Time course of changes in lung permeability and edema in the rat exposed to 100% oxygen

1990 ◽  
Vol 69 (4) ◽  
pp. 1532-1537 ◽  
Author(s):  
B. D. Royston ◽  
N. R. Webster ◽  
J. F. Nunn
Keyword(s):  
Pulmonary Edema ◽  
Time Course ◽  
Pleural Cavity ◽  
Weight Ratio ◽  
Dry Weight ◽  
Solute Flux ◽  
Pleural Effusions ◽  
End Points ◽  
Lung Permeability

Rats were exposed to 100% oxygen for up to 60 h to determine early changes in lung permeability leading to the development of pulmonary edema. The time course of development of increased solute flux was assessed by the clearance of 99mTc-labeled diethylenetriamine pentaacetate (99mTc-DTPA) from the lung and the accumulation of 125I-labeled albumin (125I-albumin) in the lung. These end points were related to the development of pulmonary edema by the measurement of the wet-to-dry weight ratio of the lung and the weight of fluid in the pleural cavity. No significant changes occurred until 48 h of hyperoxia, when sharp increases in both indexes of lung permeability and wet-to-dry weight ratio occurred. By 60 h of exposure, pleural effusions had developed. The volume of this effusion was significantly correlated to both 99mTc-DTPA clearance and 125I-albumin flux.

Sequential changes in lung metabolism, permeability, and edema after ANTU

1987 ◽  
Vol 62 (2) ◽  
pp. 491-496 ◽  
Author(s):  
B. D. Minty ◽  
C. M. Scudder ◽  
C. J. Grantham ◽  
J. G. Jones ◽  
Y. S. Bakhle
Keyword(s):  
Lung Injury ◽  
Pulmonary Edema ◽  
Time Course ◽  
Weight Ratio ◽  
Dry Weight ◽  
Capillary Barrier ◽  
Lung Weight ◽  
Perfused Lung ◽  
Time Courses ◽  
Alveolar Capillary

Lung injury and pulmonary edema were induced in rats after intraperitoneal injection of 10 mg/kg alpha-naphthylthiourea (ANTU). The time course of development of lung injury was assessed by the clearance of 99mTc-diethylenetriamine pentaacetate (99mTcDTPA) from the lung into the blood, the pharmacokinetics of tritiated prostaglandin E2 [( 3H]PGE2) in the isolated perfused lung, and by increase in the weight ratio (wet-to-dry) of lung. Two hours after ANTU administration, the clearance of 99mTcDTPA was significantly faster than in untreated animals and implied an increase in permeability of the alveolar-capillary barrier. This change preceded the increase in wet-to-dry weight ratio of lung, which was not significant until 5 h after ANTU administration. The pharmacokinetics of [3H]PGE2 were significantly altered after ANTU and these changes persisted beyond the time when both lung weight ratio and 99mTcDTPA clearance had recovered to normal values. We conclude that both 99mTcDTPA clearance and PGE2 pharmacokinetics change in ANTU-induced lung injury but with different time courses. In the progressive phase of lung injury due to ANTU, the early change in clearance of 99mTcDTPA suggests that an increased permeation of the alveolar capillary barrier by this small molecule precedes pulmonary edema due to an increased colloid permeability of the barrier. Abnormal metabolism in the pulmonary microvasculature persists when the permeability defect and edema have recovered.

Infused salbutamol accentuates acid-induced lung injury in the rat

1986 ◽  
Vol 71 (2) ◽  
pp. 205-209 ◽  
Author(s):  
Stanley Braude ◽  
David Royston
Keyword(s):  
Lung Injury ◽  
Intravenous Infusion ◽  
Time Course ◽  
Weight Ratio ◽  
Dry Weight ◽  
Adrenergic Agonist ◽  
Lung Water ◽  
Significant Difference ◽  
And Control ◽  
Control Infusion

