) were applied. The expirograms showed that the slopes of the alveolar plateau (S) were significantly positive for both He and SF6. For tA = 0 sec SHe ranged from 8.7 to 62.8% and SSF6 ranged from 24.4 to 87.8% (S is expressed in % per unit VE/TLC, where VE is expired volume). The ratio SSF6/SHe was larger than unity for each combination of VL and VT. Further, for tA = 0 sec both SHe and SSF6 showed a tendency to decrease with increasing VL and with increasing VT. For tA = 8 sec both SHe and SSF6 were close to zero. Additional single-breath washout experiments were performed with the same cat lungs by applying normal breathing where lung volume was not clamped and asynchronous unequal ventilation might have occurred. For comparable values of VL and VT, there were no clear differences between the slopes obtained at normal breathing and those obtained at pressure breathing. We conclude that asynchronous unequal ventilation plays only a minor role in the sloping alveolar plateau during normal breathing, and that the mechanism underlying the sloping alveolar plateau is diffusion dependent.

Animals↗

Collateral ventilation by diffusion across the alveolar walls and the exchange of inert gases in the lung.

The underlying hypothesis of this study is that collateral ventilation by diffusion of occluded air spaces in the lungs of patients with chronic obstructive pulmonary disease (COPD) may play a substantial role in the pulmonary gas exchange of these patients. Using a related lung model we have simulated: a) the multiple-breath washout of helium (He) and sulphur hexafluoride (SF6) from the alveolar space, and b) the washout of inert tracer gases with different blood-gas partition coefficients, range 0.01-330, from mixed venous blood. These computations were carried out for different values of the collateral diffusion capacity (CDC). Next, the results obtained at each individual value of CDC were used to compute the breath number (NCR) at the crossing-over of the He-SF6 washout curves and the inert gas shunt fraction QS/QC. NCR and QS/QC range up to about 100 and 0.04, respectively, when CDCSF6 ranges down to about 0.1 ml.min-1.mmHg-1. These ranges for NCR and QS/QC, and the typical finding of relatively large values for NCR in combination with small values for QS/QC, are also reported in the literature for patients with COPD. These agreements thus support our hypothesis. In line with the small values for QS/QC, our results further indicate that even large, well-perfused, occluded air spaces in the lung will hardly affect the recovered ventilation/perfusion distribution obtained from inert gas data when CDCSF6 exceeds 0.1 ml.min-1.mmHg-1.

Computer Simulation↗

The excretion of highly soluble gases by the lung in man.

The excretion (E) of inert gases by the lung depends on, among other things, their blood-gas partition coefficients (lambda). According to conventional gas exchange models, E should increase with increasing lambda. However, recent models that take into account the tidal character of breathing and the buffering capacity of lung tissue predict that E will show a minimum in the range of large lambda values (lambda greater than 10). Further, this local minimum should shift to larger lambda values in exercise conditions as compared to rest conditions. The aim of this study is to verify this predicted behaviour of E. The experiments were carried out with seven healthy subjects at rest and at three work loads (50 W, 100 W and 150 W) on a bicycle ergometer. The behaviour of E was determined from the results of a simultaneous washin of four tracer gases: ethyl acetate (lambda approximately 75), acetone (lambda approximately 330), ethanol (lambda approximately 2000) and acetic acid (lambda approximately 20000). The washin lasted 4 min, and E was calculated from E = 1 - PE-/PI, where PI and PE- are the partial pressures of the tracer gas in inspired and mixed expired gas determined from the recordings obtained during the last minute of washin. PI and PE- were measured with a mass spectrometer. Comparison of the E values of the four gases shows that at rest a minimum value for E is found for acetone. In exercise conditions, however, the smallest E value is found for the more soluble ethanol or acetic acid.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetates↗

The sloping alveolar plateau of tracer gases washed out from mixed venous blood in man.

