Process of critical movement of intravascular fluid into intracellular space.
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The binding in vitro of an opiate agonist, 3H-dihydromorphine, was studied using a particulate fraction obtained from rat brain homogenates and compared with that of an opiate antagonist, 3H-naloxone. The binding of 3H-dihydromorphine may be separated into two components: one a saturable component and the other nonsaturable. The saturable binding may be calculated from the differences in binding observed in the absence and presence of high concentrations of levorphanol. The use of dextrorphan results in an artifactual separation of this component, although relative stereospecificity was observed for levorphanol and dextrorphan. There were marked regional differences in the distribution of saturable 3H-dihydromorphine binding in the brain. These were primarily due to the difference in the concentration of the saturable binding sites within various brain regions. It appeared that the saturable binding sites from various brain regions had similar affinities for dihydromorphine except for the binding site from cerebral cortex which had a higher affinity. In contrast, saturable binding sites for naloxone in various brain regions had different affinities for naloxone. It appears that naloxone has at least two types of saturable binding sites, one of which is not available to dihydromorphine. This is based on observations 1) that the total concentration of saturable binding sites for naloxone was greater than that for dihydromorphine in each brain region studied irrespective of the assay medium used and 2) that unlabeled dihydromorphine inhibited the 3H-naloxone binding in striatum but failed to alter it significantly in cerebellum, whereas unlabeled naloxone reduced 3H-naloxone binding significantly in both brain regions. The difference in concentrations of saturable binding sites for naloxone and dihydromorphine was relatively small in striatum but larger in cerebellum, indicating that the saturable binding sites in cerebellum are predominantly naloxone-specific, whereas those in striatum are capable of binding both naloxone and dihydromorphine. In cerebrospinal fluid or in simulated intracellular fluid, the apparent affinity for dihydromorphine was lower and that for naloxone was higher than in Tris-HCl buffer. It is concluded that naloxone binds to dihydromorphine binding site and to another site, which has a different affinity for naloxone and is not available to dihydromorphine. Studies in which opiate receptor binding was assayed in Tris-HCl buffer may need to be re-evaluated. Further, in studies where opiate binding in vitro is assessed following pharmacologic intervention, such binding should be estimated in a relevant physiological medium rather than in Tris-HCl buffer.
Dog hearts were harvested and stored cold (0.5 degree C) for 24-hours. Cardiac arrest was induced by means of low-sodium and calcium-free cardioplegic (n = 6) or hyperkalemic cardioplegic (n = 6) solution. Nifedipine (2 micrograms/gm estimated heart weight) was added to each cardioplegic solution in two additional groups (n = 6 each). High energy phosphates (creatine phosphate and adenosine triphosphate) and catabolites (adenosine diphosphate and monophosphate, adenosine, inosine, hypoxanthine, xanthine) were determined in the myocardium before and during 24 hours of cold storage. With use of the standard hyperkalemic cardioplegic solution, breakdown of high energy phosphates was less pronounced than after the use of a low sodium, calcium-free solution: after 24 hours of cold storage myocardial ATP content was 57% of control versus 32% (p less than 0.05). The addition of nifedipine to the hyperkalemic cardioplegic solution delayed ATP breakdown during the first hours of cold storage: at 5 hours of preservation the myocardial ATP level was significantly higher (p less than 0.05) than in hearts preserved without nifedipine. Addition of nifedipine to the low-sodium, calcium-free solution did not influence catabolism of high energy phosphates significantly. It is concluded that preservation of high energy phosphates during long-term cold storage of donor hearts can be best achieved by simultaneous myocardial metabolic blockade at two specific sites: at the "fast" sodium-potassium channels by hyperkalemic depolarization and at the "slow" channels by means of calcium channel blockers.
