Lung Parenchymal Strips Research Articles

In vitro responses to antigen stimulation: comparison between human lung parenchyma resected from asthmatic patients and non-asthmatic patients.

The airway of asthmatic patients is hyperresponsive to various stimuli in vivo. There are, however, only a few reports that compared the in vivo responsiveness of asthmatic patients and non-asthmatic subjects to those of lung parenchyma in vitro. To compare the contractile response, release of various chemical mediators, and responsiveness to drugs in samples of lung parenchyma excised from asthma patients with those of non-asthmatic subjects. Human lung parenchymal strips were subjected to passive sensitization with sera of 5+ RAST titer to mites. The strip was suspended in a magnus bath containing a buffer solution. Parenchymal contraction was induced by PGF2 alpha. After washing, the baseline concentrations of thromboxane B2 (TXB2), leukotriene (LT), and histamine were measured in each bath and then contraction was induced by the addition of a mite antigen. The concentrations of TXB2, LT, and histamine were measured after contraction. The inhibitory effects of TXA2 synthetase inhibitor (DP-1904) and TXA2 receptor antagonist (AA-2414) were also evaluated in both tissue samples. There were no significant differences between lung parenchymal tissues of asthmatic and non-asthmatic patients with regard to PGF2 alpha-induced contraction, antigen-induced contraction, release of chemical mediators, and the response to drugs. Unlike the response in vivo, there are no differences in the response to stimuli in vitro between lung parenchymal tissues of asthmatic and non-asthmatic patients.

Human lung parenchyma responds to contractile stimulation.

Tissue resistance increases after agonist challenge. Parenchymal contractile cells may be the responsible element. We investigated the viscoelastic properties of human parenchymal strips before and after challenge with acetylcholine (ACh) (10(-)3 M). Thirteen subpleural strips were oscillated in the organ bath, and measurements of resistance (R), elastance (E), and hysteresivity (eta) were obtained. After physiologic measurements, tissues were fixed for morphometric and immunohistochemical analysis. We quantitated the volume proportion of alveolar, airway, and blood vessel wall in individual strips. Smooth-muscle-specific actin was identified using a monoclonal antibody and the volume proportion of actin quantitated by point counting. After ACh, there was a significant increase in tension (2.6 +/- 0.6%), R (11.0 +/- 1.8%), E (4.3 +/- 0.7%), and eta (8.2 +/- 2.4%) (p < 0.002). Four strips contained no identifiable airways, yet in strips with and without airways there was no difference in the magnitude of the mechanical response or in the volume proportion of smooth-muscle-specific actin in the alveolar walls. We conclude that human lung parenchymal strips respond to ACh challenge with changes in dynamic mechanical behavior. Furthermore, small airways are not required for such a response to occur. This implicates a direct contractile response at the level of the alveolar wall and/or the alveolar duct.

The effect of treatment with a new antidepressant: INN 00835 on platelet serotonin uptake in depressed patients

The effect of chronic administration of platelet-activating factor (PAF) on airway reactivity, cell recruitment and lung morphology in the guinea-pig has been investigated. Alzet osmotic minipumps delivering either PAF (7.2 mg/kg/14 days) in 0.25% (w/v) bovine serum albumin in saline (saline-BSA), acetylcholine or saline-BSA alone were implanted s.c. in the neck region of guinea-pigs and connected to the jugular vein. In some experiments, implanted and non-implanted animals were treated daily with the PAF antagonist, BN 52021 (15 mg/kg, twice a day, p.o.). On day 15 after minipump implantation, the animals were anesthetized with urethane (1.2 g/kg, i.p.) and tracheal cannula was inserted for mechanical ventilation. Pulmonary inflation pressure (PIP) was monitored and airway responsiveness was assessed by administration of increasing doses of histamine (0.2–100 μg/kg, i.v.). As compared to saline-BSA-treated or non-implanted guinea-pigs, chronic treatment of the animals with PAF induced a significant (p<0.01) increase in airway response. No significant change in airway responsiveness was observed following chronic acetylcholine administration. In contrast, regardless of the treatment of the animals, no change in the threshold dose of histamine inducing alteration in PIP was noted, suggesting that PAF induces bronchopulmonary hyperreactivity rather than hyperresponsiveness. In addition, no significant difference was observed in the in vitro responsiveness to histamine of lung parenchymal strips from animals having received PAF or saline-BSA. Histological evaluation of the lung from guinea-pigs receiving PAF exhibited moderate hyperplasia of airway smooth muscle cells, marked eosinophil infiltration and increase in mast cell number in the peribronchial zone as compared to those from control, acetylcholine- or solvent-treated animals. These alterations were markedly reduced or absent in guinea-pigs implanted with PAF-containing minipumps and concomitantly treated with BN 52021. In conclusion, chronic administration of PAF to guinea-pigs results in airway hyperreactivity to histamine in vivo, associated with structural changes in airway smooth muscle cell mass, but which is unlikely to be secondary to protracted bronchoconstriction.

