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The role of plasma volume, plasma renin and the sympathetic nervous system in the posture-induced decline in renal lithium clearance in man.

Excretion of lithium in urine was studied in 2 healthy males while recumbent and while upright, either walking or standing quietly. An oral dose of 24.3 mmol of Lit was taken as three lithium carbonate tablets 13 h before clearance tests. Renal lithium clearance decreased and lithium fractional reabsorption increased while upright. Standing immersed to the neck in water, which prevents the fall in plasma volume upon changing posture from recumbent to upright, prevented the fall in renal lithium clearance as well as the rise in lithium fractional reabsorption while upright. Oral doses of guanethidine (total dose of 200 mg) or oxprenolol (total dose of 140 mg) taken to prevent high levels of sympathetic nervous system activity and plasma renin, respectively, failed to prevent the fall in renal lithium clearance or the rise in lithium fractional reabsorption upon changing posture from recumbent to upright. The findings indicate that the fall in renal lithium clearance and the rise in lithium fractional reabsorption upon changing posture from recumbent to upright is related to the fall in plasma volume but not to high levels of sympathetic nervous system activity or plasma renin activity.

Absorption

Determinants of high blood pressure in salt-deprived renal hypertensive rats: role of changes in plasma volume, extracellular fluid volume and plasma angiotensin II.

1. Rats with indwelling aortic and right atrial cannulae were maintained on a sodium-free diet before and after renal arterial constriction combined with contralateral nephrectomy. Control animals underwent the same protocol except that non-constricting clips were used. 2. Plasma volumes in the salt-deprived animals were lower than previously determined values in animals with free access to sodium. After clipping plasma volume increased in the hypertensive animals. Extracellular fluid volume was increased equally in both normotensive and hypertensive animals on the second postoperative day only. 3. Before clipping and contralateral nephrectomy plasma angiotensin II values were higher than normal. After the operation angiotensin II concentrations fell to normal over a period of 14 days without significant differences between experimental and control groups. 4. It is concluded that high blood pressure after clipping may be in part maintained by increases in plasma volume. However, the results strongly suggest that other renal mechanisms are likely to be of major pathogenic importance.

Angiotensin II

Restoration of hemorrhaged plasma volume by gastrointestinal fluid in the dog.

Conscious, intact and splenectomized, male dogs were hemorrhaged 35 percent of their blood volumes (23 +/- 3 and 25 +/- 4 ml/kg, respectively) from carotid loop cannulas. Isotonic saline or glucose solutions were administered by gastric tube in volumes equal to the blood volume hemorrhaged. Plasma volume, mean arterial blood pressure, venous hematocrit, plasma protein concentration, and interstitial fluid pressure were monitored after hemorrhage and after fluid treatment. The magnitudes of plasma volume restoration 8 h after hemorrhage in the nontreated dogs averaged 56 +/- 9 percent of the hemorrhaged volume and did not differ significantly between intact and splenectomized dogs. Plasma volumes, however, were increased significantly by enterally administered fluids. The maximum rates of plasma volume restoration occurred within the 1st h after fluid treatment. Approximately 46 percent and 28 percent of the hemorrhaged plasma volume was replaced by saline and glucose solutions, respectively, during this period. Results support the hypothesis that fluid is absorbed from the gastrointestinal tract following hemorrhage, and that enterally administered fluids restore plasma volume at a rate and to an extent exceeding that provided by net interstitial fluid exchange alone.

Animals

Plasma volume changes after infusion of various plasma expanders.

In the immediate post-operative period after moderate surgical procedures, 1 litre of a colloid solution or saline was given intravenously. The plasma volume expansion after infusion of dextran 70 (Macrodex), hydroxyethylstarch (Volex), polygelatin (Haemaccel), albumin and saline was found to be between 790 and 180 ml. The most efficent plasma expander was dextran, followed by hydroxyethylstarch. Polygelatin and saline did not give full restitution, although twice the calculated loss was infused. Total plasma protein concentration was lowered in all groups in proportion to the dilution, except for the patients given albumin, in whom the concentration of total protein increased. Calculation of the total circulating protein mass showed no decrease during the period immediately after the infusion. This investigation has demonstrated that the most efficient plasma volume expander is dextran but that hydroxyethylstarch offers an almost equal alternative in terms of volume expansion. Dextran, however, exerts an advantageous effect on the microcirculation. As the metabolic pathways of hydroxyethylstarch have not yet been further explored, dextran is preferred when using artificial colloids. Judged by its secondary effects alone, including the influence on plasma protein patterns, albumin seems to be the compound of choice. Polygelatin and saline are not efficient expanders when hypovolaemia is to be corrected rapidly.