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The mammalian brain is composed of four distinct fluid compartments: blood, cerebral spinal fluid, interstitial fluid surrounding glial cells and neurons, and intracellular fluid. Maintenance of the ionic and osmotic composition and volume of these fluids is crucial for the normal functioning of the brain. Small changes in intracellular or extracellular solute composition can dramatically alter neuronal signaling and information processing. Because of the rigid confines of the skull and complex brain architecture, changes in total brain volume can cause devastating neurological damage. As a result, it is not surprising to find that the composition and volume of brain intracellular and extracellular fluids are controlled tightly under both normal conditions and in various disease states. Osmotic and ionic balance in the central nervous system is regulated by solute and water transport across the blood-brain barrier, the choroid plexus, and the plasma membrane of glial cells and neurons. Despite its clinical and physiological significance, however, little is known about the underlying cellular and molecular mechanisms by which the central nervous system's osmotic and ionic balance is maintained. In this review, the current understanding of osmoregulation in the mammalian brain and its role in various disease processes such as hyponatremia, renal failure, and hypernatremia will be summarized. A detailed understanding of brain osmoregulatory processes represents a fundamental physiological problem and is required for the treatment of numerous disease states, particularly those encountered in the practice of nephrology.
The strong complex formations of pyridine nucleotides with mercury compounds were demonstrated in artificial intracellular fluid containing oxianions (HPO42-, HCO3-), while those in artificial extracellular fluid were considerably weaker. Dissociation constants (K) of the complexes of [MC.NADP], [MC.NADPH], [MC.NAD], [MC.NADH], [MC.adenine], and [MC.nicotinamide mononucleotide] were found to be 1.0 x 10(-4), 2.6 x 10(-5), 1.2 x 10(-4), 2.9 x 10(-5), 7.2 x 10(-6), and 3.8 x 10(-3), respectively in phosphate buffer (43 mM, pH 8.0).
OBJECTIVE: This study explored whether the increased extracellular relative to intracellular fluid (ECF/ICF) ratio in obesity might reflect osmotic effects of elevated plasma solute concentrations. DESIGN: Cross-sectional, epidemiological survey. SETTING AND SUBJECTS: The present analysis used nationally representative data from the Third National Health and Nutrition Examination Survey on community-dwelling adults (aged 40-59 years) in the US without evidence of glucose dysregulation or chronic disease (n=1285). INTERVENTION: Body mass index (BMI) was estimated from measured height and weight. Total body reactance, an index of body fluid distribution, was determined by bioelectrical impedance analysis. Plasma tonicity (the cumulative index of osmotically effective plasma solute) was estimated from plasma glucose, sodium and potassium. Sex-specific relative odds of lower reactance ( or=295 mmol/l) associated with overweight (25 or=30) were estimated using logistic regression models that controlled for sociodemographic variables, smoking, leisure-time physical activity, total energy intake, serum creatinine, plasma insulin and glucose. Multinomial logistic regression models tested for associations between weight status and specific serum solute. RESULTS: Independent of covariates, in men and women, overweight and obesity were associated with increased odds of lower reactance and hypertonicity. Overweight and obese individuals with lower reactance had significantly higher serum sodium than normal weight individuals. CONCLUSIONS: Elevated plasma solute concentrations are associated with obesity in free-living adults. Physicians and researchers should be alert to a possible link between hypertonicity and obesity. SPONSORSHIP: Grants from the NIH, Nestle Waters.
Fluid flow-induced shear stress results in a variety of morphological and metabolic changes in cultured bovine articular chondrocytes (BAC). However, the mechanism by which the flow signal is transduced into a biological response is unknown. Therefore, we investigated the effects of fluid flow on intracellular Ca2+ concentration ([Ca2+]i) in BAC. Cells loaded with fura 2 were exposed to steady and pulsatile (0.5 Hz) flow at 9, 18, and 34 ml/min in a parallel-plate flow chamber. In response to flow, there was a significant and flow rate-dependent increase in the percentage of cells showing a rise in [Ca2+]i, but no effect on the [Ca2+]i response amplitude. There was no significant difference between the [Ca2+]i responses to steady and pulsatile flow. Mean intracellular Ca2+ response values ranged between 26.2 +/- 1.6 (9 ml/min) and 38.0 +/- 6.8 nM (34 ml/min) above basal [Ca2+]i (81.3 +/- 24.1 nM, n = 90). Removal of extracellular Ca2+ or addition of Gd3+ significantly reduced the percentage of cells responding, suggesting that influx of Ca2+, possibly through mechanosensitive channels, contributes to the rise in intracellular Ca2+. Our data suggest fluid flow-induced mobilization of intracellular Ca2+ may contribute to the mechanism by which mechanical loads are transduced by chondrocytes.
