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Extracellular fluid volume and central circulation after long lasting exercise and dehydration in conscious dogs.

Two aspects of the recovery period after endurance exercise were investigated: a) the fluid distribution between the intra- and extravascular parts of the extracellular fluid volume (ECFV) induced by exercise dehydration, b) the cardiovascular response pattern [blood pressure (BP), heart rate (HR), cardiac output (CO), total peripheral resistance (TPR), and central venous pressure (CVP)] to the heat load which results from the preceding exercise. Seven conscious dogs performed endurance exercise in a cool environment (16 degrees C) on a horizontal treadmill till 4% of the body weight was lost. It was found that about 70% of the total fluid loss of the body came from intracellular water. During exercise sodium and chloride concentrations rose by 6 mMol and 7 mMol respectively (P less than 0.005) and remained elevated throughout the early recovery period indicating a fluid loss of about 100-200 ml out of the ECFV. Direct measurements of the ECFV as sulfate space confirmed these values. Since the plasma volume remained unchanged, this fluid loss was carried totally by the interstitial fluid volume. Immediately after exercise body temperature was elevated by 1.5 degrees C and returned towards control within 90 min. Cardiac output was above control level for 2 h after the end of exercise, at first due to an increased HR and thereafter to an elevated stroke volume (SV) (P less than 0.02). CVP and TPR were below control levels for at least 2 h (P less than 0.01). A linear correlation was found between CVP and TPR. A close correlation existed between the body temperature and the cardiovascular parameters. It can be concluded that even long after exercise the cardiovascular system has to serve thermoregulatory needs.

Animals↗

[Extracellular fluid, plasma and interstitial volume in cirrhotic patients without clinical edema or ascites].

Extracellular fluid volume (E.C.F.) and plasma volume (P.V.), were measured with sodium sulfate labeled with 35I and 131I human serum albumin, respectively, by the dilution technique in control subjects and in cirrhotic patients without clinical ascites or edema, renal or hepatic failure, gastrointestinal bleeding or diuretics. Results are expressed as mean +/- DS in both ml/m2 and ml/kg. In normal subjects E.C.F. (n = 8) was 7,533 +/- 817 ml/m2 (201.3 +/- 182 ml/kg), P.V. (n = 11) 1,767 +/- 337 ml/m2 (47.2 +/- 9.3 ml/kg), and interstitial fluid (I.S.F.) (n = 7) 5,758 +/- 851 ml/m2 (Table 2). In cirrhotic patients E.C.F. (n = 11) was 10,318 +/- 2,980 ml/m2 (261.7 +/- 76.8 ml/kg), P.V. (n = 12) 2,649 +/- 558 ml/m2 (67.7 +/- 15.6 ml/kg) and I.S.F. (n = 11) 7,866 +/- 2,987 ml/m2 (Table 3). Cirrhotic patients compared with normal subjects have hypervolemia due to a significant E.C.F. and P.V. expansion (p less than 0.02 and less than 0.001 respectively) (Fig. 1). Reasons for E.C.F. and P.V. abnormalities in cirrhotic patients may reflect urinary sodium retention related to portal hipertension which stimulates aldosterone release or enhanced renal tubular sensitivity to the hormone. However, it is also possible that these patients, in the presence of hypoalbuminemia (Table 1), have no clinical edema or ascites due to increased glomerular filtration, suppressed release of vasopressin, increased natriuretic factor, and urinary prostaglandin excretion, in response to the intravascular expansion, all of which increased solute and water delivery to the distal nephron and improved renal water excretion. We conclude that in our clinical experience cirrhotic patients without ascites or edema have hypervolemia because of a disturbance in E.C.F.

Adult↗

Extracellular fluid and its proteins: dehydration, shock, and recovery.