We have investigated the slope of the alveolar plateau for inert tracer gases that were washed out from mixed venous blood. Two pairs of tracer gases were used (He, SF6) and (C2H2, Freon 22). The gases of each pair share almost the same blood-gas partition coefficient but they have different diffusive properties in the gas phase. The experiments were performed in healthy subjects at rest and at three levels of exercise (75, 150, 225 W). Each experiment started with the alveolar washin of the tracer gases by adding these gases to inspired air. This washin was continued for several minutes in order to dissolve sufficient amounts of the tracer gases in the body tissues. Subsequently, the tracer gases were washed out. In this paper, the slopes of the alveolar plateaus are defined as the relative increase of the concentration per second. Steeper slopes were found for the heavier gases (SF6 and Freon 22) in comparison with those for the lighter gases of the two pairs (He and C2H2). This finding may be ascribed to the contribution of diffusion-limited gas mixing in the lung to the slope of the alveolar plateau. For each gas, the slope for the first expiration during washout (alveolar washout) was considerably smaller than that for the later part of washout (mixed venous washout), and the difference amounts to about 56% and 76% of the slope during mixed venous washout at rest and at the highest level of exercise, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetylene↗

Diffusion-limited gas mixing in the lung and its consequences for transpulmonary gas transport.

The ratio of alveolar ventilations of He and SF6 (VA,He/VA,SF6) was determined in 7 healthy male subjects at rest and at three different levels of exercise on a bicycle ergometer (75, 150 and 225 W). This ratio was calculated from the ratio of the specific ventilations for these gases which were obtained from the decay of the end-tidal partial pressures of He and SF6 during a simultaneous, multiple-breath washout. In all experiments, VA for He was larger than VA for SF6. On the average, VA,He/VA,SF6 was equal to 1.09, and the mean values of this ratio at rest and at the three levels of exercise were not significantly different. Therefore, the difference in VA for He and SF6 (VA,He-VA,SF6) increased with increasing work load. Further, we used the mean value obtained for VA,He/VA,SF6 to calculate the ratio of excretion values (E1/E2) for pairs of hypothetical tracer gases with equal blood-gas partition coefficients and with different diffusivities in the gas phase. E1/E2 ranged from unity for lambda = 0 to about 1.08 for lambda = 10. At a given lambda, E1/E2 decreased with increasing ventilation-perfusion ratio of the lung. Thus, the difference between the excretion values of light and heavy tracer gases will be most pronounced under rest conditions and for gases that are well soluble in blood.

Adult↗

Transpulmonary pressure and phrenic activity in early inspiration.

The direct impact of changes in end-tidal transpulmonary pressure (P'L) on phrenic (Phr) activity has been investigated in 6 cats anaesthetized with pentobarbital or ketamine. Rapid changes in P'L were accomplished by step-like changes in tracheal pressure (Ptr), i.e., from Ptr = -12, -6, +6 and +9 cmH2O to Ptr = 0, and reversely. Phr activity was determined 0.2 and 0.4 s after the onset of Phr activity. This analysis was carried out for a few breaths immediately preceding and following the Ptr change, and the results for Ptr = 0 were used as a reference. Oppositely directed steps in Ptr, e.g., from Ptr = 0 to Ptr = +6 and, reversely, from Ptr = +6 to Ptr = 0, caused equal but opposite changes in Phr activity. Phr activity decreased with increasing P'L, and this decrease amounted to 15% and 12% for each cmH2O increase in P'L at 0.2 and 0.4 s respectively. These results imply that changes in P'L especially affect Phr activity early in inspiration. The results also show that Phr activity in the initial phase of inspiration strongly depends on P'L. Inhibition of inspiration facilitatory neurons by slowly adapting stretch receptors may be the kernel of the underlying mechanism of our findings.

Animals↗

Breathing patterns in anesthetized cats and the concept of minimum respiratory effort.

Theoretical studies dealing with the principle of minimal respiratory effort usually make use of sinusoidal or saw-tooth-like breathing patterns. Recent observations in anesthetized cats have shown that the driving pressure waveform for inspiration can be described by a power function of time and that most of expiration is passive. This driving pressure waveform, however, results in breathing patterns that differ from those described above. For this reason, we have reevaluated in anesthetized cats the principle of minimal respiratory effort by computing optimal duration of inspiration (TI) and optimal tidal volume (VT) for different ventilatory conditions using actual driving pressure waveforms. The results are in qualitative agreement with the experimental observations; i.e., optimal TI decreases and optimal VT increases with increasing minute ventilation. On the average, a good agreement is found between measured and computed values of TI. In some cats, however, there are substantial differences between observed and predicted values of TI, which can probably be ascribed to inaccuracies in the data used in our computations. Despite its limitations, the present model analysis is more realistic than previous ones because actual driving pressure waveforms are used together with actual values of effective inspiratory impedance.

