Comparative aspects of the strength of pulmonary capillaries in rabbit, dog, and horse

Birks, Eric K.; Mathieu-Costello, Odile; Fu, Zhenxing; Tyler, W. S.; West, John B.

doi:10.1016/0034-5687(94)90029-9

Cited by 66 publications

(63 citation statements)

References 16 publications

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“…In the current study, we found that the increase in V af /V as observed in wild-type lung after HiPv was absent in TRPV4 2/2 lung. These data confirm previous reports that HiPv targets the alveolar septal compartment, evoking disruption of alveolar septal capillaries and alveolar flooding (5,(22)(23)(24)31), and suggest that this is due to HiPv-induced activation of TRPV4.…”

Section: Discussionsupporting

confidence: 91%

“…West and colleagues (5) have suggested that the stress failure threshold is directly related to the thickness of the septal barrier. A thicker septal barrier, such as that in horse, apparently confers some mechanical advantage and the alveolar septal wall is able to withstand higher pressures-that is, the threshold is increased (5,24). The relation between barrier thickness and the threshold for the permeability response to HiPv mimics the relation for stress failure.…”

Section: Discussionmentioning

confidence: 97%

“…Thresholds for HiPv-induced increase in K f do indeed increase (28, 31, and 37 cm H 2 O; current study and Refs. 4 and 22) as harmonic mean thickness of the blood gas barrier increases in mouse, rat, and dog (0.44, 0.39, and 0.66 mm) (24,25), when a similar approach to measurement of K f and similar duration of HiPv challenge are used. However, this relationship does not necessarily rule out participation from HiPv-induced activation of signaling, which initiates barrier dysfunction.…”

Section: Discussionmentioning

confidence: 99%

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High Vascular Pressure–Induced Lung Injury Requires P450 Epoxygenase–Dependent Activation of TRPV4

Jian¹,

King²,

Al‐Mehdi³

et al. 2008

Am J Respir Cell Mol Biol

129

137

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High vascular pressure targets the lung septal network, causing acute lung injury. While calcium entry in septal endothelium has been implicated, the channel involved is not known. This study tested the hypothesis that the vanilloid transient receptor potential channel, TRPV4, is a critical participant in the permeability response to high vascular pressure. Isolated lungs from TRPV4 1/1 or TRPV4 2/2 mice were studied at baseline or during high pressure challenge. Permeability was assessed via the filtration coefficient. Endothelial calcium transients were assessed using epifluorescence microscopy of the lung subpleural network. Light microscopy and point counting were used to determine the alveolar fluid volume fraction, a measure of alveolar flooding. Baseline permeability, calcium intensity, and alveolar flooding were no different in TRPV4 1/1 versus TRPV4 2/2 lungs. In TRPV4 1/1 lungs, the high pressure-induced permeability response was significantly attenuated by low calcium perfusate, the TRPV antagonist ruthenium red, the phospholipase A 2 inhibitor methyl arachidonyl fluorophosphonate, or the P450 epoxygenase inhibitor propargyloxyphenyl hexanoic acid. Similarly, the high pressure-induced calcium transient in TRPV4 1/1 lungs was attenuated with ruthenium red or the epoxygenase inhibitor. High vascular pressure increased the alveolar fluid volume fraction compared with control. In lungs from TRPV4 2/2 mice, permeability, calcium intensity, and alveolar fluid volume fraction were not increased. These data support a role for P450-derived epoxyeicosatrienoic aciddependent regulation of calcium entry via TRPV4 in the permeability response to high vascular pressure.Keywords: epoxyeicosatrienoic acid; capillary permeability; respiratory distress syndrome; TRPV cation channels In lung, high vascular pressure (HiPv) exceeding a threshold of 30 to 50 cm H 2 O increases endothelial permeability (1-4). While mechanical stress failure of the alveolar septal barrier can occur at higher pressures, leading to overt alveolar flooding (5), the molecular mechanisms underlying the early HiPv-induced increase in endothelial permeability are not well understood. Kuebler and colleagues (6) have reported that moderate HiPv promotes Ca 21 entry into lung endothelium, and acute lung injury is often dependent upon such Ca 21 transients (7-10). Although HiPv-induced lung injury could plausibly be dependent upon Ca 21 entry, this has not been experimentally confirmed nor has a candidate channel been identified.The Ca 21 permeable channel TRPV4, a member of the vanilloid subfamily of transient receptor potential (TRP) channels, is expressed in the alveolar septal compartment (8). The notion that TRPV4 might subserve HiPv-induced Ca 21 entry in lung endothelium is based on the observation that the channel can be activated by mechanical stress, such as hypotonic cell swelling or shear stress (11-13). In vitro studies have shown that activation of TRPV4 with mechanical stress requires hydrolysis of membrane phospholipids via phospholipas...

