CO2 relaxes parenchyma in the liquid-filled rat lung.

CO(2) regulation of lung compliance is currently explained by pH- and CO(2)-dependent changes in alveolar surface forces and bronchomotor tone. We hypothesized that in addition to, but independently of, those mechanisms, the parenchyma tissue responds to hypercapnia and hypocapnia by relaxing and contracting, respectively, thereby improving local matching of ventilation (Va) to perfusion (Q). Twenty adult rats were slowly ventilated with modified Krebs solution (rate = 3 min(-1), 37 degrees C, open chest) to produce unperfused living lung preparations free of intra-airway surface forces. The solution was gassed with 21% O(2), balance N(2), and CO(2) varied to produce alveolar hypocapnia (Pco(2) = 26.1 +/- 2.4 mmHg, pH = 7.56 +/- 0.04) or hypercapnia (Pco(2) = 55.0 +/- 2.3 mmHg, pH = 7.23 +/- 0.02). The results show that lung recoil, as indicated from airway pressure measured during a breathhold following a large volume inspiration, is reduced approximately 30% when exposed to hypercapnia vs. hypocapnia (P < 0.0001, paired t-test), but stress relaxation and flow-dependent airway resistance were unaltered. Increasing CO(2) from hypo- to hypercapnic levels caused a substantial, significant decrease in the quasi-static pressure-volume relationship, as measured after inspiration and expiration of several tidal volumes, but hysteresis was unaltered. Furthermore, addition of the glycolytic inhibitor NaF abolished CO(2) effects on lung recoil. The results suggest that lung parenchyma tissue relaxation, arising from active elements in response to increasing alveolar CO(2), is independent of (and apparently in parallel with) passive tissue elements and may actively contribute to Va/Q matching.     

Mechanical properties of lung parenchyma during bronchoconstriction

Interdependence between airways and thelung parenchyma is thought to be a major mechanism preventing excessiveairway narrowing during bronchoconstriction. Because theelastance of the lung increases during bronchoconstriction, the lung'stethering force could also increase, further attenuatingbronchoconstriction. We hypothesized that the bulk () and shearmoduli (µ) of the lung increase similarly during bronchoconstriction.To test this hypothesis, we excised rabbit lungs and measured the lungvolume, pulmonary elastance, , and µ at transpulmonary pressuresof 4, 6, 8, 12, and 16 cmH₂O usingpressure-volume curves, slow oscillations of the lung, and anindentation test. Bronchoconstriction was induced by nebulizingcarbachol by using small tidal-volume ventilation to preventhyperinflation. The measurement of  and µ was repeated aftercarbachol treatment. After carbachol treatment, the increase in  wassignificantly greater than that in µ. The estimated value for µ was~0.5 × transpulmonary pressure both before and after carbachol treatment. These datasuggest that the tethering effect of the lung parenchyma, which servesto attenuate bronchoconstriction, is not significantly increased duringcarbachol administration unless there is hyperinflation.     

Dynamic properties of lung parenchyma: mechanical contributions of fiber network and interstitial cells

Yuan, Huichin, Edward P. Ingenito, and Béla Suki.Dynamic properties of lung parenchyma: mechanical contributions offiber network and interstitial cells. J. Appl.Physiol. 83(5): 1420-1431, 1997.We investigatedthe contributions of the connective tissue fiber network andinterstitial cells to parenchymal mechanics in a surfactant-freesystem. In eight strips of uniform dimension from guinea pig lung, weassessed the storage (G) and loss (G") moduli by usingpseudorandom length oscillations containing a specially designed set ofseven frequencies from 0.07 to 2.4 Hz at baseline, during methacholine(MCh) challenge, and after death of the interstitial cells.Measurements were made at mean forces of 0.5 and 1 g and strainamplitudes of 5, 10, and 15% and were repeated 12 h later in the same,but nonviable samples. The results were interpreted using a linearviscoelastic model incorporating both tissue damping (G) and stiffness(H). The G and G" increased linearly with the logarithmof frequency, and both G and H showed negative strain amplitude andpositive mean force dependence. After MCh challenge, the G andG" spectra were elevated uniformly, and G and H increased by<15%. Tissue stiffness, strain amplitude, and mean force dependencewere virtually identical in the viable and nonviable samples. The G andhence energy dissipation were ~10% smaller in the nonviable samplesdue to absence of actin-myosin cross-bridge cycling. We conclude thatthe connective tissue network may also dominate parenchymal mechanicsin the intact lung, which can be influenced by the tone or contractionof interstitial cells.

