Determination Of Plasma Volume Research Articles

Plasma volume determination by use of enzyme dilution in the dog.

The use of enzymes for plasma volume determination in the dog was investigated. Plasma volume was determined from dilution of intravenously injected enzymes and compared with results obtained by high molecular weight fluorescein-labelled dextran. Aspartate aminotransferase and alanine aminotransferase from liver tissue gave good results, but the activities of creatine kinase and lactate dehydrogenase from heart tissue were inhibited in plasma, resulting in an overestimation of plasma volume. Enzymes offer a useful alternative to methods presently used since no radioactive isotopes are needed. In laboratory animals the enzyme preparations are readily obtainable and there is minimal risk of immunological complications arising after repeated determinations.

Plasma volume shifts during moderate exercise in splenectomized greyhounds.

1. Plasma volume was measured in splenectomized greyhounds, using T-1824, and sequential changes in plasma volume were measured using two independent methods, based on T-1824 plasma decay characteristics and on changes in haematocrit. 2. There were no significant differences between estimates of plasma volume made by the two methods in resting or exercising dogs. Therefore it was concluded that the characteristics of the decay of dye concentration in plasma were not affected by exercise and that sequential determinations of plasma volume from a single dye injection provide a valid determination of plasma volume during exercise in dogs. 3. During submaximal exercise, the plasma volume increased by 0-11.8% of its initial value. In no case did plasma volume decrease significantly. 4. An increase in plasma volume during excercise was also seen in animals previously made acutely hypervolemic or hypovolemic. 5. It is suggested that the increase in plasma volume constitutes part of a mechanism maintaining oxygen delivery to tissues during exercise.

IgG versus albumin for measurement of plasma volume in normal and hypertensive men

Labeled IgG was evaluated versus labeled albumin for measurement of plasma volume, to see whether it would give a smaller initial dilution volume (indicating a smaller premixing extravascular loss of label) and a smaller difference between initial dilution volume and dilution volume at time 10 min (indicating a negligible extravascular loss in the first 10 min after mixing). IgG was found to have a lower transcapillary escape rate than albumin (P less than 0.01) in eight normal volunteers and in eight hypertensive subjects, hypertension being associated with an increased transcapillary escape of both proteins. Despite this, the dilution volumes obtained were indistinguishable and the need for a correction through a retropolation procedure was the same with both proteins. Albumin and IgG dilution volumes were highly correlated in 21 subjects (r=0.977) so that use of labeled IgG is a proper alternative to use of labeled albumin for plasma volume determination. However, since IgG brings no consistent advantage, labeled albumin remains the best available tracer for that purpose.

A reassessment of intravascular volume measurements in protein—calorie malnutrition

Accurate determination of plasma volume is difficult in oedematous protein--calorie malnutrition, but present studies on the equilibrium of labelled red cells have shown that red cell volume measurements are valid in this syndrome. The red cell volumes have been measured in afflicted Bantu children during a refeeding programme. Expression of the results in ml/kg, ml/m2 or ml/cm is misleading and has been replaced by expressing the results as a percentage of the means of the normal values for the height. The results show that the red cell volume increase that ought to occur at the end of refeeding programme (and hence the iron requirement) is far higher than suggested by the packed cell volume. With treatment the red cell volume increases slowly. The red cell volume and plasma volume changes that occur during treatment do not take place at the same rate.

Blood Volume Changes in Patients With Cystic Fibrosis

Simultaneous red blood cell (RBC) and plasma volume determinations were obtained in 16 patients with cystic fibrosis (CF) and moderately severe pulmonary involvement. Hypervolemia with an increase in both RBC and plasma volumes was observed. Changes in blood volume were marked when values were indexed by weight but less significant when indexed by height. Decreasing systemic arterial oxygen saturation was associated with a progressive increase in RBC mass, hematocrit value, and hemoglobin level and a decrease in mean corpuscular hemoglobin concentration. RBC and total blood volumes were highest in patients with cor pulmonale and congestive heart failure. However, the compensatory polycythemic response in patients with CF was inadequate when compared with the response to hypoxemia in patients with cyanotic congenital heart disease. The insufficient oxygen-carrying capacity may compromise tissue oxygen delivery and necessitate treatment.

Intravascular volume determinations and fetal outcome in hypertensive diseases of pregnancy

With the Evans blue technique, 178 plasma volume, blood volume, and red cell-volume determinations were studied in 51 hypertensive and 35 normotensive gravidas. Hypertensive pregnancies were classified according to the American Committee on Maternal Welfare schema. A large range and overlap in plasma and blood volume determinations was found, but mean values in patients with hypertensive disease were significantly depressed when compared with normotensive gravidas. A decrease in red cell mass was observed only in the severe hypertensive group of women. In general, those hypertensive patients with plasma and blood volume determinations approaching those of the normotensive control patients were associated with a favorable maternal and fetal outcome. Extreme hypovolemia occurred in most pregnancies associated with severe hypertensive disease and evidence of uteroplacental insufficiency.