Anesthesia↗

Excretion-retention data of steady state gas exchange in tidal breathing. I. Dependency on the blood-gas partition coefficient.

The aim of this study is to investigate the steady state gas transfer properties of the lungs. These properties can be derived from excretion-retention (E-R) data of inert tracer gases that are infused intravenously. E = PE/Pv and R = Pa/Pv, where PE, Pa and Pv represent the partial pressures of the tracer gases in mixed expired gas, arterial blood and mixed venous blood, respectively. In this paper, special attention is paid to the effects of tidal breathing on E-R data sets of tracer gases with different blood-gas partition coefficients. To that end, E-R data sets have been simulated with a lung model that takes into account tidal breathing, the morphometric geometry of the airways, diffusion limited gas mixing and gas dissolved in superficial lung tissue. The simulated E-R data sets are compared with E-R data sets obtained from anaesthetized dogs. Both the simulated E-R data sets and most of the in vivo determined E-R data sets are incompatible with a model description of pulmonary gas transfer with parallel placed compartments with different ventilation-perfusion ratios. Concerning the simulated E-R data sets, this incompatibility is due to the large buffering capacity of lung tissue for highly soluble gases in combination with the within-breath partial pressure oscillations in the airways.

Animals↗

Excretion-retention data of steady state gas exchange in tidal breathing. II. Dependency on the diffusion coefficient.

The steady state gas transfer properties of the lung can be derived from excretion-retention (E-R) data of inert tracer gases that are infused intravenously. E = PE/Pv and R = Pa/Pv, where PE, Pa and Pv represent the partial pressures of the tracer gases in mixed expired gas, arterial blood and mixed venous blood, respectively. In this paper, we investigate the influence of diffusive gas mixing in the lung on E and R. To that end, E-R data sets were simulated with a lung model that takes into account tidal breathing, the morphometric geometry of the airways, diffusion limited gas mixing in the alveolar space and gas dissolved in superficial lung tissue. The results show a linear relationship between R/E and D-0.5, where D represents the diffusion coefficient of the tracer gases in the alveolar gas mixture. This is in contrast to the results of simulations with a lung model that describes the different gas transport mechanisms, including diffusion, as a constant rate process, where a linear relationship between R/E and D-1 is predicted. It is further shown that E-R data of helium and sulphur hexafluoride cannot be used to demonstrate diffusion limited gas mixing in the lung, in particular, in the presence of a real shunt fraction. For that purpose, excretion data of pairs of tracer gases with different D but equal, medium blood-gas partition coefficients (1 less than lambda less than 30) should be used. For such pairs of tracer gases, the E values may differ by more than 10% when the D values for the two gases are 0.22 and 0.1 cm2s-1, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Blood Gas Analysis↗

Immediate response to resistive loading in anesthetized humans.

In eight spontaneously breathing anesthetized subjects (halothane: approximately 1 minimal alveolar concn; 70% N2O-30% O2), we determined 1) the inspiratory driving pressure by analysis of the pressure developed at the airway opening (Poao) during inspiratory efforts against airways occluded at end expiration; 2) the active inspiratory impedance; and 3) the immediate (first loaded breath) response to added inspiratory resistive loads (delta R). Based on these data we made model predictions of the immediate tidal volume response to delta R. Such predictions closely fitted the experimental results. The present investigation indicates that 1) in halothane-anesthetized humans the shape of the Poao wave differs from that in anesthetized animals, 2) the immediate response to delta R is not associated with appreciable changes in intensity, shape, and timing of inspiratory neural drive but depends mainly on intrinsic (nonneural) mechanisms; 3) the flow-dependent resistance of endotracheal tubes must be taken into account in studies dealing with increased neuromuscular drive in intubated subjects; and 4) in anesthetized humans Poao reflects the driving pressure available to produce the breathing movements.

Adult↗

Uptake of highly soluble gases in the epithelium of the conducting airways.