Adult

Stimulation of rhesus monkey GH release: arginine vs plasma volume expansion.

Plasma GH and cortisol responses were examined in unanesthetized adult male rhesus monkeys infused with approximately 30 ml (8.3 ml/kg) of arginine monohydrochloride (Arg 0.5 g/kg), 0.9% saline (NS) or Dextran 75 and following 15 ml infusions of acid-saline (AS), or somatostatin (GHRIH 30 mug/kg). None of the infusions were accompanied by GH elevations. Rebound GH elevations occurred after each 30 ml infusion and after GHRIH but not after 15 ml AS. Although the amplitude of GH responses were not significantly different (p greater than 0.05), responses to Arg and dextran were significantly delayed as compared to responses following NS and GHRIH which did not differ from each other. Both of the latter responses occurred within 15 min of infusion completion. The delay following dextran was significantly longer than that following Arg (p less than 0.05). Since the volume of saline and the dosage of Arg were equivalent to those used in the standard intravenous Arg test, results suggest that effects of infusion volume upon GH secretion and upon GH responses to Arg warrant examination in the human. In addition, it is suggested that GH responses to NS and to dextran are mediated via an intravascular volume control mechanism and that GHRIH may be released upon activation of such a mechanism. GH elevations may represent rebound responses upon termination of GHRIH secretion.

Animals

Effect of afterload reduction on plasma volume during acute heart failure.

Previous investigations in our unit indicated that acute cardiogenic pulmonary edema is associated not only with an increase in left ventricular end-diastolic pressure and pulmonary arterial wedge pressure but also with a relative increase in colloid osmotic (oncotic) pressure and peripheral hemoglobin concentration. This combination of changes suggested that acute congestive heart failure with pulmonary edema, unlike chronic congestive heart failure, is associated with a contraction of intravascular blood volume. In this study, plasma volume changes were measured before and during the treatment of acute cardiogenic pulmonary edema in 14 patients with arteriosclerotic heart disease. The plasma volume measurement in all 14 patients before the initiation of treatment was either normal or decreased. After treatment with the alpha adrenergic blocking agent phentolamine, the plasma volume increased rather than decreased when measured 4 and 12 hours after the initiation of treatment. During this time colloid osmotic pressure and peripheral hemoglobin concentration progressively decreased. These findings suggest that acute cardiogenic pulmonary edema is associated with the extravasation of large quantities of plasma water from the intravascular compartment into the interstitial compartment and contraction of the intravascular plasma volume. The treatment of acute cardiogenic pulmonary edema is associated with the return of hypo-oncotic fluid from the interstitial compartment back into the intravascular compartment with expansion of plasma volume and reduction of colloid osmotic pressure and hemoglobin concentration.

Acute Disease

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.

Animals

Plasma volume, intravascular albumin and its transcapillary escape rate in patients with extensive skin disease.

Plasma volume and plasma concentration and transcapillary escape rate of albumin (TER alb), i.e. the fraction of intravascular mass of albumin that passes to the extravascular space per unit time, were determined using 125I-labelled human albumin in eight patients with extensive skin disease. Plasma volume and plasma albumin concentration were reduced (P less than 0-05). Thus the intravascular albumin mass was moderately decreased to an average of 0-55 +/- 0-06 (s.d.) g/cm height compared with a normal mean value of 0-77 +/- 0-07 (s.d.) g/cm. This 29% decrease is statistically significant (P less than 0-001). The transcapillary escape rate of albumin (TER alb) was significantly elevated, mean 8-6 +/- 1-1 (s.d.) % X h-1, as compared to normal subjects, mean 5-6 +/- 1-1 (s.d.) % X h-1, (+54%, P less than 0-001). The same patients were studied again after a 1-week treatment with prednisone, 25-60 mg per day. Plasma albumin concentration, plasma volume and intravascular mass of albumin were unchanged, while TER alb decreased significantly during treatment, mean 5-9 +/- 0-8 (s.d.) % X h-1, (P less than 0-01). It is suggested that displacement of albumin into the skin and loss of albumin from the skin are the dominating mechanisms of the reduction in the intravascular albumin mass in patients with extensive skin disease.