Liver ischemia-reperfusion is known to be associated with free radical-mediated hepatocellular damage but alterations in hepatocellular fluid flux under these conditions are incompletely understood. Deficiency of the antioxidant glutathione, which increases the liver's susceptibility to ischemia-reperfusion injury, may exacerbate pathological fluid shifts. This study examined alterations in hepatic fluid dynamics during liver ischemia-reperfusion in glutathione-deficient and glutathione-replete rats. Normal and glutathione-deficient rats underwent liver ischemia-reperfusion. Changes in hepatic extra- and intracellular fluid were monitored by calculating extra- and intracellular conductance from liver multifrequency bioelectrical impedance measurements. Liver malonyl dialdehyde content and plasma transaminase concentrations were measured and correlated with changes in hepatic impedance. Hepatic extracellular conductance decreased during ischemia and returned toward baseline values during reperfusion in a similar fashion in both study groups. Intracellular conductance increased during ischemia in both groups and continued to rise during the initial phase of reperfusion before falling toward normal. Glutathione-deficient rats had a significantly higher intracellular conductance during early reperfusion compared to controls. Glutathione-depleted rats also had higher serum transaminases and liver malonyl dialdehyde content following reperfusion. Intracellular and extracellular conductance were significantly correlated with hepatic malonyl dialdehyde content. We conclude that (1) liver ischemia-reperfusion results in movement of fluid from the extracellular to intracellular space with hepatocellular swelling; (2) glutathione deficiency accentuates hepatocyte swelling following ischemia-reperfusion; and (3) changes in extra- and intracellular fluid are related to the severity of membrane damage.(ABSTRACT TRUNCATED AT 250 WORDS)
Lung water (LW) reflects the water content of the lung interstitium. Because hemodialysis patients have expanded total body water (TBW) they may also have increased LW. Hypertonic saline promotes a flux of water from lung to blood, which is measured by ultrasound flow probes on hemodialysis tubing. The volume of flux is an indirect measure of LW. Our purpose was to determine the feasibility and reproducibility of LW derived with ultrasound velocity dilution, to determine the effect of ultrafiltration on LW in stable hemodialysis patients, and to compare changes in LW with fluid compartment shifts using bioimpedance. Lung water, cardiac output, total body water, and extracellular and intracellular fluid volumes were measured in 24 stable hemodialysis patients at the beginning of hemodialysis and after ultrafiltration. The LW values at the beginning of hemodialysis (298.8 +/- 90.2 ml or 3.67 +/- 1.47 ml/kg) fell during hemodialysis (250.8 +/- 55.8 ml or 3.12 +/- 0.96 ml/kg; p < 0.05), as did TBW and extracellular fluid volumes (p < 0.001). Cardiac output, cardiac index, and central blood volume also decreased significantly with ultrafiltration (p < 0.005, p < 0.005, and p < 0.01, respectively). Results showed that stable hemodialysis patients have higher specific LW values (3.67 ml/kg) than the normal population (2 ml/kg) and ultrafiltration produces a significant decline in LW values.
