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Regional perfusion, oxygen metabolism, blood volume and immunoglobulin G accumulation at focal sites of infection in rabbits.

Infection causes remarkable changes in extracellular fluid volume, blood flow and oxygen consumption in the region of the lesion. To determine the sequence and magnitude of these changes, we performed serial scintigraphic measurements in 10 rabbits with experimental Escherichia coli abscesses. Positron emission tomography with C15O2, 15O2 and 11CO was used to measure regional blood flow, oxygen extraction (OEF) and blood volume; extracellular fluid volume was evaluated by single photon scintigraphy with indium-111 immunoglobulin G (IgG). Images were recorded following tracer administration at 1 and 7-10 days after infection. At the first imaging time, blood flow to infected muscle had increased by 40% compared with control sites (7.4 +/- 0.6 to 10.8 +/- 3.8 ml/min.100 g), OEF had decreased from 55% +/- 34% to 45% +/- 14%, and the infected-to-contralateral (I/C) ratio of IgG had increased to 3.34 +/- 1.85. At the later imaging time, flow had increased by almost threefold compared with day 1 (29.4 +/- 9.8 ml/min.100 g), OEF had decreased to 29% +/- 14%, and the I/C ratio for IgG had remained constant. Although OEF fell, oxygen delivery (OEF x flow) increased from 4.07 ml/min (control value) to 4.86 ml/min on day 1 and 8.64 ml/min on days 7-9. The infected-to-contralateral (IC) ratio of 15O2/C15O2 was 0.74 +/- 0.15 on day 1 and 0.77 +/- 0.10 at 7-9 days. These studies indicate that expansion of the extracellular fluid volume increases early in the evolution of the infection and exceeds changes in regional perfusion and oxygen delivery.

Animals↗

Assessing errors in the determination of base excess.

UNLABELLED: We compared estimates for base excess of extracellular fluid (BE(ecf); mmol/L) obtained in five clinically used blood gas analyzers: AVL Compact 2 (Roche Diagnostics, Mannheim, Germany), Ciba-Corning 860 (Bayer Diagnostics, Fernwald, Germany), IL 1620 (Instrumentation Laboratories, Lexington, MA), Stat Profile Ultra (Nova Biomedical, Waltham, MA), and ABL 510 (Radiometer, Copenhagen, Denmark). A total of 134 measurements per analyzer were obtained in arterial and venous blood samples from 10 patients undergoing cardiac surgery and 65 measurements per analyzer in venous blood samples from 2 healthy volunteers. The blood samples were equilibrated in a tonometer with gases of known composition (37 degrees C). Additional theoretical studies were performed to evaluate the relationship between pH and calculated BE(ecf) value (with varied PCO(2)) using the formulas of the various analyzers. The standard deviations of repeated measurements were 0.24 mmol/L for ABL 510 and approximately 0.45 mmol/L for the other 4 analyzers. The maximal systematic difference between the average of all measurements of each analyzer was 3.7 mmol/L; this was primarily attributable to differences in measuring pH, and, to a lesser extent, to differences in calculation and determination of PCO(2). Comparison of the results from samples with different oxygen saturation showed that the relative alkalinity of deoxygenated hemoglobin (Haldane effect) can also influence the determinations of BE(ecf). IMPLICATIONS: A clinically useful way to quantify nonrespiratory disturbances of the acid-base balance is calculation of the base excess of extracellular fluid by using blood gas analyzers. In this study, we found significant variability in estimates of base excess of extracellular fluid obtained with five analyzers from different manufacturers. This variability is attributable to multiple factors, including lack of correction for deoxygenated hemoglobin (Haldane effect).

Acid-Base Equilibrium↗

Normal renal tubular response to changes of sodium intake in hypertensive man.

