Interstitial exclusion of albumin in rat tissues measured by a continuous infusion method

1992 ◽  
Vol 263 (4) ◽  
pp. H1222-H1233 ◽  
Author(s):  
H. Wiig ◽  
M. DeCarlo ◽  
L. Sibley ◽  
E. M. Renkin
Keyword(s):  
Steady State ◽  
Serum Albumin ◽  
Interstitial Fluid ◽  
Extracellular Fluid ◽  
Rat Tissues ◽  
Rat Serum ◽  
Interstitial Fluid Volume ◽  
Hindlimb Muscle ◽  
Infusion Method ◽  
Tail Tendon

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.

Interstitial exclusion of IgG in rat tissues estimated by continuous infusion

1994 ◽  
Vol 266 (1) ◽  
pp. H212-H219 ◽  
Author(s):  
H. Wiig ◽  
G. A. Kaysen ◽  
H. A. al-Bander ◽  
M. De Carlo ◽  
L. Sibley ◽  
...  
Keyword(s):  
Interstitial Fluid ◽  
Isotonic Saline ◽  
Extracellular Fluid ◽  
Fluid Volume ◽  
Rat Tissues ◽  
Leg Muscles ◽  
Interstitial Fluid Volume ◽  
The Difference ◽  
Tail Tendon ◽  
Endogenous Albumin

Interstitial exclusion, defined as the fraction of interstitial fluid volume inaccessible to a solute, was evaluated for immunoglobulin G (IgG) in selected tissues of rats by a method previously applied to serum albumin (29). IgG distribution volumes were also measured for intestine. 125I-labeled rat IgG was infused for 5 or 7 days (n = 4 rats each) with an implanted osmotic pump (Alzet). At the termination of infusion, the rat was anesthetized, nephrectomized, and injected with 51Cr-labeled EDTA (4 h) to label total extracellular fluid volume and 131I-labeled bovine IgG (5 min) to label plasma volume. Samples of skin, muscle, and tendon were assayed for total and extractable tracer activity. Interstitial fluid from these tissues was sampled postmortem with nylon wicks for assay of 125I-labeled IgG and endogenous albumin and IgG. Exclusion of IgG was calculated from the difference between extravascular 125I-labeled IgG and 51Cr-labeled EDTA distribution volumes. In contrast to our previous experience with tracer albumin, 125I-labeled IgG was not fully extractable from minced skin, muscle, or tendon by isotonic saline; only 71-83% was recovered under conditions that eluted 92-96% of tracer albumin and 94-99% of tracer EDTA. We conclude that approximately 20% of extravascular 125I-labeled IgG in these tissues is sequestered or bound in the interstitium. Calculation of IgG fractional exclusion from extractable tracer yielded the following values (means +/- SE, n = 8 rats): leg muscles 0.37 +/- 0.09, leg skin 0.44 +/- 0.03, back skin 0.36 +/- 0.04, tail skin 0.40 +/- 0.08, and tail tendon 0.55 +/- 0.04.(ABSTRACT TRUNCATED AT 250 WORDS)

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
Keyword(s):  
Thyroid Hormones ◽  
Interstitial Fluid ◽  
Fluid Pressure ◽  
Interstitial Fluid Pressure ◽  
Albumin Concentration ◽  
Rat Serum ◽  
Interstitial Fluid Volume ◽  
Hindlimb Muscle ◽  
The Difference ◽  
And Control

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.

Interstitial exclusion of positively and negatively charged IgG in rat skin and muscle

2001 ◽  
Vol 280 (4) ◽  
pp. H1505-H1512 ◽  
Author(s):  
Helge Wiig ◽  
Olav Tenstad
Keyword(s):  
Interstitial Fluid ◽  
Volume Fraction ◽  
Specific Probe ◽  
Tissue Sampling ◽  
Rat Skin ◽  
Interstitial Fluid Volume ◽  
Hindlimb Muscle ◽  
Infusion Method ◽  
State Concentration ◽  
Infusion Period

Volume exclusion, i.e., the space not available for a specific probe, may be dependant on the probe charge. Therefore, interstitial exclusion was measured for positively and negatively charged immunoglobulin (IgG) in skin and muscle of rats by using a continuous infusion method (30). Steady-state concentration of125I-labeled IgG 1 (pI = 8.7) and131I- labeled IgG 4 (pI = 6.6) was maintained by infusion of tracer for 120–168 h with an implanted osmotic pump. At the end of the infusion period and before tissue sampling, the rat was anesthetized and nephrectomized, and51Cr-labeled EDTA was injected and allowed 4 h for equilibration to measure interstitial fluid volume (Vi). Interstitial fluid was isolated from skin and muscle by using nylon wicks implanted post mortem. The relative IgG available space was measured as the ratio between labeled IgG and51Cr-labeled EDTA wick fluid equivalent spaces, and relative excluded volume fraction (Ve/Vi) was calculated as 1 − Va/Vi. Ve/Viin hindlimb skin averaged 0.37 ± 0.05 (SE) and 0.65 ± 0.06 ( P < 0.01) for IgG 1 and 4, respectively, with corresponding figures of 0.24 ± 0.05 and 0.51 ± 0.04 ( P < 0.01) in hindlimb muscle ( n = 9 for both tissues). These experiments suggest that fixed negative charges, most likely glycosaminoglycans, influence distribution of macromolecules in the interstitium and therefore affect interstitial fluid balance.