1. The effect in the rat of salbutamol infusion (1 μg min−1 kg−1) on acid-induced lung injury has been determined. Severity of lung injury was assessed by two techniques: the pulmonary clearance of 99mTc-diethylenetriaminepenta-acetate (99mTc-DTPA) and the lung wet/dry weight ratio, giving indices of alveolar epithelial permeability and transendothelial water filtration respectively. 2. Mean half-time of clearance of 99mTc-DTPA was increased significantly in rats who had intratracheal acid-induced injury and control (saline) intravenous infusion (19.4 ± 2.6 min) compared with non-acid-treated rats (98.1 ± 7.2) (P < 0.0001). However, those animals who had intratracheal acid injury and subsequent salbutamol intravenous infusion had significantly faster clearance (11.5 ± 1.9) than the acid and control infusion group (P < 0.05). 3. Gravimetric lung water in the acid-only rats (expressed as wet/dry weight ratio) was increased significantly (6.4 ± 0.3) compared with the non-acid-treated controls (5.4 ± 0.2) (P < 0.01). Acid-treated rats who had salbutamol infused had dramatically increased lung water (10.0 ± 0.6) (P < 0.001 vs acid and control infusion). 4. Intravenous salbutamol infusion itself produced no significant difference in the results for both techniques, compared with the non-acid-treated time-course controls. 5. Infused salbutamol accentuates acid-induced lung injury in the rat. Possible factors responsible for these findings include β2-adrenergic agonist mediated inhibition of hypoxic pulmonary vasoconstriction (HPV) and a predominant β1-adrenergic agonist inotropic effect of salbutamol with resultant rise in pulmonary artery pressure.

Cyclooxygenase and lipoxygenase inhibition by BW-755C reduces acrolein smoke-induced acute lung injury

1994 ◽  
Vol 77 (2) ◽  
pp. 888-895 ◽  
Author(s):  
S. P. Janssens ◽  
S. W. Musto ◽  
W. G. Hutchison ◽  
C. Spence ◽  
M. Witten ◽  
...  
Keyword(s):  
Acute Lung Injury ◽  
Arterial Pressure ◽  
Pulmonary Edema ◽  
Pulmonary Arterial Pressure ◽  
Weight Ratio ◽  
Peak Inspiratory Pressure ◽  
Dry Weight ◽  
Lymph Flow ◽  
Pulmonary Arterial ◽  
Arterial Po2

Inhalation of smoke containing acrolein, the most common toxin in urban fires after carbon monoxide, causes vascular injury with non-cardiogenic pulmonary edema containing potentially edematogenic eicosanoids such as thromboxane (Tx) B2, leukotriene (LT) B4, and the sulfidopeptide LTs (LTC4, LTD4, and LTE4). To determine which eicosanoids are important in the acute lung injury, we pretreated sheep with BW-755C (a combined cyclooxygenase and lipoxygenase inhibitor), U-63557A (a specific Tx synthetase inhibitor), or indomethacin (a cyclooxygenase inhibitor) before a 10-min exposure to a synthetic smoke containing carbon particles (4 microns) with acrolein and compared the results with those from control sheep that received only carbon smoke. Acrolein smoke induced a fall in arterial PO2 and rises in peak inspiratory pressure, main pulmonary arterial pressure, pulmonary vascular resistance, lung lymph flow, and the blood-free wet-to-dry weight ratio. BW-755C delayed the rise in peak inspiratory pressure and prevented the fall in arterial PO2, the rise in lymph flow, and the rise in wet-to-dry weight ratio. Neither indomethacin nor U-63557A prevented the increase in lymph flow or wet-to-dry weight ratio, although they did blunt and delay the rise in airway pressure and did prevent the rises in pulmonary arterial pressure and pulmonary vascular resistance. Thus, cyclooxygenase products, probably Tx, are responsible for the pulmonary hypertension after acrolein smoke and to some extent for the increased airway resistance but not the pulmonary edema. Prevention of high-permeability pulmonary edema after smoke with BW-755C suggests that LTB4, may be etiologic, as previous work has eliminated LTC4, LTD4, and LTE4.