Antigen-induced responses in lung parenchymal strips during sinusoidal oscillation

We have recently demonstrated that tissue resistance increases during the early response to antigen challenge in sensitized Brown-Norway rats. The purpose of the present study was to investigate in vitro the dynamic tissue response to antigen challenge and the involvement of the mediators, i.e., serotonin (5HT) and leukotriene D4 (LTD4). In addition, we questioned whether strips from sensitized rats responded differently to nonspecific challenge compared with those of unsensitized controls. We sensitized Brown-Norway rats with ovalbumin and performed experiments using strips of subpleural parenchyma. Tissue strips were challenged with ovalbumin in the bath; in some experiments the tissues were exposed to methysergide (10(-6) M), a 5HT antagonist, or MK-571 (10(-6) M), a LTD4 receptor antagonist, or both, prior to challenge. At the end of the experiment all tissues were exposed to carbacholine (10(-3) M). Oscillation mechanics of tissue strips were studied and values of resistance (R), elastance (E), and hysteresivity (eta) were obtained. During ovalbumin challenge in sensitized tissues, R, E, and eta increased significantly (% change in R, 12.1 +/- 2.1%; % change in E, 3.8 +/- 1.3%; % change in eta, 9.3 +/- 2.8%). Both methysergide and MK-571 reduced the increase in R (3.0 +/- 0.6 and 3.2 +/- 0.8%, respectively, p < 0.05 vs. ovalbumin). There was no difference between sensitized and unsensitized strips in the response to carbacholine challenge. These data suggest that the oscillatory behaviour of tissue strips from sensitized rats is altered after ovalbumin challenge. The mechanism of that response is mediated by both 5HT and LTD4.

Antigen-induced responses in lung parenchymal strips during sinusoidal oscillation

We have recently demonstrated that tissue resistance increases during the early response to antigen challenge in sensitized Brown-Norway rats. The purpose of the present study was to investigate in vitro the dynamic tissue response to antigen challenge and the involvement of the mediators, i.e., serotonin (5HT) and leukotriene D4 (LTD4). In addition, we questioned whether strips from sensitized rats responded differently to nonspecific challenge compared with those of unsensitized controls. We sensitized Brown-Norway rats with ovalbumin and performed experiments using strips of subpleural parenchyma. Tissue strips were challenged with ovalbumin in the bath; in some experiments the tissues were exposed to methysergide (10-6 M), a 5HT antagonist, or MK-571 (10-6 M), a LTD4 receptor antagonist, or both, prior to challenge. At the end of the experiment all tissues were exposed to carbacholine (10-3 M). Oscillation mechanics of tissue strips were studied and values of resistance (R), elastance (E), and hysteresivity ( eta ) were obtained. During ovalbumin challenge in sensitized tissues, R, E, and eta increased significantly (% change in R, 12.1 ± 2.1%; % change in E, 3.8 ± 1.3%; % change in eta , 9.3 ± 2.8%). Both methysergide and MK-571 reduced the increase in R (3.0 ± 0.6 and 3.2 ± 0.8%, respectively, p < 0.05 vs. ovalbumin). There was no difference between sensitized and unsensitized strips in the response to carbacholine challenge. These data suggest that the oscillatory behaviour of tissue strips from sensitized rats is altered after ovalbumin challenge. The mechanism of that response is mediated by both 5HT and LTD4.Key words: tissue resistance, allergic asthma, serotonin, leukotrienes, hysteresis.

