Interstitial Fluid Hydrostatic Pressure Research Articles

Models of Hydration Dependent Lymphatic Opening, Interstitial Fluid Flows and Ambipolar Diffusion.

A theoretical understanding of fluid exchange and the role of initial lymph formation in tissues through mathematical/physical modeling is lacking. Here, we present three models for tissues rich in negative fixed charges due to glycosaminoglycans interacting with the extracellular matrix. We first model a lymphatic opening mechanism at relevant hydrations of the interstitium. At each hydration affecting tissue strain, two equations coupled in time are developed and solved with the new lymphatic opening and particle draining mechanism. The lymphatic opening mechanism is then included in a new model of interstitial fluid and macromolecular flow where the influence of different exclusion and available volumes for charged and neutral particles are quantified. For therapeutic interactions with cells, essential differences are found between electrically charged and neutral therapeutic substances. The interstitial fluid hydrostatic pressure gradient and flow are expressed through an extended Darcy equation, derived using similar methods as in kinetic theory of dense gases and fluid flows. Finally, a model for ambipolar diffusion of electrically charged macromolecules in tissue is developed. Our study will inform transport of charged and neutral macromolecules between the vasculature, interstitium, and the lymphatic system, thus having implications for tissue uptake of therapeutic agents.

Hydrostatic pressure induces profibrotic properties in hepatic stellate cells via the RhoA/ROCK signaling pathway.

Elevated interstitial fluid hydrostatic pressure is commonly observed in diseased livers. We herein examined the hypothesis that hydrostatic pressure induces hepatic stellate cells to acquire profibrotic properties under pathological conditions. Human hepatic stellate cells were exposed to 50 mmHg pressure for 24 h. Although we observed few changes of cell growth and morphology, PCR array data on the expression of fibrosis‐associated genes suggested the acquisition of profibrotic properties. The exposure of hepatic stellate cells to 50 mmHg pressure for 24 h also significantly enhanced the expression of RhoA, ROCK1, α‐SMA, TGF‐β1, p‐MLC, and p‐Smad2, and this was effectively attenuated by the ROCK inhibitor Y‐27632. Our ex vivo experimental data suggest that elevated interstitial fluid hydrostatic pressure under pathological conditions may promote liver fibrosis by inducing acquisition of profibrotic properties of hepatic stellate cells through the RhoA/ROCK signaling pathway.

Hydrostatic pressure stabilizes HIF‑1α expression in cancer cells to protect against oxidative damage during metastasis.

The tissue microenvironment is known to play a pivotal role in cancer metastasis. Interstitial fluid hydrostatic pressure generally increases along with the rapid growth of malignant tumors. The aim of the present study was to investigate the role and relevant mechanism of elevated hydrostatic pressure in promoting the metastasis of cancer cells. Using a commercial device, Lewis lung cancer (LLC) cells were exposed to 50mmHg hydrostatic pressure (HP) for 24h. The survival time and morphology of the cells did not notably change; however, the results from a PCR array revealed the upregulation of numerous metastasis‑promoting genes (Hgf, Cdh11 and Ephb2) and the downregulation of metastasis suppressing genes (Kiss1, Syk and Htatip2). In addition, compared with that in the control, the cells which had undergone exposure to 50mmHg HP showed significantly higher protein expression level of HIF‑1α and the antioxidant enzymes, SOD1 and SOD2, as well as improved tolerance to oxidative stress (P<0.05 vs. control). Following an intravenous injection of the LLC cells into healthy mice, to induce lung metastasis, it was found that the exposure of the LLC cells to 50mmHg HP for 24h, prior to injection into the mice, resulted in higher cell survival/retention in the lungs 24h later and also resulted in more metastatic tumor lesions 4weeks later (P<0.05 vs. control). Further investigation is required to confirm the molecular mechanism; however, the results from the present study suggested that elevated interstitial fluid HP in malignant tumors may promote the metastasis of cancer cells by stabilizing HIF‑1α expression to defend against oxidative damage.

