Thickness of the blood-gas barrier in premature and 1-day-old newborn rabbit lungs

2003 ◽  
Vol 285 (1) ◽  
pp. L130-L136 ◽  
Author(s):  
Zhenxing Fu ◽  
Gregory P. Heldt ◽  
John B. West
Keyword(s):  
Pulmonary Circulation ◽  
Alveolar Epithelium ◽  
Capillary Endothelium ◽  
Blood Gas ◽  
Gas Barrier ◽  
Newborn Rabbit ◽  
Pulmonary Capillaries ◽  
Normal Gestation ◽  
Neonatal Lungs ◽  
Extensive Pilot

The pulmonary capillaries of neonatal lungs are potentially vulnerable to stress failure because of the complex changes in the pulmonary circulation that occur at birth. We studied the ultrastructure of the blood-gas barrier (BGB) in premature and 1-day-old rabbit lungs and compared it with the ultrastructure of adult lungs. Normal gestation of rabbits is 30 days. After extensive pilot measurements, three premature (27 days gestation) and three newborn (1 day old) rabbit lungs were perfusion-fixed at arterial, venous, and airway pressures of 25, 0, and 10 cmH2O, respectively, and the measurements were compared with those of three adult lungs. The thickness of the capillary endothelium, alveolar epithelium, and interstitium of the BGB was measured at right angles to the barrier at random points. A striking finding was the large number of measurements of the interstitial thickness in 1-day-old lungs that were very thin (0–0.1 μm). The percentages of occurrence of very thin interstitium in premature, 1-day-old, and adult lungs were 35.3 ± 9.4, 71.7 ± 5.2, and 43.0 ± 2.6, respectively ( P < 0.02 for 1 day old vs. premature and adult). Given the previously found relationship between stress failure and interstitial thickness, this large proportion of very thin interstitial layers in the capillaries of 1-day-old lungs is a reasonable explanation for their previously demonstrated vulnerability to stress failure.

Increased fragility of pulmonary capillaries in newborn rabbit

2003 ◽  
Vol 284 (5) ◽  
pp. L703-L709 ◽  
Author(s):  
Zhenxing Fu ◽  
Gregory P. Heldt ◽  
John B. West
Keyword(s):  
Pulmonary Circulation ◽  
Alveolar Epithelium ◽  
Adult Rabbit ◽  
Mean Values ◽  
Newborn Rabbit ◽  
Airway Edema ◽  
Pulmonary Capillaries ◽  
Neonatal Lungs ◽  
Striking Contrast

The pulmonary capillaries of neonatal lungs are potentially vulnerable to stress failure because of the complex changes in the pulmonary circulation that occur at birth. We perfusion fixed the lungs from nine anesthetized newborn rabbits at capillary transmural pressures (Ptm) of 5 ± 5, 10 ± 5, and 15 ± 5 cmH2O. Normal microscopic appearances were seen at Ptm values of 5 ± 5 and 10 ± 5 cmH2O, but massive airway edema was observed in lungs perfused at a Ptm of 15 ± 5 cmH2O. Consistent with this, no disruptions of the alveolar epithelium were observed at Ptm values of 5 ± 5 cmH2O, but mean values of 0.11 and 1.22 breaks/mm epithelium were found at Ptm of 10 ± 5 and 15 ± 5 cmH2O, respectively ( P < 0.05 for 5 ± 5 vs. 15 ± 5 cmH2O). These pressures are in striking contrast to those in the adult rabbit in which, by a similar procedure, a Ptm of 52.5 cmH2O, is required before stress failure is consistently seen. We conclude that stress failure of pulmonary capillaries in newborn rabbit lungs can occur at Ptm values of less than one-third of those that are required in adult lungs.