In a comparative study the influence of changes in dietary sodium intake on blood pressure, renal function, extracellular fluid volume, the renin-angiotensin-aldosterone system and plasma concentrations of arginine vasopressin, atrial natriuretic factor and cyclic guanosine monophosphate (GMP) was investigated in 12 patients with essential hypertension and in 10 normotensive controls. The subjects were studied after 4 days on a low (50 mmol/day), medium (180 mmol/day) or high (380 mmol/day) sodium intake. Renal sodium handling was assessed by simultaneous measurements of 51Cr-ethylenediaminetetraacetic acid (EDTA), lithium and sodium clearances. Identical values for the extracellular fluid volume, glomerular filtration rate and proximal and distal tubular resorption rates of sodium and water were found in the hypertensive patients and the controls at all three levels of sodium intake. In both groups, raising the sodium intake from low to high significantly increased 51Cr-EDTA and lithium clearance (an indirect measure of end-proximal fluid delivery), with intermediate values for the medium-sodium diet. The estimated values of fractional proximal and distal sodium resorption decreased when sodium intake was raised; the absolute proximal sodium resorption rate did not change, whereas the absolute distal sodium resorption rate as well as the extracellular fluid volume and sodium clearance increased. Blood pressure and the heart rate were unaffected by sodium intake. In both hypertensives and controls, plasma concentrations of active renin, angiotensin II and aldosterone decreased with increasing sodium intake, arginine vasopressin did not change, and atrial natriuretic factor and cyclic GMP increased.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Regulation of the transport of immunoglobulin G into the male rat reproductive tract.

The net movements of IgG in the rat testis and epididymis were studied using physiological techniques in conditions of anticipated subnormal organ concentrations of testosterone (T). The volume of extracellular fluid accessible to IgG per gram whole testis (Veq, microliter/g) did not change but that per gram interstitial tissue decreased in intact rats treated with T to suppress gonadotrophin secretion. Estimates of surface areas of the exchange vessels (S, cm2/g whole tissue) did not change in any of the organs studied. The speed at which equilibrium between tissue extracellular fluid and serum was reached (magnitude of K, min-1), lymph flow (QL, microliter/g/min) and estimates of microvascular permeability (P, nm/min) to IgG decreased in the testis of T-treated intact rats. In these animals, magnitude of K and P were higher than normal in the cauda. After castration, magnitude of K and P decreased to near zero in the caput and corpus regions. The changes in magnitude of K and P due to castration could partly be prevented by T supplementation in the caput, but not in the corpus, where Veq was supra-normal after T treatment. This difference in endothelial response between caput and corpus indicates differences in control of endothelium and epithelium along the length of the epididymal duct. In the testis of efferent duct-ligated (EDL) rats, P was lower than that in the intact rats, whereas in the corpus epididymidis of EDL rats, Veq and P were higher than normal. The supra-normal Veq values in the corpus epididymidis of EDL and castrated T-treated rats suggest that the epithelial barrier leaks in the corpus when luminal testosterone is low. It is concluded that during testosterone administration to normal rats, the testicular and epididymal epithelial barrier remains intact, that trans-endothelial transport of IgG and extracellular fluid volume decrease in the testicular interstitium and that in conditions of low serum T, the endothelium of microvessels in the caput and corpus epididymidis forms a barrier to IgG.

Animals↗

Extracellular glutathione peroxidase is secreted basolaterally by human renal proximal tubule cells.

Extracellular glutathione peroxidase (eGPx) is a secreted selenoenzyme with GPx activity. eGPx protein and activity are found in blood plasma and other extracellular fluids. eGPx in plasma is predominantly derived from the proximal tubules of kidneys in humans. Two types of human proximal tubule cells were cultured on semipermeable polycarbonate membranes to determine whether these cells secrete eGPx in a polarized direction. Immortalized human proximal tubule HK-2 cells and primary human proximal tubule cells formed confluent monolayers when cultured on these membrane inserts in culture dishes, as evidenced by transepithelial resistance. Both cell lines also constituted a barrier to diffusion of a fluoresceinated dextran of 75 kDa, a size similar to eGPx homotetramers. In both cell lines, 6- to 12-fold more 35S-methionine-labeled eGPx was immunoprecipitated from the basolateral media than from the apical media, indicating basolateral secretion of eGPx. eGPx was immunolocalized to the extracellular fluid at the basolateral surface of proximal tubules in human kidney. These data support the conclusion that eGPx is secreted through the basolateral membrane of human kidney proximal tubule cells into the extracellular fluid of the kidney, and from there enters blood plasma.