This review highlights characteristics of extracellular fluid (ECF) that are often overlooked. ECF has, in addition to plasma and interstitial fluid (ISF) surrounding cells, a third large compartment, the ISF of skin and connective tissue. This acts as a reservoir that gives up ECF to plasma volume (PV) in order to sustain circulation in the event of either shock or dehydration. While Starling forces drive filtration, ECF is returned to PV more by lymph and less by Starling forces than previously appreciated. Lymph return to PV is dependent on physical activity and muscle contraction to overcome gravity. Regional change in metabolic rate alters the need for oxygen and nutrients that is met by a regional increase in capillary blood flow. Blood flow is controlled by vasoactive compounds released in response to a drop in PO(2); these relax capillary smooth muscle to increase blood flow and delivery of oxygen and nutrients. Plasma proteins, including albumin, are filtered into the interstitium through larger pores than those filtering ECF. The rate of protein filtration is set by size and charge of these larger endothelial pores and by size and charge of proteins. Charge of these pores, hence albumin permeability, is regulated by many of the same vasoactive compounds that control capillary flow. As a consequence, in response to gravitational stress and other forms of shock that reduce effective circulation, albumin as well as ECF is rapidly shifted from plasma and sequestered in ISF. When this has occurred, as in burn shock, restoration is better effected by generous expansion of ECF with Ringer's solution alone, rather than with Ringer's solution supplemented with human serum albumin or other colloid. Restoring both PV and ISF volume restores lymph circulation and returns sequestered albumin to PV.

Blood Proteins↗

Compartmentalization of pseudorabies virus and subvirion components in BHK-21 cells and in the extracellular fluid.

The intracellular and extracellular localization of pseudorabies virions and subvirion components was determined at various stages in the replicative cycle. It was discovered that infectious pseudorabies virus appears first in the nucleus of the infected cell early in the infectious cycle but later accumulates in the cytoplasm. Subvirion components (nucleoids and nucleocapsids) are restricted to the nucleus, and only the complete virion is released from the infected cell.

Animals↗

Simultaneous analysis of nitrite, nitrate and the nicotinamide nucleotides by capillary electrophoresis: application to biochemical studies and human extracellular fluids.

A simple but rapid capillary electrophoresis method was developed for the measurement of nitrite and nitrate in human extracellular fluids and other aqueous solutions. The capabilities of the method were demonstrated by the measurement of endogenous nitrite and nitrate in plasma and serum samples from healthy volunteers, and serum and synovial fluid samples from rheumatoid arthritis patients. Furthermore, this method was used to simultaneously measure nicotinamide adenine dinucleotide, reduced (NADH), nicotinamide adenine dinucleotide (NAD+), nitrite, and nitrate, when studying the nitrite reductase activity of xanthine oxidase. The stability of nitrite was also investigated and it was found that when whole blood was spiked with nitrite and then processed, the nitrite was more stable in the plasma than in the serum. Our findings may help to explain the variations in basal nitrite concentrations reported in the literature.

Body Fluids↗

Effect of alterations in extracellular fluid volume on urinary kallikrein in the conscious rat.

The effect of alterations in extracellular fluid volume (ECV) and solute concentration on excretion of urinary kallikrein was examined in conscious Sprague-Dawley rats. Animals were given infusions of either dextrose and water, saline, or albumin according to a variety of protocols. These were designed to evaluate possible relationships between excretion of kallikrein, volume, sodium, and potassium. A reproducible pattern of kallikrein excretion was noted in all volume expanded groups. This consisted of a short lived increase during the initial hour of expansion with a subsequent fall to lower levels than baseline and a gradual recovery. To define the role of aldosterone in these studies, an adrenalectomized group and a group of appropriately prepared sham controls were expanded with saline. Adrenalectomy did not effect this pattern. We postulate a tubular "washout" phenomenon as the etiology of these observations. Results of these studies fail to demonstrate a consistent relationship between urinary volume, sodium, or potassium and the simultaneous amount of kallikrein found in the urine.

Adrenal Glands↗

The generation of nerve impulses in mammalian axons by changing the concentrations of the normal constituents of extracellular fluid.