Adjuvant anti-angiogenic therapy enhances chemotherapeutic uptake in a murine model of head and neck cancer

Intratumoural metabolic demands result in excessive angiogenic cytokine release leading to unorganised vasculature. Resultant fluid dynamics oppose blood flow and drug penetration due to a marked increase in interstitial fluid hydrostatic pressure. It is hypothesised that anti-angiogenic therapy may function to ‘prune’ vasculature and lead to improved chemotherapeutic penetration. Subcutaneous, OSC19 tumour bearing mice (n = 5/dose/agent) were administered varying doses of an anti-mouse VEGFR2 (DC101) or an anti-mouse VEGFR3 (31C1) –3 d, –1 d, 0 d, +1 d and +3 d prior to 200 µg of cetuximab fluorescently labelled with IRDye800CW. Fluorescence imaging of tumours was performed 10 d post cetuximab-IRDye800CW dose to monitor therapeutic uptake. Co-administration of dual anti-angiogenic agents at 50–50%, 75–25% and 25–75% using optimal dose and time (–1 d 10 mg/kg anti-VEGFR2 and –1 d 40 mg/kg anti-VEGFR3) was also evaluated. In order to establish vessel normalisation, NG2 (pericyte marker) and CD31 (endothelial cells) ratios were assessed during immunohistochemical staining of tumour sections. Twenty-mg/kg anti-VEGFR3 + 5 mg/kg anti-VEGFR2 significantly (p < .0005) reduced tumour size (–73%) compared to control (59%). The 20 mg/kg anti-VEGFR3 + 5 mg/kg anti-VEGFR2 and 30 mg/kg anti-VEGFR3 + 2.5 mg/kg anti-VEGFR2 significantly (p < .0004) improved percent-injected cetuximab-IRDye800CW dose/gram tumour tissue compared to other groups. Adjuvant, dual anti-angiogenic therapy targeting VEGFR2 and VEGFR3 significantly enhances tumour chemotherapeutic uptake compared to control.

Burn depth affects dermal interstitial fluid pressure, free radical production, and serum histamine levels in rats.

We measured the amount of edema and the free radical production in burn-injured skin and the serum histamine levels, as well as changes in dermal interstitial fluid pressure. Thirty-six Wistar rats with 20% total body surface area burns of different depth were resuscitated by lactated Ringer's solution intravenously. The rats were divided into a deep burn (DB) group (n = 12), a superficial dermal burn (SDB) group (n = 12), and a sham burn (Sham) group (n = 12). Dermal interstitial fluid hydrostatic pressure (Pif), total skin water and xanthine oxidase activity, and serum histamine levels were measured until 60 minutes postburn. In the DB group, dermal Pif significantly fell to -35.9 +/- 11.0 and -40.9 +/- 7.0 mm Hg at 10 and 15 minutes postburn, respectively (p < 0.05); it returned to preburn values at 50 minutes postburn. In the SDB group, dermal Pif was slightly negative but did not markedly change. Total skin water was significantly higher than that of the DB and the Sham groups; however, in the SDB group, serum histamine and dermal xanthine oxidase were significantly higher than in the DB group at 15, 30, and 45 minutes postburn (p < 0.05). The fluid-resuscitated DB produced a more negative dermal Pif than the SDB, but less dermal edema. In contrast, the SDB appeared to mainly generate dermal edema formation by wound free radical production and serum histamine release. The dermal Pif is one of the factors associated with edema formation immediately after deep burns. However, an increase in vascular permeability associated with oxygen radical production plays a more important role in dermal edema formation than does dermal Pif.

Obesity and the kidney connection

The importance of the functional and structural changes that occur in the kidneys in association with obesity was discussed previously in the medical literature.1-4 These studies suggested that the kidneys are involved in the development of obesity-induced hypertension. This involvement is explained by an abnormal tubular sodium handling and by deposition of cells or matrix in the renal medulla that causes an increase in the renal interstitial fluid hydrostatic pressure.3,5

Verteilung des Ödems von Patienten mit chronischer kritischer Ischämie: Eine computertomographische Studie