Animals↗

In-vivo calibration of microdialysis probe by use of endogenous glucose as an internal recovery marker: measurement of skin distribution of tranilast in rats.

To estimate the absolute concentration of substrates surrounding a microdialysis probe in-vivo, we developed a simple calibration method using endogenous glucose as an internal recovery marker and determined the skin distribution of tranilast (N-(3,4-dimethoxy-cinnamoyl)anthranic acid), an anti-allergic agent, in rats. This calibration method was based on the assumption that the concentration of glucose in the extracellular fluid of skin tissues is the same as that in plasma and that the in-vivo recovery ratio of glucose to tranilast by microdialysis is the same as that estimated in-vitro. Based on these assumptions, the dialysate concentrations of tranilast and glucose recovered from cutaneous microdialysis, glucose concentration in plasma, and in-vitro recovery ratio of tranilast to glucose by microdialysis were determined for the estimation of absolute unbound concentration of tranilast in the extracellular fluid of skin tissues. In an in-vitro study employing plasma containing tranilast, the unbound concentration of tranilast in plasma estimated from the dialysate concentration was just comparable with that determined by ultrafiltration methods. Also in an in-vivo study under steady-state plasma concentration of tranilast in rats, the estimated concentration of tranilast in the skin extracellular fluid was the same level as the unbound concentration of tranilast in plasma. Using the present calibration method, the skin distribution of tranilast administered into the intestinal loop or transdermally was continuously monitored in a quantitative manner.

Animals↗

Intestinal transport of water and electrolytes during extracellular volume expansion in dogs.

The effects of extracellular fluid volume expansion on intestinal transport of salts and water were studied in dogs by perfusing loops of bowel in vivo. Saline loading caused depression of duodenal and jejunal absorption with net secretion of salt and water into the lumen. Studies of unidirectional transport of (22)Na(+) revealed that the negative net sodium flux was due primarily, and perhaps exclusively, to increased serosal to mucosal transport, for mucosal to serosal sodium transport was not changed during volume expansion. Net transport of water and potassium paralleled net sodium flux. Administration of deoxycorticosterone did not affect the intestinal response to saline loading. Hemodilution, accomplished by equilibrating the dogs' blood with a reservoir of saline, did not affect intestinal absorption, but isotonic, iso-oncotic expansion of the extracellular fluid produced by reinfusing the saline-blood mixture from the reservoir resulted in negative net transport of water, sodium, and potassium by the duodenum. It is suggested that the small bowel is capable of secreting salts and water through intercellular spaces, and that this process is stimulated by extracellular fluid volume expansion.

Animals↗

Impact of initial flush potassium concentration on the adequacy of lung preservation.

The effects of initial lung flushing with intracellular and extracellular fluid type solutions were studied in lungs stored with the University of Wisconsin solution. Excised Sprague-Dawley rat lungs (n = 39) were flushed first with one of the following solutions: (1) the University of Wisconsin solution (K+ = 140 mmol/L), (2) modified (low potassium) University of Wisconsin solution (K+ = 20 mmol/L), (3) phosphate buffered saline solution (K+ = 3.9 mmol/L), (4) modified low-potassium phosphate-buffered saline solution (K+ = 20 mmol/L), (5) modified high-potassium phosphate-buffered saline solution (K+ = 40 mmol/L), and (6) Euro-Collins solution (K+ = 115 mmol/L) followed by secondary flush with storage solution and cold (4 degrees C) storage in University of Wisconsin solution for 24 hours. The lungs were then reperfused in the isolated, pulsatile, blood-perfused working lung system for 2 hours or until lung failure. Blood gas analysis and shunt fraction, aerodynamic parameters (airway resistance, lung compliance, elastic work, and flow resistive work), and total pulmonary vascular resistance were measured throughout the perfusion period. The mean oxygen tensions (in millimeters of mercury) at 30 minutes after the onset of reperfusion for University of Wisconsin solution, modified University of Wisconsin solution, phosphate-buffered saline solution, modified phosphate-buffered saline solutions (20 and 40 mmol/L), and Euro-Collins solution were 56.1 +/- 4.2, 72.7 +/- 9.1, 87.7 +/- 6.9 (p < 0.01 versus University of Wisconsin solution; p < 0.01 versus Euro-Collins solution), 86.0 +/- 9.6 (p < 0.01 versus University of Wisconsin solution; p < 0.01 versus Euro-Collins solution), 87.9 +/- 7.7 (p < 0.01 versus University of Wisconsin solution; p < 0.01 versus Euro-Collins solution), and 53.5 +/- 6.0, respectively. All aerodynamic parameters in the lungs flushed with extracellular fluid type solutions were superior to those flushed with intracellular fluid type solutions. We conclude that the efficacy of initial flushing was essential for successful lung preservation and that extracellular fluid type solutions were superior to intracellular fluid type solutions, at least for flushing the lung before storage with University of Wisconsin solution. Potassium concentration in flushing solution should be 20 mmol/L or less to obtain appropriate flushing and subsequent adequate distribution of the storage solution.