     

Hypo-elastic model for lung parenchyma

A simple, isotropic, elastic constitutive model for the spongy tissue in lung is formulated from the theory of hypo-elasticity. The model is shown to exhibit a pressure dependent behavior that has been interpreted in the literature as indicating extensional anisotropy. In contrast, we show that this behavior arises naturally from an analysis of isotropic hypo-elastic invariants and is a result of non-linearity, not anisotropy. The response of the model is determined analytically for several boundary value problems used for material characterization. These responses give insight into both the material behavior as well as admissible bounds on parameters. The model predictions are compared with published experimental data for dog lung.     

A model of non-uniform lung parenchyma distortion

A finite element model of mammalian lung parenchyma is used to study the effect of large non-uniform distortions on lung elastic behaviour. The non-uniform distortion is a uni-axial stretch from an initial state of uniform pressure expansion. For small distortions, the parenchymal properties are linearly isotropic and described by two elastic moduli. However, for large distortions, the parenchyma has anisotropic non-linear elastic properties described by five independent elastic moduli dependent on the degree of distortion; they are computed for a range of distortions and initial pressures. Ez, the Young's modulus in the direction of stretch, increases significantly with distortion (epsilon(z)) while Ex, the Young's modulus in the plane perpendicular to the stretch, is approximately constant. The greater the initial pressure, the bigger the difference between the two moduli at larger distortion strains. The shear modulus G(xz) is approximately independent of degree of distortion except at the highest initial pressure. The Poisson's ratio, nu(xz) is approximately constant with distortion strain for lower initial pressures, but increases significantly with epsilon(z) at higher pressures. Model predictions of the relation between G(xz) and initial uniform inflation pressure show a good correlation with reported experimental data for small distortion strains in a range of species. The model also exhibits similar behaviour to the experimentally measured uni-axial large deformations of a tri-axially pre-loaded block of parenchyma (Hoppin et al., 1975, Journal of Applied Physiology 39, 742-751).     

Properties of lung parenchyma in distortion.

This study offers a basis for evaluating and developing models of stress-strain behavior of the lung in distortion. Tensile forces were applied along three axes to cubes of dog lung parenchyma. With axially symmetrical force-loading, expansion was reasonably symmetrical and pressure-volume relationships were reasonably conventional in range, hysteresis, and time-dependent behavior. When the force load was changed on one axis only, that axis appeared more compliant than it did during symmetrical loading and the other axes changed length in the opposite sign. Similar distortion was apparent at the alveolar level. Data for five specimens over a range of applied loads are filed with the National Auxiliary Publications Service; graphical examples are presented herein. Relationship among the compliances for symmetrical and asymmetrical loadings were consistent with elastic theory. We derived the elastic coefficients, bulk and Young's moduli, and Poisson's ratio from the data. Poison's ratio was about 0.30 in air-filled specimens, but was lower (0.16-0.24) and increases with stress in saline-filled specimens.     

A strain energy function for lung parenchyma

The strain energy for the air-filled lung is calculated from a model of the parenchymal microstructure. The energy is the sum of the surface energy and the elastic energies of two tissue components. The first of these is the peripheral tissue system that provides the recoil pressure of the saline-filled lung, and the second is the system of line elements that form the free edges of the alveolar walls bordering the alveolar ducts. The computed strain energy is consistent with the observed linear elastic behavior of parenchyma and the data on large deformations around blood vessels.