CO2 relaxes parenchyma in the liquid-filled rat lung

2007 ◽  
Vol 103 (2) ◽  
pp. 710-716 ◽  
Author(s):  
Michael J. Emery ◽  
Randy L. Eveland ◽  
Seong S. Kim ◽  
Jacob Hildebrandt ◽  
Erik R. Swenson
Keyword(s):  
Lung Parenchyma ◽  
Lung Compliance ◽  
Surface Forces ◽  
Solution Rate ◽  
Adult Rats ◽  
Pressure Volume Relationship ◽  
Glycolytic Inhibitor ◽  
Tissue Relaxation ◽  
Alveolar Surface ◽  
Parenchyma Tissue

CO2 regulation of lung compliance is currently explained by pH- and CO2-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 (V̇a) to perfusion (Q̇). Twenty adult rats were slowly ventilated with modified Krebs solution (rate = 3 min−1, 37°C, open chest) to produce unperfused living lung preparations free of intra-airway surface forces. The solution was gassed with 21% O2, balance N2, and CO2 varied to produce alveolar hypocapnia (Pco2 = 26.1 ± 2.4 mmHg, pH = 7.56 ± 0.04) or hypercapnia (Pco2 = 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 ∼30% when exposed to hypercapnia vs. hypocapnia ( P < 0.0001, paired t-test), but stress relaxation and flow-dependent airway resistance were unaltered. Increasing CO2 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 CO2 effects on lung recoil. The results suggest that lung parenchyma tissue relaxation, arising from active elements in response to increasing alveolar CO2, is independent of (and apparently in parallel with) passive tissue elements and may actively contribute to V̇a/Q̇ matching.

Distribution oand pharmacological release of histamine in canine lung in vivo

1978 ◽  
Vol 44 (3) ◽  
pp. 455-463 ◽  
Author(s):  
M. R. Nisam ◽  
A. Zbinden ◽  
S. Chesrown ◽  
D. Barnett ◽  
W. M. Gold
Keyword(s):  
Lung Parenchyma ◽  
Smooth Muscle Contraction ◽  
Lung Compliance ◽  
Internal Diameter ◽  
Cellular Interactions ◽  
Arterial Blood ◽  
Beta Adrenergic Agonists ◽  
Anesthetized Dogs ◽  
Tissue Histamine

We have examined the physiological effects of stored mediators released from airways by compound 48/80 aerosols in anesthetized dogs. In 13 dogs, both mast cell numbers and tissue histamine were related inversely to bronchial internal diameter (P less than 0.0001). Compound 48/80 aerosols degranulated mast cells and decreased histamine content (-29.0 +/- 10.0%; mean +/- SE) in 5–10 mm bronchi, but not in 3–4 mm bronchi or lung parenchyma. This was associated with increased plasma histamine (31.8 +/- 18.4 ng/ml), increased airflow resistance (Rrs: + 452 +/- 257%), decreased lung compliance (-28 +/- 10%), and decreased arterial blood pressure (-41 +/- 6.5%) at 2 min. The increased Rrs was reversed by beta-adrenergic agonists, indicating it was caused by bronchial smooth muscle contraction; prevented by chlorpheniramine, indicating it was caused by histamine action on H1-receptors; and augmented and prolonged by propranolol, suggesting that histamine triggered sympathetic mechanisms which modulated the effect of 48/80. This experimental approach permits the study of mechanisms in vivo which may be involved in the sequence of reactions initiated by antigen-IgE interaction. However, the latter involve not only stored mediators, but also unstored mediators, neural reflexes, and complex cellular interactions.

scholarly journals Effects of leptin deficiency on postnatal lung development in mice

2008 ◽  
Vol 105 (1) ◽  
pp. 249-259 ◽  
Author(s):  
Kewu Huang ◽  
Richard Rabold ◽  
Eric Abston ◽  
Brian Schofield ◽  
Vikas Misra ◽  
...  
Keyword(s):  
Surface Area ◽  
Morphometric Analysis ◽  
Lung Development ◽  
Age Groups ◽  
Lung Parenchyma ◽  
Lung Maturation ◽  
Alveolar Surface Area ◽  
Leptin Deficiency ◽  
Postnatal Lung Development ◽  
Alveolar Surface

Leptin modulates energy metabolism and lung development. We hypothesize that the effects of leptin on postnatal lung development are volume dependent from 2 to 10 wk of age and are independent of hypometabolism associated with leptin deficiency. To test the hypotheses, effects of leptin deficiency on lung maturation were characterized in age groups of C57BL/6J mice with varying Lep ob genotypes. Quasi-static pressure-volume curves and respiratory impedance measurements were performed to profile differences in respiratory system mechanics. Morphometric analysis was conducted to estimate alveolar size and number. Oxygen consumption was measured to assess metabolic rate. Lung volume at 40-cmH2O airway pressure (V40) increased with age in each genotypic group, and V40 was significantly ( P < 0.05) lower in leptin-deficient ( ob/ ob) mice beginning at 2 wk. Differences were amplified through 7 wk of age relative to wild-type (+/+) mice. Morphometric analysis showed that alveolar surface area was lower in ob/ ob compared with +/+ and heterozygote ( ob/+) mice beginning at 2 wk. Unlike the other genotypic groups, alveolar size did not increase with age in ob/ ob mice. In another experiment, ob/ ob at 4 wk received leptin replacement (5 μg·g−1·day−1) for 8 days, and expression levels of the Col1a1, Col3a1, Col6a3, Mmp2, Tieg1, and Stat1 genes were significantly increased concomitantly with elevated V40. Leptin-induced increases in V40 corresponded with enlarged alveolar size and surface area. Gene expression suggested a remodeling event of lung parenchyma after exogenous leptin replacement. These data support the hypothesis that leptin is critical to postnatal lung remodeling, particularly related to increased V40 and enlarged alveolar surface area.