Diammonium glycyrrhizinate lipid ligand ameliorates lipopolysaccharide-induced acute lung injury by modulating vascular endothelial barrier function

2020 ◽  
Author(s):  
Mei-Mei Liu ◽  
Jin Zhou ◽  
Dan Ji ◽  
Jun Yang ◽  
Yan-Ping Huang ◽  
...  
Keyword(s):  
Acute Lung Injury ◽  
Lung Injury ◽  
Pulmonary Edema ◽  
Protein Concentration ◽  
Weight Ratio ◽  
Dry Weight ◽  
Lavage Fluid ◽  
Inhibitory Effect ◽  
Vascular Endothelial ◽  
Junction Protein

Abstract Background: The present study investigated the attenuating effect of diammonium glycyrrhizinate lipid ligand (DGLL) on acute lung injury (ALI) and pulmonary edema induced by lipopolysaccharide (LPS) in rats.Methods: Rat ALI model was established by LPS (10 mg/kg) intraperitoneal injection, and DGLL (30, 60, 120 mg/kg) was administrated orall 1 hour before LPS infusion. Six hours after LPS stimulation, lung injury was evaluated by histological staining. Pulmonary edema was evaluated by lung wet-dry weight ratio, the protein concentration of bronchoalveolar lavage fluid (BALF), and the evans blue (EB) extravasation in lung tissues. The expression of cytokines and adhesion molecules in lung tissues were detected by ELISA method. The myeloperoxidase (MPO) expression was detected by immunohistochemical staining. Western blot was used to detect the expression changes of the proteins associated with pulmonary inflammation and microvascular permeability.Results: DGLL significantly inhibited LPS induced ALI, manifested as attenuation of MPO positive cells and TNF-α, IL-6, ICAM-1 expression in rat lung tissue. In addition, DGLL abrogated LPS-induced pulmonary edema, decreased the protein concentration in BALF and EB extravasation. Meanwhile, DGLL inhibited the degradation of vascular endothelial cadherin (VE-Cadherin) and tight junction protein, including ZO-1, Occludin, and JAM-1.Conclusions: DGLL has an inhibitory effect on LPS-induced rat ALI, which is related to the inhibition of inflammatory cell infiltration and microvascular barrier disruption. These results provide a theoretical basis for DGLL in the potential clinical treatment of ALI.

scholarly journals Novel Role for CFTR in Fluid Absorption from the Distal Airspaces of the Lung

2002 ◽  
Vol 119 (2) ◽  
pp. 199-208 ◽  
Author(s):  
X. Fang ◽  
N. Fukuda ◽  
P. Barbry ◽  
C. Sartori ◽  
A.S. Verkman ◽  
...  
Keyword(s):  
Pulmonary Edema ◽  
Weight Ratio ◽  
Volume Overload ◽  
Dry Weight ◽  
Mouse Lung ◽  
Fluid Absorption ◽  
Wild Type ◽  
Intact Mouse ◽  
Independent Evidence ◽  
Cl Transport

The active absorption of fluid from the airspaces of the lung is important for the resolution of clinical pulmonary edema. Although ENaC channels provide a major route for Na+ absorption, the route of Cl− transport has been unclear. We applied a series of complementary approaches to define the role of Cl− transport in fluid clearance in the distal airspaces of the intact mouse lung, using wild-type and cystic fibrosis ΔF508 mice. Initial studies in wild-type mice showed marked inhibition of fluid clearance by Cl− channel inhibitors and Cl− ion substitution, providing evidence for a transcellular route for Cl− transport. In response to cAMP stimulation by isoproterenol, clearance was inhibited by the CFTR inhibitor glibenclamide in both wild-type mice and the normal human lung. Although isoproterenol markedly increased fluid absorption in wild-type mice, there was no effect in ΔF508 mice. Radioisotopic clearance studies done at 23°C (to block active fluid absorption) showed ∼20% clearance of 22Na in 30 min both without and with isoproterenol. However, the clearance of 36Cl was increased by 47% by isoproterenol in wild-type mice but was not changed in ΔF508 mice, providing independent evidence for involvement of CFTR in cAMP-stimulated Cl− transport. Further, CFTR played a major role in fluid clearance in a mouse model of acute volume-overload pulmonary edema. After infusion of saline (40% body weight), the lung wet-to-dry weight ratio increased by 28% in wild-type versus 64% in ΔF508 mice. These results provide direct evidence for a functionally important role for CFTR in the distal airspaces of the lung.