Glycerol solutions are a safe, effective means to achieve a long-term state of hyperhydration. The effects of glycerol-induced hyperhydration (GIH) on the total body water (TBW), extracellular fluid (ECF), plasma volume (PV), intracellular fluid (ICF), and interstitial fluid (ISF) were investigated in the rat. Ten rats were intragastrically administered either 20 ml/kg of water or 5% glycerol. The TBW, ECF, and PV were determined by 3H2O, 14C-inulin and dye dilution, respectively at 2 h postingestion. Urine volumes and fluid retention were measured throughout the experiment. Fluid retention was increased by 50% with the 5% glycerol solution when compared to water. When the fluid compartment data at 2 h are expressed in terms of percent of body weight, the TBW and ICF of the glycerol-treated rats exceeds that of the water-treated rats, and the values for the ECF, PV, and ISF were similar after the glycerol solution and water regimens. Glycerol solutions appear to have a greater effect in expanding TBW and ICF than equal volumes of water.
The effect of 1,4,8,11-tetraazacyclotetradecane (Cyclam), triethylenetetramine (TETA), reduced glutathione (GSH), ethylenediamine tetraacetic acid (EDTA), cyclohexanediamine tetraacetic acid (CDTA), diethylene triamine pentaacetic acid (DTPA), and hydroxyethylenediamine triacetic acid (HEDTA) on the alleviation of nickel-induced biochemical and trace-metal alterations in serum, liver, and kidney of nickel-treated rats was studied. The lipophilic chelating agents Cyclam and TETA exhibited a higher order of effectiveness in alleviating nickel-induced alterations compared to EDTA, CDTA, DTPA, and HEDTA, the hydrophilic chelating agents. The higher efficacy of lipophilic agents may be due to their ability to bind to nickel present in extracellular fluid as well as in intracellular fluid, while the hydrophilic agents may bind only to nickel present in extracellular fluid. Our data also suggest that the efficacy of Cyclam to ameliorate nickel-induced alterations is exceptionally high.
This study examined the ability of bullfrogs to correct a non-respiratory acidosis by renal and cutaneous mechanisms. Acidosis was induced by intravascular infusions of HCl (3 mmole/kg) or NH4Cl (4 mmole/kg). The acid load was removed primarily by increased renal excretion of NH4+, while urine pH and titratable buffer acid excretion changed little. Acid loading resulted in an increase in cutaneous permeability, shown by large ion losses and elevated water uptake across the skin. It is concluded that infused mineral acids were immediately buffered by the extracellular fluids, moved rapidly into the intracellular fluid compartment, and only later were slowly cleared.
Erythromycin is a macrolide that acts by inhibiting the translocation reaction during protein synthesis. Erythromycin is inactive against the Enterobacteriaceae and Pseudomonas aeruginosa except under alkaline conditions. Erythromycin is active against most gram-positive bacteria; some gram-negative bacteria, including Neisseria, Bordetella, Brucella, Campylobacter, and Legionella; and Treponema, Chlamydia, and Mycoplasma. The emergence of resistance to erythromycin is closely associated with its use and is often plasmid mediated. After its oral or parenteral administration, erythromycin diffuses readily into intracellular fluids and is actively concentrated intracellularly by polymorphonuclear leukocytes and alveolar macrophages.
OBJECTIVE: To determine the relative distribution of fluid within the extracellular fluid volume (ECFV) after infusing either normal saline or 5% albumin in septic, critically ill patients. DESIGN: Prospective, randomized, unblinded, interventional study. SETTING: Intensive care unit in a 450-bed, tertiary care, teaching hospital. PATIENTS: Septic, critically ill patients (n = 18). INTERVENTIONS: Infusion of either normal saline or 5% albumin to a hemodynamic end point determined by the patient's clinician. MEASUREMENTS AND MAIN RESULTS: Plasma volume (PV), ECFV, cardiac index, and arterial oxygen content were measured immediately before (baseline) and after each fluid infusion. PV and ECFV were measured by dilution of 131I-albumin and 35S sodium sulfate, respectively. Interstitial fluid volume (ISFV) was calculated as ECFV - PV. Baseline values for PV, ISFV, ECFV, and oxygen delivery index did not differ between treatment groups. Infusion of normal saline increased the ECFV by approximately the volume infused, and the expansion of the PV to ISFV was in a ratio of 1:3. Infusion of 5% albumin increased the ECFV by double the volume infused, with both the PV and ISFV expanding by approximately equal amounts. Oxygen delivery index did not increase after either infusion due to the effect of hemodilution. CONCLUSION: Expansion of the ECFV in excess of the volume of 5% albumin infused suggests that fluid may move from the intracellular fluid volume to the ECFV in septic patients who receive this fluid.
