How changes in the serial distribution of bronchoconstriction affect lung mechanics

It is generally accepted that methacholine (MCh) acts predominantly on the central airways and histamine (H) acts on the lung periphery. We hypothesized therefore that lung mechanics would be affected differently by H and MCh aerosols. In 12 anesthetized paralyzed open-chest mongrel dogs, we obtained MCh (0.1-30 mg/ml, n = 6) and H (0.1-30 mg/ml, n = 6) concentration-response curves. The alveolar capsule technique was used to partition lung resistance (RL) into airway (Raw) and tissue (Rti) components. The degree of mechanical heterogeneity across the lung was assessed by computing the coefficient of variation for five alveolar pressures during relaxed expirations. RL increased 823 +/- 202% after H and 992 +/- 219% after MCh. Rti increased 784 +/- 192% after H and 1,014 +/- 279% after MCh. Raw increased 1,098 +/- 297% after H and 1,275 +/- 332% after MCh. Elastance increased 342 +/- 53% after H and 423 +/- 88% after MCh. The coefficient of variation increased 279 +/- 65% after H and 252 +/- 55% after MCh. The patterns of change were similar throughout the H and MCh concentration-response curves. We conclude that H and MCh have comparable effects on lung mechanics and that the degree and pattern of heterogeneity inside the lung after constriction are the same regardless of the agent used. These data support the hypothesis that H and MCh have some similar direct effect on the lung parenchyma. Parenchymal deformation after MCh-induced central airway constriction alone would be unlikely to explain increases in Rti of this magnitude or changes in lung mechanics so similar to those induced by

Contribution of quasi-static tissue hysteresis to the dynamic alveolar pressure-volume loop

We obtained dynamic and flow-interrupted (quasi-static) pressure-volume loops from the lungs of anesthetized paralyzed open-chest mongrel dogs by measuring tracheal flow and pressure and alveolar pressure (PA) in three different regions using alveolar capsules. We used continuous tidal ventilation to obtain dynamic PA-volume loops and used the single-breath-interrupter technique to construct quasi-static pressure-volume loops for the same tidal volume (VT). We used three different VT's (15 and 20 ml/kg and inspiratory capacity) under control conditions and a VT of 15 ml/kg after methacholine-induced bronchoconstriction. We found that quasi-static hysteresis was negligible under control conditions for VT of 15 and 20 ml/kg. Quasi-static hysteresis became more important (36 +/- 11% of the corresponding dynamic PA-volume loop) during inspiratory capacity ventilation and after induced bronchoconstriction (27 +/- 12% of the corresponding dynamic PA-volume loop). We conclude that during tidal breathing near functional residual capacity "true" static hysteresis is negligible and that purely viscoelastic processes can explain lung mechanical behavior. For higher volume ventilation and after methacholine-induced constriction, quasi-static hysteresis accounted for a more important portion of dynamic tissue hysteresis. This suggests either that a more complex model, e.g., one including plastic processes, should be invoked or that the lung exhibits longer viscoelastic time constants as peak distending stresses become greater

Assessment of respiratory system viscoelasticity in spontaneously breathing rabbits

Airflow, volume (V), inspiratory time (Ti), tracheal pressure (Ptr), abdomen (Dab) and rib cage diameters (Drc), peak diaphragm (Adi) and parasternal muscle activity (Aic) were measured in thirteen anaesthetized and vagotomized rabbits and in six vagotomized rabbits with cordotomy at T1 during unimpeded inspirations followed by rapid end-inspiratory airway occlusion, relaxation against closed airways, and inspiratory effort. To modify the inspiratory flow pattern, such sequences were performed at different volume, levels of chemical drive, and body temperatures (BT). Under all conditions, Adi, Aic, Ti, Drc and Dab at iso-volume were the same for unimpeded and occluded inspirations; end-inspiratory Ptr was lower for occluded than for unimpeded inspirations, the difference (Pdiff) being larger the lower the volume at which occlusions were performed and the higher the chemical drive and BT. After paralysis, the viscoelastic constants of the respiratory system, modelled as a Kelvin body, were assessed according to the rapid airway occlusion method and used together with the inspiratory flow waveform to predict the end-inspiratory viscoelastic pressure (Pvisc) of unimpeded inspirations. Since the slope of the Pdiff vs Pvisc relationship never differed from unity, Pdiff under the specified conditions should represent the effective Pvisc of unimpeded inspirations. Copyright (C) 1998 Elsevier Science B.V