Responses of guinea-pig lung parenchymal strips to tracheobronchial lavage fluid from horses affected with summer pasture-associated obstructive pulmonary disease.

The response of parenchymal strips from guinea-pig lungs to tracheobronchial lavage fluid (TBLF) collected from 8 normal horses and from 8 affected with summer pasture-associated obstructive pulmonary disease (SPAOPD) was determined. TBLF was collected during the summer (July) and winter (February) seasons. The serum/TBLF urea nitrogen ratio was used to standardize the mediator concentration in the TBLF. Four strips were used from each guinea-pig. The first strip did not receive any antagonist and served as the control. The second, third and fourth strips received antagonists of PGE2, LTD4 and PAF, respectively at 10(-6) mol/L for 30 min. The tissues were then precontracted with a dose of histamine (10(-5) mol/L) and their responses to 1 ml of TBLF were determined. The study showed that TBLF obtained in the summer from unaffected horses produced a significantly greater relaxation than that from the affected horses, whereas TBLF obtained in the winter from unaffected or affected horses did not cause a significantly different degree of relaxation. Among the antagonist-treated strips, only those exposed to the PGE2 blocker showed a significant reduction in the relaxation caused by TBLF obtained in the summer from SPAOPD horses. This suggests that PGE2 is an important mediator present in the summer in the TBLF from horses affected with SPAOPD.

Glucocorticoid modulation of muscarinic and beta-adrenergic receptors in guinea pig lung.

We investigated the effect of the in vivo treatment of guinea pigs with methylprednisolone, 10 mg/kg daily, on lung muscarinic and beta-adrenergic receptors. Receptor densities were assessed by saturation experiments of tritiated N-methylscopolamine and dihydroalprenolol binding to lung membranes. After 3 h of treatment, methylprednisolone induced a decrease of 19.2% (P < 0.05) of muscarinic receptors but was without effect on beta-adrenergic receptor density. After 24 h, an increase of 39.7% (P < 0.01) and 16.9% (P < 0.05) was observed for muscarinic and beta-adrenergic receptors, respectively. For muscarinic receptors, this increase reached 53.4% (P < 0.01) within 48 h and stayed at this level until 96 h. The increase of beta-adrenergic receptors was maximal (24.9%) after 72 h and returned to the control value after 96 h. The dissociation constant (Kd) values of both ligands were not affected by the glucocorticoid treatment. Functional studies showed that the 96 h treatment did not affect the contractile response of guinea pig lung parenchymal strips to carbachol since the 50% concentration value (EC50) and the maximal contraction value (Emax) were not significatively different from control values. These data show that glucocorticoids control the expression of both muscarinic and beta-adrenergic receptors in guinea pig lung but with different time courses and to a larger extent for muscarinic receptors. The glucocorticoid treatment did not modify the contractile response of lung strips to carbachol, confirming the absence of effect on the affinity of muscarinic receptors and suggesting that the receptor reserve exceed the increase of their density by the steroid.

Inhibitory effect of thromboxane A2 synthetase inhibitor, DP-1904, on antigen-induced contraction of human lung parenchyma.

Several mediators are released from mast cells during allergic reactions. These substances cause contraction of airway smooth muscles, increase the permeability of blood vessels, and enhance mucous secretion. Among these mediators, thromboxane A2 (TXA2) has a particularly strong bronchoconstrictive effect. We examined antigen-induced contraction of excised human lungs and the suppressive effects of TXA2 synthetase inhibitor on TXA2 release. Human lung parenchymal strips were subjected to passive sensitization with sera of 5+ RAST titer to the mite. They were suspended in magnus baths, to which buffer and 10(-4) to 10(-8) M of DP-1904, an inhibitor of TXA2 synthetase, were added. Following the measurement of TXB2 and leukotriene (LT) concentrations in each bath, parenchymal contraction was induced by the addition of a mite antigen. The concentration of TXB2 and LT was measured after contraction. Antigen-induced release of TXB2 was significantly suppressed by DP-1904 in a concentration-dependent manner. DP-1904 did not inhibit parenchymal contraction and the release of LT. Antigen-induced parenchymal contraction was not suppressed by inhibition of TXA2 release, suggesting that DP-1904 may not be effective in asthma.

