Interstitial Colloid Osmotic Pressure Research Articles

Transcapillary fluid flux and inflammatory response during neonatal therapeutic hypothermia: an open, longitudinal, observational study

BackgroundTherapeutic hypothermia is neuroprotective in asphyxiated neonates by counteracting mechanisms contributing to brain injury. Although an initial increased permeability is part of an inflammatory reaction and thereby a natural healing process, an excessive endothelial permeability with edema formation may result in impaired hemodynamics. Reduced permeability may, however, benefit healing. Although plasma and interstitial colloid osmotic pressure are accessible and essential parameters for understanding fluid imbalance, the mechanisms of fluid exchange remain poorly understood. The potential influence of therapeutic hypothermia on plasma and interstitial colloid osmotic pressure, and the relationship between inflammatory markers and colloid osmotic pressure in asphyxiated neonates, was investigated.MethodsSeventeen neonates with moderate to severe hypoxic ischemic encephalopathy, born after 35 weeks gestation, received servo-controlled whole body cooling before 6 h of age, followed by gradual rewarming after 72 h. All infants were treated according to a national hypothermia protocol. Interstitial fluid in the skin was collected at 7, 13, 25, 49, and 73 h after birth by subcutaneous implantation of multifilamentous nylon wicks with 60 min of implantation time. Biomarkers of inflammation and colloid osmotic pressure were measured in serum and interstitial fluid.ResultsA modest decrease in serum and interstitial colloid osmotic pressure was measured, leaving an unaltered difference in colloid osmotic pressure gradient. A decline in mean arterial pressure was observed between 7 and 13 h of life, with a concomitant decrease in positive fluid balance within the same time frame. White blood cell count and leukocyte subclasses dropped significantly throughout treatment, with elevated interstitial interleukin (IL)-1α and decreased serum IL-1RA, IL-6, and IL-10 during treatment time points.ConclusionsColloid osmotic pressures measured in serum and interstitial fluid during asphyxia is lower than previously reported, with small alteration of pressure differences across capillaries, reducing vascular filtration. An inherent local and systemic regulation of inflammation together with changes in colloid osmotic pressure may indicate a possible preventive mechanism of edema generation during neonatal asphyxia and therapeutic hypothermia.Trial registrationClinicalTrials.gov Identifier: NCT01044940. Date of registration: January 8, 2010.

Interstitial Fluid Colloid Osmotic Pressure in Healthy Children

ObjectiveThe colloid osmotic pressure (COP) of plasma and interstitial fluid play important roles in transvascular fluid exchange. COP values for monitoring fluid balance in healthy and sick children have not been established. This study set out to determine reference values of COP in healthy children.Materials and MethodsCOP in plasma and interstitial fluid harvested from nylon wicks was measured in 99 healthy children from 2 to 10 years of age. Nylon wicks were implanted subcutaneously in arm and leg while patients were sedated and intubated during a minor surgical procedure. COP was analyzed in a colloid osmometer designed for small fluid samples.ResultsThe mean plasma COP in all children was 25.6 ± 3.3 mmHg. Arbitrary division of children in four different age groups, showed no significant difference in plasma or interstitial fluid COP values for patients less than 8 years, whereas patients of 8-10 years had significant higher COP both in plasma and interstitial fluid. There were no gender difference or correlation between COP in interstitial fluid sampled from arm and leg and no significant effect on interstitial COP of gravity. Prolonged implantation time did not affect interstitial COP.ConclusionPlasma and interstitial COP in healthy children are comparable to adults and COP seems to increase with age in children. Knowledge of the interaction between colloid osmotic forces can be helpful in diseases associated with fluid imbalance and may be crucial in deciding different fluid treatment options.Trial RegistrationClinicalTrials.gov NCT01044641

