Airflow obstruction after substance P aerosol: contribution of airway and pulmonary edema

1990 ◽  
Vol 69 (4) ◽  
pp. 1473-1478 ◽  
Author(s):  
J. O. Lotvall ◽  
R. J. Lemen ◽  
K. P. Hui ◽  
P. J. Barnes ◽  
K. F. Chung
Keyword(s):  
Substance P ◽  
Pulmonary Edema ◽  
Evans Blue ◽  
Guinea Pigs ◽  
Airflow Obstruction ◽  
Maximum Effect ◽  
Blue Dye ◽  
Evans Blue Dye ◽  
Microvascular Leakage ◽  
Lung Resistance

We have studied the effects of aerosolized substance P (SP) in guinea pigs with reference to lung resistance and dynamic compliance changes and their recovery after hyperinflation. In addition, we have examined the concomitant formation of airway microvascular leakage and lung edema. Increasing breaths of SP (1.5 mg/ml, 1.1 mM), methacholine (0.15 mg/ml, 0.76 mM), or 0.9% saline were administered to tracheostomized and mechanically ventilated guinea pigs. Lung resistance (RL) increased dose dependently with a maximum effect of 963 +/- 85% of baseline values (mean +/- SE) after SP (60 breaths) and 1,388 +/- 357% after methacholine (60 breaths). After repeated hyperinflations, methacholine-treated animals returned to baseline, but after SP, mean RL was still raised (292 +/- 37%; P less than 0.005). Airway microvascular leakage, measured by extravasation of Evans Blue dye, occurred in the brain bronchi and intrapulmonary airways after SP but not after methacholine. There was a significant correlation between RL after hyperinflation and Evans Blue dye extravasation in intrapulmonary airways (distal: r = 0.89, P less than 0.005; proximal: r = 0.85, P less than 0.01). Examination of frozen sections for peribronchial and perivascular cuffs of edema and for alveolar flooding showed significant degrees of pulmonary edema for animals treated with SP compared with those treated with methacholine or saline. We conclude that the inability of hyperinflation to fully reverse changes in RL after SP may be due to the formation of both airway and pulmonary edema, which may also contribute to the deterioration in RL.

Peptidase modulation of noncholinergic vagal bronchoconstriction and airway microvascular leakage

1991 ◽  
Vol 70 (6) ◽  
pp. 2730-2735 ◽  
Author(s):  
J. O. Lotvall ◽  
K. Tokuyama ◽  
C. G. Lofdahl ◽  
A. Ullman ◽  
P. J. Barnes ◽  
...  
Keyword(s):  
Nerve Stimulation ◽  
Evans Blue ◽  
Enzyme Inhibitors ◽  
Airflow Obstruction ◽  
Neutral Endopeptidase ◽  
Blue Dye ◽  
Enalapril Maleate ◽  
Evans Blue Dye ◽  
Microvascular Leakage ◽  
Degradative Enzymes

We investigated whether inhibition of neutral endopeptidase 24.11 (NEP) and/or angiotensin-converting enzyme (ACE) modifies vagally induced nonadrenergic noncholinergic (NANC) airflow obstruction and airway microvascular leakage as measured by extravasation of Evans blue dye (intravenous) in anesthetized guinea pigs. We gave phosphoramidon to inhibit NEP and enalapril maleate or captopril to inhibit ACE. Animals pretreated with inhaled phosphoramidon (7.5 or 75 nmol), enalapril maleate (87 or 870 nmol), or captopril (350 nmol) reached higher peak lung resistance (RL) values (14.3 +/- 2.7, 15.7 +/- 3.8, 16.7 +/- 3.8, 11.4 +/- 1.6, and 24.6 +/- 3.5 cmH2O.ml-1.s, respectively) than saline-treated animals (5.9 +/- 1.1; P less than 0.05) after bilateral vagus nerve stimulation (5 Hz, 10 V, 10 ms, 150 s). Intravenous phosphoramidon (1 mg/kg), but not intravenous captopril (6 mg/kg), potentiated peak RL (22.9 +/- 6.9 and 7.1 +/- 1.5 cmH2O.ml-1.s, respectively). Vagal nerve stimulation (1 and 5 Hz) increased the extravasation of Evans blue dye in tracheobronchial tissues compared with sham-stimulated animals, but this was not potentiated by inhaled enzyme inhibitors or intravenous captopril. However, intravenous phosphoramidon significantly augmented the extravasation of Evans blue dye in main bronchi and intrapulmonary airways. We conclude that degradative enzymes regulate both NANC-induced airflow obstruction and airway microvascular leakage.