Ultrastructural appearances of pulmonary capillaries at high transmural pressures

1991 ◽  
Vol 71 (2) ◽  
pp. 573-582 ◽  
Author(s):  
K. Tsukimoto ◽  
O. Mathieu-Costello ◽  
R. Prediletto ◽  
A. R. Elliott ◽  
J. B. West
Keyword(s):  
Autologous Blood ◽  
Alveolar Epithelium ◽  
Basement Membranes ◽  
Capillary Endothelium ◽  
Blood Gas ◽  
Gas Barrier ◽  
Pulmonary Capillaries ◽  
The Mean ◽  
Cell Lining

Electronmicroscopic appearances of pulmonary capillaries were studied in rabbit lungs perfused in situ when the capillary transmural pressure (Ptm) was systematically raised from 12.5 to 72.5 +/- 2.5 cmH2O. The animals were anesthetized and exsanguinated, and after the chest was opened, the pulmonary artery and left atrium were cannulated and attached to reservoirs. The lungs were perfused with autologous blood for 1 min, and this was followed by saline-dextran and then buffered glutaraldehyde to fix the lungs for electron microscopy. Normal appearances were seen at 12.5 cmH2O Ptm. At 52.5 and 72.5 cmH2O Ptm, striking discontinuities of the capillary endothelium and alveolar epithelium were seen. A few disruptions were seen at 32.5 cmH2O Ptm (mostly in one animal), but the number of breaks per millimeter cell lining increased markedly up to 72.5 cmH20 Ptm, where the mean frequency was 27.8 +/- 8.6 and 13.6 +/- 1.4 (SE) breaks/mm for endothelium and epithelium, respectively. In some instances, all layers of the blood-gas barrier were disrupted and erythrocytes could be seen moving into the alveolar spaces. In about half the endothelial and epithelial breaks, the basement membranes remained intact. The average break lengths for both endothelium and epithelium did not change significantly with pressure. The width of the blood-gas barrier increased at 52.5 and 72.5 cmH2O Ptm as a result of widening of the interstitium caused by edema. The cause of the disruptions is believed to be stress failure of the capillary wall. The results show that high capillary hydrostatic pressures cause major changes in the ultrastructure of the walls of the capillaries, leading to a high-permeability form of edema.

Role of the fragility of the pulmonary blood-gas barrier in the evolution of the pulmonary circulation

2013 ◽  
Vol 304 (3) ◽  
pp. R171-R176 ◽  
Author(s):  
John B. West
Keyword(s):  
Pulmonary Circulation ◽  
Complete Separation ◽  
Blood Gas ◽  
Gas Barrier ◽  
Pulmonary Capillaries ◽  
Pulmonary Capillary ◽  
Resolution Electron ◽  
Two Factors ◽  
Key Factor ◽  
Capillary Pressures

In 1953 Frank Low published the first high-resolution electron micrographs of the human pulmonary blood-gas barrier. These showed that a structure only 0.3-μm thick separated the capillary blood from the alveolar gas, immediately suggesting that the barrier might be vulnerable to mechanical failure if the capillary pressure increased. However, it was 38 years before stress failure was recognized. Initially it was implicated in the pathogenesis of High Altitude Pulmonary Edema, but it was soon clear that stress failure of pulmonary capillaries is common. The vulnerability of the blood-gas barrier is a key factor in the evolution of the pulmonary circulation. As evolution progressed from the ancestors of fishes to amphibians, reptiles, and finally birds and mammals, two factors challenged the integrity of the barrier. One was the requirement for the barrier to become increasingly thin because of the greater oxygen consumption. The other was the high pulmonary capillary pressures that were inevitable before there was complete separation of the pulmonary and systemic circulations.

Solute conductance of blood-gas barrier in hamsters exposed to hyperoxia

1986 ◽  
Vol 60 (6) ◽  
pp. 1908-1916 ◽  
Author(s):  
D. Wangensteen ◽  
R. Piper ◽  
J. A. Johnson ◽  
A. A. Sinha ◽  
D. Niewoehner
Keyword(s):  
Bovine Serum Albumin ◽  
Alveolar Epithelium ◽  
Capillary Endothelium ◽  
Blood Gas ◽  
Lung Weight ◽  
Gas Barrier ◽  
Functional Changes ◽  
Isolated Perfused Lung ◽  
Perfused Lung ◽  
Wet Weight