Aged

Transcapillary escape rate of albumin and plasma volume in patients with varying degrees of psoriasis.

Plasma albumin, plasma volume and the transcapillary escape rate of albumin (TERalb), i.e. the fraction of the intravascular mass of albumin that passes to the extravascular space per unit time, were determined using 125I-labelled albumin in 26 patients with varying degrees of psoriasis. For the patients as a group the plasma albumin concentration and the TERalb values were not significantly different from the control group. This contrasts with earlier findings in erythrodermic patients. The plasma volume was significantly reduced whether it was expressed in relation to body weight, height or surface area (P less than 0.001). Thus the intravascular mass of albumin (IVM), determined as the product of the plasma volume and the plasma albumin concentration, was also significantly reduced (P less than 0.001). We found no correlation between the involved skin area and any of the above mentioned parameters. The possible mechanisms in the reduction of the plasma volume and the IVM are discussed. It is suggested that reduced IVM may reflect reduced total albumin mass due to lowered rates of albumin synthesis or increased rates of turnover.

Adolescent

Plasma volumes and hematocrits in rats with chronic sinoaortic denervation hypertension.

Plasma volume changes were assessed in female Wistar rats with neurogenic hypertension induced by sinoaortic denervation, SAD. Tail veins of conscious, restrained rats were used for injection of Evans blue dye and for sampling into microhematocrit tubes. Only at 3 days did total plasma volume of SAD rats show a modest reduction of about 16% (P less than 0.05 vs. sham-operated plus unoperated controls). At 3, 6, and 13 wk, SAD mean body weight, plasma volume, and sodium concentration were similar to sham values. SAD hematocrits, however, like arterial pressures, were elevated at all postoperative times studied. In anesthetized SAD and sham rats, red blood cell (51Cr method) and plasma volumes were the same and so were hematocrits. The latter was unlike the finding in unanesthetized groups. Hematocrits from the same SAD rats were lower after induction of anesthesia than before (P less than 0.025). Thus, elevated hematocrits apparently resulted from the release of sequestered red blood cells into the circulation by unanesthetized SAD rats. In conclusion, plasma volume is within the normal range in SAD rats except for the first few postoperative days. Factors affecting volume regulation at that time are discussed.

Animals

Relationship of basal plasma norepinephrine to blood pressure, plasma renin activity, mineralocorticoids, and plasma volume in essential hypertension.

The basal levels of plasma norepinephrine have been measured in 113 carefully characterized patients with essential hypertension, and the results have been correlated with the PRA sub-grouping and the levels of blood pressure, plasma aldosterone, plasma 18-hydroxy-deoxycorticosterone, and plasma volume. In addition, the influence of furosemide on plasma norepinephrine concentration has been assessed. Essential hypertensives, when considered as a whole, did not exhibit any significant abnormality in basal plasma norepinephrine concentration, but interesting alterations were observed in certain specific sub-groups. High renin patients had significantly elevated levels of basal plasma norepinephrine. In addition, a sub-group of the low renin population who were relatively young had reduced plasma norepinephrine conentration. In these individuals with both reduced PRA and plasma norepinephrine, the levels of both increased concomitantly to the normal range with marked salt depletion. Furosemide administration induced increases in plasma norepinephrine in all PRA sub-groups. Plasma norepinephrine correlated significantly with blood pressure in normal and low renin hypertensives, but the relationships were confined only to male subjects. Significant correlations were also observed between plasma norepinephrine and plasma aldosterine in males with normal PRA but not in the other sub-categories. No significant relationships between plasma volume and either plasma norepinephrine or blood pressure could be detected. Plasma 18-hydroxy-deoxycorticosterone was greater in males as compared with females and appeared elevated above control levels in normal and high renin essential hypertensives. Significant positive correlations between plasma aldosterone and plasma 18-hydroxy-deoxycorticosterone were observed in both males and females with normal renin hypertension. These studies have demonstrated abnormalities in basal plasma norepinephrine concentration in certain patients with essential hypertension. They also suggest that the levels of blood pressure and plasma aldosterone may be related to peripheral sympathetic activity in essential hypertension.

18-Hydroxydesoxycorticosterone

Plasma volume changes during rest and exercise in different postures in a hot humid environment.