Background: A substantial number of patients with chronic critical limb ischaemia (CLI) have considerable oedema at the distal leg and foot of non deep venous thrombosis origin. The primary aim of the pre-sent study was to quantify the distribution of oedema in the different tissues of the leg and foot by applying computed tomography and planimetry. The interstitial fluid hydrostatic pressure (Pif) in the subcutaneous tissue was measured to evaluate the effect of oedema on local tissue pressure. Patients and methods: Six men and 12 women with unilateral CLI and peripheral pitting oedema were included. Cross sectional areas (CSA) of subcutaneous tissue, muscle and bone were measured by computer tomography combined with planimetry to assess the distribution of oedema within the soft tissues. Pif was measured by “wick-in-needle” technique. Results: The median total CSA of soft tissue, subcutaneous and muscle tissues at the foot level were respectively 17%, 34% and 9% greater in the limbs with CLI compared to the contralateral limb (p &lt; 0.001). At ankle level these differences were 13%, 30% and 4%, respectively (p &lt; 0.001). At the level of the calf these differences were not significant. Mean Pif in the limbs with CLI was 0.3 mmHg, significantly higher than in limbs without CLI (–1.8 mmHg), (p &lt; 0.003). Conclusion: The study verified oedema of considerable magnitude at the ankle and foot. The great part of the oedema was located within the subcutaneous tissue, which was associated with a relatively moderate, but significant increase in Pif confirming the high compliance of the subcutaneous tissue. The combination of the excessive fluid and increased Pif in the interstitial tissue might aggravate the microcirculation. The aetiology of oedema formation is probably multifactorial.

High dose vitamin C counteracts the negative interstitial fluid hydrostatic pressure and early edema generation in thermally injured rats

Background and objective: edema formation after thermal injury is rapid and fulminant within the first hour after injury and increased microvascular permeability has been claimed to be the main responsible mechanism. An acute decrease in interstitial fluid hydrostatic pressure ( P if) down to −150 mm Hg has recently been reported in dermal burns. This strong negative tissue pressure creates a ‘suction’ on the fluid in the capillaries. Furthermore, high dose vitamin C (VC) has been shown to reduce postburn edema and fluid requirements following major burn injuries. This led to the present study, aimed at investigating whether VC administered after thermal injury in rats, could attenuate the strongly negative P if. Edema volume was measured by total tissue water content (TTW) and extravasation of albumin (Ealb). Study design: a prospective, open experimental study. Materials and methods: pentobarbital-anesthetized rats received either a full-thickness burn injury covering 10% of total body surface area, or a sham burn. The rats were given VC or equal volumes normal saline (NS) either before the burn, 5 or 30 min after the injury. VC (25 mg/ml in NS, osmolality 272 mOsm/l) was administered as a bolus (66 mg/kg) followed by infusion (33 mg/kg/h). The animals were divided into 7 groups (6 animals in each) according to the timing of VC/NS administration: (1) VC-preburn, (2) VC-5 min postburn, (3) VC-30 min postburn, (4) NS-preburn, (5) NS-5 min postburn, (6) NS-30 min postburn and (7) VC-pre sham burn group. All groups were duplicated for series I and II. Measurements: in series I; P if was measured using a sharpened glass micropipette connected to a servo-controlled counter pressure system. Measurements were averaged in the following time periods: preburn, 5–20, 21–40, 41–60 and 61–90 min postburn. In series II; Ealb and TTW were measured in burned and non-burned skin by radio-labelled albumin and wet–dry weights, respectively. Results: in the sham control group (VC-pre-sham burn), P if ranged between −1 and −2 mm Hg and did not change throughout the experimental period. In the NS group (placebo), P if fell to −46.8±10.1 (1 S.D.) mm Hg at 5–20 min after the injury and were −23.1±13.4 and −11.6±4.1 mm Hg at 21–40 and 41–60 min postburn. P if returned to preburn values at 61–90 min post injury. In the VC groups, there was a marked attenuation of the negative P if to average −10.1±11.8 mm Hg at 5–20 min, −2±1.7 and −0.6±1.2 mm Hg at 21–40 and 41–60 min after injury, respectively (all p<0.01 compared to NS). TTW in burned skin of the NS-5 min groups was 3.12±0.28, VC5-min group was 2.57+0.69 and VC sham was 1.77+0.19 ml/g DW, respectively ( p<0.01 compared to sham control for all values). In all the VC-groups TTW values were higher than sham control and lower than in the corresponding NS-groups ( p>0.05 both ways). No statistical significant differences were found between Ealb-values in the VC- and NS-groups. Conclusion: high dose vitamin C attenuates the development of strongly negative P if in burned dermis and reduces the edema as measured by TTW. No significant change in Ealb was found. Vitamin C was thus found to have potential beneficial effects on the acute postburn edema generation.

