Cytochalasin D induces edema formation and lowering of interstitial fluid pressure in rat dermis

2001 ◽  
Vol 281 (1) ◽  
pp. H7-H13 ◽  
Author(s):  
Ansgar Berg ◽  
Kristofer Rubin ◽  
Rolf K. Reed
Keyword(s):  
Extracellular Matrix ◽  
Interstitial Fluid ◽  
Acute Inflammation ◽  
Cultured Cells ◽  
Circulatory Arrest ◽  
Fluid Pressure ◽  
Cytochalasin D ◽  
Interstitial Fluid Pressure ◽  
Edema Formation ◽  
Fluid Filtration

The increased capillary fluid filtration required to create a rapid edema formation in acute inflammation can be generated by lowering the interstitial fluid pressure (PIF). The lowering of PIF appears to involve dynamic β1-integrin-mediated interactions between dermal cells and extracellular matrix fibers. The present study specifically investigates the role of the cell cytoskeleton, i.e., the contractile apparatus of cells, in controlling PIF in rat skin as the integrins are linked to both the cytoskeleton and the extracellular matrix. PIF was measured using a micropuncture technique in the dorsal skin of the hind paw at a depth of 0.2–0.5 mm and following the induction of circulatory arrest with the intravenous injection of KCl in pentobarbital anesthesia. This procedure prevented the transcapillary flux of fluid and protein leading to edema formation in acute inflammation, which in turn can increase the PIF and therefore potentially mask a decrease of PIF. Control PIF ( n = 42) averaged −0.8 ± 0.5 (means ± SD) mmHg. In the first group of experiments, subdermal injection of 2 μl cytochalasin D, a microfilament-disrupting drug, lowered PIF to an average of −2.8 ± 0.7 mmHg within 40 min postinjection ( P< 0.05 compared with control). Subdermal injection of vehicle (10% DMSO in PBS or PBS alone) did not change the PIF( P > 0.05). Lowering of the PIF was not observed after the injection of colchicine or nocodazole, which specifically disrupts microtubuli in cultured cells. In the second group of experiments, 2 μl of cytochalasin D injected subdermally into rats with intact circulation increased the total tissue water (TTW) and albumin extravasation rate ( E ALB) by 0.7 ± 0.2 and 0.4 ± 0.3 ml/g dry wt, respectively ( P < 0.05 compared with vehicle). Nocodazole and colchicine did not significantly alter the TTW or E ALB compared with the vehicle ( P > 0.05). Taken together, these findings strongly suggest that the connective tissue cells can participate in control of PIF via the actin filament system. In addition, the observation that subdermal injection of cytochalasin D lowered PIF indicates that a dynamic assembly and disassembly of actin filaments also occurs in the cells of dermal tissues in vivo.

Micropuncture measurements of interstitial fluid pressure in rat nasal mucosa during early inflammatory reactions

1998 ◽  
Vol 85 (2) ◽  
pp. 465-470 ◽  
Author(s):  
Ansgar Berg ◽  
Arne Kirkebø ◽  
Karin J. Heyeraas
Keyword(s):  
Nasal Mucosa ◽  
Interstitial Fluid ◽  
Circulatory Arrest ◽  
Fluid Pressure ◽  
Nasal Bone ◽  
Interstitial Fluid Pressure ◽  
Edema Formation ◽  
Inflammatory Reactions ◽  
Inflammatory Stimuli ◽  
Transvascular Fluid Shifts