Effect of lung-protective ventilation on severePseudomonas aeruginosapneumonia and sepsis in rats

2004 ◽  
Vol 287 (2) ◽  
pp. L402-L410 ◽  
Author(s):  
Kiyoyasu Kurahashi ◽  
Shuhei Ota ◽  
Kyota Nakamura ◽  
Yoji Nagashima ◽  
Takuya Yazawa ◽  
...  
Keyword(s):  
Lung Injury ◽  
Protective Effect ◽  
Time Course ◽  
Left Lung ◽  
Weight Ratio ◽  
Dry Weight ◽  
High Rate ◽  
Lung Protective Ventilation ◽  
High Peep ◽  
Beneficial Effects

Pneumonia caused by Pseudomonas aeruginosa carries a high rate of morbidity and mortality. A lung-protective strategy using low tidal volume (VT) ventilation for acute lung injury improves patient outcomes. The goal of this study was to determine whether low VTventilation has similar utility in severe P. aeruginosa infection. A cytotoxic P. aeruginosa strain, PA103, was instilled into the left lung of rats anesthetized with pentobarbital. The lung-protective effect of low VT(6 ml/kg) with or without high positive end-expiratory pressure (PEEP, 10 or 3 cmH2O) was then compared with high VTwith low PEEP ventilation (VT12 ml/kg, PEEP 3 cmH2O). Severe lung injury and septic shock was induced. Although ventilatory mode had little effect on the involved lung or septic physiology, injury to noninvolved regions was attenuated by low VTventilation as indicated by the wet-to-dry weight ratio (W/D; 6.13 ± 0.78 vs. 3.78 ± 0.26, respectively) and confirmed by histopathological examinations. High PEEP did not yield a significant protective effect (W/D, 4.03 ± 0.32) but, rather, caused overdistension of noninvolved lungs. Bronchoalveolar lavage revealed higher concentrations of TNF-α in the fluid of noninvolved lung undergoing high VTventilation compared with those animals receiving low VT. We conclude that low VTventilation is protective in noninvolved regions and that the application of high PEEP attenuated the beneficial effects of low VTventilation, at least short term. Furthermore, low VTventilation cannot protect the involved lung, and high PEEP did not significantly alter lung injury over a short time course.

Genetic differences in response to pulmonary cytochrome P-450 inducers and oxygen toxicity

1988 ◽  
Vol 64 (4) ◽  
pp. 1376-1381 ◽  
Author(s):  
H. Mansour ◽  
M. Levacher ◽  
E. Azoulay-Dupuis ◽  
J. Moreau ◽  
C. Marquetty ◽  
...  
Keyword(s):  
Superoxide Dismutase ◽  
Protective Effect ◽  
Pulmonary Edema ◽  
Cytochrome B5 ◽  
Weight Ratio ◽  
Oxygen Toxicity ◽  
Dry Weight ◽  
Lung Lipid ◽  
Specific Tissue ◽  
Cytochrome P 450

