L.A. Engel

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.

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.

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.

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.

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.

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.

Influence of diaphragmatic contraction and expiratory flow on the pattern of lung emptying.

Transdiaphragmatic pressure (Pdi) and expiratory flow (V) were monitored during vital capacity single breath N2 washouts in 7 seated subjects. Transient increases in V were produced (1) actively, by subjects increasing mouth pressure while expiring through a constant resistance of (2) passively, by the operator transiently decreasing the resistance. Voluntary contraction of the diaphragm (increased Pdi) was achieved when abdominal muscles were tensed while maintaining V constant. In 5 subjects a transient increase in Pdi of 25-150 cm H2O consistently produced a transient increase in expired N2 concentration of 1.80 +/- 0.06% (Mean +/- 1 SE); in 1 subject N2 concentration decreased by 0.8% to 2.7% N2, and in one subject the alveolar plateau was uninfluenced by changes in Pdi. Passive increases in V up to 21/sec had no effect on FEN2 in any of the subjects. Active increase in V changed FEN2 only when associated with increases in Pdi. Qualitatively similar results were obtained during helium (He) bolus washouts. However, whereas diaphragmatic contraction, maintained throughout expiration, had no measurable influence on the N2 washout, it changed the slope of the He alveolar plateau in 6 out of 7 subjects. We conclude that in normal subjects the alveolar N2 plateau is relatively insensitive to flow variations up to 21/sec. The fluctuations in FEN2 observed when the expiratory flow is varied are due to concomittant changes in Pdi. We propose that diaphragmatic contraction changes the pattern of lung emptying by altering the vertical gradient of pleural pressure.

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.