In vivo effects of hydrostatic pressure on interstitium of abdominal wall muscle.

Fluid loss from the peritoneal cavity to surrounding tissue varies directly with intraperitoneal hydrostatic pressure (Pip). According to Darcy's law [Q = -KA(dPif/dx)], fluid flux (Q) across a cross-sectional area (A) of tissue will increase with an increase in either hydraulic conductivity (K) or the interstitial fluid hydrostatic pressure gradient (dPif/dx, where x is distance). Previously, we demonstrated that in the anterior abdominal muscle (AAM) of rats, dPif/dx increases by only 40%, whereas K rises fivefold between Pip of 1.5 and 8 mmHg. Because K is a function of interstitial volume (thetaif), we hypothesized that perturbations of Pip would change Pif and expand the interstitium, increasing thetaif. To test this hypothesis, we used dual-label quantitative autoradiography (QAR) to measure extracellular fluid volume (thetaec) and intravascular volume (thetaiv) in the AAM of rats within the Pip range from -2.8 to +8 mmHg. thetaif was obtained by subtraction (thetaec - thetaiv). dPif/dx was measured with a micropipette and a servo-null system. Local thetaiv did not vary with Pip and averaged 0.010 +/- 0.002 ml/g, and thetaif averaged 0. 19 +/- 0.01 ml/g at Pif </=1.2 mmHg. However, thetaif doubled between Pif of 1.2 and 4.2 mmHg (from 0.20 +/- 0.00 to 0.39 +/- 0.01 ml/g, respectively) but did not increase with further increases in Pif. This nonlinear pressure-volume relationship does not explain the fivefold increase in K with Pip. Because the interstitial matrix contributes to the interstitial resistance to fluid flow, and because hyaluronan (HA) is the only component of the matrix that is not anchored to the tissue, we hypothesized that the loss of interstitial HA was responsible for the continued decrease in interstitial resistance to fluid flow. We determined HA concentration in the rat AAM and adjacent subcutaneous tissue (SC) at Pip = 0 mmHg and after 2 h of dialysis at constant Pip = 6 mmHg. The HA content (normalized to dry weight) in the AAM was reduced from 487 +/- 16 to 360 +/- 27 micrograms/g dry tissue (n = 4, P < 0.05) and increased from 528 +/- 72 to 1,050 +/- 136 mg/g dry tissue (n = 4, P > 0.001) in the SC. We conclude that the mechanisms responsible for the increase in K with Pip include expansion of the interstitium, dilution of interstitial macromolecules, and washout from the AAM to SC of interstitial macromolecules responsible for resistance to fluid flow.

Hypertonic saline and dextran in normovolaemic and hypovolaemic healthy volunteers increases interstitial and intravascular fluid volumes.

Hypertonic saline (HS) is increasingly used for fluid resuscitation in hypovolaemic patients. Although the effects of HS have been investigated in animal models, controlled studies in healthy human individuals are few. The effects of i.v. hypertonic saline 75 mg.ml-1 in dextran 70, 60 mg.ml-1 (HSD) infusion on fluid shifts between the interstitial and intravascular fluid spaces, diuresis and haemodynamics were studied in normovolaemic and moderately hypovolaemic healthy volunteers. Nine fasting subjects received 4 ml.kg-1 HSD as a 10-min infusion in a normovolaemic situation. Seven days later they served as their own controls in a hypovolaemic situation after 10% of the calculated blood volume had been withdrawn during a 15-min period. Before and after the HSD infusion, interstitial colloid osmotic pressure (COPi) and interstitial fluid hydrostatic pressure (Pi) were measured on the lateral part of the thorax. During the study, blood sampling and pressure measurements were performed through a radial artery cannula, and central venous pressure measured through a catheter in the cubital vein. In these awake and normovolaemic healthy volunteers, HSD infusion caused a transitory unpleasant sensation of headache and heat in the thorax up to the throat. A transitory haemodynamic effect was found with increased heart rate (HR), increased mean arterial pressure (MAP) from 77 +/- 5 mmHg to 92 +/- 13 mmHg (P < 0.05) and CVP increase from 5 +/- 1 mmHg to 8 +/- 1 mmHg (P < 0.05) after end of infusion. A haemodilution with increase in calculated blood volume lasting longer than the MAP increase was observed, with decreased COPi from 14.4 +/- 2.2 mmHg to 12.1 +/- 2.0 mmHg (P < 0.05). The diuresis measured at 180 min was higher in the normovolaemic than in the hypovolaemic situation. More pronounced effects of the infused fluid (HSD) on calculated blood volume, interstitial compartment and CVP were observed during moderate hypovolaemia. HSD infusion resulted in increased calculated blood volume with increased HR, MAP, and CVP. These effects were greater in a hypovolaemic situation. The haemodilution was most likely caused by fluid shifts from the intracellular compartment to the interstitial and vascular fluid spaces, eventually increasing diuresis.

