Interstitial fluid pressure, composition of interstitium, and interstitial exclusion of albumin in hypothyroid rats

2000 ◽  
Vol 278 (5) ◽  
pp. H1627-H1639 ◽  
Author(s):  
Helge Wiig ◽  
Rolf K. Reed ◽  
Olav Tenstad

Lack of thyroid hormones may affect the composition and structure of the interstitium. Hypothyrosis was induced in rats by thyroidectomy 4–12 wk before the experiments. In hypothyroid rats ( n = 16), interstitial fluid pressure measured with micropipettes in hindlimb skin and muscle averaged +0.1 ± 0.2 and +0.5 ± 0.2 mmHg, respectively, with corresponding pressures in control rats ( n = 16) of −1.5 ± 0.1 ( P < 0.001) and −0.8 ± 0.1 mmHg ( P < 0.001). Interstitial fluid volume, measured as the difference between the distribution volumes of 51Cr-EDTA and125I-labeled BSA, was similar or lower in skin and higher in hypothyroid muscle. Total protein and albumin concentration in plasma and interstitial fluid (isolated from implanted wicks) was lower in hypothyroid compared with control rats. Hyaluronan content ( n = 9) in rat hindlimb skin was 2.05 ± 0.15 and 1.92 ± 0.09 mg/g dry wt ( P > 0.05) in hypothyroid and control rats, respectively, with corresponding content in hindlimb skeletal muscle of 0.35 ± 0.07 and 0.23 ± 0.01 mg/g dry wt ( P < 0.01). Interstitial exclusion of albumin in skin and muscle was measured after 125I-labeled rat serum albumin infusion for 120–168 h with an implanted osmotic pump. Relative excluded volume for albumin (Ve/Vi) was calculated as 1 − Va/Vi, and averaged 28 and 28% in hindlimb muscle ( P > 0.05), 44 and 45% in hindlimb skin ( P > 0.05), and 19 and 32% in back skin ( P < 0.05) in hypothyroid and control rats, respectively. Albumin mass was higher in back skin in spite of a lower interstitial fluid albumin concentration, a finding explained by a reduced Ve/Vi in back skin in hypothyroid rats. These experiments suggest that lack of thyroid hormones in rats changes the interstitial matrix again leading to reduced interstitial compliance and changes in the transcapillary fluid balance.

2001 ◽  
Vol 281 (3) ◽  
pp. H1085-H1092 ◽  
Author(s):  
Helge Wiig ◽  
Tjøstolv Lund

There is clinical and experimental evidence that lack of thyroid hormones may affect the composition and structure of the interstitium. This can influence the relationship between volume and pressure during changes in hydration. Hypothyrosis was induced in rats by thyroidectomy 8 wk before the experiments. Overhydration was induced by infusion of acetated Ringer, 5, 10, and 20% of the body weight, while fluid was withdrawn by peritoneal dialysis with hypertonic glucose. Interstitial fluid pressure (Pi) in euvolemia (euvolemic control situation) and experimental situation was measured with micropipettes connected to a servocontrolled counterpressure system. The corresponding interstitial fluid volume (Vi) was found as the difference between extracellular fluid volume measured as the distribution volume of 51Cr-labeled EDTA and plasma volume measured using125I-labeled human serum albumin. In euvolemia, Vi was similar or lower in the skin and higher in skeletal muscle of hypothyroid than in euthyroid control rats, whereas the corresponding Pi was higher in all tissues. During overhydration, Pi rose to the same absolute level in both types of rats, whereas during peritoneal dialysis there was a linear relationship between volume and pressure in all tissues and types of rats. Interstitial compliance (Ci), calculated as the inverse value of the slope of the curve relating changes in volume and pressure in dehydration, did not differ significantly in the hindlimb skin of hypothyroid and euthyroid rats. However, in skeletal muscle, Ci was 1.3 and 2.0 ml · 100 g−1 · mmHg−1 in hypothyroid and euthyroid rats ( P < 0.01), with corresponding numbers for the back skin of 2.7 and 5.0 ml · 100 g−1 · mmHg−1 ( P < 0.01). These experiments suggest that lack of thyroid hormones in rats changes the interstitial matrix, again leading to reduced Ci and reduced ability to mobilize fluid from the interstitium.