The effects of cytochrome P-450 inducers on O2 toxicity were studied in mice. We first examined three cytochrome P-450 inducers, which differ by their specific tissue affinity: phenobarbital sodium (PB), essentially active in the liver, and 3-methylcholanthrene (3-MC) and beta-naphthoflavone (BNF), which are also active in the lung. Both BNF and 3-MC increased the survival rate and significantly decreased pulmonary edema (pulmonary water and wet-to-dry weight ratio) in C57BL/6J mice exposed to hyperoxia (O2 greater than or equal to 95%), whereas PB had no protective effect. In the second part of this study, we compared the action of BNF in two strains of mice. In one (C57BL/6J), cytochrome P-450 can be induced by aromatic hydrocarbons, whereas in the other (DBA/2J) cytochrome P-450 is not inducible by these compounds. Protection against O2 toxicity was assessed in terms of lethality and pulmonary edema and of lung lipid peroxidation (assessed by measuring malondialdehyde). BNF only protected against O2 toxicity in the inducible strain. This protective effect of BNF on O2 toxicity in C57BL/6J mice was associated mainly with a large increase in the components of the cytochrome P-450 system (cytochrome P-450 and cytochrome b5) in the lung. The activity of pulmonary superoxide dismutase was also slightly increased, but the enhancement was not statistically significant. In contrast, in DBA/2J mice neither the components of the cytochrome P-450 system nor the activity of superoxide dismutase showed any increase.(ABSTRACT TRUNCATED AT 250 WORDS)

Smoke aldehyde component influences pulmonary edema

1992 ◽  
Vol 72 (2) ◽  
pp. 555-561 ◽  
Author(s):  
C. A. Hales ◽  
S. W. Musto ◽  
S. Janssens ◽  
W. Jung ◽  
D. A. Quinn ◽  
...  
Keyword(s):  
Pulmonary Edema ◽  
Weight Ratio ◽  
Dry Weight ◽  
Leukotriene B4 ◽  
Smoke Inhalation ◽  
High Dose ◽  
Lung Water ◽  
Protein Ratio ◽  
Arterial Blood ◽  
Lung Lymph

The pulmonary edema of smoke inhalation is caused by the toxins of smoke and not the heat. We investigated the potential of smoke consisting of carbon in combination with either acrolein or formaldehyde (both common components of smoke) to cause pulmonary edema in anesthetized sheep. Seven animals received acrolein smoke, seven animals received a low-dose formaldehyde smoke, and five animals received a high-dose formaldehyde smoke. Pulmonary arterial pressure, pulmonary capillary wedge pressure, and cardiac output were not affected by smoke in any group. Peak airway pressure increased after acrolein (14 +/- 1 to 21 +/- 2 mmHg; P less than 0.05) and after low- and high-dose formaldehyde (14 +/- 1 to 21 +/- 1 and 20 +/- 1 mmHg, respectively; both P less than 0.05). The partial pressure of O2 in arterial blood fell sharply after acrolein [219 +/- 29 to 86 +/- 9 (SE) Torr; P less than 0.05] but not after formaldehyde. Only acrolein resulted in a rise in lung lymph flow (6.5 +/- 2.2 to 17.9 +/- 2.6 ml/h; P less than 0.05). Lung lymph-to-plasma protein ratio was unchanged for all three groups, but clearance of lymph protein was increased after acrolein. After acrolein, the blood-free extravascular lung water-to-lung dry weight ratio was elevated (P less than 0.05) compared with both low- and high-dose formaldehyde groups (4.8 +/- 0.4 to 3.3 +/- 0.2 and 3.6 +/- 0.2, respectively). Lymph clearance (ng/h) of thromboxane B2, leukotriene B4, and the sulfidopeptide leukotrienes was elevated after acrolein but not formaldehyde.(ABSTRACT TRUNCATED AT 250 WORDS)

Importance of vasoconstriction in lipid mediator-induced pulmonary edema

1989 ◽  
Vol 66 (6) ◽  
pp. 2667-2674 ◽  
Author(s):  
A. Sakai ◽  
S. W. Chang ◽  
N. F. Voelkel
Keyword(s):  
Pulmonary Edema ◽  
Weight Ratio ◽  
Dry Weight ◽  
Lipid Mediator ◽  
Lung Edema ◽  
Rat Lung ◽  
Edema Formation ◽  
Mediators Of Inflammation ◽  
Isolated Rat Lung ◽  
Isolated Rat