Lung tissue behavior during methacholine challenge in rabbits in vivo

Previous studies have shown that lung challenge with smooth muscle agonists increases tissue viscance (Vti), which is the pressure drop between the alveolus and the pleura divided by the flow. Passive inflation also increases Vti. The purpose of the present study was to measure the changes in Vti during positive end-expiratory pressure- (PEEP) induced changes in lung volume and with a concentration-response curve to methacholine (MCh) in rabbits and to compare the effects of induced constriction vs. passive lung inflation on tissue mechanics. Measurements were made in 10 anesthetized open-chest mechanically ventilated New Zealand male rabbits exposed first to increasing levels of PEEP (3-12 cmH2O) and then to increasing concentrations of MCh aerosol (0.5-128 mg/ml). Lung elastance (EL), lung resistance (RL), and Vti were determined by adjusting the equation of motion to tracheal and alveolar pressures during tidal ventilation. Our results show that under base-line conditions, Vti accounted for a major proportion of RL; during both passive lung inflation and MCh challenge this proportion increased progressively. For the same level of change in EL, however, the increase in Vti was larger during MCh challenge than during passive inflation; i.e., the relationship between energy storage and energy dissipation or hysteresivity was dramatically altered. These results are consistent with a MCh-induced change in the intrinsic rheological properties of lung tissues unrelated to lung volume change per se. Lung tissue constriction is one possible explanatio

Tissue viscance during induced constriction in rabbit lungs : morphological-physiological correlations

Tissue viscance (Vti), the pressure drop across the lung tissues in phase with flow, increases after induced constriction. To gain information about the possible site of response, we induced increases in Vti with methacholine (MCh) and attempted to correlate these changes with alterations in lung morphology. We measured tracheal (Ptr) and alveolar pressure (PA) in open-chest rabbits during mechanical ventilation [frequency = 1 Hz, tidal volume = 5 ml/kg, positive end-expiratory pressure (PEEP) = 5 cmH2O] under control conditions and after administration of saline or MCh (32 or 128 mg/ml) aerosols. We calculated lung elastance (EL), lung resistance (RL), Vti, and airway resistance (Raw) by fitting the equation of motion to changes in Ptr and PA. The lungs were then frozen in situ with liquid nitrogen (PEEP = 5 cmH2O), excised, and processed using freeze substitution techniques. Airway constriction was assessed by measuring the ratio of the airway lumen (A) to the ideally relaxed area (Ar). Tissue distortion was assessed by measuring the mean linear intercept between alveolar walls (Lm), the standard deviation of Lm (SDLm), and an atelectasis index (ATI) derived by calculating the ratio of tissue to air space using computer image analysis. RL, Vti, and EL were significantly increased after MCh, and Raw was unchanged. A/Ar, Lm, SDLm, and ATI all changed significantly with MCh. Log-normalized change (% of baseline) in Vti significantly correlated with A/Ar (r = -0.693), Lm (r = 0.691), SDLm (r = 0.648), and ATI (r = 0.656). Hence, changes in lung tissue mechanics correlated with changes in morphometric indexes of parenchymal distortion and airway constriction.(ABSTRACT TRUNCATED AT 250 WORDS

Lung tissue resistance during contractile stimulation : structural damping decomposition