Characterization of the anatomical structures involved in the contractile response of the rat lung periphery

1. When lung parenchymal strips are challenged with different smooth muscle agonists, the tensile and viscoelastic properties change. It is not clear, however, which of the different anatomical elements present in the parenchymal strip, i.e., small vessel, small airway or alveolar wall, contribute to the response. 2. Parenchymal lung strips from Sprague Dawley rats were suspended in an organ bath filled with Krebs solution (37 degrees C, pH = 7.4) bubbled with 95%O2/5%CO2. Resting tension (T) was set at 1.1 g and sinusoidal oscillations of 2.5% resting length (L0) at a frequency of 1 Hz were applied. Following 1 h of stress adaptation, measurements of length (L) and T were recorded under baseline conditions and after challenge with a variety of pharmacological agents, i.e., acetylcholine (ACh), noradrenaline (NA) and angiotensin II (AII). Elastance (E) and resistance (R) were calculated by fitting changes in T, L and delta L/ delta t to the equation of motion. Hysteresivity (eta, the ratio of the energy dissipated to that conserved) was obtained from the equation eta = (R/E)2 pi f. 3. In order to determine whether small airways or small vessels accounted for the responses to the different pharmacologic agents, further studies were carried out in lung explants. Excised lungs from Sprague Dawley rats were inflated with agarose. Transverse slices of lung (0.5-1.0 mm thick) were cultured overnight. By use of an inverted microscope and video camera, airway and vascular lumen area were measured with an image analysis system. 4. NA, ACh and AII constricted the parenchymal strips. Airways constricted after all agonists, vessels constricted only after All. Atropine (Atr) pre-incubation decreased the explanted airway and vessel response to AII, but no difference was found in the parenchymal strip response. 5. Preincubation with the arginine analogue N omega-nitro-L-arginine (L-NOARG) did not modify the response to ACh but mildly increased the oscillatory response to NA after co-preincubation with propranolol (Prop). 6. These results suggest that during ACh and NA challenge, small vessels do not contribute substantially to the parenchymal strip response. The discrepancy between results in airways, vessels and strips when Atr was administered prior to AII implicates a direct contractile response in the parenchymal strip.

Bombesin-induced contractions of guinea pig lung strips are modulated by endogenous nitric oxide.

We have investigated the effects of a nitric oxide (NO) biosynthesis inhibitor N omega-nitro-L-arginine methyl ester (L-NAME) on the bombesin-evoked contraction of guinea pig parenchymal lung strips. The bombesin-induced contractions of lung strips were significantly increased after L-NAME (300 micro)) pre-treatment. The maximal response was increased (P < 0.01) by 37% after L-NAME treatment when compared with the control group. The pD2 value was not influenced by L-NAME pre-treatment. The enhancement of the bombesin-induced contraction caused by L-NAME was reversed by addition of an excess of the NO precursor L-arginine (600 microM) but not by the addition of its inactive enantiomer D-arginine (600 microM). Like L-NAME, methylene blue (1 microM), an agent that inhibits the soluble guanylyl cyclase activated by NO, significantly increased (P < 0.01) the maximal contraction induced by bombesin (183 +/- 16 mg) when compared with the control group (141 +/- 15 mg). When tested against other agonist-induced contractions, L-NAME did not change the responsiveness of parenchymal lung strips to bradykinin or carbachol but significantly increased lung contraction induced by histamine. NO synthesis inhibition resulted in a pronounced increase in the bombesin-induced contraction of guinea-pig lung strips. Our results suggest that bombesin contributes to NO synthesis and release which then acts to reduce the contraction of the lungstrip in response to bombesin.

Does the anatomic makeup of parenchymal lung strips affect oscillatory mechanics during induced constriction?