Adenosine↗

Bioimpedance, dry weight and blood pressure control: new methods and consequences.

PURPOSE OF REVIEW: Chronic overhydration contributes to the development of left ventricular hypertrophy and a high cardiovascular mortality in end-stage renal disease. Assessment of dry weight is highly dependent on clinical assessment. Bioimpedance technology offers the potential to quantify body fluid compartments and to facilitate dry weight prescription. This review covers recent innovative approaches to dry weight assessment using bioimpedance technology. RECENT FINDINGS: Three different bioimpedance approaches to determine dry weight have been published. The normovolemic/hypervolemic slope method applies whole body multifrequency bioimpedance to assess predialysis total body extracellular fluid volume and compares the extracellular fluid volume/body weight relation at hypervolemia with the standard value in normovolemic individuals. The resistance-reactance graph method uses whole body single frequency bioimpedance for assessment of hydration state and nutritional status from height-adjusted resistance and reactance. The resulting resistance-reactance vector is set in relation to a distribution range in a normovolemic population. An alternative method uses segmental bioimpedance in the form of continuous intradialytic calf bioimpedance to record changes in calf extracellular volume during dialysis. Dry weight by this method is defined as the weight at which calf extracellular volume is not further reduced despite ongoing ultrafiltration. SUMMARY: Although promising, none of these methods has gained much popularity, probably due to the difficulties in understanding bioimpedance and the lack of gold standard methods for dry weight determination. Bioimpedance will improve dry weight assessment, but further refinement of the methods as well as large-scale clinical studies to demonstrate the accuracy and the clinical value of objective dry weight determination are needed.

Blood Pressure↗

Suppression of plasma renin activity by cyclosporine.

Cyclosporine treatment is associated with hypertension and suppression of plasma renin activity, the causes of which are unclear. To determine whether suppressed plasma renin activity is due to extracellular fluid volume expansion, 10 cyclosporine-treated renal transplant recipients were compared with 10 azathioprine-treated renal transplant recipients and seven patients with renal insufficiency. Glomerular filtration rate and effective renal plasma flow were significantly lower in cyclosporine-treated patients than in azathioprine-treated patients. Upright plasma renin activity was suppressed in cyclosporine-treated patients (cyclosporine 2.9 +/- 0.9, azathioprine 4.7 +/- 0.9, renal insufficiency 5.2 +/- 1.9 ng/ml/hour) but could be stimulated by a four-day period of dietary sodium restriction and diuretic administration (cyclosporine 15.8 +/- 4.4 ng/ml/hour). Extracellular fluid volume tended to be higher in cyclosporine-treated patients (cyclosporine 30.7 +/- 2.3, azathioprine 26.7 +/- 2.5, renal insufficiency 25.5 +/- 1.4 percent lean body mass), although the difference between cyclosporine-treated and azathioprine-treated patients did not attain statistical significance. There were no differences in the urinary excretion of prostaglandin E2 or 6-keto prostaglandin F1 alpha between the two groups of renal transplant recipients. It is concluded that suppression of plasma renin activity by cyclosporine is physiologic and may reflect expansion of extracellular fluid volume, which can be reversed by sodium depletion.

