Effects of heterogeneities on the partitioning of airway and tissue properties in normal mice

2007 ◽  
Vol 102 (3) ◽  
pp. 859-869 ◽  
Author(s):  
Satoru Ito ◽  
Kenneth R. Lutchen ◽  
Béla Suki

We measured the mechanical properties of the respiratory system of C57BL/6 mice using the optimal ventilation waveform method in closed- and open-chest conditions at different positive end-expiratory pressures. The tissue damping (G), tissue elastance (H), airway resistance (Raw), and hysteresivity were obtained by fitting the impedance data to three different models: a constant-phase model by Hantos et al. (Hantos Z, Daroczy B, Suki B, Nagy S, Fredberg JJ. J Appl Physiol 72: 168–178, 1992), a heterogeneous Raw model by Suki et al. (Suki B, Yuan H, Zhang Q, Lutchen KR. J Appl Physiol 82: 1349–1359, 1997), and a heterogeneous H model by Ito et al. (Ito S, Ingenito EP, Arold SP, Parameswaran H, Tgavalekos NT, Lutchen KR, Suki B. J Appl Physiol 97: 204–212, 2004). Both in the closed- and open-chest conditions, G and hysteresivity were the lowest and Raw the highest in the heterogeneous Raw model, and G and H were the largest in the heterogeneous H model. Values of G, Raw, and hysteresivity were significantly higher in the closed-chest than in the open-chest condition. However, H was not affected by the conditions. When the tidal volume of the optimal ventilation waveform was decreased from 8 to 4 ml/kg in the closed-chest condition, G and hysteresivity significantly increased, but there were smaller changes in H or Raw. In summary, values of the obtained mechanical properties varied among these models, primarily due to heterogeneity. Moreover, the mechanical parameters were significantly affected by the chest wall and tidal volume in mice. Contribution of the chest wall and heterogeneity to the mechanical properties should be carefully considered in physiological studies in which partitioning of airway and tissue properties are attempted.

1995 ◽  
Vol 79 (3) ◽  
pp. 861-869 ◽  
Author(s):  
B. Suki ◽  
F. Petak ◽  
A. Adamicza ◽  
Z. Hantos ◽  
K. R. Lutchen

The purpose of this study was to investigate under physiological breathing conditions whether airway and lung tissue properties are different in situ and in open-chest conditions. We measured lung input impedance in dogs from 0.2 to 8 Hz with an optimal ventilator waveform at four tidal volumes (VT; from 75 to 450 ml) in intact animals using an esophageal balloon as well as after opening the chest. The lung impedance from both conditions was partitioned into airway and tissue compartments as characterized by airway resistance and inertance (Iaw) and tissue damping (G) and elastance (H) parameters respectively. All parameters except Iaw depended to some extent on VT. The in situ tissue G and H slightly decreased with VT while in the open-chest condition; G decreased and H increased slightly with VT. We found small but significant differences between the mechanical properties of the airway and lung tissues in situ and in open-chest conditions. Over the total population, the G, airway resistance, and Iaw parameters were 13% (not significant), 35% (P < 0.001), and 31% (P < 0.001) smaller, respectively, in situ than in the open-chest condition. However, the H was 15% larger in situ (P < 0.001). Although we cannot completely rule out certain artifacts, these differences most likely reflect real alterations in the lung due to the different configurations and possible differences in the distribution of pleural pressures in the two conditions. The G being smaller and E being larger in situ resulted in hysteresivity (G/H) 36% smaller in situ (P < 0.001).


1992 ◽  
Vol 73 (6) ◽  
pp. 2643-2647 ◽  
Author(s):  
A. M. Lauzon ◽  
G. Dechman ◽  
J. H. Bates