1980 ◽  
Vol 238 (6) ◽  
pp. H886-H888
Author(s):  
J. L. Christian ◽  
R. A. Brace

Membrane osmometry was used to estimate the four transcapillary Starling pressures in subcutaneous tissue of rats, guinea pigs, and dogs. Isolated subcutaneous tissue samples were either placed on a large-pore or small-pore osmometer that measured the interstitial fluid pressure (Pif) and the difference between the interstitial fluid pressure and the interstitial protein osmotic pressure (Pif-pi if), respectively. The colloid osmotic pressure of the interstitial fluid (pi if) was obtained from the difference in these two pressures. A plasma sample placed on the small-pore osmometer yielded the colloid osmotic pressure of the plasma proteins (pi c). Finally the capillary pressure (Pc) was calculated from the three other Starling forces. In the rat, guinea pig, and dog, respectively, the estimated Starling forces were as follows: Pif -2.2, -2.1, and -4.8 mmHg; pi if, 7.3, 4.8, and 4.4 mmHg; pi c, 21.3, 19.5, and 19.2 mmHg; and Pc, 11.8, 12.6, and 10.0 mmHg. A comparison with data obtained in other studies using different methods shows good agreement and strongly supports membrane osmometry as a method for measuring the Starling pressures in subcutaneous tissue.


Physiology ◽  
1997 ◽  
Vol 12 (1) ◽  
pp. 42-49 ◽  
Author(s):  
RK Reed ◽  
K Woie ◽  
K Rubin

The present review summarizes recent information on the physiology of connective tissues, in particular, control of interstitial fluid pressure (Pif) and, thereby, interstitial volume. A combination of classic physiological techniques and techniques from cellular and molecular biology have provided new insights into control of Pif by connective tissue cells and the adhesion receptors anchoring them to structural connective tissue components.


2009 ◽  
Vol 297 (1) ◽  
pp. R6-R16 ◽  
Author(s):  
R. M. Dongaonkar ◽  
G. A. Laine ◽  
R. H. Stewart ◽  
C. M. Quick

The individual processes involved in interstitial fluid volume and protein regulation (microvascular filtration, lymphatic return, and interstitial storage) are relatively simple, yet their interaction is exceedingly complex. There is a notable lack of a first-order, algebraic formula that relates interstitial fluid pressure and protein to critical parameters commonly used to characterize the movement of interstitial fluid and protein. Therefore, the purpose of the present study is to develop a simple, transparent, and general algebraic approach that predicts interstitial fluid pressure ( P i) and protein concentrations ( C i) that takes into consideration all three processes. Eight standard equations characterizing fluid and protein flux were solved simultaneously to yield algebraic equations for P i and C i as functions of parameters characterizing microvascular, interstitial, and lymphatic function. Equilibrium values of P i and C i arise as balance points from the graphical intersection of transmicrovascular and lymph flows (analogous to Guyton's classical cardiac output-venous return curves). This approach goes beyond describing interstitial fluid balance in terms of conservation of mass by introducing the concept of inflow and outflow resistances. Algebraic solutions demonstrate that P i and C i result from a ratio of the microvascular filtration coefficient (1/inflow resistance) and effective lymphatic resistance (outflow resistance), and P i is unaffected by interstitial compliance. These simple algebraic solutions predict P i and C i that are consistent with reported measurements. The present work therefore presents a simple, transparent, and general balance point characterization of interstitial fluid balance resulting from the interaction of microvascular, interstitial, and lymphatic function.