Interstitial fluid pressure (Pif) has been studied in rat nasal mucosa during early inflammatory reactions induced by dextran anaphylaxis and local application of histamine. Pif was measured by using sharpened micropipettes connected to a servo-controlled counterpressure system. Access to the nasal mucosa was obtained from the facial side of the head through a small cavity drilled in the nasal bone. During dextran anaphylaxis, Pif increased significantly from control values of 2.2 ± 0.4 to 3.8 ± 0.21 mmHg ( P < 0.05) within 1 h. Corresponding Pif values for histamine were 1.6 ± 0.9 and 2.9 ± 0.9 mmHg ( P < 0.05), respectively. These measurements support the hypothesis that a major driving force for the rapid exudation across inflamed respiratory mucosa is a hydrostatic pressure gradient created by increased mucosa Pif. When the transvascular fluid shifts accompanying the inflammatory reactions are prevented by circulatory arrest, Pif decreased significantly to subatmospheric values, −0.8 ± 0.8 and −3.3 ± 1.2 mmHg in the dextran and histamine group, respectively ( P < 0.05). The decrease in Pif in the nasal mucosa after inflammatory stimuli, during circulatory arrest, provides further evidence for “active” modulation of Pif through changes in mechanical properties of the interstitial matrix. The decrease in Pif seen under these circumstances reveals a possible mechanism participating in the rapid and initial edema formation after inflammatory provocations.

Dynamics of Interstitial Fluid Pressure in Extracellular Matrix Hydrogels in Microfluidic Devices

2015 ◽  
Vol 137 (9) ◽  
Author(s):  
Joe Tien ◽  
Le Li ◽  
Ozgur Ozsun ◽  
Kamil L. Ekinci
Keyword(s):  
Extracellular Matrix ◽  
Pressure Distribution ◽  
Interstitial Fluid ◽  
Scaling Laws ◽  
Fluid Pressure ◽  
Interstitial Fluid Pressure ◽  
External Loading ◽  
Interstitial Pressure ◽  
Time Resolved ◽  
Long Time

In order to understand how interstitial fluid pressure and flow affect cell behavior, many studies use microfluidic approaches to apply externally controlled pressures to the boundary of a cell-containing gel. It is generally assumed that the resulting interstitial pressure distribution quickly reaches a steady-state, but this assumption has not been rigorously tested. Here, we demonstrate experimentally and computationally that the interstitial fluid pressure within an extracellular matrix gel in a microfluidic device can, in some cases, react with a long time delay to external loading. Remarkably, the source of this delay is the slight (∼100 nm in the cases examined here) distension of the walls of the device under pressure. Finite-element models show that the dynamics of interstitial pressure can be described as an instantaneous jump, followed by axial and transverse diffusion, until the steady pressure distribution is reached. The dynamics follow scaling laws that enable estimation of a gel's poroelastic constants from time-resolved measurements of interstitial fluid pressure.

scholarly journals The α11β1 Integrin Has a Mechanistic Role in Control of Interstitial Fluid Pressure and Edema Formation in Inflammation

2009 ◽  
Vol 29 (11) ◽  
pp. 1864-1870 ◽  
Author(s):  
Ø.S. Svendsen ◽  
M.M. Barczyk ◽  
S.N. Popova ◽  
Å Lidén ◽  
D. Gullberg ◽  
...  
Keyword(s):  
Interstitial Fluid ◽  
Fluid Pressure ◽  
Interstitial Fluid Pressure ◽  
Edema Formation

scholarly journals Integrin αvβ3 acts downstream of insulin in normalization of interstitial fluid pressure in sepsis and in cell-mediated collagen gel contraction

2008 ◽  
Vol 295 (2) ◽  
pp. H555-H560 ◽  
Author(s):  
Øyvind Sverre Svendsen ◽  
Åsa Lidén ◽  
Torbjørn Nedrebø ◽  
Kristofer Rubin ◽  
Rolf K. Reed
Keyword(s):  
Interstitial Fluid ◽  
Driving Forces ◽  
Fluid Pressure ◽  
Collagen Gel ◽  
Interstitial Fluid Pressure ◽  
C2c12 Cells ◽  
Insulin Administration ◽  
Edema Formation ◽  
Collagen Gel Contraction