1. Experiments have been performed to determine what changes in normal constituents of extracellular fluid are necessary to generate action potentials in mammalian axons. 2. Single and multifibre preparations of rat spinal roots were tested with Krebs solutions in which Na+, K+, Ca2+, Mg2+, pH, PCO2 or osmotic pressure were varied. 3. [Ca2+] below 1.0 mM produced impulses in all preparations. Lowering [Mg2+] did not generate any impulses but did enhance the response to low [Ca2+]. 4. Increasing [Na+] or [K+] caused excitation in some of the multifibres; increased [Na+] evoked 'off' responses in two single fibre preparations. The response to low [Ca2+] was enhanced by increasing [Na+] and depressed by increasing [K+]. 5. Increasing the osmotic pressure (with glucose) did not generate impulses and depressed the response to low [Ca2+]. 6. Changing the pH of Krebs solution did not generate impulses, but modified the response to other stimuli. The response to low [Ca2+] was increased as pH increased from pH 7.4 to 8.2, and decreased with pH in the range pH 7.4--6.2. 7. Altering pCO2 did not have any effect on the responses to low [Ca2+] unless pH also changed.

Action Potentials↗

Extracellular fluid volume and composition changes during sodium pentobarbitone anaesthesia in the dog.

Serial measurements of extracellular fluid (ECF), and plasma volumes were evaluated in dogs before and during general anaesthesia with sodium pentobarbitone and under controlled conditions of arterial pH, pO2, pCO2, and blood pressure. Sodium pentobarbitone anaesthesia caused an early, significant rise in ECF volume with a fall in haematocrit, plasma protein, and plasma potassium concentrations. Plasma osmolality and sodium concentrations were unchanged. The lack of change in ECF sodium concentration suggests that the total ECF sodium content increased in parallel with the expansion of this compartment. Sodium bound to macromolecules in the interstitial space or to bone is suggested as a possible source of sodium ions. It is unlikely that intracellular sodium stores contribute to a significant extent in these changes. During prolonged anaesthesia plasma volume progressively increased while total ECF volume returned towards control values. This work clarifies previous observations and suggests that major fluid movements occur during sodium pentobarbitone anaesthesia primarily associated with altered cell membrane properties and generalised haemodynamic changes.

Anesthesia, General↗

Derivation of extracellular fluid volume fraction and equivalent dielectric constant of the cell membrane from dielectric properties of the human body. Part 2: A preliminary study for tracking the progression of surgical tissue injury.

A study is conducted to determine whether the extracellular fluid (ECF) volume fraction and equivalent dielectric constant of the cell membrane epsilon m, derived from the dielectric properties of the human body can track the progression of surgical tissue injury. Frequency-dependent dielectric constants and electrical conductivities of body segments are obtained at surgical (trunk) and non-surgical sites (arm and leg) from five patients who have undergone oesophageal resections, before and at the end of surgery and on the day after the operation. The ECF volume fraction and the equivalent epsilon m of body segments are estimated by fitting the dielectric data for body segments to the cell suspension model incorporating fat tissue, and their time-course changes are compared between body segments. By the day after the operation, the estimated ECF volume fraction has increased in all body segments compared with that before surgery, by 0.13 in the arm, 0.16 in the trunk and 0.14 in the leg (p < 0.05), indicating postoperative fluid accumulation in the extracellular space. In contrast, the estimated equivalent epsilon m shows a different time course between body segments on the day after the operation, characterised by a higher change ratio of epsilon m of the trunk (1.34 +/- 0.66, p < 0.05), from that of the arm (0.66 +/- 0.34) and leg (0.61 +/- 0.11). The results suggest that the equivalent epsilon m of a body segment at a surgical site can track pathophysiological cell changes following surgical tissue injury.

Aged↗

Effects of furosemide on plasma volume and extracellular fluid volume in horses.

The effects of IV administered furosemide upon plasma volume (PV) and extracellular fluid volume were determined in horses at rest and after exercise. Serum sodium, potassium, chloride, and osmolality determinations were made. Furosemide caused a significant (P less than 0.05) decrease in PV and serum potassium concentrations in resting horses only. Furosemide's effects upon PV and electrolytes were evident longer than its hemodynamic effects.