Transcapillary escape rate of albumin in humans during exercise-induced hypervolemia.

To test the hypotheses that plasma volume (PV) expansion 24 h after intense exercise is associated with reduced transcapillary escape rate of albumin (TERalb) and that local changes in transcapillary forces in the previously active tissues favor retention of protein in the vascular space, we measured PV, TERalb, plasma colloid osmotic pressure (COPp), interstitial fluid hydrostatic pressure (Pi), and colloid osmotic pressure in leg muscle and skin and capillary filtration coefficient (CFC) in the arm and leg in seven men and women before and 24 h after intense upright cycle ergometer exercise. Exercise expanded PV by 6.4% at 24 h (43.9 +/- 0.8 to 46.8 +/- 1.2 ml/kg, P < 0.05) and decreased total protein concentration (6.5 +/- 0.1 to 6.3 +/- 0.1 g/dl, P < 0.05) and COPp (26.1 +/- 0.8 to 24.3 +/- 0.9 mmHg, P < 0.05), although plasma albumin concentration was unchanged. TERalb tended to decline (8.4 +/- 0.5 to 6.5 +/- 0.7%/h, P = 0.11) and was correlated with the increase in PV (r = -0.69, P < 0.05). CFC increased in the leg (3.2 +/- 0.2 to 4.3 +/- 0.5 microl . 100 g-1 . min-1 . mmHg-1, P < 0. 05), and Pi showed a trend to increase in the leg muscle (2.8 +/- 0. 7 to 3.8 +/- 0.3 mmHg, P = 0.08). These data demonstrate that TERalb is associated with PV regulation and that local transcapillary forces in the leg muscle may favor retention of albumin in the vascular space after exercise.

Effect of venous stasis and hypoproteinemia in gingival fluid formation in rats.

Experiments were performed to provide information on the mechanisms of the formation of gingival fluid in rats and on the determinants of its flow and composition. For this purpose we studied the effect of increasing net capillary filtration by venous stasis induced by multiple ligations of the jugular vein or by hypoproteinemia induced through puromycine nephrosis. A 1 microliter glass capillary was placed in the sulcus of the first maxillary molar for collection of gingival fluid (GF). Colloid osmotic pressure (COP) was determined in GF, in wick fluid from attached gingiva and buccal mucosa, and in plasma. Interstitial fluid hydrostatic pressure (Pi) was measured by micropuncture technique and the fractional removal rate of radio-labelled human serum albumin (kAlb) was recorded in attached gingiva and buccal mucosa. During venous stasis the gingival fluid flow increased from 1.7 microliters/h to 3.8 microliters/h, whereas COPGF fell from 14.1 mmHg to 8.8 mmHg. COP in wick fluid from gingiva was reduced from 10.3 to 4.3 mmHg. Pi increased from 6.8 to 13.1 mmHg, and kAlb in sham-operated controls increased from 0.068 to 0.189 h-1. In buccal mucosa COPi was significantly decreased to 7.1 mmHg in rats with venous stasis, whereas Pi and kAlb remained unchanged compared to the sham-operated controls. In hypoproteinemic rats COPGF was 5.0 mmHg and COPp was reduced from 18.9 to 8.0 mmHg. COPi declined from 8.9 mmHg to 2.4 mmHg in gingiva and from 8.1 mmHg to 2.7 mmHg in buccal mucosa.(ABSTRACT TRUNCATED AT 250 WORDS)

Alpha-Trinositol inhibits edema generation and albumin extravasation in thermally injured skin.