The administration of insulin is recommended to patients with severe sepsis and hyperglycemia. Previously, we demonstrated that insulin may have direct anti-inflammatory properties and counteracted fluid losses from the circulation by normalizing the interstitial fluid pressure (PIF). PIF is one of the Starling forces determining fluid flux over the capillary wall, and a lowered PIF is one of the driving forces in early edema formation in inflammatory reactions. Here we demonstrate that insulin restores a lipopolysaccharide (LPS)-lowered PIF via a mechanism involving integrin αvβ3. In C57 black mice ( n = 6), LPS lowered PIF from −0.2 ± 0.2 to −1.6 ± 0.3 ( P < 0.05) and after insulin averaged −0.8 ± 0.2 mmHg ( P = 0.098 compared with after LPS). Corresponding values in wild-type BALB/c mice ( n = 5) were −0.8 ± 0.1, −2.1 ± 0.3 ( P < 0.05), and −0.8 ± 0.3 mmHg ( P < 0.05 compared with LPS) after insulin administration. In BALB/c integrin β3-deficient (β3−/−) mice ( n = 6), LPS lowered PIF from −0.1 ± 0.2 to −1.5 ± 0.3 mmHg ( P < 0.05). Insulin did not, however, restore PIF in these mice (averaged −1.7 ± 0.3 mmHg after insulin administration). Cell-mediated collagen gel contraction can serve as an in vitro model for in vivo measurements of PIF. Insulin induced αvβ3-integrin-dependent collagen gel contraction mediated by C2C12 cells. Our findings suggest a beneficiary effect of insulin for patients with sepsis with regard to the fluid balance, and this effect may in part be due to a normalization of PIF by a mechanism involving the integrin αvβ3.

Interstitial fluid pressure gradient measured by micropuncture in excised dog lung

1984 ◽  
Vol 56 (2) ◽  
pp. 271-277 ◽  
Author(s):  
J. Bhattacharya ◽  
M. A. Gropper ◽  
N. C. Staub
Keyword(s):  
Fluid Flow ◽  
Pressure Gradient ◽  
Pressure Difference ◽  
Airway Pressure ◽  
Interstitial Fluid ◽  
Fluid Pressure ◽  
Interstitial Fluid Pressure ◽  
Pleural Pressure ◽  
Alveolar Wall ◽  
Fluid Filtration

We have directly measured lung interstitial fluid pressure at sites of fluid filtration by micropuncturing excised left lower lobes of dog lung. We blood-perfused each lobe after cannulating its artery, vein, and bronchus to produce a desired amount of edema. Then, to stop further edema, we air-embolized the lobe. Holding the lobe at a constant airway pressure of 5 cmH2O, we measured interstitial fluid pressure using beveled glass micropipettes and the servo-null method. In 31 lobes, divided into 6 groups according to severity of edema, we micropunctured the subpleural interstitium in alveolar wall junctions, in adventitia around 50-micron venules, and in the hilum. In all groups an interstitial fluid pressure gradient existed from the junctions to the hilum. Junctional, adventitial, and hilar pressures, which were (relative to pleural pressure) 1.3 +/- 0.2, 0.3 +/- 0.5, and -1.8 +/- 0.2 cmH2O, respectively, in nonedematous lobes, rose with edema to plateau at 4.1 +/- 0.4, 2.0 +/- 0.2, and 0.4 +/- 0.3 cmH2O, respectively. We also measured junctional and adventitial pressures near the base and apex in each of 10 lobes. The pressures were identical, indicating no vertical interstitial fluid pressure gradient in uniformly expanded nonedematous lobes which lack a vertical pleural pressure gradient. In edematous lobes basal pressure exceeded apical but the pressure difference was entirely attributable to greater basal edema. We conclude that the presence of an alveolohilar gradient of lung interstitial fluid pressure, without a base-apex gradient, represents the mechanism for driving fluid flow from alveoli toward the hilum.