Parenchymal tissue strips have been used to investigate the mechanical behavior of the lung parenchyma. We questioned whether the relative amounts of alveolar, blood vessel, and bronchial walls would be important when the contractile response of parenchymal strips from Sprague-Dawley rats was studied. One group of strips was cut from the subpleural edge and another from between 1 and 3 mm proximal to the pleura. Strips were suspended in an organ bath filled with Krebs solution (37 degrees C, pH 7.4) bubbled with 95% O2-5% CO2. Resting tension (T) was set at 1.1 g, and sinusoidal oscillations of 2.5% resting length at a frequency of 1 Hz were applied. Measurements of length and T were recorded during baseline conditions and after acetylcholine (10(-3) M) was added to the bath. Elastance, resistance, and hysteresivity (the ratio of the energy dissipated to that conserved) were calculated. Strips were fixed in Formalin at a T of 1 g, histological sections were prepared, and the fractional areas of alveolar, blood vessel, and bronchial walls were measured by using point counting. Significant differences were found between the two groups of strips in the acetylcholine response and anatomic makeup. The magnitude of the changes of all the mechanical parameters were correlated with the volume proportions of the different anatomic constituents when all the strips were plotted together but not when the subpleural strips were considered alone. We conclude that subpleural parenchymal strips are a sound model of parenchymal lung behavior. When more proximal strips are studied, the amount of bronchial wall may play an important role in determining the hysteretic response.

Tachykinin receptors mediating contraction of guinea pig lung strips

The aim of this study was to determine which tachykinin receptors mediate contraction in guinea pig lung parenchymal strips in vitro. Contraction caused by selective neurokinin-1 (NK-1), neurokinin-2 (NK-2), and neurokinin-3 (NK-3) receptor agonists and the natural agonists substance P (SP) and neurokinin A (NKA) was measured in the absence or presence of the NK-1 antagonist CP-96,345 and/or the NK-2 antagonist SR 48968. The NK-1 agonist [Sar 9, Met(O 2) 11]-substance P and the NK-2 agonist [Nle 10]-neurokinin A 4–10 caused similar concentration-dependent contractions that were inhibited by CP-96,345 and SR 48968, respectively. The NK-3 agonist [MePhe 7]-neurokinin B also caused contraction, albeit at 10-fold higher concentrations, and this contraction was unaffected by either the NK-1 or NK-2 antagonist or the combination of both antagonists. Either CP-96,345 or SR 48968 alone had little effect on NKA-mediated contraction but administration of both antagonists virtually eliminated force generation. SP-induced tension was partially inhibited by SR 48968 and unaffected by CP-96,345. A second NK-1 receptor antagonist CP-99,994 also had no effect on SP-mediated tension. Therefore, NK-1, NK-2, and NK-3 agonists can all cause contraction in guinea pig lung strips, NKA-induced tension is mediated by both NK-1 and NK-2 receptors, and SP-induced contraction is mediated in part by NK-2 receptors. Both the SP and the [MePhe 7]-neurokinin B data suggest that activation of a third neurokinin receptor subtype that is unaffected by an NK-1 receptor antagonist or an NK-2 receptor antagonist can cause contraction in guinea pig lung strips.

Corrigenda for vol. 77, Pages 2029-2035

Pages 2029–2035: M.S. Ludwig and M.J. Dallaire. “Structural composition of lung parenchymal strip and mechanical behavior during sinusoidal oscillation.” Page 2031, figure numbers were cited incorrectly: instead of Figs. 2–4, Figs. 2,4, and 5 should have been cited and instead of Figs. 5–7, Figs. 3,6, and 7 should have been cited. The text below contains the correct information.

Possible role of thromboxane A2 in hyperresponsiveness of isolated rat lung tissue in a Sephadex-induced eosinophilia model.

Antigen-stimulated contraction and release of chemical mediators were examined in saline- or Sephadex-treated rat lung parenchymal strips. Sephadex treatment caused eosinophilia in the blood and the lung tissue. Antigen challenge of the isolated parenchymal strips in Sephadex-treated rat was followed by passive sensitization, resulted in an augmented contraction and elevated releases of thromboxane (TX) B2 and peptide-leukotrienes (p-LTs) in bath fluid compared with those of saline-treated control. Although 5-hydroxytryptamine (5-HT) and histamine were significantly released after antigen challenge, the levels were not different between saline- and Sephadex-treated groups. DP-1904, a selective thromboxane synthetase inhibitor, and methysergide but not atropine significantly reduced the augmented contraction and inhibited the elevated TXB2 release in the Sephadex-treated group. Similar increased contraction and the elevated TXB2 release above were observed when Sephadex-treated rat lung strips were stimulated by exogenous 5-HT and LTD4. These augmented contractions were closely correlated with the increase in TXB2 level (r = 0.83; p < 0.01). In addition, contraction to U-46619, a thromboxane mimetic, was significantly greater in Sephadex-treated rat lung strips. Our results indicate that the ability of Sephadex-treated rat lung tissue to synthesize newly generated mediators such as TXA2 and p-LTs is increased, and the spasmogenic susceptibility of the lung tissue to TXA2 itself is modified by Sephadex treatment, suggesting these are due to the augmented contraction in an established hyperresponsiveness state induced by Sephadex.