6-Ketoprostaglandin F1 alpha↗

Utilization and formation of amino acids by chicken epiphyseal chondrocytes: comparative studies with cultured cells and native cartilage tissue.

Utilization and production of amino acids by primary cultures of chicken growth plate epiphyseal chondrocytes grown in Dulbecco's modified Eagle's medium supplemented with 10% fetal bovine serum were investigated in both short-term (6-72 h) and long-term (3-24 day) cultures. Comparative studies were made on levels of free amino acids in chicken blood plasma and serum, and in extracellular fluids from different regions of growth plate cartilage and from two types of muscle. Chondrocytes rapidly consumed glutamine from the medium, and to lesser extents, various other amino acids. In contrast, free ammonia, alanine, glycine, glutamate, proline, and aspartate were released into the medium. The utilization of certain amino acids changed, depending on the stage of culture. Initially glutamate was released into the medium but after confluency was consumed. Conversely, histidine, lysine, and phenylalanine were initially utilized but later were released into the medium. Levels of total free amino acids in extracellular fluids of cartilage and muscle were higher than those in plasma and serum, while in cartilage the levels increased progressively from the resting to the hypertrophic zones. In these sequential regions certain amino acids increased proportionally, whereas others decreased. These interrelationships generally correlated closely with metabolism of amino acids by the cultured chondrocytes. They indicate that significant differences in amino acid metabolism exist between tissue areas and are reflected in the extracellular fluid composition. Accordingly, adjustment of specific amino acids may optimize culture conditions, enabling more normal phenotypic expression in vitro.

Amino Acids↗

Surface localization of virus production on a glucocorticoid-stimulated oncornavirus-producing mouse mammary tumor cell line by scanning electron microscopy.

A chronically infected continuous mouse mammary tumor cell line containing virus particles of type B morphology, free of contaminating type C virions, has been grown in tissue culture. These cells were treated with dexamethasone, a synthetic glucocorticoid, a potent stimulator of mouse mammary tumor virus expression. Surfaces of untreated and dexamethasone-treated cells were investigated by scanning electron microscopy. Untreated cells demonstrated a moderate expression of mouse mammary tumor virus (80 particles/cell) distributed diffusely over the cell surface. However, virions on dexamethasone-treated cells were localized in clusters of 100 to greater than 2000 virus particles, often with more than one cluster per cell. Dexamethasone-treated cells typically showed a 10-fold increase in cell-associated virus over untreated cells. Concentrated extracellular fluids from untreated and dexamethasone-treated cultures were quantitated for free virus. Dexamethasone-treated culture fluids demonstrated a similar 10-fold increase of extracellular particles, in contrast to untreated cultures. This increase in virus particles on the cell surfaces as well as in the extracellular fluids supports the theory that dexamethasone has a stimulatory effect on viral replication, not just on the release of budding particles. The ultrastructure of budding mouse mammary tumor virus during dexamethasone stimulation, determined by scanning and transmission electron microscopy, and the significance of such an in vitro system for viral immunodiagnosis are discussed.

Cell Line↗

Effect of acute hypoxia on respiration and brain stem blood flow in the piglet.

Changes in local brain stem perfusion that alter extracellular fluid Pco2 and/or [H+] near central chemoreceptors may contribute to the decrease in respiration observed during hypoxia after peripheral chemoreceptor denervation and to the delayed decrease observed during hypoxia in the newborn. In this study, we measured the changes in respiration and brain stem blood flow (BBF) during 2-4 min of hypoxic hypoxia in both intact and denervated piglets and calculated the changes in brain stem Pco2 and [H+] that would be expected to occur as a result of the changes in BBF. All animals were anesthetized, spontaneously breathing, and between 2 and 7 days of age. Respiratory and other variables were measured before and during hypoxia in all animals, and BBF (microspheres) was measured in a subgroup of intact and denervated animals at 0, 30, and 260 s and at 0 and 80 s, respectively. During hypoxia, minute ventilation increased and then decreased (biphasic response) in the intact animals but decreased only in the denervated animals. BBF increased in a near linear fashion, and calculated brain stem extracellular fluid Pco2 and [H+] decreased over the first 80 s both before and after denervation. We speculate that a rapid increase in BBF during acute hypoxia decreases brain stem extracellular fluid Pco2 and [H+], which, in turn, negatively modulate the increase in respiratory drive produced by peripheral chemoreceptor input to the central respiratory generator.