Predictability of skeletal muscle tension from architectural determinations in guinea pig hindlimbs

1984 ◽  
Vol 57 (6) ◽  
pp. 1715-1721 ◽  
Author(s):  
P. L. Powell ◽  
R. R. Roy ◽  
P. Kanim ◽  
M. A. Bello ◽  
V. R. Edgerton
Keyword(s):  
Muscle Tension ◽  
Lung Parenchyma ◽  
Lung Compliance ◽  
Considerable Variability ◽  
Anatomical Basis ◽  
Topographical Orientation ◽  
Pleural Surface ◽  
Regional Lung ◽  
Airway Opening ◽  
Vertical Height

The position of small metallic markers embedded within the lung parenchyma and glued to the pleural surface of four excised right caudal dog lobes were determined during stepwise deflation from an airway opening pressure of 25 cmH2O in air-filled suspended lobes and 8 cmH2O in saline-filled lobes submerged in saline. Changes in the volumes of tetrahedrons formed by four noncoplanar markers were taken as regional lung volume changes at the centroids of the tetrahedron. In both air- and saline-filled lobes at all volumes below total lobe capacity (TLC) there was considerable variability in regional volume. The variability occurred at the first step below TLC and increased with deflation. Regions behaved consistently; regions that were proportionally larger or smaller than the overall lobe at any step tended to be larger or smaller, respectively, at all steps. There was a significant correlation between the regional behavior of the air- and saline-filled lobes. The variability of regional volume did not follow any clear topographical orientation. These results indicate there is considerable variability of lung compliance within small regions. This heterogeneity of regional parenchymal properties may be the anatomical basis of the nonuniformity of regional ventilation known to occur in intact animals and excised lobes within small regions at the same vertical height.

Sympathetic influence on alveolar surface activity in hyperventilated dog

1978 ◽  
Vol 44 (3) ◽  
pp. 327-332 ◽  
Author(s):  
T. Kobayashi ◽  
S. Kishizuchi ◽  
S. Murakami
Keyword(s):  
Surface Activity ◽  
Stability Index ◽  
Positive Pressure ◽  
Sympathetic Block ◽  
Volume Relationship ◽  
Anesthetized Dogs ◽  
Pressure Volume Relationship ◽  
Sympathetic Influence ◽  
Intermittent Positive Pressure Breathing ◽  
Alveolar Surface

Hyperventilating IPPB, defined as intermittent positive-pressure breathing with a frequency of 32 beats/min and inspiratory pressure of 30 cmH2O, was administered for 14 h to open-chested anesthetized dogs in which nerves to one bronchus were operatively blocked. In the nerve-intact lungs, the lung stability index calculated from the pressure-volume relationship decreased with the duration of the hyperventilating IPPB (correlation coefficient r = -0.66, P less than 0.001), and atelectasis and hemorrhage appeared. In the nerve-blocked lungs, the index did not decrease during the 14 h of hyperventilating IPPB, and the appearance was almost normal. After pharmacologic sympathetic block with phenoxybenzamine, the lung stability index of both the operatively nerve-blocked lung and the nerve-intact lung was not decreased by hyperventilating IPPB. From these findings, we conclude that sympathetic block can protect pulmonary surface activity from the adverse effects of hyperventilating IPPB.

Regional differences in expansion in excised dog lung lobes

1984 ◽  
Vol 57 (6) ◽  
pp. 1710-1714 ◽  
Author(s):  
L. E. Olson ◽  
J. R. Rodarte
Keyword(s):  
Lung Parenchyma ◽  
Lung Compliance ◽  
Considerable Variability ◽  
Anatomical Basis ◽  
Topographical Orientation ◽  
Pleural Surface ◽  
Regional Lung ◽  
Airway Opening ◽  
Vertical Height ◽  
Lung Lobes

The position of small metallic markers embedded within the lung parenchyma and glued to the pleural surface of four excised right caudal dog lobes were determined during stepwise deflation from an airway opening pressure of 25 cmH2O in air-filled suspended lobes and 8 cmH2O in saline-filled lobes submerged in saline. Changes in the volumes of tetrahedrons formed by four noncoplanar markers were taken as regional lung volume changes at the centroids of the tetrahedron. In both air- and saline-filled lobes at all volumes below total lobe capacity (TLC) there was considerable variability in regional volume. The variability occurred at the first step below TLC and increased with deflation. Regions behaved consistently; regions that were proportionally larger or smaller than the overall lobe at any step tended to be larger or smaller, respectively, at all steps. There was a significant correlation between the regional behavior of the air- and saline-filled lobes. The variability of regional volume did not follow any clear topographical orientation. These results indicate there is considerable variability of lung compliance within small regions. This heterogeneity of regional parenchymal properties may be the anatomical basis of the nonuniformity of regional ventilation known to occur in intact animals and excised lobes within small regions at the same vertical height.

