Computer simulation of neutrophil transit through the pulmonary capillary bed

1993 ◽  
Vol 74 (4) ◽  
pp. 1647-1652 ◽  
Author(s):  
C. C. Hanger ◽  
W. W. Wagner ◽  
S. J. Janke ◽  
T. C. Lloyd ◽  
R. L. Capen
Keyword(s):  
Computer Simulation ◽  
Computer Model ◽  
Pulmonary Circulation ◽  
Cell Deformation ◽  
In Vivo Microscopy ◽  
Pulmonary Capillaries ◽  
Pulmonary Capillary ◽  
Capillary Bed ◽  
Diameter Distributions

One-half of the neutrophils that enter the pulmonary circulation become temporarily trapped in capillaries. The neutrophils that are impeded make complete stops between free-flowing movements. These observations, based on in vivo microscopy, suggest that pulmonary margination is caused by neutrophils being impeded at focal sites in the capillary bed. To investigate the frequency with which impeding sites had to occur in the pulmonary capillaries to trap one-half of the circulating neutrophils, we developed a computer model to simulate neutrophils encountering discrete obstructions in a capillary-like network. Surprisingly, if only 1% of the capillaries in the network acted as traps, one-half of the neutrophils stopped at least once. The trapping ability of a given percentage of obstructions was independent both of the geometry of the network was whether the obstructions occurred in the segments or junctions. To simulate neutrophil transit more realistically, both neutrophil and capillary diameters were randomly selected from published diameter distributions. Every neutrophil was trapped multiple times by this model, suggesting that cell deformation contributes importantly to neutrophil passage through the pulmonary capillary bed.

Comparison of neutrophil and capillary diameters and their relation to neutrophil sequestration in the lung

1993 ◽  
Vol 74 (6) ◽  
pp. 3040-3045 ◽  
Author(s):  
C. M. Doerschuk ◽  
N. Beyers ◽  
H. O. Coxson ◽  
B. Wiggs ◽  
J. C. Hogg
Keyword(s):  
Pulmonary Circulation ◽  
Blood Cells ◽  
Polymorphonuclear Leukocytes ◽  
Neutrophil Sequestration ◽  
Pulmonary Capillaries ◽  
Pulmonary Capillary ◽  
Capillary Bed ◽  
The Mean ◽  
Pass Through ◽  
Capillary Size

Neutrophils [polymorphonuclear leukocytes (PMNs)] are sequestrated in the lung capillary bed because PMNs are delayed with respect to red blood cells (RBCs) as they pass through these microvessels. The present study examines circulating PMN size in relation to the distribution of capillary segment diameters in human, dog, and rabbit lungs and compares the shape of PMNs in suspension to that found within the pulmonary capillaries. The data show that 61, 67, and 38% of the capillary segments are narrower than the mean diameter of spherical PMNs in the rabbit, dog, and human, respectively. They also show that PMNs deform from a spherical to an ellipsoid shape in the pulmonary capillaries of all three species. These findings are consistent with previous studies showing that the pulmonary circulation restricts the passage of PMNs through the lungs and suggest that PMNs are delayed because they must deform to pass through restrictions encountered in the pulmonary capillary bed. We conclude that the discrepancy between PMN and pulmonary capillary size and the decreased deformability of PMNs with respect to RBCs are major determinants of the delay that PMNs experience with respect to RBCs in the pulmonary circulation.

Contributions of capillary pathway size and neutrophil deformability to neutrophil transit through rabbit lungs

1994 ◽  
Vol 77 (1) ◽  
pp. 463-470 ◽  
Author(s):  
B. R. Wiggs ◽  
D. English ◽  
W. M. Quinlan ◽  
N. A. Doyle ◽  
J. C. Hogg ◽  
...  
Keyword(s):  
Pulmonary Circulation ◽  
Blood Cells ◽  
Random Distribution ◽  
Large Fraction ◽  
Pulmonary Capillaries ◽  
Transit Times ◽  
Pulmonary Capillary ◽  
Time Required ◽  
Rapid Deformation