1992 ◽  
Vol 263 (4) ◽  
pp. H1222-H1233 ◽  
Author(s):  
H. Wiig ◽  
M. DeCarlo ◽  
L. Sibley ◽  
E. M. Renkin

Steady-state 125I-labeled rat serum albumin (125I-labeled RSA) concentration in plasma was maintained by intravenous infusion of tracer for 72-168 h with an implanted osmotic pump. At the end of the infusion period, the rat was anesthetized and nephrectomized, and extracellular fluid was equilibrated with intravenous 51Cr-labeled EDTA for 4 h. Five minutes before final plasma and tissue sampling, 131I-labeled bovine serum albumin (131I-labeled BSA) was injected intravenously as a plasma volume marker. Samples of skin, muscle, tendon, and intestine were assayed for all three tracers. Apparent distribution volumes were calculated as tissue tracer content/plasma tracer concentration. Interstitial fluid volume (Vi) was calculated as V51Cr-EDTA-V131I-BSA. Steady-state extravascular distribution of 125I-labeled RSA as plasma equivalent volume (Va,p) was calculated as V125I-RSA-V131I-BSA. Steady-state interstitial fluid concentrations of 125I-labeled RSA in skin, muscles, and tendon were measured with nylon wicks implanted postmortem, and steady-state interstitial albumin distribution volumes were recalculated as wick-fluid equivalent volumes (Va,w). Relative albumin exclusion fraction (Ve/Vi) was calculated as 1-Va,w/Vi. For skin and muscle, steady-state 125I-labeled RSA tissue concentrations were reached at 72 h. Ve/Vi for albumin averaged 26% in hindlimb muscle, 41% in hindlimb skin, 30% in back skin, 39% in tail skin, and 54% in tail tendon. For muscle, Ve/Vi corresponds to expectation if all tissue collagen and hyaluronan is dispersed in the interstitium. However, for skin and tendon, albumin exclusion is considerably lower than expected on this basis, suggesting that much of their collagen is organized into dense bundles of fibers containing no fluid accessible to 51Cr-labeled EDTA or 125I-labeled RSA.


2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 4043-4043
Author(s):  
M. Dani ◽  
B. Vojnovic ◽  
R. Newman ◽  
D. Honess ◽  
I. Wilson ◽  
...  

4043 Background: Interstitial fluid pressure (IFP) of most solid tumours is increased relative to normal tissues; this is thought to be associated with the development of structurally and functionally abnormal blood and lymphatic vessels and interstitial fibrosis. Such interstitial hypertension creates a barrier for tumour transvascular transport, consequently compromising the delivery and efficacy of chemotherapy. We investigated the effect of Bevacizumab on IFP of a human rectal cancer xenograft. Methods: SCID mice bearing subcutaneous HT29 tumours of =8.5 mm diameter received a single dose of 10 mg/kg Bevacizumab intraperitoneally; controls received saline. Tumour IFP was measured in sedated mice (Hypnorm) on days 1, 3 and 5 post injection, using the wick-in-needle technique. Experiments were conducted under Home Office licence and approved by the local ethical committee. Results: Groups of 8 treated and control tumours were examined on days 1, 3 and 5 (n = 48). IFP was significantly lower (p<0.0001) on day 5 in treated than control tumours (mean ± SD 15.1 ± 4.7 cf 36.9 ± 5.6 mm Hg). No significant differences (p>0.05) between treated and control groups were seen on day 1 (31.8 ± 3.5 cf 30.6 ± 3.1 mm Hg) or day 3 (33.4 ± 5.5 cf 31.5 ± 3.2 mm Hg). No data were acquired on day 7 as the tumours ulcerated. Conclusions: Our data show that Bevacizumab causes a significant reduction of tumour IFP, but not until 5 days after treatment. Reduced IFP could augment uptake of cytotoxic drugs into tumour cells, hence timing of Bevacizumab relative to the first dose of chemotherapy could be of critical importance. No significant financial relationships to disclose.