PO-0027 Interstitial Fluid Colloid Osmotic Pressure In Healthy Children

Background and aims Colloid osmotic pressure (COP) of plasma and interstitial fluid play important roles in transvascular fluid exchange were small pressure alterations may result in fluid shifts into or out of the capillaries optimising homeostasis. This study was conducted to determine reference values of COP in healthy children, and to evaluate the methodology of harvesting interstitial fluid. Methods COP in plasma and interstitial fluid isolated from nylon wicks implanted subcutaneously was measured in 99 healthy children from 2 to 10 years of age. Patients were sedated and intubated during wick implantation in arm and leg, and COP was analysed in a colloid osmometer. Results Mean plasma COP in all children was 25.6 ± 3.3 mmHg. Arbitrary division of children in age groups, showed no significant difference in plasma or interstitial fluid COP values for patients less than 8 years, whereas patients of 8–10 years had significant higher COP both in plasma and interstitial fluid. There was no gender difference or correlation between COP in interstitial fluid sampled from arm and leg and no significant effect on interstitial COP of gravity. Prolonged implantation time did not affect interstitial COP. Conclusions This study justifies the presumption that plasma and interstitial COP in healthy children are similar to adults. Children between 8 and 10 years had higher values than younger age groups. Knowledge of interaction between colloid osmotic forces in health and disease can be helpful in diseases associated with fluid imbalance and may be crucial in deciding different fluid treatment options.

Isoflurane in Contrast to Propofol Promotes Fluid Extravasation during Cardiopulmonary Bypass in Pigs

A highly positive intraoperative fluid balance should be prevented as it negatively impacts patient outcome. Analysis of volume-kinetics has identified an increase in interstitial fluid volume after crystalloid fluid loading during isoflurane anesthesia. Isoflurane has also been associated with postoperative hypoxemia and may be associated with an increase in alveolar epithelial permeability, edema formation, and hindered oxygen exchange. In this article, the authors compare fluid extravasation rates before and during cardiopulmonary bypass (CPB) with isoflurane- versus propofol-based anesthesia. Fourteen pigs underwent 2 h of tepid CPB with propofol (P-group; n = 7) or isoflurane anesthesia (I-group; n = 7). Fluid requirements, plasma volume, colloid osmotic pressures in plasma and interstitial fluid, hematocrit levels, and total tissue water content were recorded, and fluid extravasation rates calculated. Fluid extravasation rates increased in the I-group from the pre-CPB level of 0.27 (0.13) to 0.92 (0.36) ml·kg·min, but remained essentially unchanged in the P-group with significant between-group differences during CPB (pb = 0.002). The results are supported by corresponding changes in interstitial colloid osmotic pressure and total tissue water content. During CPB, isoflurane, in contrast to propofol, significantly contributes to a general increase in fluid shifts from the intravascular to the interstitial space with edema formation and a possible negative impact on postoperative organ function.

Effect of Topical Anaesthetics on Interstitial Colloid Osmotic Pressure in Human Subcutaneous Tissue Sampled by Wick Technique

ObjectivesTo measure colloid osmotic pressure in interstitial fluid (COPi) from human subcutaneous tissue with the modified wick technique in order to determine influence of topical application of anaesthetics, dry vs. wet wick and implantation time on COPi.Material and MethodsIn 50 healthy volunteers interstitial fluid (IF) was collected by subcutaneous implantation of multi-filamentous nylon wicks. Study subjects were allocated to two groups; one for comparing COPi obtained from dry and saline soaked wicks, and one for comparing COPi from unanaesthetized skin, and skin after application of a eutectic mixture of local anaesthetic (EMLA®, Astra Zeneca) cream. IF was sampled from the skin of the shoulders, and implantation time was 30, 60, 75, 90 and 120 min. Colloid osmotic pressure was measured with a colloid osmometer. Pain assessment during the procedure was compared for EMLA cream and no topical anaesthesia using a visual analogue scale (VAS) in a subgroup of 10 subjects.ResultsThere were no significant differences between COPi obtained from dry compared to wet wicks, except that the values after 75 and 90 min. were somewhat higher for the dry wicks. Topical anaesthesia with EMLA cream did not affect COPi values. COPi decreased from 30 to 75 min. of implantation (23.2±4.4 mmHg to 19.6±2.9 mmHg, p = 0.008) and subsequently tended to increase until 120 min. EMLA cream resulted in significant lower VAS score for the procedure.ConclusionCOPi from subcutaneous tissue was easily obtained and fluid harvesting was well tolerated when topical anaesthetic was used. The difference in COPi assessed by dry and wet wicks between 75 min. and 90 min. of implantation was in accordance with previous reports. The use of topical analgesia did not influence COPi and topical analgesia may make the wick technique more acceptable for subjects who dislike technical procedures, including children.Trial RegistrationClinicalTrials.gov NCT01044979