Plasma Exudation into Airways Induced by Inhaled Platelet-Activating Factor: Effect of Peptidase Inhibition

1991 ◽  
Vol 80 (3) ◽  
pp. 241-247 ◽  
Author(s):  
Jan O. Lötvall ◽  
Wayne Elwood ◽  
Kenichi Tokuyama ◽  
Peter J. Barnes ◽  
K. Fan Chung
Keyword(s):  
Angiotensin Converting Enzyme ◽  
Evans Blue ◽  
Guinea Pigs ◽  
Platelet Activating Factor ◽  
Neutral Endopeptidase ◽  
Blue Dye ◽  
Converting Enzyme ◽  
Evans Blue Dye ◽  
Plasma Exudation ◽  
Lung Resistance

1. To evaluate whether endogenous peptide release is involved in the airway responses to inhaled platelet-activating factor, we measured lung resistance and airway microvascular leakage in anaesthetized guinea pigs pre-treated with inhalation of either saline or a combination of the peptidase inhibitors phosphoramidon (0.1 mmol/l: 60 breaths; 7.5 nmol), to inhibit neutral endopeptidase, and captopril (4.6 mmol/l: 60 breaths; 350 nmol), to inhibit angiotensin-converting enzyme. 2. Airway microvascular leakage was determined by the albumin marker Evans Blue dye injected intravenously (20 mg/kg) before platelet-activating factor or sham challenge. 3. Inhaled platelet-activating factor induced a maximum increase in lung resistance (1.43 ± 0.33 cmH2O s−1 ml−1) which was not significantly different after pretreatment with phosphoramidon and captopril (1.44 ± 0.21 cmH2O s−1 ml−1). 4. Inhalation of platelet-activating factor caused a significant increase in extravasated Evans Blue dye at all airway levels, an effect which was not potentiated by peptidase inhibition. Similar results were obtained with dye extravasated into the airway lumen and absorbed by a filter paper placed on the tracheal mucosa. Approximately 11% of the total tracheal dye was found in the lumen. There was a high correlation between tracheal tissue and tracheal lumen Evans Blue dye (r = 0.91; P < 0.001). 5. We found a significantly lower dry to wet weight ratio in proximal intrapulmonary airways of animals exposed to platelet-activating factor, suggesting that platelet-activating factor caused airway oedema at this airway level. 6. Inhaled platelet-activating factor does not induce immediate release of peptides degraded by either neutral endopeptidase or angiotensin-converting enzyme in high enough quantities to cause bronchoconstriction. Inhaled platelet-activating factor may cause airway narrowing in guinea pigs largely due to plasma exudation into the airway wall and lumen.

Relationship between airway microvascular leakage, edema, and baseline airway functions

1998 ◽  
Vol 84 (1) ◽  
pp. 77-81
Author(s):  
Melissa Matheson ◽  
Ann-Christine Rynell ◽  
Melissa McClean ◽  
Norbert Berend
Keyword(s):  
Evans Blue ◽  
Airway Resistance ◽  
Respiratory Physiology ◽  
Blue Dye ◽  
Wall Area ◽  
Evans Blue Dye ◽  
Microvascular Leakage ◽  
Airway Function ◽  
Significant Difference ◽  
Before And After