Hamsters were exposed to greater than 95% O2 continuously for up to 5 days to determine longitudinal changes in the diffusive conductance of the alveolar epithelium and capillary endothelium as a result of hyperoxia. Permeability X surface area (PS, cm3/s X 10(-4)) was measured by isolated, perfused lung techniques. Alveolar epithelium PS for [14C]sucrose and 125I-bovine serum albumin (BSA) were determined at seven exposure times. Control PS (sucrose) and PS(BSA) averaged 1.00 and 0.022, respectively. Values were unchanged until 4.5 days, when significant increases in both, but especially PS(BSA), occurred. After 5 days, PS values were 4.69 and 0.691, respectively. Capillary endothelium PS for 125I-BSA and fluoresceinisothiocyanate dextran-150 (D-150) were measured at four exposure times. Control endothelium PS(BSA) and PS(D-150) averaged 0.232 and 0.048, respectively. These values were also unchanged after 4 days but increased to 0.440 and 0.131 after 5 days. Wet lung weight significantly increased after only 4 days. Hyperoxia thus increased both endothelium and epithelium PS, but epithelium changes were much greater. These functional changes do not occur for several days, occur simultaneously, and follow increases in lung wet weight.

scholarly journals Frank Low and the first images of the ultrastructure of the pulmonary blood-gas barrier

2016 ◽  
Vol 310 (5) ◽  
pp. L387-L392 ◽  
Author(s):  
John B. West
Keyword(s):  
Extracellular Matrix ◽  
Alveolar Epithelium ◽  
Capillary Endothelium ◽  
Blood Gas ◽  
Major Event ◽  
Gas Barrier ◽  
Pulmonary Physiology ◽  
Pulmonary Capillary ◽  
Matrix Layer ◽  
First Time

Frank N. Low (1911–1998) has the distinction of publishing the first electron micrographs showing the ultrastructure of the pulmonary capillary and particularly the blood-gas barrier. This work in 1952 and 1953 was enabled by the progress in fixation and staining of tissue made by George Palade and was part of the very rapid advance in electron microscopy during the previous 25 years. Low's micrographs clearly showed the three layers of the blood-gas barrier: capillary endothelium, extracellular matrix, and alveolar epithelium. The images immediately resolved the debate about the composition of the blood-gas barrier that had been raging for 100 years. The first published micrographs were rather poor, but the quality rapidly improved and a major event was the first electron micrograph of the human blood-gas barrier published in 1953. These images had an enormous influence on the development of pulmonary physiology and biology. For example, for the first time it became clear that the barrier separating the blood from the alveolar gas was vanishingly thin. The discovery of the extracellular matrix layer ultimately clarified how this barrier, despite its extraordinary thinness, was sufficiently strong to avoid mechanical failure. Despite the major advances made by Low, his name is almost unknown in pulmonary physiology and biology, and perhaps this tribute will help to give him his due.

Ultrastructure of pulmonary microvasculature in acute endotoxemia

1978 ◽  
Vol 36 (2) ◽  
pp. 470-471
Author(s):  
R. G. Gerrity ◽  
M. Richardson
Keyword(s):  
Polymorphonuclear Leukocytes ◽  
Alveolar Epithelium ◽  
Endothelial Damage ◽  
Capillary Endothelium ◽  
Type Ii Cells ◽  
Type Ii ◽  
Interstitial Edema ◽  
Pulmonary Capillaries ◽  
Lung Ultrastructure ◽  
Fibrin Thrombi