Isolation of interstitial fluid in skin during volume expansion: evaluation of a method in pigs

The ability to isolate interstitial fluid (IF) from skin would make it possible to study the microcirculation and proteins in this environment both during normal and pathophysiological conditions. Traditional IF sampling using implanted wicks suffer from low volumes with risk of contamination by local inflammatory, intracellular, and vascular proteins. To sample larger volumes of true IF, a recently described tissue centrifugation method was compared with dry and wet wicks from porcine skin under normal conditions and following volume expansion. With all three methods, volume expansion caused a significant lowering of interstitial colloid osmotic pressure as expected, and the fluid was similar to plasma when compared using size-exclusion HPLC. The centrifugation method was superior with respect to isolating larger amounts of true IF for further studies. Mass spectrometry of IF sampled with centrifugation showed that most of the proteins reflected the major plasma proteins with some tissue-specific proteins like decorin, gelsolin, and orosomucoid-1. Lumican, pigment epithelium-derived factor, and fatty acid-binding protein 4 were only identified in IF after volume expansion, possibly reflecting a local response to increased fluid filtration. Tissue centrifugation to collect IF from skin should be applicable to both clinical and experimental studies on IF balance during different pathophysiological conditions and interventions.

Capillary leakage in post-cardiac arrest survivors during therapeutic hypothermia - a prospective, randomised study

BackgroundFluids are often given liberally after the return of spontaneous circulation. However, the optimal fluid regimen in survivors of cardiac arrest is unknown. Recent studies indicate an increased fluid requirement in post-cardiac arrest patients. During hypothermia, animal studies report extravasation in several organs, including the brain. We investigated two fluid strategies to determine whether the choice of fluid would influence fluid requirements, capillary leakage and oedema formation.Methods19 survivors with witnessed cardiac arrest of primary cardiac origin were allocated to either 7.2% hypertonic saline with 6% poly (O-2-hydroxyethyl) starch solution (HH) or standard fluid therapy (Ringer's Acetate and saline 9 mg/ml) (control). The patients were treated with the randomised fluid immediately after admission and continued for 24 hours of therapeutic hypothermia.ResultsDuring the first 24 hours, the HH patients required significantly less i.v. fluid than the control patients (4750 ml versus 8010 ml, p = 0.019) with comparable use of vasopressors. Systemic vascular resistance was significantly reduced from 0 to 24 hours (p = 0.014), with no difference between the groups. Colloid osmotic pressure (COP) in serum and interstitial fluid (p < 0.001 and p = 0.014 respectively) decreased as a function of time in both groups, with a more pronounced reduction in interstitial COP in the crystalloid group. Magnetic resonance imaging of the brain did not reveal vasogenic oedema.ConclusionsPost-cardiac arrest patients have high fluid requirements during therapeutic hypothermia, probably due to increased extravasation. The use of HH reduced the fluid requirement significantly. However, the lack of brain oedema in both groups suggests no superior fluid regimen. Cardiac index was significantly improved in the group treated with crystalloids. Although we do not associate HH with the renal failures that developed, caution should be taken when using hypertonic starch solutions in these patients.Trial registrationNCT00347477.

