scholarly journals Pulmonary Interstitial Matrix and Lung Fluid Balance From Normal to the Acutely Injured Lung

2021 ◽  
Vol 12 ◽  
Author(s):  
Egidio Beretta ◽  
Francesco Romanò ◽  
Giulio Sancini ◽  
James B. Grotberg ◽  
Gary F. Nieman ◽  
...  

This review analyses the mechanisms by which lung fluid balance is strictly controlled in the air-blood barrier (ABB). Relatively large trans-endothelial and trans-epithelial Starling pressure gradients result in a minimal flow across the ABB thanks to low microvascular permeability aided by the macromolecular structure of the interstitial matrix. These edema safety factors are lost when the integrity of the interstitial matrix is damaged. The result is that small Starling pressure gradients, acting on a progressively expanding alveolar barrier with high permeability, generate a high transvascular flow that causes alveolar flooding in minutes. We modeled the trans-endothelial and trans-epithelial Starling pressure gradients under control conditions, as well as under increasing alveolar pressure (Palv) conditions of up to 25 cmH2O. We referred to the wet-to-dry weight (W/D) ratio, a specific index of lung water balance, to be correlated with the functional state of the interstitial structure. W/D averages ∼5 in control and might increase by up to ∼9 in severe edema, corresponding to ∼70% loss in the integrity of the native matrix. Factors buffering edemagenic conditions include: (i) an interstitial capacity for fluid accumulation located in the thick portion of ABB, (ii) the increase in interstitial pressure due to water binding by hyaluronan (the “safety factor” opposing the filtration gradient), and (iii) increased lymphatic flow. Inflammatory factors causing lung tissue damage include those of bacterial/viral and those of sterile nature. Production of reactive oxygen species (ROS) during hypoxia or hyperoxia, or excessive parenchymal stress/strain [lung overdistension caused by patient self-induced lung injury (P-SILI)] can all cause excessive inflammation. We discuss the heterogeneity of intrapulmonary distribution of W/D ratios. A W/D ∼6.5 has been identified as being critical for the transition to severe edema formation. Increasing Palv for W/D > 6.5, both trans-endothelial and trans-epithelial gradients favor filtration leading to alveolar flooding. Neither CT scan nor ultrasound can identify this initial level of lung fluid balance perturbation. A suggestion is put forward to identify a non-invasive tool to detect the earliest stages of perturbation of lung fluid balance before the condition becomes life-threatening.

1994 ◽  
Vol 77 (4) ◽  
pp. 1750-1754 ◽  
Author(s):  
W. F. Waltz ◽  
J. A. Burbach ◽  
E. H. Schlenker ◽  
B. E. Goodman

Gravimetric and sodium transport characteristics of lungs from BIO 14.6 (dystrophic) hamsters were compared with those of lungs from golden Syrian (normal) hamsters at 30 and 150 days of age. Isolated perfused lungs were used to determine lung permeability and fluid balance differences between normal and dystrophic animals at both ages. Apparent permeability-surface area products for air space-to-vascular space sodium, sucrose, and fluorescein isothiocyanate-labeled dextran fluxes were compared in the four groups of hamsters. Morphometric analysis of fixed lungs of representative hamsters from each group was also performed. Dystrophic hamsters exhibited higher lung wet-to-dry weight ratios than normal hamsters at both ages. Lungs from dystrophic hamsters were less sensitive to inhibition of sodium transport by amiloride than lungs from age-matched normal hamsters. Dystrophic hamster lungs had higher absolute permeabilities of the passively transported solutes, lower permeability values for sodium, and only one-half of the amiloride-sensitive sodium transport of lungs from age-matched normal hamsters. Differences in lung fluid balance between dystrophic and normal hamsters may be related to differences in sodium clearance.


1985 ◽  
Vol 58 (3) ◽  
pp. 882-891 ◽  
Author(s):  
G. A. Patterson ◽  
W. A. Mitzner ◽  
J. T. Sylvester