Responses of lung parenchyma and airways to tachykinin peptides in piglets

1994 ◽  
Vol 77 (1) ◽  
pp. 147-151 ◽  
Author(s):  
I. A. Dreshaj ◽  
R. J. Martin ◽  
M. J. Miller ◽  
M. A. Haxhiu
Keyword(s):  
Lung Parenchyma ◽  
Neutral Endopeptidase ◽  
Smooth Muscle Contraction ◽  
Lung Compliance ◽  
Neurokinin A ◽  
Tidal Breathing ◽  
Tissue Resistance ◽  
Lung Resistance ◽  
Dynamic Lung Compliance ◽  
Total Lung Resistance

The tachykinin peptides substance P (SP) and neurokinin A (NKA) have been shown to induce tracheal smooth muscle contraction in piglets, and the enzyme neutral endopeptidase has been shown to modulate this effect. In these studies, we compared the SP and NKA responsiveness of piglet airways and lung parenchymal tissues in anesthetized paralyzed open-chest piglets 2–3 wk old, partitioning total lung resistance (RL) into airway resistance (Raw) and tissue resistance (Rti). During tidal breathing, pressure was measured at the trachea and in two alveolar regions by means of alveolar capsules. Intravenous administration of SP caused concentration-dependent increases in Rti and Raw and a decrease in dynamic lung compliance. Under baseline conditions, Rti contributed 74.6 +/- 1.9% (SE) of RL, and at any level of constriction, Rti accounted for > 50% of RL. The responses of Rti and Raw to NKA were negligible and were always significantly weaker than those to SP. These results indicate that both central airways and tissue contractile elements respond vigorously to SP, but not to NKA, in maturing piglets.

scholarly journals The efficacy and safety of pinocembrin in a sheep model of bleomycin-induced pulmonary fibrosis

PLoS ONE ◽  
2021 ◽  
Vol 16 (12) ◽  
pp. e0260719
Author(s):  
Habtamu B. Derseh ◽  
Jason Q. D. Goodger ◽  
Jean-Pierre Y. Scheerlinck ◽  
Chrishan S. Samuel ◽  
Ian E. Woodrow ◽  
...  
Keyword(s):  
Animal Model ◽  
Pulmonary Fibrosis ◽  
Inflammatory Cells ◽  
Lung Parenchyma ◽  
Lung Compliance ◽  
Large Animal Model ◽  
Large Animal ◽  
Lung Pathology ◽  
Sheep Model ◽  
Anti Inflammatory

The primary flavonoid, pinocembrin, is thought to have a variety of medical uses which relate to its reported anti-oxidant, anti-inflammatory, anti-microbial and anti-cancer properties. Some studies have reported that this flavonoid has anti-fibrotic activities. In this study, we investigated whether pinocembrin would impede fibrosis, dampen inflammation and improve lung function in a large animal model of pulmonary fibrosis. Fibrosis was induced in two localized lung segments in each of the 10 sheep participating in the study. This was achieved via two infusions of bleomycin delivered bronchoscopically at a two-week interval. Another lung segment in the same sheep was left untreated, and was used as a healthy control. The animals were kept for a little over 5 weeks after the final infusion of bleomycin. Pinocembrin, isolated from Eucalyptus leaves, was administered to one of the two bleomycin damaged lung segments at a dose of 7 mg. This dose was given once-weekly over 4-weeks, starting one week after the final bleomycin infusion. Lung compliance (as a measure of stiffness) was significantly improved after four weekly administrations of pinocembrin to bleomycin-damaged lung segments. There were significantly lower numbers of neutrophils and inflammatory cells in the bronchoalveolar lavage of bleomycin-infused lung segments that were treated with pinocembrin. Compared to bleomycin damaged lung segments without drug treatment, pinocembrin administration was associated with significantly lower numbers of immuno-positive CD8+ and CD4+ T cells in the lung parenchyma. Histopathology scoring data showed that pinocembrin treatment was associated with significant improvement in inflammation and overall pathology scores. Hydroxy proline analysis showed that the administration of pinocembrin did not reduce the increased collagen content that was induced by bleomycin in this model. Analyses of Masson’s Trichrome stained sections showed that pinocembrin treatment significantly reduced the connective tissue content in lung segments exposed to bleomycin when compared to bleomycin-infused lungs that did not receive pinocembrin. The striking anti-inflammatory and modest anti-fibrotic remodelling effects of pinocembrin administration were likely linked to the compound’s ability to improve lung pathology and functional compliance in this animal model of pulmonary fibrosis.

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