Matheson, Melissa, Ann-Christine Rynell, Melissa McClean, and Norbert Berend. Relationship between airway microvascular leakage, edema, and baseline airway functions. J. Appl. Physiol. 84(1): 77–81, 1998.—This study was designed to examine the relationship among microvascular leakage, edema, and baseline airway function. Microvascular leakage was induced in the airways of anesthetized, tracheostomized New Zealand White rabbits ( n = 22) by using nebulized N-formyl-methionyl-leucyl-phenylalanine (10 mg) and was measured in the trachea by using the Evans blue dye technique. Airway wall thickness was assessed morphometrically in the right main bronchus after Formalin fixation at a pressure of 25 cmH2O. Areas calculated included the mucosal wall area, the adventitial wall area, the total wall area, and the percentage of total wall area consisting of blood vessels. A neutrophil count was also performed by analyzing numbers of cells in both the mucosal wall area and the adventitial wall area. Airway function was assessed before and 30 min after challenge with N-formyl-methionyl-leucyl-phenylalanine by determining airway resistance, functional residual capacity, specific airway resistance, and flow-volume and pressure-volume curves (after paralysis of the animals with suxamethonium). The concentration of Evans blue dye in tracheal tissue ranged from 31.3 to 131.2 μg. There was a significant correlation between this concentration and both the adventitial wall area ( P < 0.01) and mucosal neutrophil numbers ( P < 0.005). There was no correlation between Evans blue concentration and either blood vessel area or changes in respiratory physiology parameters before and after challenge. There was no significant difference between any respiratory physiology measurements before and after challenge. We conclude that an increase in microvascular leakage correlates with airway edema in the adventitia; however, these airway changes have no significant effect on airway elastic or resistive properties.

Tumor necrosis factor inhibits a polymorphonuclear leukocyte-dependent airway edema in guinea pigs

1988 ◽  
Vol 64 (4) ◽  
pp. 1688-1692 ◽  
Author(s):  
T. Gordon ◽  
D. Sheppard
Keyword(s):  
Tumor Necrosis Factor ◽  
Evans Blue ◽  
Polymorphonuclear Leukocyte ◽  
Guinea Pigs ◽  
Tumor Necrosis ◽  
Toluene Diisocyanate ◽  
Blue Dye ◽  
Evans Blue Dye ◽  
Airway Edema ◽  
Necrosis Factor

Intravenously administered endotoxin inhibits the polymorphonuclear leukocyte (PMN)-dependent airway edema produced in guinea pigs exposed to toluene diisocyanate (TDI). Tumor necrosis factor (TNF) is produced in vivo by peripheral blood monocytes and tissue macrophages stimulated with endotoxin and has been shown to activate PMN's and vascular endothelial cells. To determine whether the inhibition of airway edema is mediated by TNF, guinea pigs were treated with intravenous saline or 75,000 U/kg recombinant human TNF 1.5 h before exposure to air or 3 ppm TDI for 1 h. Animals were then injected intravenously with 50 mg/kg Evans blue dye as a marker of protein extravasation. Saline-treated animals exposed to TDI had a significant increase in tracheal Evans blue dye extravasation (85 +/- 6.5 micrograms dye/g trachea, mean +/- SE) compared with saline-treated animals exposed to air (31.3 +/- 2.5, P less than 0.001). The tracheal extravasation of Evans blue dye was significantly inhibited (P less than 0.05) in TDI-exposed animals treated with TNF (64.7 +/- 7.5). Neither heat-inactivated TNF (104.9 +/- 9.5) nor TNF neutralized with a monoclonal antibody against TNF (99.7 +/- 17.9) inhibited TDI-induced airway edema. In addition, treatment with 15,000 U/kg (99.9 +/- 21.3) or 150,000 U/kg (103.2 +/- 17.6) interleukin 1, a monokine also produced in response to endotoxin, did not prevent airway edema. These results suggest that TNF released in response to endotoxin mediates endotoxin's inhibition of a PMN-dependent airway edema.

Neuropeptide Y inhibits neurogenic inflammation in guinea pig airways

1993 ◽  
Vol 75 (1) ◽  
pp. 103-107 ◽  
Author(s):  
T. Takahashi ◽  
M. Ichinose ◽  
H. Yamauchi ◽  
M. Miura ◽  
N. Nakajima ◽  
...  
Keyword(s):  
Substance P ◽  
Neuropeptide Y ◽  
Evans Blue ◽  
Neurogenic Inflammation ◽  
Sensory Nerve ◽  
Blue Dye ◽  
Plasma Extravasation ◽  
Dependent Manner ◽  
Evans Blue Dye ◽  
Exogenous Substance