Plasma and Blood Volume in the Calf from Birth Till 90 Days of Age

Determinations of plasma volume were made of 9 clinically healthy Swedish Red and White calves from birth to 90 days of age by means of the isotop dilution technique. Commercially available 131I labelled human serum albumin was used. Calculation of the total blood volume was based on the plasma volume and packed cell volume. The plasma and blood volumes increased per kg body weight in average 17 and 14% respectively from directly after birth to 24 hrs. old. From 1 to 90 days of age the plasma and blood volume fell steadily per kg body weight. Plasma volume expressed as a percentage of body weight was 5.3% at birth, 6.5% at 1 day old, and 4.9% at 90 days old. Corresponding values for blood volume were 8.4, 9.3 and 7.0%.

Plasma Volume after Dextran Infusion in Rats Sensitive and Non-Sensitive to Dextran

Plasma volume determinations were done with RIHSA under normal conditions and after intravenous infusion of dextran solutions. The plasma volume of normal rats in millilitre was found to be 0.026 X body weight + 0.92. Infusion of dextran into dextran-sensitive Sprague-Dawley rats was followed by a marked plasma volume reduction and haemoconcentration as consequence of an anaphylactoid reaction. This reaction could be partially inhibited by pretreatment with cyproheptadine chloride. Plasma volume determination with the method used in this study can be used to evaluate the dextran-anaphylactoid reaction. In dextran non-sensitive Wistar rats, infusion of dextran had a strong plasma volume-expanding effect comparable to the plasma volume-expanding effect of dextran in humans. No signs of abnormal leakage of fluid out into the extravascular space were evident, which indicated that the Wistar rats really were non-sensitive to dextran.

The rôle of plasma proteins in chronic expansion of plasma volume in tropical splenomegaly syndrome: III. The interrelationships of albumin, immunoglobulins and plasma volume

The effect of alterations in serum protein levels on plasma volume in tropical splenomegaly syndrome has been investigated by determining plasma volume, serum albumin, globulin and immunoglobulin levels in 64 adult New Guineans suffering from this disease. Plasma volumes ranged from 51.2 to 129 ml./kg. Significant positive correlations were found between plasma volume and intravascular pools of albumin, IgG and IgM. Multiple regression analysis demonstrated that 70% of the variance in plasma volume in this series was attributable to increases in these three pools, IgM and IgG accounting for 42% of the total and albumin for 28%. It is probable that the unexplained 30% of plasma volume expansion arises through a splenic arterio-venous shunt effect. It is suggested that initially in tropical splenomegaly syndrome the splenic shunt and immunoglobulin overproduction combine to produce expansion of plasma volume and a fall in intravascular colloid osmotic pressure; that the latter provides the stimulus to increased albumin synthesis, and that this further aggravates the plasma volume expansion and the consequent dilutional anaemia commonly seen in this disease.

Physiological changes in blood volume.

Measurement of blood volume is an important clinical tool in establishing a diagnosis as in polycythemia vera, in assessing the true significance of a low blood count in a patient with splenomegaly, and in evaluating a bleeding patient. In theory, blood volume measurements should be of great value in treating acute blood loss, but this is often too time-consuming to be practicable. The main value of blood volume studies so far has been in clinical research where it is essential for correct interpretation of the peripheral blood measurements. Estimates using the hematocrit (packed cell volume) could be misleading since this measurement does not take into account total blood volume and changes in the plasma volume. A variety of isotopes that tag the red blood cell have been used to measure total blood volume and red cell mass. Most commonly used at present is autologous 51-Cr labeled red cells, thus eliminating the risk of hepatitis in transfusion to the subjects. Radio labeled albumin and other plasma proteins were used to measure plasma volume. A large molecular protein is ideal to eliminate overestimation from extravascular diffusion of labeled material for accurate determination of plasma volume. Physiologic changes in the newborn, in pregnant women, during exercise, bed rest, and altitude in the nonpathologic state are discussed. Studies in the normal subject's adaptation in different physiologic conditions have revealed a variety of factors that regulate blood volume.