Elevated flow rate during cardiopulmonary bypass is associated with fluid accumulation

High flow rates during cardiopulmonary bypass are assumed to increase fluid accumulation. This study aimed to determine whether two different flow rates during cardiopulmonary bypass alter the intraoperative fluid balance and extravasation rate. Sixteen pigs underwent 60 minutes of normothermic bypass, followed by 90 minutes of hypothermic bypass. A high-flow group (HF group, n = 8) had a cardiopulmonary bypass flow rate of 110 mL x kg(-1) x min(-1) and a low-flow group (LF group, n = 8) had a rate of 80 mL x kg(-1) x min(-1). Blood chemistry, hemodynamic parameters, plasma and interstitial colloid osmotic pressure, net fluid balance, plasma volume, fluid extravasation rate, and total tissue water content were measured or calculated. Results are presented as mean (standard deviation). The average net fluid balance during cardiopulmonary bypass was 1.02 (0.25) and 0.73 (0.23) mL x kg(-1) x min(-1) in the HF group and LF group, respectively (P < .05). The average fluid extravasation rate was 0.98 (0.22) and 0.77 (0.22) mL x kg(-1) x min(-1) in the HF group and the LF group (P = .07). Total water content was higher in the kidneys (P < .05) and tended to be higher in the lungs (P = .05), liver (P = .07), and brain (P = .07) of the HF group than in those of the LF group. The between-group differences in net fluid balance and fluid extravasation rate were present during the first 30 minutes of normothermic cardiopulmonary bypass. Thereafter, the values stabilized and remained similar in the two groups. Plasma volume and systemic vascular resistance differed between the groups. Cardiopulmonary bypass flow rate of 110 mL x kg(-1) x min(-1) was associated with higher positive net fluid balance and fluid extravasation rate than 80 mL x kg(-1) x min(-1). The effect was mainly observed in the initial phase of cardiopulmonary bypass.

Of mice and men; the translational physiology of a genetic form of lymphoedema

Of mice and men; the translational physiology of a genetic form of lymphoedema

Transcapillary fluid balance consequences of missing initial lymphatics studied in a mouse model of primary lymphoedema

To investigate the phenotypic consequences of a deranged lymphangiogenesis in relation to tissue fluid accumulation and the possible role of inflammation in the pathogenesis of lymphoedema, we measured determinants of transcapillary fluid filtration and inflammatory mediators in the interstitial fluid in genetically engineered Chy mice, a model for primary congenital lymphoedema (Milroy's disease). Although initial lymphatics were not present in dermis in any of the areas studied (fore paw, hind paw, thigh and back skin) interstitial fluid pressure (P(if)), measured with micropipettes, and tissue fluid volumes were significantly increased only in the areas with visible swelling - the fore and hind paw, whereas interstitial colloid osmotic pressure (COP(if)) was increased in all the skin areas examined. A volume load of 15% of body weight resulted in a more pronounced increase in P(if) as well as a four-fold increase in interstitial fluid volume in Chy relative to wild-type (wt) mice, showing the quantitative importance of lymphatics for fluid homeostasis during acute perturbations. A similar level of proinflammatory markers in interstitial fluid in early established lymphoedema (3-4 months) in Chy and wt suggests that inflammation does not have a major pathogenetic role for the development of lymphoedema, whereas a reduced level of the immunomodulatory cytokine interleukin (IL)-4 may result in a reduced immunological defence ability and thus lead to the increase in inflammatory cytokines IL-2 and IL-6 observed at a later stage (11-13 months). Our data suggest that primary lymphoedema results in a high interstitial fluid protein concentration that does not induce an interstitial inflammatory reaction per se, and furthermore shows the paramount importance of the initial lymphatics in tissue fluid homeostasis, especially during perturbations of transcapillary fluid balance.