Animals↗

In vivo release of interleukin-1 beta into hypothalamic extracellular fluid in rats: effects of repeated sampling.

Interleukin-1 beta (Il-1 beta) concentrations in extracellular fluid (ECF) withdrawn at 10-min intervals through a push-pull cannula (PPC) located in the hypothalamus were studied in freely behaving male rats for 1 h at 24 and 72 h and again at 7 days after PPC implantation. Il-1 beta concentrations in ECF were similar in the latter. However, when ECF was sampled at 3 h and again 7 days after PPC implantation, Il-1 beta concentrations were greatly elevated at 7 days when compared to all other intervals. These results demonstrate how the relationships between Il-1 beta measured in ECF and the conditions of measurement appear to be integral parts of a whole intracerebral system: cytokine concentrations appear to be inextricably bound to intrahypothalamic conditions created by the sampling device presence and frequency of use.

Animals↗

Modification of the serum bromide assay for the measurement of extracellular fluid volume in small subjects.

Serum bromide has been used in the past to measure extracellular fluid volume in infants. In this report, a modification and refinement of a previously described spectrophotometric assay suitable for determining bromide levels in blood is presented. The assay involves sample deproteinization with perchloric acid followed by spectrophotometric analysis of the complexes formed by the reaction between sodium bromide and gold chloride. Linear standard curves were obtained by diluting 1:2 with pooled serum at the following bromide concentrations: 10, 20, 30 and 40 mg%. Intra- and interassay variation using this technique was extremely small (n = 6, correlation coefficient, 0.995, and n = 5, correlation coefficient, 0.988, respectively). For toxicological analysis, a linear standard curve was derived from sodium bromide standards at the following concentrations: 40, 60, 80, and 100 mg%. The reproducibility and reliability of this assay have been excellent and the correlation with neutron activation analysis was excellent. The assay is easily adapted for the analysis of large numbers of samples, is easy to perform, and requires only small sample volumes.

Age Factors↗

Ventral medullary extracellular fluid pH and PCO2 during hypoxemia.

We designed experiments to study changes in ventral medullary extracellular fluid (ECF) PCO2 and pH during hypoxemia. Measurements were made in chloralose-urethan-anesthetized spontaneously breathing cats (n = 12) with peripherial chemodenervation. Steady-state measurements were made during normoxemia [arterial PO2 (PaO2) = 106 Torr], hypoxemia (PaO2 = 46 Torr), and recovery (PaO2 = 105 Torr), with relatively constant arterial PCO2 (approximately 44 Torr). Mean values of ventilation were 945, 683, and 1,037 ml/min during normoxemia, hypoxemia, and recovery from hypoxemia, respectively. Ventilatory depression occurred in each cat during hypoxemia. Mean values of medullary ECF PCO2 were 57.7 +/- 7.2 (SD), 59.4 +/- 9.7, and 57.4 +/- 7.2 Torr during normoxemia, hypoxemia, and recovery to normoxemia, respectively; respective values for ECF [H+] were 60.9 +/- 8.0, 64.4 +/- 11.6, and 62.9 +/- 9.2 neq/l. Mean values of calculated ECF [HCO3-] were 22.8 +/- 3.0, 21.7 +/- 3.3, and 21.4 +/- 3.1 meq/l during normoxemia, hypoxemia, and recovery, respectively. Changes in medullary ECF PCO2 and [H+] were not statistically significant. Therefore hypoxemia caused ventilatory depression independent of changes in ECF acid-base variables. Furthermore, on return to normoxemia, ventilation rose considerably, still independent of changes in ECF PCO2, [H+], and [HCO3-].

Acid-Base Equilibrium↗

Saturable distribution of tacrine into the striatal extracellular fluid of the rat: evidence of involvement of multiple organic cation transporters in the transport.