This article discusses the dissolution of mineral fibers in simulated physiological fluids (SPF), and the parameters that affect the solubility measurement in a dynamic test where an SPF runs through a cell containing fibers (Scholze and Conradt test). Solutions simulate either the extracellular fluid (pH 7.6) or the intracellular fluid (pH 4.5). The fibers have various chemical compositions and are either continuously drawn or processed as wool. The fiber solubility is determined by the amount of SiO2 (and occasionally other ions) released in the solution. Results are stated as percentage of the initial silica content released or as dissolution rate v in nm/day. The reproducibility of the test is higher with the less soluble fibers (10% solubility), than with highly soluble fibers (20% solubility). The influence of test parameters, including SPF, test duration, and surface area/volume (SA/V), has been studied. The pH and the inorganic buffer salts have a major influence: industrial glasswool composition is soluble at pH 7.6 but not at pH 4.5. The opposite is true for rock- (basalt) wool composition. For slightly soluble fibers, the dissolution rate v remains constant with time, whereas for highly soluble fibers, the dissolution rate decreases rapidly. The dissolution rates believed to occur are v1, initial dissolution rate, and v2, dissolution rate of the residual fibers. The SA of fibers varies with the mass of the fibers tested, or with the fiber diameter at equal mass. Volume, V, is the chosen flow rate. An increase in the SA/V ratio leads to a decrease in the dissolution rate.(ABSTRACT TRUNCATED AT 250 WORDS)
One of the main causes of hypotension during extracorporeal renal replacement therapy is an insufficient substitution of the ultrafiltrated plasma water by tissue water. To investigate the fluid balance and its effects on hypotension in dialysed patients, the following variables were studied: intracellular fluid volume (IFV) and extracellular fluid volume (EFV), blood volume (BV) and blood pressure. IFV and EFV were measured by means of non-invasive electrical conductivity measurements using four electrodes round the leg. Fifteen haemofiltration (HF) and 15 haemodialysis (HD) patients were studied. The latter group was dialysed in three ways: (1) conventionally, i.e. with dialysate sodium of 138 mmol/l (HD) (2) with a variable dialysate sodium (first half: 138 mmol/l; second half: 146 mmol/l) (HDS), and (3) with the same variable dialysate sodium and an ultrafiltration profile (two-thirds was withdrawn during the first half of treatment, the remainder during the second half) (HDSU). Hypotension frequency was less during HDS, HDSU, and HF compared to HD. This was caused by a more stable blood volume due to a better refill. During HD a fluid shift occurred from the EC to the IC compartment. The use of a high sodium dialysate concentration led to a transcellular fluid shift in the opposite direction. This fluid shift increased the refill, thereby stabilising blood volume. HF gave a better refill than HDS and HDSU, probably due to a reduced urea clearance.
The cell volume, cell water, intracellular ionic concentrations, and transmembrane potential of rat alveolar macrophages were determined. The measurements were made on cells which had been separated from the medium by centrifugation through dibutyl phthalate in order to greatly reduce the trapped extracellular space. The mean cell volume of the alveolar macrophages is 1,525 cubic microns and 72% of this volume is water. The intracellular fluid is high in Na+ (97 mM) and lower in K+ (50 mM) and the intracellular Cl- concentration in 64 mM. The transmembrane potential, as measured from the equilibrium distribution of tritiated triphenylmethyl phosphonium and by using the fluorescent probe, Di-S-C3(5), is approximately -37 millivolts. Neither Na+, K+, nor Cl- is distributed at equilibrium. However, the K+ permeability of alveolar macrophage membranes appears to be greater than Na+ permeability.