Effect of tumor necrosis factor-α, IL-1β, and IL-6 on interstitial fluid pressure in rat skin

1999 ◽  
Vol 277 (5) ◽  
pp. H1857-H1862 ◽  
Author(s):  
Torbjørn Nedrebø ◽  
Ansgar Berg ◽  
Rolf K. Reed
Keyword(s):  
Tumor Necrosis Factor ◽  
Tumor Necrosis ◽  
Tumor Necrosis Factor Α ◽  
Interstitial Fluid ◽  
Circulatory Arrest ◽  
Fluid Pressure ◽  
Edema Formation ◽  
Tnf Α ◽  
Factor Α ◽  
Necrosis Factor

Interstitial fluid pressure (Pif) decreases in several experimental models of acute inflammation, enhancing edema formation. The present study was designed to determine the effect of tumor necrosis factor-α (TNF-α), interleukin (IL)-6, and IL-1β as well as lipopolysaccharides (LPS) on Pif in a model of gram-negative sepsis. Pif was measured in the paw skin of anesthetized rats (pentobarbital sodium, 50 mg/kg ip) using micropipettes (3–7 μm) and servo-controlled counterpressure technique. Test substances were injected intra-arterially (ia), intravenously (iv), or subdermally (sd). After intra-arterial or intravenous administration, the test substances were circulated for 1 min before circulatory arrest was induced with an intravenous injection of KCl while the rats were under pentobarbital anesthesia. Circulatory arrest was induced to avoid edema formation, which would raise interstitial fluid volume to cause a more positive Pif. Administration of 0.5 ml of LPS (5 mg/ml ia) lowered Pif significantly from control values of −0.2 ± 0.3 to −2.0 ± 0.3 mmHg ( P < 0.05) within 1 h. Corresponding values for TNF-α (500 ng/ml iv) were −0.4 ± 0.2 to −2.3 ± 0.1 mmHg ( P < 0.05). Administration of 5 μl (5 mg/ml sd) of LPS did not affect Pif significantly ( P > 0.05), but TNF-α, IL-1β, and IL-6 had a significant effect on Pif when given subdermally. IL-6 (50 ng/ml) caused a decrease in Pif from control values of −1.2 ± 0.3 to −2.8 ± 0.5 mmHg ( P < 0.05) within 1 h. The experiments demonstrate that LPS, TNF-α, IL-1β, and IL-6 induce lowering of Pif when given intravenously or intra-arterially, whereas only TNF-α, IL-1β, and IL-6 induce lowering of Pif when given subdermally. We therefore suggest that the lowering of Pif in this experimental model of sepsis is related to the release of and a local effect in skin of TNF-α, IL-1β, and IL-6.

Lowering of interstitial fluid pressure in rat submandibular gland: a novel mechanism in saliva secretion

2006 ◽  
Vol 290 (4) ◽  
pp. H1460-H1468 ◽  
Author(s):  
Ellen Berggreen ◽  
Helge Wiig
Keyword(s):  
Osmotic Pressure ◽  
Submandibular Gland ◽  
Interstitial Fluid ◽  
Fluid Transport ◽  
Fluid Pressure ◽  
Myoepithelial Cells ◽  
Colloid Osmotic Pressure ◽  
Interstitial Fluid Pressure ◽  
High Rate ◽  
Fluid Filtration

The submandibular gland transports fluid at a high rate through the interstitial space during salivation, but the exact level of all forces governing transcapillary fluid transport has not been established. In this study, our aim was to measure the relation between interstitial fluid volume (Vi) and interstitial fluid pressure (Pif) in salivary glands during active secretion and after systemically induced passive changes in gland hydration. We tested whether interstitial fluid could be isolated by tissue centrifugation to enable measurement of interstitial fluid colloid osmotic pressure. During control conditions, Vi averaged 0.23 ml/g wet wt (SD 0.014), with a corresponding mean Pif measured with micropipettes of 3.0 mmHg (SD 1.3). After induction of secretion by pilocarpine, Pif dropped by 3.8 mmHg (SD 1.5) whereas Vi was unchanged. During dehydration and overhydration of up to 20% increase of Vi above control, a linear relation was found between volume and pressure, resulting in a compliance (ΔVi/ΔPif) of 0.012 ml·g wet wt−1·mmHg−1. Interstitial fluid was isolated, and interstitial fluid colloid osmotic pressure averaged 10.4 mmHg (SD 1.2), which is 64% of the corresponding level in plasma. We conclude that Pif drops during secretion and, thereby, increases the net transcapillary pressure gradient, a condition that favors fluid filtration and increases the amount of fluid available for secretion. The reduction in Pif is most likely induced by contraction of myoepithelial cells and suggests an active and new role for these cells in salivary secretion. The relatively low interstitial compliance of the organ will enhance the effect of the myoepithelial cells on Pif during reduced Vi.