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Section: Discussionsupporting

confidence: 91%

Section: Discussionmentioning

confidence: 97%

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

High Vascular Pressure–Induced Lung Injury Requires P450 Epoxygenase–Dependent Activation of TRPV4

Jian¹,

King²,

Al‐Mehdi³

et al. 2008

Am J Respir Cell Mol Biol

129

137

View full text Add to dashboard Cite

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“…The fact that some disruptions were seen at a pressure as low as 24 mmHg is remarkable in view of the evidence presented above that some of the capillaries of the human lung during severe exercise have a transmural pressure as high as 36 mmHg. However, of course, we cannot assume that stress failure occurs at the same pressures in rabbit and human lung, and indeed we have shown that different pressures are required in rabbit, dog, and horse lung (4).…”

Section: Stress Failure Of the Bgbmentioning

confidence: 84%

Thoughts on the pulmonary blood-gas barrier

West

2003

American Journal of Physiology-Lung Cellular and Molecular Phys

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The pulmonary blood-gas barrier is an extraordinary structure because of its extreme thinness, immense strength, and enormous area. The essential components of the barrier were determined early in evolution and have been highly conserved. For example, the barriers of the African, Australian, and South American lungfish that date from as much as 400 million years ago have essentially the same structure as in the modern mammal or bird. In the evolution of vertebrates from bony fishes through amphibia, reptiles, and ultimately mammals and birds, changes in the pulmonary circulation occurred to limit the stresses in the blood-gas barrier. Only in mammals and birds is there a complete separation of the pulmonary and systemic circulations, which is essential to protect the extremely thin barrier from the necessary high-vascular pressures. To provide the blood-gas barrier with its required strength, evolution has exploited the high ultimate tensile strength of type IV collagen in basement membrane. Nevertheless, stress failure of the barrier occurs under physiological conditions in galloping Thoroughbred racehorses and also apparently in elite human athletes at maximal exercise. The human blood-gas barrier maintains its integrity during all but the most extreme physiological conditions. However, many pathological conditions cause stress failure. The structure of the blood-gas barrier is apparently continually regulated in response to wall stress, and this regulation is essential to maintain the extreme thinness but adequate strength. The mechanisms of this regulation remain to be elucidated and constitute one of the fundamental problems in lung biology.

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“…Therefore, prints of each negative were available for positive identification of structures on the computer screen, as needed, during measurement. This allowed an unequivocal identification of small endothelial and epithelial disruptions as well as the presence (or absence) of basement membrane at all sites of rupture, as was the case with our previous studies (2,12).…”

Section: Morphometric Analysismentioning

confidence: 54%

Increased fragility of pulmonary capillaries in newborn rabbit

Heldt

West

2003

American Journal of Physiology-Lung Cellular and Molecular Phys

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.-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 (P tm) of 5 Ϯ 5, 10 Ϯ 5, and 15 Ϯ 5 cmH2O. Normal microscopic appearances were seen at Ptm values of 5 Ϯ 5 and 10 Ϯ 5 cmH2O, but massive airway edema was observed in lungs perfused at a Ptm of 15 Ϯ 5 cmH2O. Consistent with this, no disruptions of the alveolar epithelium were observed at Ptm values of 5 Ϯ 5 cmH2O, but mean values of 0.11 and 1.22 breaks/mm epithelium were found at Ptm of 10 Ϯ 5 and 15 Ϯ 5 cmH2O, respectively (P Ͻ 0.05 for 5 Ϯ 5 vs. 15 Ϯ 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. neonatal lung; lung morphometry; capillary wall stress; stress failure IF THE PULMONARY CAPILLARIES of adult lungs are exposed to transmural pressures (P tm ) that exceed the normal maximal physiological values, ultrastructural changes occur in the walls, and a common result is the development of a high-permeability form of pulmonary edema (12,15). This condition is known as stress failure because it is caused by the high circumferential stresses in the extremely thin capillary walls. There is evidence that the strength of the walls is attributable to the type IV collagen in the basement membranes of the alveolar epithelial and capillary endothelial cells (14), and on the thin side of the blood-gas barrier, these fused basement membranes make up the whole of the interstitial layer. In a recent study, we measured the thickness of the interstitium, epithelium, and endothelium from premature and term newborn rabbit lungs and compared these with adult lungs. A surprising finding was that the interstitium of the blood-gas barrier of newborn lungs was the thinnest among the three groups, and this suggested that the structure of the capillary wall might predispose to stress failure.If true, this finding could have important potential clinical implications in the setting of neonatal lung disease. At birth, a complex series of events occur, including a rapid increase in the pulmonary blood flow from ϳ15% of the cardiac output before birth, to nearly the whole of the cardiac output. This is accomplished by a dramatic reduction in pulmonary vascular resistance brought about, in part, by the relief of hypoxia vasoconstriction, and also by inflation of the lung. These changes might be expected to greatly increase the P tm of the pulmonary capillaries if not for the fact that the pulmonary artery pressure is simultaneously reduced by narrowing of the ductus arteriosus, although the hemodynamic events are complex, and the details are poorly understood. Ho...

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Comparative aspects of the strength of pulmonary capillaries in rabbit, dog, and horse

Cited by 66 publications

References 16 publications

High Vascular Pressure–Induced Lung Injury Requires P450 Epoxygenase–Dependent Activation of TRPV4

High Vascular Pressure–Induced Lung Injury Requires P450 Epoxygenase–Dependent Activation of TRPV4

Thoughts on the pulmonary blood-gas barrier

Increased fragility of pulmonary capillaries in newborn rabbit

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