Dogs were injected intravenously with E_. coli endotoxin (2 mg/kg), and lung samples were taken at 15 min., 1 hr. and 24 hrs. At 15 min., occlusion of pulmonary capillaries by degranulating platelets and polymorphonuclear leukocytes (PML) was evident (Fig. 1). Capillary endothelium was intact but endothelial damage in small arteries and arterioles, accompanied by intraalveolar hemorrhage, was frequent (Fig. 2). Sloughing of the surfactant layer from alveolar epithelium was evident (Fig. 1). At 1 hr., platelet-PML plugs were no longer seen in capillaries, the endothelium of which was often vacuolated (Fig. 3). Interstitial edema and destruction of alveolar epithelium were seen, and type II cells had discharged their granules into the alveoli (Fig. 4). At 24 hr. phagocytic PML's were frequent in peripheral alveoli, while centrally, alveoli and vessels were packed with fibrin thrombi and PML's (Fig. 5). In similar dogs rendered thrombocytopenic with anti-platelet serum, lung ultrastructure was similar to that of controls, although PML's were more frequently seen in capillaries in the former (Fig. 6).

scholarly journals Comparative physiology of the pulmonary blood-gas barrier: the unique avian solution

2009 ◽  
Vol 297 (6) ◽  
pp. R1625-R1634 ◽  
Author(s):  
John B. West
Keyword(s):  
Gas Exchange ◽  
Complete Separation ◽  
External Support ◽  
Blood Gas ◽  
Large Area ◽  
Gas Barrier ◽  
Type Iv ◽  
Pulmonary Capillaries ◽  
The Face ◽  
Flow Through

Two opposing selective pressures have shaped the evolution of the structure of the blood-gas barrier in air breathing vertebrates. The first pressure, which has been recognized for 100 years, is to facilitate diffusive gas exchange. This requires the barrier to be extremely thin and have a large area. The second pressure, which has only recently been appreciated, is to maintain the mechanical integrity of the barrier in the face of its extreme thinness. The most important tensile stress comes from the pressure within the pulmonary capillaries, which results in a hoop stress. The strength of the barrier can be attributed to the type IV collagen in the extracellular matrix. In addition, the stress is minimized in mammals and birds by complete separation of the pulmonary and systemic circulations. Remarkably, the avian barrier is about 2.5 times thinner than that in mammals and also is much more uniform in thickness. These advantages for gas exchange come about because the avian pulmonary capillaries are unique among air breathers in being mechanically supported externally in addition to the strength that comes from the structure of their walls. This external support comes from epithelial plates that are part of the air capillaries, and the support is available because the terminal air spaces in the avian lung are extremely small due to the flow-through nature of ventilation in contrast to the reciprocating pattern in mammals.

Pulmonary capillaries are more resistant to stress failure in dogs than in rabbits

1995 ◽  
Vol 79 (3) ◽  
pp. 908-917 ◽  
Author(s):  
O. Mathieu-Costello ◽  
D. C. Willford ◽  
Z. Fu ◽  
R. M. Garden ◽  
J. B. West
Keyword(s):  
Autologous Blood ◽  
Transmural Pressure ◽  
Blood Gas ◽  
Barrier Thickness ◽  
Rabbit Lung ◽  
Gas Barrier ◽  
Athletic Ability ◽  
Pulmonary Capillaries ◽  
Glutaraldehyde Solution

We previously showed that stress failure of pulmonary capillaries occurs at transmural pressures of approximately 50 cmH2O (40 mmHg) and above in rabbit lung. In this study, we examined whether pulmonary capillaries are more resistant to failure in dogs than in rabbits. This might be expected because of the greater athletic ability of dogs and therefore their presumably greater tolerance to large cardiac outputs and higher pulmonary vascular pressures. The lungs of 12 anesthetized mongrel dogs [22.1 +/- 5.2 (SD) kg] were perfused in situ with autologous blood and then with saline-dextran (5 min) and glutaraldehyde solution (10 min), all three perfusions at the same preset transmural pressure of 32.5, 72.5, 92.5, or 112.5 cmH2O. In dogs, the stress failure curves relating break number per millimeter of epithelium and endothelium were right shifted by approximately 40 cmH2O compared with rabbits. Blood-gas barrier thickness was significantly greater than in rabbits at 32.5 cmH2O, and unlike in rabbits, neither total nor interstitial thickness increased significantly with increasing pressure. These results indicate that pulmonary capillaries are more resistant to stress failure in dogs than rabbits.