We studied the dynamics of respiratory mechanical parameters in anesthetized tracheostomized paralyzed dogs challenged with a bolus of histamine injected either venously (venous group) or arterially (arterial group). The venous group was further divided into two groups: the first was bilaterally vagotomized and received hexamethonium bromide (denervated group), and the second also received atropine sulfate (atropine group). In the venous group, tissue resistance (Rti) and tissue elastance (Eti) increased biphasically, whereas airway resistance was monophasic and synchronized with the second rise of the tissue parameters. In the arterial group, Rti, Eti, and airway resistance increased synchronously. The denervated and atropine groups showed dynamics similar to those of the venous group. We postulate that the first phase observed in Rti and Eti in the venous group is due to constriction of the smooth muscles of the peripheral airways and blood vessels distorting the parenchyma. The second and larger phase is then due to histamine reaching the bronchial circulation and constricting the central airways, again distorting the parenchyma. The results from the arterial group support this hypothesis, whereas those from the denervated group ascertain that none of the phases observed in the venous group was due to nervous reflexes.


1993 ◽  
Vol 74 (5) ◽  
pp. 2286-2293 ◽  
Author(s):  
G. M. Barnas ◽  
J. Sprung

Dependencies of the dynamic mechanical properties of the respiratory system on mean airway pressure (Paw) and the effects of tidal volume (VT) are not completely clear. We measured resistance and dynamic elastance of the total respiratory system (Rrs and Ers), lungs (RL and EL), and chest wall (Rcw and Ecw) in six healthy anesthetized paralyzed dogs during sinusoidal volume oscillations at the trachea (50–300 ml; 0.4 Hz) delivered at mean Paw from -9 to +23 cmH2O. Changes in end-expiratory lung volume, estimated with inductance plethysmographic belts, showed a typical sigmoidal relationship to mean Paw. Each dog showed the same dependencies of mechanical properties on mean Paw and VT. All elastances and resistances were minimal between 5 and 10 cmH2O mean Paw. All elastances, Rrs, and RL increased greatly with decreasing Paw below 5 cmH2O. Ers and EL increased above 10 cmH2O. Ecw, Ers, Rcw, and Rrs decreased slightly with increasing VT, but RL and EL were independent of VT. We conclude that 1) respiratory system impedance is minimal at the normal mean lung volume of supine anesthetized paralyzed dogs; 2) the dependency of RL on lung volume above functional residual capacity is dependent on VT and respiratory frequency; and 3) chest wall, but not lung, mechanical behavior is nonlinear (i.e., VT dependent) at any given lung volume.


1987 ◽  
Vol 63 (2) ◽  
pp. 603-608 ◽  
Author(s):  
D. W. Hudgel ◽  
M. Mulholland ◽  
C. Hendricks

The purposes of this study were 1) to characterize the immediate inspiratory muscle and ventilation responses to inspiratory resistive loading during sleep in humans and 2) to determine whether upper airway caliber was compromised in the presence of a resistive load. Ventilation variables, chest wall, and upper airway inspiratory muscle electromyograms (EMG), and upper airway resistance were measured for two breaths immediately preceding and immediately following six applications of an inspiratory resistive load of 15 cmH2O.l–1 X s during wakefulness and stage 2 sleep. During wakefulness, chest wall inspiratory peak EMG activity increased 40 +/- 15% (SE), and inspiratory time increased 20 +/- 5%. Therefore, the rate of rise of chest wall EMG increased 14 +/- 10.9% (NS). Upper airway inspiratory muscle activity changed in an inconsistent fashion with application of the load. Tidal volume decreased 16 +/- 6%, and upper airway resistance increased 141 +/- 23% above pre-load levels. During sleep, there was no significant chest wall or upper airway inspiratory muscle or timing responses to loading. Tidal volume decreased 40 +/- 7% and upper airway resistance increased 188 +/- 52%, changes greater than those observed during wakefulness. We conclude that 1) the immediate inspiratory muscle and timing responses observed during inspiratory resistive loading in wakefulness were absent during sleep, 2) there was inadequate activation of upper airway inspiratory muscle activity to compensate for the increased upper airway inspiratory subatmospheric pressure present during loading, and 3) the alteration in upper airway mechanics during resistive loading was greater during sleep than wakefulness.


2005 ◽  
Vol 99 (1) ◽  
pp. 108-113 ◽  
Author(s):  
Elizabeth M. Bozanich ◽  
Rachel A. Collins ◽  
Cindy Thamrin ◽  
Zoltán Hantos ◽  
Peter D. Sly ◽  
...  