The kinetics and mechanism by which tacrine is distributed in the rat brain were examined. Tacrine levels in plasma and striatal extracellular fluid were used to evaluate the pharmacokinetics of this process. The K(D,brain) was decreased with the dose for tacrine, indicating that the distribution to the brain is saturable. The uptake of organic cations such as choline, 1-methyl-4-phenylpyridinium (MPP), tetraethylammonium (TEA), and carnitine was inhibited by the addition of tacrine to cultures of mouse immortalized brain capillary endothelial cells. In addition, the apical to basal transport and basal to apical transport of tacrine were inhibited by the addition of organic cations to cultures of LLC-PK1 cells, suggesting that tacrine transport across the blood-brain barrier (BBB) is mediated by organic cation transport system(s). Consistent with the in vitro results, a standard reverse transcription-polymerase chain reaction procedure was able to amplify the message of mOCT2 and mOCTN2, but not mOCT1, in MBEC4 (mouse brain microvessel endothelial cell line 4) cells. Similarly, mRNAs for rOCT2 and rOCTN2 were present in representative rat brain samples. To determine whether OCT2 and/or OCTN2 transport tacrine, these transporters were cloned and then transfected in SK-HEP1 and HEK 293 cells. The uptake of choline, MPP, and TEA was inhibited by the presence of tacrine in rOCT2-expressing SK-HEP1 cells, whereas the uptake of carnitine was inhibited by the presence of tacrine in rOCTN2-expressing HEK 293 cells. Collectively, these observations suggest that the transport of tacrine across the BBB is mediated, at least in part, by multiple organic cation transport systems in rats.

Animals↗

Measurement of extracellular fluid volume and blood volume in sheep.

Methods are described for the simultaneous measurement of extracellular fluid volume (ECFV) and plasma volume (PV) in sheep using dilution of 82Br (as sodium bromide) and 131I-labelled ovine gamma globulin. Following injection of 82Br (100 micronCi), equilibrium in blood was reached after 3 h at which time only 4% of the injected dose was in rumen water. The ECFV was measured as the mean of the 2- and 3-h bromide space after correction for the relative water content of plasma, the Gibbs-Donnan factor and the loss of 82Br into red blood cells. 131I-labelled ovine gamma globulin (20 micronCi) was injected after the 3-h 82 Br space was obtained and blood samples were taken at 10, 20, 30 and 40 min. In 16 determinations in 11 sheep (25-47 kg body weight) the mean (+/- s.e.m.) ECFV was 9112 +/- 289 ml (or 245 +/- 9 ml/kg). The mean PV for 16 observations in 11 sheep measured together with ECFV was 1597 +/- 62 ml (or 42-8 +/- 1-8 ml/kg). Although there was no relationship between body weight and PV there was a significant correlation between ECFV and body weight and also significant negative correlations between body weight and ECFV or PV when these were expressed as a function of body weight. The variation in ECFV measured on four occasions over 7-10 days in four sheep was 3-5% (range 2-6-4-6%). For PV measured in two animals on two consecutive days at the same time as ECFV the coefficient of variation was 1-5 and 2-1%. Acute sodium depletion (250-670 mmol) by parotid duct cannulation in three sheep resulted in a fall in ECFV which would account for only 15-20% of the sodium deficit. The remainder is presumably derived from ruminal sodium stores.

Animals↗

Studies on the ultrastructure of Bordetella pertussis. I. Morphology, origin, and biological activity of structures present in the extracellular fluid of liquid cultures of Bordetella pertussis.

Two distinct particles have been recognized in the extracellular fluid of B. pertussis cultures. Both appeared to arise from the surface (cell wall) of the organism. One of these, a membranous particle, seemed to derive from long projections on the organism composed of the outer membrane of the cell wall. The second particle, a fine filament, was not readily comparable with any previously described bacterial structure. The two particles could be separated from each other by gradient centrifugation in CsCl. Lymphocytosis-promoting factor and histamine-sensitizing activity were only associated with fractions containing the fine filaments.

Animals↗