Short duration washin and washout experiments were carried out with the gases ether (diethyl ether), ethyl acetate and acetone in order to study the excretion behaviour in the lung of gases highly soluble in blood and tissues. Carbon dioxide (CO2) was analyzed as a reference gas during the washout. The excretion values for acetone were generally the lowest, those for ether the highest, and intermediate ones were obtained for ethyl acetate. These results are in accord with the experimental data of others. Analysis of the washout curves shows that for acetone the volume of gas expired before the beginning of phase II is considerably smaller than found for CO2 and ether. During washout, the slope of the alveolar plateau for acetone is negative for the first few breaths and becomes positive thereafter; however, it remains lower than the slopes for CO2 and ether, which are always positive. These two phenomena occurring during washout clearly demonstrate that the acetone in the expired air must originate from the epithelial tissue lining the conducting airways. We conclude, therefore, that, in terms of gas transport, the conducting airways behave differently for poorly and highly soluble gases and this provides a physiological basis for the deviating excretion behaviour of highly soluble gases.

Acetates↗

Longitudinal dispersion of gases measured in a model of the bronchial airways.

We investigated the longitudinal dispersion of helium (He), methane, acetylene, butane, sulfur hexafluoride, and octafluorocyclobutane (C4F8) in a clear plastic model of the human bronchial airways. The dimensions of the seven airway generations (0-6) of the model were chosen to be equal to those given by Weibel's model A (Morphometry of the Human Lung; New York: Academic, 1963). Total volume of the model amounts to 52 ml. A small bolus of each of the tracer gases was injected within 1 ms into a constant airflow at the inlet of the model, and the bolus dispersion curve was measured at the outlet by means of a mass spectrometer. Both inspirations and expirations were simulated; the four selected values of the flow rate (V) for each simulation were 0.25, 0.5, 1, and 2 1/s, respectively. The measured bolus dispersion curves were corrected for the response characteristics of the mass spectrometer. In this way, the basal shape of the dispersion curve could be shown to be Gaussian. No significant changes in the standard deviation (sigma v) (Ultman et al., J. Appl. Physiol. 44: 297-303, 1978) of each tracer gas are found for the V values applied. sigma v increases significantly (approximately 50%), however, between the lightest (He) and the heaviest (C4F8) tracer gas used. The mean sigma v values of the 24 results (4 V values and 6 tracer gases) obtained for inspirations and expirations are 15.3 and 13.6 ml, respectively.

Acetylene↗

Effect of resistive loading on inspiratory work output in anesthetized cats.

In five spontaneously breathing anesthetized cats, we determined the inspiratory elastic (Wel), resistive (Wres), and total (WI) mechanical work rates (power) during control and first loaded inspirations through graded linear resistances (delta R) by "Campbell diagrams" based on measurement of esophageal pressure. WI did not change with delta R's up to 0.31 cmH2O X ml-1 X s, the concomitant decrease in Wel being balanced by an increase in Wres. The stability of WI in the face of delta R's was due to the vagally mediated prolongation of inspiration and the intrinsic properties of the respiratory system and of the contracting inspiratory muscles. To assess the separate contributions of volume-related and flow-related intrinsic mechanisms to the stability of WI, we made model predictions of the immediate effects of delta R's on inspiratory mechanical work output based on measurements of inspiratory driving pressure waves and passive and active respiratory resistance and elastance on the same five cats. The results suggest that the intrinsic stability of WI in the face of delta R's is provided primarily by the active elastance.

Airway Resistance↗

Expiratory and arterial partial pressure relations under different ventilation-perfusion conditions.

Inert tracer gas exchange across the human respiratory system is simulated in an asymmetric lung model for different oscillatory breathing patterns. The momentary volume-averaged alveolar partial pressure (PA), the expiratory partial pressure (PE), the mixed expiratory partial pressure (PE), the end-tidal partial pressure (PET), and the mean arterial partial pressure (Pa), are calculated as functions of the blood-gas partition coefficient (lambda) and the diffusion coefficient (D) of the tracer gas. The lambda values vary from 0.01 to 330.0 inclusive, and four values of D are used (0.5, 0.22, 0.1, and 0.01). Three ventilation-perfusion conditions corresponding to rest and mild and moderate exercise are simulated. Under simulated exercise conditions, we compute a reversed difference between PET and Pa compared with the rest condition. This reversal is directly reflected in the relation between the physiological dead space fraction (1--PE/Pa) and the Bohr dead space fraction (1--PE/PET). It is argued that the difference (PET--Pa) depends on the lambda of the tracer gas, the buffering capacity of lung tissue, and the stratification caused by diffusion-limited gas transport in the gas phase. Finally some determinants for the reversed difference (PET--Pa) and the significance for conventional gas analysis are discussed.

Humans↗

Within-breath PCO2 levels in the airways and at the pulmonary stretch receptor sites.