Structure-Activity Studies of the C-Terminal Segment of Structurally Reduced Analogues of ET-1

Structurally reduced analogues of endothelin-1 (ET-1) were synthesized by linking via aminocaproic acid (Aca) the segment 3-11 of ET-1 to C-terminal fragments of various lengths [16-21, 17-21,...,21]. Analogues were studied in their linear or cyclic form in the absence or presence of a formyl group on the Trp21 side-chain, and their biologic activities were tested using guinea pig lung parenchymal strips. The absence of the first disulfide bridge and the presence of the Aca spacer caused a slight decrease in activity. The presence of His16 is essential for the contractile activity of the monocyclic peptides. Formylation of these monocyclic analogues did not modify this behavior. Similarly, linear analogues carrying S-acetamidomethyl (Acm) functions and an Aca linker were still active. However, most formylated linear derivatives were partial agonists, whereas the addition of His16 caused a decrease in contractile activity. In these latter analogues, molecular modeling studies suggested that formylation produces different conformations.

Reversibility of tachyphylaxis to C5a in guinea pig tissues, perfused human placental lobule, and umbilical artery

The spasmogenic effect of C5a is mediated by histamine and/or eicosanoids. Tachyphylaxis to this effect of C5a occurs rapidly, but the spasmogenic effects of C5a on a guinea pig lung parenchymal strips, field-stimulated ventricular papillary muscle, and human umbilical artery were completely restored by a 1-h period of drug-free rest, whereas that of guinea pig ileum was not. Perfusion of the isolated human placental lobule with C5a caused a transient pressor response that was largely abolished by indomethacin (5 microM), indicating mediation by cyclooxygenase metabolites. This pressor response to C5a was also completely restored following a 1-h rest period. The results show that tissue rest reverses tachyphylaxis to the spasmogenic effects of C5a in tissues where the response is mediated by cyclooxygenase metabolites. Where the response is mediated by histamine released by mast cells, restoration does not occur, presumably because of the catastrophic nature of mast cell degranulation. Histamine released in guinea pig papillary muscle by C5a may be from non-mast-cell sources.

Human FcERI-IgG and humanized anti-IgE monoclonal antibody MaE11 block passive sensitization of human and rhesus monkey lung

IgE antibodies are thought to play an important role in the induction of allergic inflammation of the bronchi. In this study we assessed the capacity of two inhibitors, FcERI-IgG, an immunoadhesin made up of the a chain of the high-affinity IgE receptor joined to a truncated IgG heavy chain, and MaE11, a humanized murine anti-human IgE antibody, to prevent allergen sensitization. Lung parenchyma strips from rhesus monkeys and human beings were passively sensitized for 20 hours with serum from a ragweed-sensitive patient in the presence of 0, 1-, 5-, or 10-fold concentrations of the inhibitors relative to IgE. The parenchymal strips were then suspended in a superfusion apparatus for measurement of isometric tone and collection of superfusate for histamine analysis in response to challenge with antigen E (AgE). Nonsensitized tissues did not react to AgE challenge, whereas AgE challenge of passively sensitized tissues resulted in a time-dependent parenchymal contraction and histamine release. Both FcERI-IgG and MaE11 completely abolished the AgE-induced contraction and histamine release in a dose-dependent manner. In addition, passively sensitized lung tissues failed to respond to direct challenge with either FcERI-IgG or MaE11. The results of this study suggest that FcERI-IgG and MaE11 may have important immunotherapeutic benefit for the amelioration of IgE-mediated diseases.

Lung tissue rheology and 1/f noise.