The Effect of Hosiery on Interstitial Fluid Pressure and Arm Volume Fluctuations in Breast Cancer Related Arm Oedema

1995 ◽  
Vol 10 (2) ◽  
pp. 46-50 ◽  
Author(s):  
D. O. Bates ◽  
A. W. B. Stanton ◽  
J. R. Levick ◽  
P. S. Mortimer
Keyword(s):  
Breast Cancer ◽  
Interstitial Fluid ◽  
Fluid Pressure ◽  
Interstitial Fluid Pressure ◽  
Fluid Filtration ◽  
Drainage Rate ◽  
Arm Swelling ◽  
The Mean ◽  
Arm Lymphoedema ◽  
The Stability

Objectives: (1) To measure interstitial fluid pressure under one brand of hosiery in arm lymphoedema. (2) To assess the stability of the swelling over various time scales. Setting: Human microvascular studies laboratory of a teaching hospital. Subjects: Patients with arm oedema following successful breast cancer treatment. Main outcome measures: (1) Arm volume calculations using multiple circumferential measurements by tape measure. (2) Interstitial fluid pressure measurements by wick-in-needle technique in subcutis. Results: The mean swollen arm was 33% greater in volume than the contralateral arm ( n = 50). There was no significant correlation between the size of the arm and the duration of the swelling. There was no significant change in arm volume over 2 weeks ( n = 8) but there was a small (50 ml), significant increase overnight ( p < 0.05). The mean (SD) interstitial fluid pressure while wearing one brand of hosiery (Sigvaris) was 18.7 (5.8) cmH2O compared with 1.2 (2.8) cmH2O after its removal. There was a significant correlation between the pressure under the sleeve and the pressure without the sleeve ( r = 0.68, p < 0.05). Conclusions: The Sigvaris sleeve exerts sufficient compression to underlying tissue to raise interstitial fluid pressure. This may control arm swelling by reducing fluid filtration rate and/or raising fluid drainage rate from the arm.

Increased negativity of interstitial fluid pressure during the onset stage of inflammatory edema in rat skin

1991 ◽  
Vol 260 (6) ◽  
pp. H1985-H1991 ◽  
Author(s):  
R. K. Reed ◽  
S. A. Rodt
Keyword(s):  
Interstitial Fluid ◽  
Circulatory Arrest ◽  
Fluid Pressure ◽  
Interstitial Fluid Pressure ◽  
System Control ◽  
Rat Skin ◽  
Glass Capillaries ◽  
Inflammatory Edema ◽  
Rat Paw ◽  
Observation Period

Interstitial fluid pressure (Pif) was measured in skin of pentobarbital-anesthetized rats during anaphylaxis toward dextran and after subdermal injection of histamine by using sharpened glass capillaries (tip diam 5–7 microns) connected to a servo-controlled counterpressure system. Control Pif averaged -1.5 mmHg (SD = 1.0). After intravenous dextran Pif in the rat paw fell transiently to -3 mmHg up to 20 min and thereafter increased to +1-2 mmHg when edema had developed. To study the full magnitude of the increased negativity of Pif, circulatory arrest was induced 1 min after dextran injection. This procedure prevents accumulation of edema that will cause underestimation of Pif. In this group Pif fell to about -10 mmHg in 20 min and remained at this level throughout the observation period of 90 min. Subdermal injection of 1–10 micrograms histamine in 10 microliters saline reduced Pif to about -6 mmHg within 5 min after injection. Injection of 10 microliters saline increased Pif by +2 mmHg. Indomethacin or cyproheptadine did not alter the response in the above situations. The increased negativity in Pif of about 6–8 mmHg will add directly to normal transcapillary net filtration pressure of 0.5 mmHg and increase the latter pressure 10–20 times.

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