Relationship between interstitial fluid volume and pressure (compliance) in hypothyroid rats

2001 ◽  
Vol 281 (3) ◽  
pp. H1085-H1092 ◽  
Author(s):  
Helge Wiig ◽  
Tjøstolv Lund
Keyword(s):  
Skeletal Muscle ◽  
Peritoneal Dialysis ◽  
Thyroid Hormones ◽  
Interstitial Fluid ◽  
Experimental Situation ◽  
Fluid Pressure ◽  
Extracellular Fluid ◽  
Fluid Volume ◽  
The Body ◽  
Interstitial Fluid Volume

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.

scholarly journals The Biosynthesis of Rat Serum Albumin

1972 ◽  
Vol 247 (12) ◽  
pp. 3858-3863 ◽  
Author(s):  
Theodore Peters ◽  
James C. Peters
Keyword(s):  
Serum Albumin ◽  
Rat Serum ◽  
Rat Serum Albumin

Atrial Natriuretic Peptide as a Regulator of Transvascular Fluid Balance

Physiology ◽  
1996 ◽  
Vol 11 (3) ◽  
pp. 138-143 ◽  
Author(s):  
EM Renkin ◽  
VL Tucker
Keyword(s):  
Atrial Natriuretic Peptide ◽  
Natriuretic Peptide ◽  
Plasma Volume ◽  
Fluid Balance ◽  
Interstitial Fluid ◽  
Fluid Volume ◽  
Interstitial Fluid Volume ◽  
Atrial Natriuretic

Unlike other natriuretics, which act via the kidneys to reduce interstitial fluid volume with little change in plasma volume, atrial natriuretic peptide has important extrarenal actions that enable it to reduce plasma volume preferentially.

scholarly journals Evaluation of renal and cardiovascular protection mechanisms of SGLT2 inhibitors: model-based analysis of clinical data

2018 ◽  
Vol 315 (5) ◽  
pp. F1295-F1306 ◽  
Author(s):  
K. Melissa Hallow ◽  
Peter J. Greasley ◽  
Gabriel Helmlinger ◽  
Lulu Chu ◽  
Hiddo J. Heerspink ◽  
...  
Keyword(s):  
Renal Impairment ◽  
Clinical Data ◽  
Healthy Subjects ◽  
Interstitial Fluid ◽  
Sglt2 Inhibitors ◽  
Fluid Volume ◽  
Diabetic Patients ◽  
Pressure Reduction ◽  
Physiological Variables ◽  
Interstitial Fluid Volume

The mechanisms of cardiovascular and renal protection observed in clinical trials of sodium-glucose cotransporter 2 (SGLT2) inhibitors (SGLT2i) are incompletely understood and likely multifactorial, including natriuretic, diuretic, and antihypertensive effects, glomerular pressure reduction, and lowering of plasma and interstitial fluid volume. To quantitatively evaluate the contribution of proposed SGLT2i mechanisms of action on changes in renal hemodynamics and volume status, we coupled a mathematical model of renal function and volume homeostasis with clinical data in healthy subjects administered 10 mg of dapagliflozin once daily. The minimum set of mechanisms necessary to reproduce observed clinical responses (urinary sodium and water excretion, serum creatinine and sodium) was determined, and important unobserved physiological variables (glomerular pressure, blood and interstitial fluid volume) were then simulated. We further simulated the response to SGLT2i in diabetic virtual patients with and without renal impairment. Multiple mechanisms were required to explain the observed response: 1) direct inhibition of sodium and glucose reabsorption through SGLT2, 2) SGLT2-driven inhibition of Na+/H+ exchanger 3 sodium reabsorption, and 3) osmotic diuresis coupled with peripheral sodium storage. The model also showed that the consequences of these mechanisms include lowering of glomerular pressure, reduction of blood and interstitial fluid volume, and mild blood pressure reduction, in agreement with clinical observations. The simulations suggest that these effects are more significant in diabetic patients than healthy subjects and that while glucose excretion may diminish with renal impairment, improvements in glomerular pressure and blood volume are not diminished at lower glomerular filtration rate, suggesting that cardiorenal benefits of SGLT2i may be sustained in renally impaired patients.

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