Neutrophil margination within the pulmonary capillary is due to a delay in their transit compared with that of red blood cells (RBC). This delay has been attributed to the large fraction of capillary segments that are narrower than spherical neutrophils and differences between the time required for deformation of neutrophils and that required for deformation of RBC. This study investigated the characteristics of neutrophil deformation in vivo and the perfusion patterns of segments within capillary pathways. Studies comparing the extraction of neutrophils with that of nondeformable microspheres in one transit through the pulmonary circulation suggest that neutrophils can undergo a rapid deformation from 6.4 to 5.0–5.1 microns, whereas larger deformations require a delay. Effective diameters of the perfused capillary pathways were larger than expected for a random distribution of capillary segment diameters within these pathways. The longer transit times of neutrophils in the upper regions of the lung were associated with a greater fraction of pathways containing narrow segments. These studies suggest that neutrophil deformability and capillary pathway diameters are important in determining the size of the marginated pool of neutrophils within the pulmonary capillaries.

scholarly journals Computational modeling of RBC and neutrophil transit through the pulmonary capillaries

2001 ◽  
Vol 90 (2) ◽  
pp. 545-564 ◽  
Author(s):  
Yaqi Huang ◽  
Claire M. Doerschuk ◽  
Roger D. Kamm
Keyword(s):  
Transpulmonary Pressure ◽  
Temporal Variations ◽  
Local Pressure ◽  
In Vivo Experiments ◽  
Pulmonary Capillaries ◽  
Transit Times ◽  
Capillary Bed ◽  
Pulmonary Microcirculation ◽  
Preferential Pathways

A computational model of the pulmonary microcirculation is developed and used to examine blood flow from arteriole to venule through a realistically complex alveolar capillary bed. Distributions of flow, hematocrit, and pressure are presented, showing the existence of preferential pathways through the system and of large segment-to-segment differences in all parameters, confirming and extending previous work. Red blood cell (RBC) and neutrophil transit are also analyzed, the latter drawing from previous studies of leukocyte aspiration into micropipettes. Transit time distributions are in good agreement with in vivo experiments, in particular showing that neutrophils are dramatically slowed relative to the flow of RBCs because of the need to contract and elongate to fit through narrower capillaries. Predicted neutrophil transit times depend on how the effective capillary diameter is defined. Transient blockage by a neutrophil can increase the local pressure drop across a segment by 100–300%, leading to temporal variations in flow and pressure as seen by videomicroscopy. All of these effects are modulated by changes in transpulmonary pressure and arteriolar pressure, although RBCs, neutrophils, and rigid microspheres all behave differently.

scholarly journals Effect of mechanical deformation on structure and function of polymorphonuclear leukocytes

1997 ◽  
Vol 82 (5) ◽  
pp. 1397-1405 ◽  
Author(s):  
Yuko Kitagawa ◽  
Stephan F. Van Eeden ◽  
Darlene M. Redenbach ◽  
Maleki Daya ◽  
Blair A. M. Walker ◽  
...  
Keyword(s):  
Polymorphonuclear Leukocytes ◽  
Polarization Characteristic ◽  
Mechanical Deformation ◽  
Structure And Function ◽  
Functional Changes ◽  
Flow Cytometric ◽  
Pulmonary Capillaries ◽  
Pulmonary Capillary ◽  
Capillary Bed ◽  
And Function

Kitagawa, Yuko, Stephan F. Van Eeden, Darlene M. Redenbach, Maleki Daya, Blair A. M. Walker, Maria E. Klut, Barry R. Wiggs, and James C. Hogg. Effect of mechanical deformation on structure and function of polymorphonuclear leukocytes. J. Appl. Physiol. 82(5): 1397–1405, 1997.—The present studies were designed to test the hypothesis that mechanical deformation of polymorphonuclear leukocytes (PMN) leads to functional changes that might influence their transit in the pulmonary capillaries. Human leukocytes were passed through 5- or 3-μm-pore polycarbonate filters under controlled conditions. Morphometric analysis showed that the majority of PMN were deformed and that this deformation persisted longer after filtration through 3-μm filters than through 5-μm filters ( P < 0.05) but did not result in the cytoskeletal polarization characteristic of migrating cells. Flow cytometric studies of the filtered PMN showed that there was a transient increase in the cytosolic free Ca2+ concentration after both 3- and 5-μm filtration ( P< 0.01) with an increase in F-actin content after 3-μm filtration ( P < 0.05). AlthoughL-selectin expression on PMN was not changed by either 5- or 3-μm filtration, CD18 and CD11b were increased by 3-μm filtration ( P < 0.05). Priming of the PMN with N-formyl-methionyl-leucyl-phenylalanine (0.5 nM) before filtration resulted in an increase of CD11b by both 5 ( P < 0.05)- and 3-μm ( P < 0.01) filtration. Neither 5- nor 3-μm filtration induced hydrogen peroxide production. We conclude that mechanical deformation of PMN, similar to what occurs in the pulmonary microvessels, induces both structural and functional changes in the cells, which might influence their passage through the pulmonary capillary bed.