Most studies using mice to model human lung diseases are carried out in adults, although there is emerging interest in the effects of allergen, bacterial, and viral exposure early in life. This study aims to characterize lung function in BALB/c mice from infancy (2 wk) through to adulthood (8 wk). The low-frequency forced oscillation technique was used to obtain impedance data, partitioned into components representing airway resistance, tissue damping, tissue elastance, and hysteresivity (tissue damping/tissue elastance). Measurements were made at end-expiratory pause (transrespiratory system pressure = 2 cmH2O) and during relaxed slow expiration from 20 to 0 cmH2O. Airway resistance decreased with age from 0.63 cmH2O·ml−1·s at 2 wk to 0.24 cmH2O·ml−1·s at 8 wk ( P < 0.001). Both tissue damping and tissue elastance decreased with age ( P < 0.001) from 2 to 5 wk, then plateaued through to 8 wk ( P < 0.001). This pattern was seen both in measurements taken at end-expiratory pause and during expiration. There were no age-related changes seen in hysteresivity when measured at end-expiratory pause, but the pattern of volume dependence did differ with the age of the mice. These changes in respiratory mechanics parallel the reported structural changes of the murine lung from the postnatal period into adulthood.


2001 ◽  
Vol 90 (2) ◽  
pp. 571-578 ◽  
Author(s):  
Kristin R. Black ◽  
Bela Suki ◽  
Jeffrey B. Madwed ◽  
Andrew C. Jackson

Ascaris suum (AS) challenge in nonhuman primates is used as an animal model of human asthma. The primary goal of this study was to determine whether the airways and respiratory tissues in monkeys that are bronchoconstricted by AS inhalation behave similarly to those in asthmatic humans. Airway resistance (Raw) and tissue elastance (Eti) were estimated from respiratory system input (Zin) or transfer (Ztr) impedance. Zin (0.4–20 Hz) and Ztr (2–128 Hz) were measured in anesthetized cynomolgus monkeys ( n = 10) under baseline (BL) and post-AS challenge conditions. Our results indicate that AS challenge in monkeys produces 1) predominately an increase in Raw and not tissue resistance, 2) airway wall shunting at higher AS doses, and 3) heterogeneous airway constriction resulting in a decrease of lung parenchyma effective compliance. We investigated whether the airway and tissue properties estimated from Zin and Ztr were similar and found that Raw estimated from Zin and Ztr were correlated [ r 2 = 0.76], not significantly different at BL (13.6 ± 1.4 and 13.1 ± 0.9 cmH2O · l−1 · s−1, respectively), but significantly different post-AS (20.5 ± 4.5 cmH2O · l−1 · s−1and 18.5 ± 5.2 cmH2O · l−1 · s−1). There was no correlation between Eti estimated from Zin and Ztr. The changes in lung mechanical properties in AS-bronchoconstricted monkeys are similar to those recently reported in human asthma, confirming that this is a reasonable model of human asthma.


1994 ◽  
Vol 76 (1) ◽  
pp. 166-175 ◽  
Author(s):  
G. M. Barnas ◽  
R. J. Watson ◽  
M. D. Green ◽  
A. J. Sequeira ◽  
T. B. Gilbert ◽  
...  

From measurements of airway and esophageal pressures and flow, we calculated the elastance and resistance of the total respiratory system (Ers and Rrs), chest wall (Ecw and Rcw), and lungs (EL and RL) in 11 anesthetized-paralyzed patients immediately before cardiac surgery with cardiopulmonary bypass and immediately after chest closure at the end of surgery. Measurements were made during mechanical ventilation in the frequency and tidal volume ranges of normal breathing. Before surgery, frequency and tidal volume dependences of the elastances and resistances were similar to those previously measured in awake seated subjects (Am. Rev. Respir. Dis. 145: 110–113, 1992). After surgery, Ers and Rrs increased as a result of increases in EL and RL (P < 0.05), whereas Ecw and Rcw did not change (P > 0.05). EL and RL exhibited nonlinearities (i.e., decreases with increasing tidal volume) that were not seen before surgery, and RL showed a greater dependence on frequency than before surgery. The changes in RL or EL after surgery were not correlated with the duration of surgery or cardiopulmonary bypass time (P > 0.05). We conclude that 1) frequency and tidal volume dependences of respiratory system properties are not affected by anesthesia, paralysis, and the supine posture, 2) open-chest surgery with cardiopulmonary bypass does not affect the mechanical properties of the chest, and 3) cardiac surgery involving cardiopulmonary bypass causes changes in the mechanical behavior of the lung that are generally consistent with those caused by pulmonary edema induced by oleic acid (J. Appl. Physiol. 73: 1040–1046, 1992) and decreases in lung volume.