In this study we demonstrate the validity and utility of an isolated lung preparation developed for the study of pulmonary fluid balance. Lungs of 2- to 3-mo-old sheep were perfused in situ with autologous blood treated with indomethacin (20 micrograms/ml). Lung lymph flow (QL), uncontaminated by systemic lymph, was measured from either the efferent duct of the caudomediastinal lymph node or the thoracic duct in the superior mediastinum. Lung weight change (delta W) was measured as the opposite of the change in weight of the extracorporeal blood reservoir. A unique feature of this experimental model is the ability to assess lung fluid balance from simultaneous measurements of delta W and QL. In addition, hemodynamic and blood gas variables can be tightly controlled. Our results show that changes in QL and the lymph-to-plasma oncotic pressure ratio caused by an increase in microvascular pressure were comparable with those seen previously in intact sheep. When microvascular pressure was returned to control levels, QL fell despite a sustained increase in the amount of extravascular lung water, suggesting compartmentalization of the filtrate and/or effects of intravascular volume on lymph-driving pressure or resistance. Lymph flow was directly proportional to respiratory frequency over the range of 0–30 min-1 when the change in frequency was maintained for periods as long as 30 min. This preparation should prove useful in the study of lung fluid balance, particularly when it is desired to use interventions which are precluded or difficult in intact animals.


1990 ◽  
Vol 34 (5) ◽  
pp. 362-369 ◽  
Author(s):  
C. Frostell ◽  
H. Blomqvist ◽  
C. J. Wickerts ◽  
G. Hedenstierna

1982 ◽  
Vol 53 (4) ◽  
pp. 992-1004 ◽  
Author(s):  
R. D. Bland ◽  
T. N. Hansen ◽  
C. M. Haberkern ◽  
M. A. Bressack ◽  
T. A. Hazinski ◽  
...  

To study lung fluid balance before and after birth, we measured lung lymph flow and concentrations of protein in lymph and plasma of 22 unanesthetized fetal lambs and compared results with previous studies done on 26 newborn lambs, 1–2 wk old. Lymph flow, relative to lung mass, was less in fetuses than in newborns; lymph protein clearance was not significantly different. Less lymph flow before birth probably reflects less available surface area for fluid exchange in microcirculation of fetal lungs, compared with newborn lungs, with no difference in endothelial permeability to protein. Extravascular lung water, measured gravimetrically for 24 fetuses (10 without labor, nine in labor, five 6 h after vaginal birth), decreased by 45% (15 +/- 2 g/kg body wt) before birth and by an additional 38% (6 +/- 1 g/kg) after birth. In five lambs killed after birth, we measured lung lymph flow before and during labor and for 6 h after breathing began. Lymph flow was unaffected by labor but increased transiently after birth, accounting for 11% of the liquid removed from lungs postnatally. Liquid clearance studies performed in eight anesthetized 3-wk-old lambs confirmed the observation that lung lymphatics drain only a small fraction of liquid in potential air spaces. Most of that liquid probably leaves the lungs directly through pulmonary circulation.


2011 ◽  
Vol 25 (S1) ◽  
Author(s):  
Bryan Taylor ◽  
Maile Ceridon ◽  
Eric Snyder ◽  
Alex Carlson ◽  
Minelle Hulsebus ◽  
...  

1984 ◽  
Vol 56 (2) ◽  
pp. 489-494 ◽  
Author(s):  
J. C. Gabel ◽  
T. N. Hansen ◽  
R. E. Drake

We used a gravimetric technique to test for increased pulmonary capillary permeability after Escherichia coli endotoxin infusion in unanesthetized sheep. The sheep were chronically prepared with cannulas placed into the left atrium and pulmonary artery 1–2 wk before the experiments. We estimated pulmonary capillary pressure (Pc) as the average of pulmonary arterial and left atrial pressures, and used the modified method of Pierce to estimate the ratio of extravascular fluid weight (EVF) to blood-free dry weight. In 15 sheep we inflated a left atrial balloon to raise Pc to -10.7, 5, 10, or 15 mmHg above plasma oncotic pressure (IIc) for 3 h, then measured EVF. EVF averaged 4.0 +/- 0.2 (base line), 4.3 +/- 0.1, 4.5 +/- 0.1, and 5.1 +/- 0.5 (SD), respectively, for the four levels of Pc - IIc. We gave seven additional sheep 1 microgram/kg of E. coli endotoxin (0127:B8) and measured EVF after 3 h of stable Pc. Endotoxin increased Pc in each sheep. EVF was higher than control for the endotoxin sheep with Pc - IIc greater than -1. This finding is consistent with an increase in pulmonary capillary permeability caused by endotoxin. However, EVF was not elevated in the endotoxin sheep with Pc - IIc less than 1 mmHg. This shows that the increased permeability was insufficient to cause edema unless Pc was elevated. Thus endotoxin may cause edema by two mechanisms, 1) an increase in capillary permeability, and 2) an increase in Pc.