Research in the mechanics of soft tissue, and lung tissue in particular, has emphasized that dissipative processes depend predominantly on the viscous stress. A corollary is that dissipative losses may be expressed as a tissue viscous resistance, (Rti). An alternative approach is offered by the structural damping hypothesis, which holds that dissipative processes within soft tissue depend directly more on the elastic stress than on the viscous stress. This implies that dissipative and elastic processes within lung tissues are coupled at a fundamental level. We induced alterations of Rti by exposing canines to aerosols of the constrictors prostaglandin F2 alpha, histamine, and methacholine and by changing volume history. Using the structural damping paradigm, we could separate those alterations in Rti into the product of two distinct contributions: change in the coefficient of coupling of dissipation to elastance (eta) and change in the elastance itself (Edyn). Response of Edyn accounted for most of the response of resistance associated with contractile stimulation; it accounted for almost all the response associated with differences in volume history. The eta changed appreciably with constriction but accounted for little of the response of Rti with volume history. According to the structural damping hypothesis, induced changes in eta with constriction must reflect changes in the kinetics of the stress-bearing process, i.e., differences in cross-bridge kinetics within the target contractile cell and/or differences in the influence of the target cell on other stress-bearing systems. We conclude that, regardless of underlying processes, the structural damping analysis demonstrates a fundamental phenomenological simplification: when Edyn responds, Rti is obligated to respond to a similar degree

Effect of lung volume on plateau response of airways and tissue to methacholine in dogs

We have recently shown in dogs that much of the increase in lung resistance (RL) after induced constriction can be attributed to increases in tissue resistance, the pressure drop in phase with flow across the lung tissues (Rti). Rti is dependent on lung volume (VL) even after induced constriction. As maximal responses in RL to constrictor agonists can also be affected by changes in VL, we questioned whether changes in the plateau response with VL could be attributed in part to changes in the resistive properties of lung tissues. We studied the effect of changes in VL on RL, Rti, airway resistance (Raw), and lung elastance (EL) during maximal methacholine (MCh)-induced constriction in 8 anesthetized, paralyzed, open-chest mongrel dogs. We measured tracheal flow and pressure (Ptr) and alveolar pressure (PA), the latter using alveolar capsules, during tidal ventilation [positive end-expiratory pressure (PEEP) = 5.0 cmH2O, tidal volume = 15 ml/kg, frequency = 0.3 Hz]. Measurements were recorded at baseline and after the aerosolization of increasing concentrations of MCh until a clear plateau response had been achieved. VL was then altered by changing PEEP to 2.5, 7.5, and 10 cmH2O. RL changed only when PEEP was altered from 5 to 10 cmH2O (P < 0.01). EL changed when PEEP was changed from 5 to 7.5 and 5 to 10 cmH2O (P < 0.05). Rti and Raw varied significantly with all three maneuvers (P < 0.05). Our data demonstrate that the effects of VL on the plateau response reflect a complex combination of changes in tissue resistance, airway caliber, and lung recoi

Pulmonary and chest wall mechanics in anesthetized paralyzed humans

Pulmonary and chest wall mechanics were studied in 18 anesthetized paralyzed supine humans by use of the technique of rapid airway occlusion during constant-flow inflation. Analysis of the changes in transpulmonary pressure after flow interruption allowed partitioning of the overall resistance of the lung (RL) into two compartments, one (Rint,L) reflecting airway resistance and the other (\u394RL) representing the viscoelastic properties of the pulmonary tissues. Similar analysis of the changes in esophageal pressure indicates that chest wall resistance (Rw) was due entirely to the viscoelastic properties of the chest wall tissues (\u394Rw = Rw). In line with previous measurements of airway resistance, Rint,L increased with increasing flow and decreased with increasing volume. The opposite was true for both \u394RL and \u394Rw. This behavior was interpreted in terms of a viscoelastic model that allowed computation of the viscoelastic constants of the lung and chest wall. This model also accounts for frequency, volume, and flow dependence of elastance of the lung and chest wall. Static and dynamic elastances, as well as \u394R, were higher for the lung than for the chest wall