Blood volume

During the past decade the diagnostic use of blood volume determinations has declined as a result of the generation of largely inaccurate results and inappropriate normalization and interpretation. After historical development of more than 50 years, current methodology employs 125I-labeled human serum albumin and 51Cr-labeled red blood cells to determine plasma volume and red cell volume, respectively. Accurate blood volume determinations require (1) abandoning the use of the mean body hematocrit:venous hematocrit ratio and using simultaneous independent measurements of both volumes; (2) delaying multiple postinjection patient samples until complete mixing and equilibration are complete; (3) backextrapolation of plasma concentrations of 125I to account for albumin loss from the plasma, and, rarely, back-extrapolation of red cell concentrations to account for dilution by red cells transfused during the procedure; (4) normalization of volumes by adjusting patient weight to normal correspondence with lean tissue mass, whenever necessary. A rapid, routine method that fulfills these four requirements is presented. A number of surgical and medical conditions in which blood volume determinations are very useful in diagnosis and therapy are discussed. Recently developed techniques for blood volume measurements include neutron acativation analysis and fluorescent excitation analysis. Correct normalization of accurate blood volume measurements will provide a valuable service to the entire medical community.

Simultaneous determination of plasma volume and transcapillary escape rate with 131 I-labelled albumin and T-1824 in the newborn.

SummaryA new micro method for plasma volume determination with T‐1824 was investigated in 10 newborn infants. Dye concentration was measured with a two wavelength spectrophotometric method. The method was found to be easy, rapid to perform and requires only 150 μl plasma. Thus several plasma samples could be obtained and the dye loss during mixing time calculated and corrected for. This is of special importance in the newborn due to the high transcapillary albumin loss mentioned below. Plasma volume was determined with 131I human serum albumin (RIHSA) serving as reference. Identical results were obtained, mean 43 ml/kg. Consequently it is concluded that the dye method, being a non‐radioactive method, should be preferred for plasma volume determination in the newborn. Transcapillary escape rate of albumin (fraction of intra‐vascular mass of albumin escaping to the extravascular space per unit time) was determined from the disappearance of intravenously injected RIHSA and T‐1824 during the first hour after the injection. The mean transcapillary escape rate with RIHSA was: 18.4%/hour, with T‐1824: 20.7%/hour (p<0.1). These values are 3 to 4 times higher than those obtained in adults thus indicating a high capillary permeability to albumin in newborns.

Quantitation of Fibrin Deposition and Elimination in Organs of Rats Injected with Labelled Fibrinogen and Albumin

SummaryA method for quantitation of fiprin deposits in organs of rats, using labelled fibrinogen and albumin, is described. In rats previously injected with 125I-fibrinogen, thrombin was used to induce intravascular deposition of fibrin in various organs. 131I-albumin was injected shortly before sacrifice for determination of the organ plasma volume. The fibrin content of the organ was calculated by subtraction of the plasma and extravascular 125I-radioactivities from the total 125I-content of the organ. The organ plasma radioactivity was obtained as the product of 12 5I in plasma and the organ plasma volume and the extravascular radioactivity as the difference between total and plasma radioactivity in organs of rats before the thrombin infusion. It was found that the method is especially suited for quantitation of fibrin deposition and elimination in the lungs, but it should be also applicable to other organs. In the liver and kidneys certain problems occur which interfere especially with fibrin elimination studies in these organs.

Dynamics of water-isotope distribution.

Dynamics of water-isotope distribution.

Distribution and circulation of extracellular fluid and protein during different states of hydration in the cat.

1. Determinations of plasma volume (PV) and circulating protein in 13 anaesthetized cats before and after dehydration by deprivation of water for 48 h revealed an 11.5% decrease of PV and a 13.5% decrease of circulating protein, the plasma protein concentration and the albumin/globulin ratio remaining essentially constant. Extracellular fluid volume (ECFV) was reduced by 13.8% in 9 dehydrated animals as compared to 10 control animals. 2. The fractional disappearance rate of radio albumin revealed that half a pool of albumin is exchanging with the extravascular space in 10 h in control animals as well as in dehydrated animals. The observation that lymph flow and lymph protein transport from the thoracic duct were closely correlated with the state of filling of the interstitial space explains why half a pool of plasma albumin was returned to the blood stream in 16.5 h in dehydrated animals as compared to 10 h in controls. The reduction of plasma albumin due to dehydration was calculated to result from the disturbance of the dynamic equilibrium between transcapillary albumin shift and lymphatic return. 3. During rehydration by saline infusion, dehydrated animals kept larger percentages of the infused fluid inside the intravascular space demonstrating a decrease of net transcapillary fluid shift. The increase of lymph flow during infusion was shown to be closely correlated with the filtration rate. There was an increase of transcapillary protein shift and a decrease of transport rates for lymph protein during infusion.