Animals↗

Body fluids and their distribution in experimental hypertension.

The relation between blood pressure level and extracellular fluid volume and its distribution was studied in rats subjected to the following hypertensive stimuli--1K1C and 2K1C renal artery constriction, subtotal nephrectomy-salt and DOCA-salt. In all experimental groups the blood pressure increase was accompanied by increased extracellular fluid volume which was not always distributed proportionally between intravascular (PV) and interstitial (IFV) compartments. The blood pressure rise was further potentiated by plasma volume expansion so that the increased PV/IFV ratio was associated with a more pronounced hypertensive response (1K1C vs 2K1C, DOCA-salt vs subtotal nephrectomy-salt). However, adequate expansion of interstitial fluid is a necessary prerequisite for the hypertensive response. In DOCA-salt treated DI Brattleboro rats (lacking antidiuretic vasopressin action) plasma volume expansion per se was not accompanied by severe DOCA-salt hypertension. It is concluded that the expansion of both compartments of extracellular space, i.e. plasma volume and interstitial fluid volume, was necessary for a full development of severe hypertension. The expansion of only one of these compartments was accompanied by a mild blood pressure increase or blood pressure did not change significantly.

Animals↗

Effects of L-arginine and furosemide on blood pressure and renal function in volume-expanded rats.

1. The aim of the present study was to investigate the effects of L-arginine (L-Arg) on blood pressure and water and electrolyte excretion in control and extracellular fluid volume-expanded rats (10% bodyweight with 0.9% NaCl) and to determine whether diuretic treatment with furosemide (FUR) can be optimized by the administration of L-Arg in this model. 2. Both groups of animals were anaesthetized, divided into groups and treated with either 7.5 mg/kg FUR, 250 mg/kg L-Arg, 1 mg/kg NG-nitro-L-arginine methyl ester (L-NAME), FUR + L-NAME or FUR + L-Arg. Mean arterial pressure (MAP), diuresis, natriuresis and kaliuresis were determined. 3. Extracellular fluid volume expansion induced no changes in MAP in control and volume-expanded rats (92+/-6 vs 100+/-8 mmHg, respectively). The hypotension induced by FUR in control and volume-expanded rats (69+/-7 and 76+/-5 mmHg, respectively) was significantly (P < 0.01) enhanced by the administration of L-Arg (54+/-3 and 64+/-3 mmHg, respectively). 4. Injection of L-NAME increased MAP and diminished diuresis, natriuresis and kaliuresis in both groups. 5. Furosemide-induced water and electrolyte excretion was blunted by the administration of L-NAME. 6. The combination of L-Arg + FUR increased diuresis induced by FUR alone (control rats: 29.33+/-1.68 vs 12.91+/- 0.41 microL/min per 100 g, respectively; volume-expanded rats: 248.5+/-25.4 vs 112,6+/-8.3 microL/min per 100 g, respectively; P < 0.01). 7. The administration of the combination of L-Arg + FUR promoted a decrease in the sodium/water excretion ratio compared with the administration of FUR alone (control rats: 0.230+/-0.018 vs 0.45+/-0.03, respectively, P < 0.001; volume-expanded rats: 0.091+/-0.010 vs 0.22+/-0.03, respectively, P < 0.01). 8. The potassium/water excretion rate induced by FUR alone and in the presence of L-Arg followed a pattern similar to that seen for natriuresis (control rats: 0.35+/-0.05 vs 0.20+/-0.05 microEq/min per 100 g, respectively; volume-expanded rats: 0.045+/-0.008 vs 0.014+/-0.003 microEq/min per 100 g, respectively; P < 0.01). 9. The decrease in the electrolyte/water excretion ratio observed with FUR + L-Arg in volume-expanded rats was greater than in control animals. 10. The results of the present study show that the administration of FUR with L-Arg contributes to enhanced hypotensive and diuretic effects of FUR, thus diminishing the relative electrolyte excretion in normal conditions and in extracellular fluid volume expansion.