Pharmacologic attempts to reduce edema generation and albumin extravasation into thermally injured skin have until recently been disappointing unless the drugs (usually antiphlogistic or anti-inflammatory drugs) were given before injury. We have studied the effect of alpha-trinositol (PP56, i.e., 1D-myo-inositol-1,2,6-trisphosphate) given after the injury in an experimental full-thickness 10% TBSA scald burn in anesthetized rats. Total tissue water content (TTW) and albumin extravasation (Ealb) were determined in injured and noninjured skin (series I, n = 12). Interstitial fluid hydrostatic pressure (Pif) was measured in injured skin (series II, n = 14). alpha-Trinositol was administered (alpha-trinositol groups) as an i.v. bolus (40 mg/kg) at 5 minutes after injury followed by an i.v. infusion (1.3 mg/kg/min). In both series a placebo group received burn injury and normal saline in equal volumes instead of alpha-trinositol. Compared with placebo, alpha-trinositol reduced TTW and Ealb as well as the increased negatively of Pif in injured tissue significantly. The effect on Ealb was most prominent, with a reduction from 153.9 +/- 35.6 (SEM) microL/g in the NaCl group to 23.1 +/- 6.3 after alpha-trinositol (p < 0.005). Total tissue water was reduced from 2.51 +/- 0.13 to 2.17 +/- 0.06 mL/g (p < 0.05) and Pif (measured between 21 and 40 minutes postinjury) from -24.7 +/- 4.1 to -3.2 +/- 1.1 mm Hg (p < 0.005).(ABSTRACT TRUNCATED AT 250 WORDS)

Cold and warm infusion of Ringer's acetate in healthy volunteers: the effects on haemodynamic parameters, transcapillary fluid balance, diuresis and atrial peptides

The effects of Ringer's acetate (RAc) infusion with different temperatures, 18 degrees C compared to 36 degrees C, were studied in 20 healthy volunteers. An infusion volume of 20% of the estimated extracellular volume was given over 45 min. Before and after the RAc infusion, interstitial colloid osmotic pressure and interstitial fluid hydrostatic pressure were measured on the lateral part of the thorax and in the lower leg. Blood sampling and pressure measurements were performed through a cannula placed in the left radial artery, and arterial oxygen saturation was measured by pulse oximetry. Atrial peptides ANF (99-126) and ANF (1-98) in plasma were measured as indicators of volume loading. Cold RAc infusion increased mean arterial pressure from 82 (s.d. +/- 7) to 96 (s.d. +/- 9) mmHg (10.9-12.8 kPa) at the end of the infusion with a simultaneous fall in heart rate. Warm RAc infusion gave no changes in blood pressure or heart rate. The arterial oxygen saturation during the infusion of cold RAc was higher than during warm RAc infusion. Cold infusion produced the expected haemodilution with a fall in erythrocyte volume fraction (EVF) from 0.39 (+/- 0.03) to 0.33 (+/- 0.03) and a fall in plasma colloid osmotic pressure (COPp) from 21.7 (+/- 1.1) mmHg to 15.0 (+/- 1.3) mmHg (2.9-2.0 kPa). Warm infusion induced a nearly identical haemodilution. Interstitial colloid osmotic pressure fell from 11.6 (+/- 2.3) mmHg to 8.9 (+/- 2.7) mmHg (1.5-1.2 kPa) after warm infusion while cold infusion gave no changes. The changes in interstitial fluid hydrostatic pressure were not significant.(ABSTRACT TRUNCATED AT 250 WORDS)