Lipid mediators of inflammation cause pulmonary edema, yet it is unclear to what degree hemodynamic alterations or increased vascular permeability contribute to lung edema formation. The isolated rat lung preparation was used to examine the effect of leukotriene C4 (LTC4) and platelet-activating factor (PAF) on pulmonary arterial pressure (Ppa), lung microvascular pressure (Pmv), lung wet-to-dry weight ratio, and the 125I-albumin escape index. We first defined the response of the isolated rat lung perfused with protein-free salt solution to hydrodynamic stress by raising the lung outflow pressure. Sustained elevation of the lung outflow pressure less than 5.5 cmH2O (4.01 mmHg) caused a negligible increase in Ppa and wet-to-dry lung weight ratio. Elevation of outflow pressures greater than 7.5 cmH2O (5.4 mmHg) increased the vascular albumin escape index more than the lung wet-to-dry weight ratio. Dibutyryl adenosine 3′,5′-cyclic monophosphate (db-cAMP) inhibited the increase in albumin escape index because of increased lung outflow pressure, suggesting perhaps a pressure-independent microvascular membrane effect of db-cAMP. Both LTC4 (2-micrograms bolus) and PAF (2–2,000 ng/ml perfusate) increased the albumin escape index in association with increases in Ppa and Pmv. Because the increased albumin escape index after LTC4 or PAF injection was largely accounted for by the increased vascular pressures and because db-cAMP and papaverine inhibited the rise in vascular pressures and in the albumin escape index, we conclude that vasoconstriction is an important contributor to LTC4- and PAF-induced edema formation in rat lungs.

Pulmonary interstitial compartments and tissue resistance to fluid flux

1984 ◽  
Vol 57 (5) ◽  
pp. 1512-1519 ◽  
Author(s):  
H. W. Unruh ◽  
H. S. Goldberg ◽  
L. Oppenheimer
Keyword(s):  
Hydrostatic Pressure ◽  
Time Course ◽  
Weight Ratio ◽  
Dry Weight ◽  
Pressure Change ◽  
Weight Changes ◽  
Fluid Flux ◽  
Fluid Exchange ◽  
Tissue Resistance ◽  
Resistance Pathway

We have produced interstitial fluid exchange in six isolated plasma-perfused canine lobes by introducing small increases in microvascular hydrostatic pressure. We measured early fast fluid exchange with a colorimetric technique and used weight changes to follow slow exchange. The observed biphasic time course suggested fluid flux across the microvascular membrane into two interstitial compartments in series (perimicrovascular and central). We related the initial rate of fluid flux into each compartment to the applied hydrostatic pressure change to obtain membrane (Kf1) and tissue conductances (Kf2) and to the exchanged volume to determine perimicrovascular (C1) and central (C2) interstitial compliances. C2 (0.25 +/- 0.193) was twice C1 (0.10 +/- 0.031 ml X cmH2O-1 X g DW-1, where DW represents dry weight. C2 increased significantly with hydration (C2 = 0.06 X WW/DW - 0.15) ml X cmH2O-1 X g DW-1 (WW/DW, wet-to-dry weight ratio), whereas C1 did not. Kf1 (0.26 +/- 0.17) was one order of magnitude larger than Kf2 (0.027 +/- 0.014 ml X min-1 X cmH2O-1 X g DW-1). Kf2 increased with hydration (Kf2 = 0.005 X WW/DW - 0.007) ml X min-1 X cmH2O-1 X g DW-1, whereas Kf1 did not. Our data point to the tissues and not the microvascular membranes as the major rate-limiting structure. Our data suggest an interstitium composed of a smaller rigid perimicrovascular space which communicates to a larger looser downstream space by a high-resistance pathway. As hydration increases, fluid accumulation becomes easier because tissue resistance to fluid flux drops and the compliance of the downstream compartment doubles.

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