We examined the effect of neuropeptide Y (NPY) on neurogenic airway microvascular leakage. Male Dunkin-Hartley guinea pigs (250–350 g) were anesthetized with urethan (2 g/kg ip). The cervical artery and vein were cannulated for monitoring blood pressure and injecting drugs, respectively. Atropine and propranolol (each 1 mg/kg i.v.) were administered 30 min before the experiment. After pretreatment with saline (vehicle for NPY) or NPY (1–100 micrograms/kg i.v.), Evans blue dye (30 mg/kg iv) was administered. Then, bilateral vagal nerves were electrically stimulated (5 V, 7 Hz, 5-ms duration for 3 min) to induce airway plasma leakage. Airways were divided into four sections [trachea (Tr), main bronchi, central intrapulmonary airways (IPA), and peripheral IPA] and incubated in formamide (37 degrees C for 16 h). The concentration of Evans blue dye was measured by spectrophotometer. Furthermore, we examined the effect of NPY on exogenous substance P- (0.3 microgram/kg i.v.) induced plasma extravasation. Bilateral vagal stimulation significantly increased leakage of dye in Tr to peripheral IPA. NPY did not affect basal leakage but did significantly inhibit neurogenic plasma extravasation in a dose-dependent manner with maximal inhibitions of 42.3 (Tr), 67.7 (main bronchi), 38.2 (central IPA), and 26.3% (peripheral IPA) at 30 micrograms/kg. Exogenous substance P-induced plasma extravasation was not inhibited by NPY. We conclude that NPY inhibits neurogenic inflammation by prejunctional inhibition of neuropeptide release from airway sensory nerve terminals.

Regional Deposition of Inhaled Evans Blue Dye in Mechanically Ventilated Rabbits with Air or Helium Oxygen Mixture

1998 ◽  
Vol 24 (2) ◽  
pp. 159-172 ◽  
Author(s):  
Magnus Svartengren ◽  
Patrik Skogward ◽  
Ola Nerbrink ◽  
Magnus Dahlbäck
Keyword(s):  
Evans Blue ◽  
Oxygen Mixture ◽  
Blue Dye ◽  
Mechanically Ventilated ◽  
Evans Blue Dye ◽  
Regional Deposition

scholarly journals Acoustic enhanced Evans blue dye perfusion in neurological tissues

2007 ◽  
Author(s):  
George K. Lewis Jr. ◽  
Willam L. Olbricht ◽  
George Lewis
Keyword(s):  
Evans Blue ◽  
Blue Dye ◽  
Evans Blue Dye

Flow of edema fluid into pulmonary airways

1983 ◽  
Vol 55 (4) ◽  
pp. 1262-1268 ◽  
Author(s):  
G. R. Mason ◽  
R. M. Effros
Keyword(s):  
Evans Blue ◽  
Left Atrial ◽  
Blue Dye ◽  
Edema Formation ◽  
Evans Blue Dye ◽  
Colloid Particles ◽  
Edema Fluid ◽  
Pulmonary Airways ◽  
99Mtc Sulfur Colloid

An in situ rabbit preparation was used to characterize the manner in which edema fluid enters the airways when left atrial pressures are elevated. The airways were initially filled with fluid to minimize retrograde flow of edema fluid into the alveoli. The airway solution contained 125I-albumin and in some studies [14C]sucrose, and the lungs were perfused with a comparable solution which contained albumin labeled with Evans blue dye and 99mTc-diethylenetriaminepentaacetate (DTPA) or 99mTc-sulfur-colloid particles (0.4-1.7 micron diam). After 30 min of perfusion, fluid was pumped from the airways into serial tubes. When left atrial pressures were low, there was very little transfer of labels detectable between the airway and perfusate solutions. However when left atrial pressures were increased to either 15 or 22 cmH2O, fluid entered the airways containing approximately the same concentrations of Evans blue dye and 99mTc-DTPA as those present in the perfusate. In contrast, the concentration of colloid particles averaged less than 5% perfusate concentrations, indicating that the fluid had not escaped through a tear in the barriers separating the vascular and airway compartments. Concentrations of the perfusate fluid and indicators were highest in the initial samples pumped from the airways. These observations suggest that some of the fluid entering the airways may be derived from peribronchial cuffs or that there are marked regional differences in edema formation from alveoli.

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