The discharge frequency of pulmonary stretch receptors (PSRs) shows an inverse responsiveness to the CO2 partial pressure (PCO2), which is limited to an extremely hypocapnic range. During inspiration extremely hypocapnic PCO2 levels are obtained in a large part of the respiratory tract due to the diffusion limited gas mixing. The question remains whether PSRs in combination with these low levels of PCO2 are involved in the regulation of breathing. As a necessary first step to be able to answer this question, this paper is devoted to the calculation of the within-breath PCO2 transients in the respiratory tract and the corresponding PCO2 oscillations in the superficial airway tissue. For PSRs located in the smooth muscles of large bronchi, the calculations predict a time delay of a few seconds to adapt their discharge frequency to a change in PCO2 in the airway lumen. The result is in good agreement with the observed time delay reported in the literature. For the PSRs located in the acini the calculated time constant of their discharge response to PCO2 variations in the lumen is much smaller than 250 ms. This implies a within-breath response to the oscillating luminal PCO2. Further, the calculations show that a CO2 diffusion front is established within the acini during early inspiration. This diffusion front penetrates further and further into the acini with increasing work load due to the concomitant increase in inspiratory flow. As a consequence, the discharge frequency vs. volume response curve of PSRs, especially those located in distal airways, may be modified by a flow-induced PCO2-related contribution.(ABSTRACT TRUNCATED AT 250 WORDS)

Arteries↗

Inert tracer gas washout from mixed venous blood: the sloping alveolar plateau.

The aim of this model study was to investigate the mechanisms underlying the sloping alveolar plateau for inert tracer gases supplied to the lung by mixed venous blood. Transpulmonary gas exchange was simulated in an asymmetric lung model for conditions at rest and in exercise. For highly soluble gases, the calculations show that the varying amount of tracer gas dissolved in superficial parenchymal tissue and capillary blood causes a sustained stratification in the acinus during expiration and that this is mainly responsible for the slope. For this type of tracer gas, the slope is almost independent of variations in the molecular diffusion coefficient (D) of the gases. In contrast, for poorly soluble gases, the contributions of local parallel inhomogeneities of gas concentrations in the acinus and the continued gas exchange across the alveolo-capillary membrane are mainly responsible for the slope. The first factor, which depends on the asymmetric branching pattern of intra-acinar airways, increases with decreasing D values. The contribution of continued gas exchange to the slope is most pronounced under exercise conditions. This contribution is almost independent of the blood/gas partition coefficient, lambda, for lambda values less than 4.0.

Diffusion↗

Excretion-retention diagram to evaluate gas exchange properties of vertebrate respiratory systems.

Excretion [E = (PE - PI)/(PV - PI)] and retention [R = (Pa - PI)/(PV -PI)]are completely model-free defined variables which describe the dual input-output black-box representation of vertebrate respiratory systems under steady-state conditions. In the excretion-retention diagram (E-R diagram), E is plotted as a function of R. The application of the principle of mass conservation confines the possible combinations of E and R for a gas with a blood-gas partition coefficient, lambda, in a respiratory system with an overall ventilation, VT, and an overall perfusion, QT, to E = (lambda QT/VT) (1 - R). In general, E can be described as a continuous function of R. The mathematical formulation of this function depends on the configuration of the respiratory system. Easily recognizable curvatures are obtained for counter-cross, and cocurrent systems with and without parallel inhomogeneities. Visual inspection of actual E and R data displayed in an E-R diagram therefore allows the correct choice of the configuration of the respiratory system to be eventually used for further parameter estimation schemes. The E-R diagram is also a powerful tutorial tool for visualizing the complex relationships between the gas exchange of agents with different physical properties and the consequences of changes in ventilation and perfusion distribution within the respiratory system on gas transport.

Animals↗

Gas mixing in the small airways, described by old and new models.

This is a review of models built to explain the inefficiency of intrapulmonary gas mixing observed during multibreath tests, or to explain the slope of the alveolar plateau of the expiratory concentration-volume curve during single breath tests. The question, raised in 1917, whether diffusion was the limiting factor, received a negative answer in 1946. It then became necessary to postulate parallel unequal ventilation in combination with asynchronism. After 1966 diffusion was held responsible for stratification, a form of series inequality. However, a quantitative agreement with experimental data could only be achieved after the introduction of asymmetrical branching into the models.

Humans↗