Hypervolemia at the polyethylene glycol induced onset of drinking

Latency to drink and blood plasma conditions of rats were measured at the initiation of drinking following hyperoncotic colloid dialysis. Experiment 1 determined plasma osmolality and volume levels at the initiation of drinking following subcutaneous injection of 5 ml of 20% polyethylene glycol (PG) solution (400 molecular weight). The onset of drinking was associated with: (a) 3.1 per cent increase in osmotic and/or oncotic pressure of the plasma; and, (b) no change in vascular volume. Due to the possibility of plasma contamination by the small molecular weight PG used, Experiment 2 was conducted using 5 ml of 25% PG (20,000 molecular weight) solution. Plasma osmolality and volume determinations were made at the following times post PG or Sham injection: at the initiation of drinking (mean = 17 min), at two times the latency to drink (mean = 34 min), and at four times the latency to drink (mean = 68 min). The onset of drinking in this experiment was associated with no change in plasma osmolality, but with an increase in vascular volume, i.e. hypervolemia not hypovolemia. A reduced vascular volume was not measured until 68 min post PG injection. The results are discussed in terms of the possibility that cellular dehydration and/or cellular volume decrease is the adequate internal stimulus for thirst motivated behavior.

Blood volume changes in cyanotic congenital heart disease

Simultaneous red cell volume and plasma volume determinations were performed in 20 patients with cyanotic congenital heart disease. Significant hypervolemia was shown to result from an increased red cell volume. Plasma volume may be reduced but usually remains within the normal range. The good correlation between the venous hematocrit and red cell volume per kilogram provides the basis for the estimation of the red cell volume from the venous hematocrit. The common clinical practice of estimating the degree of hypoxemia from the red cell volume (or hematocrit) is at best very gross due to the large variability of the red cell volume at any given level of arterial oxygen saturation in patients with cyanotic heart disease. Red cell volume and plasma volume should be independently and simultaneously measured if accurate estimates of total blood volume changes are desired. Blood volume measurements serve as an index and guide in the medical and surgical treatment of polycythemic cyanotic patients.

Changes in plasma and extracellular fluid volumes in patients with essential hypertension during long-term treatment with hydrochlorothiazide.

In 13 untreated patients with essential hypertension, the plasma volume (T-1824) and the extracellular fluid volume ( 82 Br - distribution space) were determined three times. During treatment with 50 to 100 mg of hydrochlorothiazide daily, determinations of plasma volume and extracellular fluid volume were repeated after treatment for 1 mo (13 patients), 2 mo (13 patients), 4 mo (eight patients), and 6 mo ( seven patients). In all cases the average plasma and extracellular fluid volumes were reduced compared with the averages of three control values. The plasma volume was significantly reduced at the 5% level after treatment for 1, 2, and 4 mo. Corresponding studies from the literature have been reviewed and, on the basis of these studies and our own results, it is concluded that thiazides have a volume-depleting effect which is continued during long-term treatment of patients with essential hypertension.

Plasma renin activity in hypertensive diseases.

Plasma renin activity was determined in normotensive and hypertensive human subjects by a modification of the method of Boucher and co-workers. Simultaneous determination of plasma volume, serum electrolyte concentration and plasma renin activity was performed. The plasma renin activity was normal in essential hypertension and in pheochromocytoma, normal or subnormal in Cushing's syndrome with adrenal hyperplasia, increased in Cushing's syndrome with adrenal carcinoma and in renal or renovascular hypertension and decreased in primary aldosteronism. Three hours after taking upright posture, patients with essential hypertension showed two to fivefold increase of plasma renin activity, while those with primary aldosteronism did not. In renovascular hypertension and primary aldosteronism, plasma renin activity returned to normal range after operation. Diurnal variation of plasma renin activity was investigated under a standard condition. In normotensive subjects, highest value was observed in the forenoon and lowest value in the afternoon. As respects the diurnal variation of plasma renin activity, an inverse relationship between plasma renin activity and plasma volume was exhibited.

Effects of saline loading on the renin, erythropoietin, and blood pressure responses to canine renal allotransplantation

Serial determinations of plasma erythropoietin and renin activities and mean arterial blood pressure were done in five dogs before and after renal allotransplantation. Throughout the experiment, the animals were given 154 mEq of NaCl per day, starting 1 week before transplantation. No immunosuppressive therapy was given. Onset of immunological rejection was determined by daily measurement of endogenous creatinine clearance. Arterial pressure and plasma erythropoietin concentration increased markedly at the time of rejection, with the curves for the two variables closely paralleling each odier in all animals. Serial determinations of plasma volume done in two of the dogs did not show any significant change at the time when hypertension appeared. Plasma renin activities remained very low throughout the experiments, indicating that even with the vascular lesions of rejection renin release is still subject to normal control mechanisms. It is concluded that elevated plasma renin activity is not an essential causal factor of the hypertension which occurs with renal allograft rejection. Since it is possible to suppress renin release without substantially inhibiting erythropoietin release, different stimuli appear to cause release of these substances.