1991 ◽  
Vol 71 (2) ◽  
pp. 498-508 ◽  
Author(s):  
F. R. Shardonofsky ◽  
M. Skaburskis ◽  
J. Sato ◽  
W. A. Zin ◽  
J. Milic-Emili

Using the technique of rapid airway occlusion during constant-flow inflation, we studied the effects of inflation volume, different baseline tidal volumes (10, 20, and 30 ml/kg), and vagotomy on the resistive and elastic properties of the lungs and chest wall in six anesthetized tracheotomized paralyzed mechanically ventilated cats. Before vagotomy, airway resistance decreased significantly with increasing inflation volume at all baseline tidal volumes. At any given inflation volume, airway resistance decreased with increasing baseline tidal volume. After vagotomy, airway resistance decreased markedly and was no longer affected by baseline tidal volume. Prevagotomy, pulmonary tissue resistance increased progressively with increasing lung volume and was not affected by baseline tidal volume. Pulmonary tissue resistance decreased postvagotomy. Chest wall tissue resistance increased during lung inflation but was not affected by either baseline tidal volume or vagotomy. The static volume-pressure relationships of the lungs and chest wall were not affected by either baseline tidal volume or vagotomy. The data were interpreted in terms of a linear viscoelastic model of the respiratory system (J. Appl. Physiol. 67: 2276–2285, 1989).


2021 ◽  
Vol 8 (5) ◽  
pp. 70
Author(s):  
Marco Ferroni ◽  
Beatrice Belgio ◽  
Giuseppe M. Peretti ◽  
Alessia Di Giancamillo ◽  
Federica Boschetti

The menisci of the knee are complex fibro-cartilaginous tissues that play important roles in load bearing, shock absorption, joint lubrication, and stabilization. The objective of this study was to evaluate the interaction between the different meniscal tissue components (i.e., the solid matrix constituents and the fluid phase) and the mechanical response according to the developmental stage of the tissue. Menisci derived from partially and fully developed pigs were analyzed. We carried out biochemical analyses to quantify glycosaminoglycan (GAG) and DNA content according to the developmental stage. These values were related to tissue mechanical properties that were measured in vitro by performing compression and tension tests on meniscal specimens. Both compression and tension protocols consisted of multi-ramp stress–relaxation tests comprised of increasing strains followed by stress–relaxation to equilibrium. To better understand the mechanical response to different directions of mechanical stimulus and to relate it to the tissue structural composition and development, we performed numerical simulations that implemented different constitutive models (poro-elasticity, viscoelasticity, transversal isotropy, or combinations of the above) using the commercial software COMSOL Multiphysics. The numerical models also allowed us to determine several mechanical parameters that cannot be directly measured by experimental tests. The results of our investigation showed that the meniscus is a non-linear, anisotropic, non-homogeneous material: mechanical parameters increase with strain, depend on the direction of load, and vary among regions (anterior, central, and posterior). Preliminary numerical results showed the predominant role of the different tissue components depending on the mechanical stimulus. The outcomes of biochemical analyses related to mechanical properties confirmed the findings of the numerical models, suggesting a specific response of meniscal cells to the regional mechanical stimuli in the knee joint. During maturation, the increase in compressive moduli could be explained by cell differentiation from fibroblasts to metabolically active chondrocytes, as indicated by the found increase in GAG/DNA ratio. The changes of tensile mechanical response during development could be related to collagen II accumulation during growth. This study provides new information on the changes of tissue structural components during maturation and the relationship between tissue composition and mechanical response.


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