Animals↗

Effect of different calcium antagonists on transcapillary fluid shift.

Chronic treatment with dihydropyridines, and to a lesser extent other calcium antagonists, often results in peripheral edema without fluid retention. The possibility that calcium antagonists affect extracellular fluid volume partition was tested by comparing the effects of nicardipine (Nic), diltiazem (Dil) and Vehicle (Veh) on hematocrit and plasma protein concentration in anephric anesthetized rats. In response to a 45 min infusion of Nic (0.1 or 1 micrograms/kg/min) and Dil (10 or 100 micrograms/kg/min), blood pressure decreased by 4 or 21%, and 4 or 19%, respectively, whereas hematocrit increased only with both doses of Nic (5.3 +/- 0.2 and 5.5 +/- 0.2%). Plasma protein concentration also increased significantly, although slightly, in the Nic group. The possibility of protein extravasation was then assessed using Evans blue dye as a marker. The drug-induced extravasation of dyed albumin in skeletal and cardiac muscles, but not other organs, was significantly increased following Nic, as compared to Dil or Veh. These observations suggest that two structurally different calcium antagonists used at equihypotensive doses may exert different effects on extracellular fluid partition.

Animals↗

A comparison of the haemodynamic and hormonal effects of low and conventional dose cyclopenthiazide in normal volunteers.

In this study we compared low (125 micrograms) and conventional (500 micrograms) doses of cyclopenthiazide on the renin angiotensin system, plasma and extracellular fluid volumes and the pressor responsiveness to angiotensin II since we have previously shown that the two doses have the same antihypertensive effect but different effects on plasma renin activity. Following a two week placebo run-in period, 8 healthy male volunteers received 125 micrograms or 500 micrograms of cyclopenthiazide for 2 treatment periods of 4 weeks as part of a double blind, 2-part crossover study with treatment periods separated by a 4-week placebo washout phase. Measurements were made on two study days at the beginning and end of the active treatment periods. On the first day serum potassium, plasma renin activity and plasma angiotensin II levels were measured after a 1 h period of supine rest. Plasma and extracellular fluid volumes were also measured after appropriate equilibration times. The blood pressure responses to angiotensin II were assessed on day 2. The 500 micrograms dose of cyclopenthiazide had a greater effect than the 125 micrograms dose on plasma renin activity, serum potassium, angiotensin II levels and extracellular fluid volumes. Neither drug had any effect on plasma volume or the responsiveness to infused angiotensin II. Low dose cyclopenthiazide failed to increase angiotensin II levels, contract body fluid volumes or attenuate vascular reactivity in normotensive volunteers.

Adult↗

Distribution of normal saline and 5% albumin infusions in cardiac surgical patients.

OBJECTIVE: To determine the relative distribution of fluid within the extracellular fluid volume (ECFV) and the effect on oxygen delivery after infusing either normal saline or 5% albumin in cardiac surgical patients. DESIGN: Prospective, randomized, unblinded, interventional study. SETTING: Cardiac surgical intensive care unit in a 450-bed teaching hospital. PATIENTS: Postoperative cardiac surgical patients (n = 40). 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 (131)I-albumin and [(35)S]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 and 5% albumin increased PV by 9 +/- 23% and 52 +/- 84% of the volume infused, respectively (p <.05), whereas there was no significant difference between saline and albumin in the change in ISFV per volume infused. Only 5% albumin significantly increased cardiac index, although oxygen delivery did not change significantly after either infusion. CONCLUSIONS: In postoperative cardiac surgical patients, infusion of 5% albumin is approximately five times as efficient as a PV expander but has comparable effects on changes in ISFV and oxygen delivery relative to normal saline.

Cardiopulmonary Bypass↗