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.

Temporal capillary perfusion patterns in single alveolar walls of intact dogs

1994 ◽  
Vol 76 (1) ◽  
pp. 380-386 ◽  
Author(s):  
O. Okada ◽  
R. G. Presson ◽  
P. S. Godbey ◽  
R. L. Capen ◽  
W. W. Wagner
Keyword(s):  
Original Work ◽  
Alveolar Wall ◽  
In Vivo Microscopy ◽  
Capillary Perfusion ◽  
Pulmonary Capillary ◽  
Pulmonary Arterial ◽  
Preferential Pathways ◽  
Variable Group ◽  
Over Time

Pulmonary gas exchange reserve in the form of recruitable capillaries was first described in the 1930s, when in vivo microscopy was used to demonstrate that not all capillaries were perfused during basal conditions and that perfusion of individual capillaries varied over time. These important observations have never been directly confirmed, nor have the hemodynamic causes of the variation been investigated. We used videomicroscopy to record nine consecutive pulmonary capillary perfusion patterns during a 40-min period. Confirming the original work, we found considerable perfusion variation in about one-half of the capillaries. These variations did not correlate with changes in pulmonary arterial pressures or cardiac outputs, suggesting that factors more subtle than large-vessel hemodynamics affected capillary perfusion consistency. In contrast to this variable group, one-half of the capillary segments were consistently perfused during at least eight of the nine observations and were interconnected to form preferential pathways across the alveolar wall.

Capillary perfusion patterns in single alveolar walls

1992 ◽  
Vol 72 (5) ◽  
pp. 1838-1844 ◽  
Author(s):  
O. Okada ◽  
R. G. Presson ◽  
K. R. Kirk ◽  
P. S. Godbey ◽  
R. L. Capen ◽  
...  
Keyword(s):  
Left Atrium ◽  
Elevated Pressure ◽  
Strong Indication ◽  
In Vivo Microscopy ◽  
Capillary Perfusion ◽  
Pulmonary Hemodynamics ◽  
Pulmonary Capillary ◽  
Anesthetized Dogs ◽  
Flowing Blood

We studied capillary perfusion patterns in single alveolar walls through a transparent thoracic window implanted in pentobarbital-anesthetized dogs. The capillaries were maximally opened by brief inflation of a balloon in the left atrium to raise pressure. After the balloon was deflated and pulmonary hemodynamics returned to zone 2 baseline conditions, the capillaries that remained perfused in the observed field were videotaped with the use of in vivo microscopy. The cycle of elevated pressure and baseline observation was repeated three times. Perfusion of different capillaries during each of the observations would imply that the capillaries had characteristics that permitted flow to switch between segments. Perfusion of a specific set of pathways through the network each time would demonstrate that flowing blood sought a unique and repeatable combination of segments, presumably with the least total pathway resistance. We found that the same capillary segments were perfused 79% of the time, a strong indication that a reproducible combination of individual segmental resistances determined the predominant pattern of pulmonary capillary perfusion.

Effect of changing venoarterial pH difference on in vivo arterial pH

1991 ◽  
Vol 70 (4) ◽  
pp. 1586-1592 ◽  
Author(s):  
E. Takahashi ◽  
E. A. Phillipson
Keyword(s):  
Computer Simulation ◽  
Significant Contribution ◽  
Regression Coefficient ◽  
Glass Electrode ◽  
Pulmonary Capillaries ◽  
Arterial Ph ◽  
Anesthetized Dogs ◽  
Unique Relationship