Acute Peritoneal Dialysis in Rats Results in a Marked Reduction of Interstitial Colloid Osmotic Pressure

The aim of this study was to investigate whether the interstitial colloid osmotic pressure (COP(i)) of peritoneum is of importance for peritoneal fluid reabsorption during peritoneal dialysis (PD). For testing this hypothesis, a method to isolate interstitial fluid from the peritoneal membrane and to measure the interstitial COP(i) in the normal peritoneum and directly after the initiation of PD needed to be developed and validated. Eighteen female rats were anesthetized subcutaneously in the neck region with fentanyl-midazolam (1:1). Nylon wicks were implanted postmortem by means of a plastic catheter in the tissue just underneath the peritoneal surface. The characteristics of this fluid were compared with that isolated from wicks that were implanted in intermuscular spaces in hindlimb muscle and back subcutis. All wicks were removed after 20 min and centrifuged. The wick fluid was collected and analyzed in a colloid osmometer constructed for submicroliter samples, and interstitial fluid COP was compared with that of plasma. PD was initiated by injecting 20 ml of 3.86% glucose-containing PD fluid (Dianeal) into the peritoneal cavity, over a dwell time of 4 h. Control rats received no PD. The ratio of COP(i) to that of plasma (COP(p)) during control was 0.65 +/- 0.05 in peritoneum, 0.53 +/- 0.04 in muscle, and 0.59 +/- 0.05 in skin. After a PD dwell, the ratio was 0.29 +/- 0.03 in peritoneum, 0.54 +/- 0.08 in muscle, and 0.41 +/- 0.06 in skin. Thus, the COP ratio in peritoneum fell by 55% (P = 0.014) and in skin by 30% (P = 0.03), whereas the COP ratio in muscle was unchanged. The results suggest that acute PD results in a marked fall of the COP(i) in the peritoneal membrane, shifting the Starling equilibrium toward an absorptive state. The effect was restricted to the peritoneal membrane and, to some extent, the skin. It is speculated that the increase in peritoneal hydrostatic pressure after PD causes an increase in interstitial tissue volume, with primarily a dilution of interstitial colloids.

Model of interstitial pressure as a result of cyclical changes in the capillary wall fluid transport

Reported interstitial pressures range from –8 to +6 mm Hg in different tissues and from <–20 mm Hg in burned tissue or more than +30 mm Hg in tumors. We have tried to link interstitial pressure to the here proposed cyclical changes in the fluid transport across the capillary wall.In the presented model interstitial pressure is considered as an average of pressures in numerous pericapillary spaces. A single pericapillary pressure is a dynamic difference between the net outward (hydraulic pressure+interstitial colloid osmotic pressure) and inward (plasma colloid oncotic pressure) forces. Hence, dominating net outward forces would result in a positive pericapillary interstitial pressure, while stronger inward forces would produce negative pressures in the pericapillary space. All interruptions of blood flow leave some blood in capillaries with a normal oncotic pressure and no hydrostatic pressure that might act as a strong absorber of interstitial fluid until the blood flow is reestablished.Model assumptions for the systemic circulation capillaries include (a) precapillary sphincters can almost entirely stop the capillary flow, (b) only a minority of sphincters are normally open in the tissue, and (c) hydrostatic pressures in unperfused capillaries are similar to the pressures at their venous ends.The key proposal is that capillaries with closed precapillary sphincters along their entire length have low hydrostatic pressure of 10 to 15 mm Hg. This pressure cannot force filtration, so these capillaries reabsorb interstitial fluid from the pericapillary space along their entire length. In the open capillaries, hydrostatic pressure filtrates fluid to the pericapillary space along most of their length. Fluid enters, moves some 20 or 30 micrometers away and back to be reabsorbed at the same point. Closed periods are periods of intense fluid reabsorption, while the short open periods refill the space with fresh fluid. It can be calculated that subcutaneous tissue interstitial pressure values might develop if the closed periods are 1.14 to 2.66 times longer than the open periods. Positive interstitial pressures observed in some organs might develop if open periods are longer than the closed periods.High interstitial colloid pressure in lungs makes both perfused and unperfused capillaries absorptive, resulting in more negative values of lung interstitial pressure. The same model is used to explain interstitial pressure values in tumors, burned tissue and intestinal villi.