1983 ◽  
Vol 244 (6) ◽  
pp. H763-H768
Author(s):  
R. L. Scott ◽  
D. K. Adcock ◽  
R. E. Drake ◽  
J. C. Gabel

Endotoxin may cause an increase in pulmonary capillary permeability and thus promote edema formation. We used a gravimetric technique to estimate the pulmonary capillary filtration coefficient (KF) and the maximum capillary pressure at which the lung could maintain a constant weight (Pccritical) in dogs after intravenous administration of Escherichia coli (E. coli) endotoxin. KF should be increased and Pccritical should be decreased by an increase in permeability. Four groups of three to four dogs were given 1, 10, 1,000, or 3,000 micrograms/kg of endotoxin. A fifth group of five dogs, which served as controls, was given no endotoxin. KF was significantly (P less than 0.05) greater than control [0.049 +/- 0.031 (SD) ml . min-1 . mmHg-1] in only the 1-micrograms/kg group (0.100 +/- 0.027), indicating a possible increase in permeability. However, changes in capillary surface area may have affected KF. Pccritical was not significantly different from control (20.7 +/- 2.4 mmHg) in any of the E. coli groups. We conclude from these results that E. coli endotoxin may have caused a slight increase in permeability; however, the lung retained its ability to resist edema formation.


1993 ◽  
Vol 74 (1) ◽  
pp. 126-132 ◽  
Author(s):  
D. B. Pearse ◽  
E. M. Wagner ◽  
J. T. Sylvester

Edema may be cleared from the lung by lymphatic drainage, transudation across the visceral pleural, vascular reabsorption, and movement into the mediastinum. To determine the quantity and mechanisms of edema clearance associated with spontaneous edema formation in isolated sheep lungs, we perfused six lungs for 180 min with blood (100 ml.kg-1.min-1) at subatmospheric left atrial pressure (Pla) from a weighed reservoir. In six other lungs, Pla was increased to 20 mmHg at 30–75 min to further augment edema. Fluid drainage from the lung was fractionated into blood and water components by serial measurements of drainage and perfusate hematocrit. Changes in weight of circulating intravascular blood and extravascular lung water (EVLW) were also directly measured by dye dilution and standard gravimetric techniques, respectively. From these measurements, we calculated that 3.04 +/- 0.53 g/g blood-free dry lung of water filtered into the extravascular space during perfusion. Of this amount, 42% was reabsorbed into the pulmonary vasculature; 18% drained from the lung via lymphatics, visceral pleura, and mediastinum; and 40% was retained in the lung. Compared with low Pla lungs, transient elevation of Pla increased lung hemorrhage and the final change in reservoir weight, but the quantity and clearance of cumulative filtered water and the final values of EVLW and wet-to-dry weight ratio (WW/DW) were not altered. These results suggest that 1) significant edema clearance occurred in isolated sheep lungs, primarily by vascular reabsorption, and 2) measurements of EVLW and WW/DW under-estimated injury in the presence of lung hemorrhage and significant edema clearance.


1987 ◽  
Vol 63 (5) ◽  
pp. 1705-1710
Author(s):  
T. Horie ◽  
T. Izumi ◽  
K. Hodaka ◽  
T. Akashiba ◽  
Y. Hosokawa ◽  
...  

Effects of tidal volume (VT), end-expiratory pressure (EEP), and environmental temperature (Tenv) on elastic recoil force (Pel) and edema formation were examined in open-chest anesthetized rabbits. Sixty-two rabbits in four groups were ventilated for 3 h with VT of either 10 or 25 ml/kg body wt, EEP of 0 or 2 cmH2O, and Tenv of 18 or 35 degrees C. After ventilation, Pel at 80% of total lung capacity (P80) was significantly increased when ventilation was performed with the combination of large VT, 0 EEP, and low Tenv. This change was prevented by altering any one of the three conditions, e.g., small VT, positive EEP, or high Tenv. Similarly, elevation of minimum surface tension and reduction of surface activity index of lavages from excised lungs after ventilation were observed only when increased P80 was noted. Additionally, the increase of P80 was well correlated with increment of wet weight-to-dry weight ratio and degree of perivascular cuffing and alveolar edema formation of excised lungs. These results indicate that elevation of Pel after high tidal ventilation in open-chest animals in vivo was influenced by level of EEP and Tenv and that the degree of edema formation was closely related to the increase of Pel. The increased Pel is presumably primary and causes fluid accumulation.


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