The use of MRI in the investigation of leg oedema

Magnetic resonance imaging (MRI) was used in the diagnosis of various conditions giving rise to leg oedema, with special attention to the oedema after femoro-distal vascular reconstruction for obliterative atherosclerosis (n = 14). Patients with deep venous thrombosis (n = 6), chronic lymphoedema (n = 6) and closed muscular compartment syndrome (n = 2) were also investigated. Leg volume increase was measured according to the formula of a truncated cone. Interstitial fluid hydrostatic pressure (Pif) was recorded with the wick-in-needle technique. Spin echo series with 10 mm transverse slices were obtained with MRI. Following vascular reconstructions, leg volume increased 26% on the operated side. In the operated leg, no gradient in Pif was found between the posterior muscular compartment and the subcutaneous tissue. However, there was a significantly higher Pif in the subcutaneous tissue compared to the anterior muscular compartment (p less than 0.05). In the operated group, MRI revealed oedema around the entire circumference of the leg, mainly restricted to the subcutaneous tissue. In contrast, oedema of the leg muscles, particularly in the posterior compartments, was typical for patients having deep venous thrombosis. The group with chronic lymphoedema showed circumferential subcutaneous oedema alone or in combination with a fibrotic honeycomb pattern. Oedema of the affected muscular compartment was easily observed in patients who had a closed compartment syndrome. In conclusion, the use of MRI is promising in the investigation of conditions giving rise to leg oedema. It is likely that the formation of post-reconstructive oedema is taking place in the subcutaneous tissue.(ABSTRACT TRUNCATED AT 250 WORDS)

Effect of longstanding venous stasis and hypoproteinaemia on lymph flow in the rat tail

This study was performed to provide information on the determinants of lymph flow by comparing the effect of venous stasis and hypoproteinaemia in the rat tail. This low-compliant tissue was chosen in an attempt to induce preferential changes in interstitial pressure or volume. The removal rate (kAlb) of 125I-labelled human serum albumin (I-HSA) injected subcutaneously was monitored with external gamma-counting equipment and used as a measure of lymph flow. Interstitial fluid hydrostatic pressure (Pi) was measured with wick-in-needle technique, and interstitial fluid was collected post mortem by dry wicks. Colloid osmotic pressure of plasma (COPp) and wick fluid (COPi) was measured with a colloid osmometer. In a separate group of experiments, 51Cr-EDTA and [125I]HSA were used to measure the interstitial fluid volume. Venous stasis, induced by bilateral ligation of the external tail veins, increased interstitial fluid hydrostatic pressure from 1.7 to 16 mmHg and kAlb from 0.030 to 0.063 h-1, whereas tail circumference was nearly constant. Interstitial volume averaged 1.17 ml/g dry weight in control animals and 1.27 ml/g during increased venous pressure. Daily injections of aminonucleoside in salt-loaded rats (0.3% NaCl as drinking water) reduced colloid osmotic pressure of plasma from 19.1 to 8.5 mmHg and of wick fluid from 11.2 to 2.9 mmHg, while interstitial fluid hydrostatic pressure increased to 5.2 mmHg. The removal rate of 125I-labelled human serum albumin increased to 0.113 h-1, compared to 0.051 h-1 in salt-loaded controls. The interstitial volume showed a marked increase in salt-loaded hypoproteinaemic rats, 1.75 ml/g dry weight, compared to 1.30 ml/g in salt-loaded controls.(ABSTRACT TRUNCATED AT 250 WORDS)

Thermal skin injury: Effect of fluid therapy on the transcapillary colloid osmotic gradient

The effects of fluid therapy on interstitial colloid osmotic and hydrostatic pressures in thermally injured skin were investigated in anesthetized rats subjected to full-thickness scald burns to 40% of the body surface area and resuscitation for 3 hr by either lactated Ringer's or plasma. Interstitial fluid hydrostatic pressure ( P if) was reduced from −2 mm Hg to −20 to −40 mm Hg after injury, which will profoundly increase transcapillary filtration. Following the onset of fluid therapy, P if increased to slightly positive values. In control, colloid osmotic pressure in plasma (COP p) was 20.6 ± 0.4 mm Hg and in interstitial fluid (COP if) 13.7 ± 0.3 mm Hg (means ± SEM). The transcapillary oncotic pressure gradient (COP grad = COP p − COP if) was 6.9 ± 0.4 mm Hg. Following nonresuscitated thermal injury, COP p declined to 18–19 mm Hg ( P < 0.05) and COP if was reduced to 10.4 ± 0.5 mm Hg ( P < 0.05). Fluid therapy by lactated Ringer's markedly reduced COP p (12.3 ± 0.3 mm Hg; P < 0.05), and COP grad was almost abolished (2.6 ± 0.7 mm Hg; P < 0.05). In contrast, plasma infusion maintained COP p, whereas COP grad increased significantly (11.1 ± 1.2 mm Hg; P < 0.05). Noncolloid saline solutions have been preferred for the initial fluid therapy for burns. The present study provides evidence that this will reduce both COP p and COP grad, a situation in which edema formation will be favored.