A model of fluid and solute exchange in the human: validation and implications

In order to understand better the complex, dynamic behaviour of the redistribution and exchange of fluid and solutes administered to normal individuals or to those with acute hypovolemia, mathematical models are used in addition to direct experimental investigation. Initial validation of a model developed by our group involved data from animal experiments lGyenge, C.C., Bowen, B D, Reed, R.K. & Bert, J.L. 1999b. Am J Physiol 277 (Heart Circ Physiol 46), H1228-H1240). For a first validation involving humans, we compare the results of simulations with a wide range of different types of data from two experimental studies These studies involved administration of normal saline or hypertonic saline with Dextran to both normal and 10% haemorrhaged subjects We compared simulations with data including the dynamic changes in plasma and interstitial fluid volumes V PL and V IT respectively, plasma and interstitial colloid osmotic pressures Π PL and Π IT respectively, haematocrit (Hct), plasma solute concentrations and transcapillary flow rates. The model predictions were overall in very good agreement with the wide range of experimental results considered Based on the conditions investigated, the model was also validated for humans We used the model both to investigate mechanisms associated with the redistribution and transport of fluid and solutes administered following a mild haemorrhage and to speculate on the relationship between the timing and amount of fluid infusions and subsequent blood volume expansion.

Resuscitation of severe thermal injury with hypertonic saline dextran: effects on peripheral and visceral edema in sheep.

Edema of tissue not directly injured by heat is a common complication after resuscitation of burn shock. Hypertonic 7.5% NaCl 6% dextran (HSD) infusion reduces early fluid requirements in burn shock, but the effects of HSD on peripheral and visceral tissue edema are not well-defined. We measured the microcirculatory absorptive pressures of burned and nonburned skin and tissue water content of skin and other tissues in anesthetized sheep after 70% to 85% total body surface area scald and resuscitation. Fluid infusion was initiated 30 minutes after injury using 10 mL/kg HSD (n = 11) or lactated Ringer's (LR) (n = 12), with infusion rates titrated to restore and maintain preburn oxygen delivery (DO2). Thereafter, both groups received LR infusions as needed to maintain DO2 until the study's end at 8 hours. Colloid osmotic pressure was measured in plasma, and combined interstitial colloid osmotic and hydrostatic pressures were measured in skin. Both treatments successfully restored DO2, but fluid requirements were less with the HSD group than with the LR group (43+/-19 mL/kg vs. 194+/-38 mL/kg, respectively, p < 0.05). The peripheral and visceral tissue water contents at 8 hours postinjury until the end of the study in both burn groups were significantly higher than in nonburn controls. However, HSD-treated sheep had significantly less water content in the colon (less 28%), liver (less 9%), pancreas (less 55%), skeletal muscle (less 21%), and nonburned skin (less 12%) compared with LR-treated sheep (p < 0.05 for each). HSD-treated sheep maintained significantly higher (3 to 5 mm Hg) plasma colloid osmotic pressure than LR-treated sheep. There were no observed differences in edema in burn skin between the two treatment groups. The early volume-sparing effect of HSD and reduction in tissue edema are likely attributed to an increased extracellular osmolarity and a better maintenance of the plasma oncotic pressure.

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.

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)

A model of human microvascular exchange: parameter estimation based on normals and nephrotics

A mathematical model is formulated and used to describe the distribution and transport of fluid and albumin in the human circulation, interstitium and lymphatics. Two transcapillary mass exchange mechanisms are investigated: a homoporous ‘coupled Starling model’, in which transcapillary albumin diffusion and convection occur within the same pathway, and a heteroporous ‘plasma leak model’, in which variations in structure and pressure are permitted along the length of the capillary. Parameters used in the transport models are determined based on statistical fitting of simulation predictions to experimental data from normal humans and nephrotic patients. The data consists of interstitial fluid volumes and interstitial colloid osmotic pressures as functions of plasma colloid osmotic pressure. Model validation is carried out based on comparison of (i) simulation predictions with experimental data used in parameter estimation, (ii) estimated transport parameters with experimentally determined values, and (iii) simulation predictions with a set of dynamic data from an albumin infusion study. While both models with their best-fit parameter estimates provide a good representation of experimental data, the drawbacks of the plasma leak model are three-fold: it requires more estimated parameters than the coupled Starling model, little experimental information exists with which to compare these parameters and, with the best fit values obtained, the plasma leak mechanism becomes insignificant. The model that employs a Starling-type exchange mechanism will therefore be favoured in future applications.