Plasma pH has been postulated to change slowly in blood leaving the pulmonary capillaries because of the uncatalyzed dehydration of CO2. If so, there could be a difference between in vivo and in vitro arterial pH, the magnitude of which would be dependent on the venoarterial pH difference (v-aDpH). We tested this hypothesis in anesthetized dogs by changing v-aDpH by airway CO2 loading and by comparing arterial pH measured in vivo by a rapidly responding intravascular pH electrode with that measured in vitro by a conventional glass electrode. Using a multiple regression analysis, we found a small but significant contribution of venous pH to in vivo arterial pH, with a regression coefficient of 0.0718 (P less than 0.0001), suggesting a postcapillary increase of in vivo arterial pH. When carbonic anhydrase was inhibited by the administration of acetazolamide, the effect of venous pH on arterial pH was abolished, and a unique relationship between in vivo and in vitro arterial pH was established (regression coefficient 1.02; P greater than 0.05, comparison with unity). These results could be accounted for in a computer simulation of gas exchange among alveolus, plasma, and erythrocyte. We conclude that there exists a small but measurable postcapillary increase in arterial pH.

Sites of leukocyte sequestration in the pulmonary microcirculation

1995 ◽  
Vol 79 (2) ◽  
pp. 493-497 ◽  
Author(s):  
S. A. Gebb ◽  
J. A. Graham ◽  
C. C. Hanger ◽  
P. S. Godbey ◽  
R. L. Capen ◽  
...  
Keyword(s):  
Major Axis ◽  
Minor Axis ◽  
Capillary Networks ◽  
Aspect Ratios ◽  
Pulmonary Capillaries ◽  
Capillary Bed ◽  
Pass Through ◽  
Pulmonary Microcirculation ◽  
Rolling Leukocytes

The location and mechanisms of leukocyte sequestration in the pulmonary circulation have been investigated by using high-magnification in vivo videomicroscopy to record the passage of unlabeled native leukocytes through canine pulmonary capillaries. Of 650 leukocytes traversing capillary networks, 46 +/- 6% (SE) of the leukocytes passed through without stopping, 42 +/- 9% stopped in segments between junctions, and 12 +/- 4% stopped in junctions. Leukocytes rolling along arteriolar walls were nearly spherical, as 94% had aspect ratios (major axis divided by minor axis) < or = 1.25. To pass through the capillary bed, the leukocytes deformed into elongated shapes. Many leukocytes remained elongated after entering the venules (53% had aspect ratios > or = 1.25). Venular rolling was blocked by fucoidin (blocking both L- and P-selectin) but not by anti-P-selectin antibodies alone, indicating that rolling leukocytes adhered to the venular endothelium by L-selectin. These observations demonstrate that leukocytes deform to transit the capillary bed, that they stop more frequently in segments than in junctions, and that rolling leukocytes in the venular marginated pool adhere via L-selectin.

Pulmonary capillary diameters and recruitment characteristics in subpleural and interior networks

1996 ◽  
Vol 80 (5) ◽  
pp. 1568-1573 ◽  
Author(s):  
A. C. Short ◽  
M. L. Montoya ◽  
S. A. Gebb ◽  
R. G. Presson ◽  
W. W. Wagner ◽  
...  
Keyword(s):  
Cross Sections ◽  
Blood Cells ◽  
Alveolar Wall ◽  
Lung Inflation ◽  
Capillary Recruitment ◽  
Cell Counts ◽  
Pulmonary Capillaries ◽  
Pulmonary Capillary ◽  
Wide Range

In vivo microscopic observations of pulmonary capillaries are limited to subpleural networks that are less dense than interior networks. In addition to the density difference, subpleural and interior capillary diameters may differ, although there are conflicting data on this point. We measured the diameters of subpleural and interior capillaries in rats and dogs. Subpleural diameters were 30% larger in rats and 20% larger in dogs. Because diameter and density differences might cause differences in recruitment between subpleural and interior networks, we measured subpleural and interior recruitment by counting the number of red blood cells per 10 microns of alveolar wall in histological cross sections of rapidly frozen rat lungs. Lung inflation pressures of 4, 12, and 25 cmH2O created a wide range of capillary recruitment in different groups of animals. Red blood cell counts for interior and subpleural capillaries moved in parallel and progressively increased as inflation pressures were reduced. These data demonstrate that recruitment in subpleural capillaries accurately reflect recruitment in interior capillaries and validate the use of in vivo microscopic observations of subpleural capillaries to investigate pulmonary capillary recruitment in general.

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