Very high pressures are required to cause stress failure of pulmonary capillaries in Thoroughbred racehorses

1997 ◽  
Vol 82 (5) ◽  
pp. 1584-1592 ◽  
Author(s):  
Eric K. Birks ◽  
Odile Mathieu-Costello ◽  
Zhenxing Fu ◽  
Walter S. Tyler ◽  
John B. West
Keyword(s):  
High Pressures ◽  
Autologous Blood ◽  
Pulmonary Hemorrhage ◽  
Capillary Endothelium ◽  
Gas Barrier ◽  
Thoroughbred Racehorses ◽  
Pulmonary Capillaries ◽  
Thoroughbred Horses ◽  
Exercise Induced ◽  
Very High

Birks, Eric K., Odile Mathieu-Costello, Zhenxing Fu, Walter S. Tyler, and John B. West. Very high pressures are required to cause stress failure of pulmonary capillaries in Thoroughbred racehorses. J. Appl. Physiol. 82(5): 1584–1592, 1997.—Thoroughbred horses develop extremely high pulmonary vascular pressures during galloping, all horses in training develop exercise-induced pulmonary hemorrhage, and we have shown that this is caused by stress failure of pulmonary capillaries. It is known that the capillary transmural pressure (Ptm) necessary for stress failure is higher in dogs than in rabbits. The present study was designed to determine this value in horses. The lungs from 15 Thoroughbred horses were perfused with autologous blood at Ptm values (midlung) of 25, 50, 75, 100 and 150 mmHg, and then perfusion fixed, and samples (dorsal and ventral, from caudal region) were examined by electron microscopy. Few disruptions of capillary endothelium were observed at Ptm ≤ 75 mmHg, and 5.3 ± 2.2 and 4.3 ± 0.7 breaks/mm endothelium were found at 100 and 150 mmHg Ptm, respectively. Blood-gas barrier thickness did not change with Ptm. At low Ptm, interstitial thickness was greater than previously found in rabbits but not in dogs. We conclude that the Ptm required to cause stress failure of pulmonary capillaries is between 75 and 100 mmHg and is greater in Thoroughbred horses than in both rabbits and dogs.

Morphometry of the extremely thin pulmonary blood-gas barrier in the chicken lung

2007 ◽  
Vol 292 (3) ◽  
pp. L769-L777 ◽  
Author(s):  
Rebecca R. Watson ◽  
Zhenxing Fu ◽  
John B. West
Keyword(s):  
Type I Collagen ◽  
Arithmetic Mean ◽  
Type I ◽  
Blood Gas ◽  
Gas Barrier ◽  
Structural Support ◽  
Pulmonary Capillaries ◽  
Mammalian Lung ◽  
Avian Lung ◽  
To Come

The gas exchanging region in the avian lung, although proportionally smaller than that of the mammalian lung, efficiently manages respiration to meet the high energetic requirements of flapping flight. Gas exchange in the bird lung is enhanced, in part, by an extremely thin blood-gas barrier (BGB). We measured the arithmetic mean thickness of the different components (endothelium, interstitium, and epithelium) of the BGB in the domestic chicken lung and compared the results with three mammals. Morphometric analysis showed that the total BGB of the chicken lung was significantly thinner than that of the rabbit, dog, and horse (54, 66, and 70% thinner, respectively) and that all layers of the BGB were significantly thinner in the chicken compared with the mammals. The interstitial layer was strikingly thin in the chicken lung (∼86% thinner than the dog and horse, and 75% thinner than rabbit) which is a paradox because the strength of the BGB is believed to come from the interstitium. In addition, the thickness of the interstitium was remarkably uniform, unlike the mammalian interstitium. The uniformity of the interstitial layer in the chicken is attributable to a lack of the supportive type I collagen cable that is found in mammalian alveolar lungs. We propose that the surrounding air capillaries provide additional structural support for the pulmonary capillaries in the bird lung, thus allowing the barrier to be both very thin and extremely uniform. The net result is to improve gas exchanging efficiency.

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