Evidence for altered transcapillary fluid balance in women with the premenstrual syndrome.

Redistribution of body fluids has been suggested as a possible pathophysiological mechanism for the premenstrual syndrome (PMS). To elucidate this hypothesis, transcapillary fluid balance was studied in ten women with well defined PMS. Wick-methods were used for measuring colloid osmotic and hydrostatic interstitial pressures on the thorax and on the leg. The capillary filtration coefficient was measured by strain gauge plethysmography. From the follicular to the luteal phase the interstitial colloid osmotic pressure on the leg was significantly reduced (mean 3.6 mm Hg, p = 0.005), whereas the interstitial colloid osmotic pressure on the thorax remained constant. The capillary filtration coefficient increased 30% (mean 5.3 x 10(-4) ml/min/100 gm/mm Hg, p = 0.04) from the follicular to the luteal phase. No change was observed in body weight. These findings indicate an instability of vascular regulation in women with premenstrual syndrome, and lend support to the hypothesis that redistribution of fluid, rather than water retention, is responsible for the subjective symptoms such as bloatedness, in the premenstrual syndrome.

Plasma Volume Regulation: Defences against Edema Formation (with Special Emphasis on Hypoproteinemia)

In hypoproteinemia, increased interstitial hydrostatic and decreased interstitial colloid osmotic pressures, together with increases in lymph flow, prevent interstitial fluid volume expansion, thus forming the edema-preventing mechanisms. Transfer of a substantial portion of the interstitial protein pool into the vascular compartment by increased lymph flow is the major edema-preventing mechanism. The increase in interstitial pressure during progressive interstitial fluid volume expansion is limited by the high compliance of the interstitium in most tissues. During hypoproteinemia low interstitial colloid osmotic pressure and high interstitial compliance permit augmented changes in plasma volume in response to rapid increases (orthostasis, venous constriction) and decreases (hemorrhage) in capillary pressure. Nevertheless, these same forces are responsible for the finding that during the relatively slow changes in sodium balance that occur during volume retention or after treatment with diuretics, the change in plasma volume is relatively small. These phenomena are illustrated by observations gathered in experimental hypoproteinemia and in patients with the nephrotic syndrome.

Increased capillary permeability for plasma proteins in oral contraceptive users

The transcapillary fluid balance was examined in eleven women before administration of a monophasic oral contraceptive (desogestrel 0.15 mg, ethinylestradiol 0.03 mg), and after three and six months of use. The interstitial colloid osmotic pressure was measured by the “wick” method, and the interstitial hydrostatic pressure by the “wick-in-needle” method in subcutaneous tissue on thorax and leg. During the six-month observation period, the following changes were observed: Plasma colloid osmotic pressure decreased (mean 1.8 mmHg, p = 0.047), as well as serum albumin (mean 5.1 g/l, p = 0.0006), total protein concentration (mean 2.8 g/l, p = 0.0006), hemoglobin (mean 0.5 g/dl, p = 0.014) and hematocrit (mean 1.8 %, p = 0.047). Blood pressure and body weight remained unchanged, but foot volume showed a significant increase. The colloid osmotic pressure gradient (plasma-interstitium) was significantly reduced. The results indicate an increase in plasma volume in addition to an increased capillary permeability to plasma proteins during oral contraceptive use. We suggest that the observed changes in transcapillary fluid balance is caused by the estrogen component of the oral contraceptive pill.