1993 ◽  
Vol 74 (5) ◽  
pp. 2135-2139 ◽  
Author(s):  
M. E. Koller ◽  
K. Woie ◽  
R. K. Reed

The present study was performed to investigate whether the increased negativity of interstitial fluid pressure (Pif) observed after intravenous injection of dextran could be mediated via mast cell degranulation induced by C48/80 and polymyxin B sulfate. Increased negativity of Pif, concomitant with edema formation and increased albumin extravasation, was seen with both substances. However, the two substances differed in that polymyxin B sulfate induced less negativity in Pif and a larger but transient increase in capillary albumin extravasation and interstitial fluid volume. Total tissue water (TTW) increased from 2.11 to 2.71 ml/g dry wt 10 min after polymyxin B and returned to control level at 30 and 60 min. Injection of C48/80 increased TTW to 2.68 ml/g dry wt at 30 min, and TTW was still elevated at 60 min. Albumin extravasation followed a similar pattern; polymyxin B sulfate increased albumin extravasation from < 0.08 to 1.18 ml/g dry wt during the first 5 min after administration. C48/80 was less potent, and maximal albumin leakage was seen after 10–25 min (0.25 ml/g dry wt). The observations demonstrate the importance of the interstitium and the loose connective tissues as "active" participants in the edema-generating process and suggest an interaction with the structural components of the interstitium, as well as an important role for the mast cells in the chain of events creating increased negativity of Pif.


1987 ◽  
Vol 253 (2) ◽  
pp. H283-H290 ◽  
Author(s):  
H. Wiig ◽  
R. K. Reed ◽  
K. Aukland

Interstitial fluid pressure (IFP) was measured with two acute (micropipettes and wick-in-needle) and two chronic methods (perforated and porous capsules) in dog skin/subcutis. In control conditions all techniques gave similar mean pressures, approximately -2 mmHg. Overhydration induced by intravenous Ringer infusion, 10% of body wt, caused two to three times greater increase in pressure recorded with chronic than with acute methods but 2 h after the end of the infusion all methods gave similar pressures. An almost opposite pattern was observed during dehydration induced by peritoneal dialysis with hypertonic glucose. The fall in pressure recorded with the perforated capsule exceeded that of the porous capsule, both exceeding the pressure reduction measured with the acute methods by a factor of 2-5. The difference between pressures measured with both acute methods and the perforated capsule increased in the 90 min following dialysis. Acute overhydration or dehydration as well as aspiration from or infusion into perforated capsules caused a pressure gradient between lumen, capsule wall, and surrounding skin. We propose that the transient pressure differences recorded by acute vs. chronic methods during changes in hydration result from different physical properties of the capsule lining compared with that of the surrounding skin, in addition to a possible osmometer effect of the capsule lining.


2001 ◽  
Vol 280 (4) ◽  
pp. H1807-H1813 ◽  
Author(s):  
Per Ole Iversen ◽  
Ellen Berggreen ◽  
Gunnar Nicolaysen ◽  
Karin Heyeraas

The volume and fluid pressure characteristics of the intact bone marrow is incompletely understood. We used microspheres and lipoproteins for measurements of intravascular volume (IVV) and EDTA for interstitial fluid volume (IFV) within the rat bone marrow. Interstitial fluid pressure (IFP) was determined with micropipettes connected to a servo-controlled counter-pressure system. Both the microspheres and the lipoproteins yielded estimates of IVV of ∼1 ml/100 g. After a brief reactive hyperemia, IVV increased to 2.5 ml/100 g, whereas IFV decreased with ∼1.5 ml/100 g, so that total extracellular volume did not change. Baseline bone marrow IFP was 9.7 mmHg. The hyperemia led to a transient twofold increase in IFP, whereas a marked blood loss decreased IFP by almost one-half. These novel data suggest that extracellular volume and IFP within the bone marrow can be measured with tracer methods and the micropuncture technique. The responses of IVV, IFV, and IFP during changes in blood flow to the bone marrow suggest a tight regulation and are thus compatible with those for a low-compliant tissue.


Sign in / Sign up

Export Citation Format

Share Document