Transcapillary filtration in lower limbs with deep venous thrombosis; the role of the capillary filtration coefficient

The capillary filtration coefficient (CFC) of the Starling equation was measured with strain gauge plethysmography at calf level of lower limbs with deep venous thrombosis (DVT). CFC was significantly elevated in limbs with DVT compared to the contralateral limb (0.0037(0.0005) ml min-1 100 g-1 mmHg-1 rise in filtration pressure and 0.0026(0.0010) ml min-1 100 g-1 mmHg-1 rise in filtration pressure, p less than 0.01) (Mean(SD]. Calf blood flow was also measured with strain-gauge plethysmography and was significantly increased in limbs with DVT compared to the contralateral (2.9(1.4)ml min-1 100 g-1 and 2.3(1.4) ml min-1 100 g-1, p less than 0.05). Increased venous pressure (Pv) found in lower limbs with DVT could be expected to lead to reduced blood flow. Our results point to an inflammatory reaction over-ruling increased venous resistance. No correlation was found between CFC and blood flow but this may have methodological explanations since increased Pv will influence both CFC and blood flow recordings obtained with plethysmography. Interstitial fluid hydrostatic pressure (Pif) measured with the 'wick-in-needle' technique in the deep posterior muscle compartment was significantly increased compared to the contralateral limb (6.3(3.5) mmHg and -1.2(3.4) mmHg, p less than 0.001). No correlation was found between CFC and Pif. Increase in CFC and blood flow at calf level is probably important in oedema in lower limbs with DVT.

The venous pump of the human foot

Pressures in the flexor digitorum muscle, posterior tibial and anterior tibial muscles and subcutaneous pressure in the lower leg were recorded in 18 volunteers with a non-infusion technique. The venous plexus of the sole of the foot was compressed by a pneumatic foot pump. Activation of this device creates oscillations of intramuscular and subcutaneous interstitial fluid hydrostatic pressure in the lower leg. The mechanism for this is explained by intermittent passive muscle stretch. The interstitial fluid pressure decreased following active muscle contractions during venous stasis of the limb, but not following activation of the pneumatic pump. Although the pneumatic foot pump may on theoretical grounds be useful in early treatment of postoperative and post-traumatic oedema of the leg, complementary studies are necessary to establish its effectiveness.

Acute postburn edema: Role of strongly negative interstitial fluid pressure

Interstitial fluid hydrostatic pressure (Pif) was measured with micropipettes during the acute edema generation that followed thermal skin injury in rats. Intradermal Pif was reduced from normal level of -1 mmHg to very negative values after thermal injury. The strongly negative Pif reflects a tissue imbibition pressure created by the thermal injury. The magnitude and duration of this pressure was dependent on the extent of the injury and the availability of fluid. After in vivo injury to 10 and 40% of the total body surface area (TBSA), mean intradermal Pif was temporarily reduced to -20 and -31 mmHg, respectively. Intravenous fluid infusion resulted in a rapid return of Pif to slightly positive values. Fluid available for transfer from the circulation was reduced by inducing the injury after killing the animal (postmortem injury) and even more by the subcutaneous insertion of a plastic barrier: this led to more pronounced reductions in Pif to average minimum values of -95 and -135 mmHg, respectively. Our data show that increased tissue imbibition pressure and increased net filtration pressure (tissue mechanisms) are responsible for a major part of the acute fluid shifts into thermally injured skin. Vascular mechanisms (permeability changes and intravascular pressure) are involved in the postburn edema development but are clearly less important than hitherto believed.