The mechanical properties of lung tissue are important contributors to both the elastic and dissipative properties of the entire organ at normal breathing frequencies. A number of detailed studies have shown that the stress adaptation in the tissue of the lung following a step change in volume is very accurately described by the function t-k, for some small positive constant k. We applied step increases in length to lung parenchymal strips and found the ensuing stress recovery to be extremely accurately described by t-k over almost 3 decades of time, despite the quasi-static stress-length characteristics of the strips being highly nonlinear. The corresponding complex impedance of lung tissue was found to have a magnitude that varied inversely with frequency. We note that this is highly reminiscent of a phenomenon known as 1/f noise, which has been shown to occur ubiquitously throughout the natural world. 1/f noise has been postulated to be a reflection of the complexity of the system that produces it, something like a central limit theorem for dynamic systems. We have therefore developed the hypothesis that the t-k nature of lung tissue stress adaptation follows from the fact that lung tissue itself is composed of innumerable components that interact in an extremely rich and varied manner. Thus, although the constant k is no doubt determined by the particular constituents of the tissue, we postulate that the actual functional form of the stress adaptation is not.

Structural composition of lung parenchymal strip and mechanical behavior during sinusoidal oscillation

The lung parenchymal strip is comprised of many different anatomic elements, including small vessels, small airways, and alveolar walls. We questioned whether the relative amounts of these different structures are important in determining the mechanical behavior of this preparation during dynamic oscillations. We studied 16 parenchymal strips (10 x 2 x 2 mm) from 12 Sprague-Dawley rats. The strips were suspended in an organ bath filled with Krebs solution, bubbled with 95% O2-5% CO2, and maintained at 37 degrees C. One end of the strip was attached to a force transducer, and the other end was attached to a lever system that effected length (L) changes. We oscillated the strips at various resting tensions (T) (0.9 and 1.5 g), frequencies (0.1, 0.3, 0.6, and 1.0 Hz), and amplitudes (1.1, 2.4, and 5.3% of optimal L). We obtained T vs. L curves and calculated the resistance, elastance, and hysteresivity (ratio of energy dissipated to energy stored) of the tissue. At the end of the experiment, the strips were fixed in Formalin at T = 1 g. Histological sections were examined, and the amounts of airway, blood vessel, and alveolar wall were quantified using point counting techniques. We found that whereas resistance varied significantly with frequency and T, elastance and hysteresivity varied with only T. The fractional areas of alveolar, blood vessel, and bronchial wall were 86.3 +/- 0.5 (SE), 8.4 +/- 0.3, and 5.3 +/- 0.4%. Only hysteresivity and the fractional area of alveolar wall were significantly correlated at the lower resting tension (r = -0.76, P = 0.02).(ABSTRACT TRUNCATED AT 250 WORDS)

Effect of elastase on oscillation mechanics of lung parenchymal strips

Using isolated parenchymal strips from degassed rat lungs, we studied the contribution of the collagen-elastin network to lung tissue hysteretic behavior. Strips were suspended in an organ bath filled with Krebs solution (37 degrees C, pH 7.4) continuously bubbled with 95% O2-5% CO2. One end of the strip was attached to a force transducer and the other to a servo-controlled lever arm. Sinusoidal oscillations of 2.5% of resting length were applied at 1 Hz. Measurements were sampled under baseline conditions at different levels of stress (sigma = 10-26 g/cm). Porcine pancreatic elastase (0.05 IU.mg tissue-1.ml Krebs solution-1) was then added to the bath, and tension and length were measured continuously for 15 min at sigma = 15 g/cm. After washout, measurements were repeated at sigma = 10-26 g/cm. Elastance (E) and resistance (R) were calculated using the equation of motion. Hysteresivity (eta), the structural damping coefficient, was obtained using the following equation: eta = (R/E) pi 2f, where f is frequency. At baseline, we found that E and R were significantly dependent on sigma (P < 0.01), whereas eta was unchanged. During enzymatic digestion with elastase, there were significant decreases of tension, E, and R and no change in eta. Significant increases in E and R were found when these parameters were compared at the same sigma before and after treatment. Again, eta did not change. The constancy of eta after elastase suggests that disruption of the elastin-collagen network does not alter the coupling between elastic and dissipative processes in lung tissue.