Plasma volume shifts were investigated in five male subjects who rested and exercised in the upright, low-sit, and supine postures in a hot humid environment (49.5 degrees C, 28.9 Torr). The resting and exercise periods were each 45 min in duration. Weight losses during rest were 0.3% with an additional weight loss of 1.1% during exercise. During exercise subjects worked at either 360 or 540 kpm.min-1 in each of three postures. Each experiment was preceded by a 30-min control period in the supine posture at an ambient temperature of 22 degrees C. At rest plasma volume was reduced 17.3% in the upright, 9.0% in the low-sit, and 2.2% in the supine postures (using the end of the supine rest as the zero reference point). Supine exercise resulted in a plasma volume decrease of 11%, the low-sit 7.1%, and the upright 2.7%. The total reduction in plasma volume during the rest and exercise period was 20% in the upright, 16.1% in the low-sit, and 13.3% in the supine. No significant differences in plasma volume shifts were observed between the high and low work loads. The results indicate that the plasma volume shifts observed during rest and exercise in the heat are qualitatively similar to those observed in a cool environment.

Adult

Effects of food or protein restriction on plasma volume expansion in pregnant rats.

The effects of either food restriction or a low protein diet on the plasma volume expansion of pregnancy was determined in Sprague-Dawley rats. Rats fed ad libitum a standard diet or fed a 25% casein diet were used as controls. Both the food restricted and protein restricted rats had a significant reduction in body weight and fetal and placental weights. The total plasma volumes were also significantly lower in the restricted groups. Plasma volume expressed per 100 g of maternal net body weight or 100 g of conceptus weight was significantly reduced only in the rats fed the 6% casein diet. Correlations between plasma volume and maternal net body weight or conceptus weight in the control groups suggested that although the conceptus can influence the degree of expansion of maternal plasma volume, maternal factors such as net body weight are more important determinants of plasma volume expansion.

Animals

[Second increase in plasma volume after single infusion of hydroxyethyl starch (author's transl)].

6 patients without evidence for renal, hepatic or pancreatic disease were treated with intravenous infusions of 500 ml hydroxyethyl starch (6%) over a period of 60 min. In the course of the infusion we observed an increase in plasma volume from 2.72 +/- 0.101 to 3.36 +/- 0.141. After 2 h plasma volume decreased to 3.02 +/- 0.101 but showed a second peak of 3.23 +/- 0.121 after 4 h (p less than 0.01). 24 h following infusion an increase in plasma volume of 4,8% was found as compared to preinfusion values. The second increase in plasma volume cannot be explained by the total concentration of hydroxyethyl starch since the latter decreased continuously. The increase in plasma volume was accompanied by a decrease in average molecular weight (-Mw and -Mn). It is suggested that serum amylase produces small osmotic active molecules by degradation of hydroxyethyl starch, thus leading to an increase in plasma volume. 12--24 h after the infusion of hydroxyethyl starch serum amylase was more than twice as high basal values. This is caused by the formation of a high molecular hydroxyethyl starch-amylase-complex which cannot be eliminated easily. When hydroxyethyl starch is given repeatedly to normovolemic patients, the second increase in plasma volume should be considered as a possible cause for acute hypervolemia. This is especially true for patients with myocardial insufficiency.

Adult

Plasma volume in isosmotic hypervolaemia.

The Evans-blue distribution volume, haematocrit, and plasma protein concentration were investigated in non-hydrated (control), hydrated, and acutely nephrectomized hydrated, anaesthetized dogs. In control anaesthetized dogs a decrease of the plasma protein level was observed as part of the plasma proteins was lost into the extravascular space and did not return into the circulating plasma during the experimental period. Under the effect of hydration, the Evans-blue distribution volume increased significantly, while the haematocrit and plasma volume did not change. The phenomenon was ascribed to an increase in capillary permeability. During hydration following acute nephrectomy, the Evans-blue distribution volume increased but the haematocrit disecreased and the circulating plasma volume increased. It is concluded that a material (or materials) orginating from the kidney may influence capillary permeability.

Animals

Plasma volume contraction: a significant factor in both pregnancy-associated hypertension (pre-eclampsia) and chronic hypertension in pregnancy.

The role of plasma volume in hypertension in pregnancy (pre-eclampsia) was investigated. Significant volume expansion from non-pregnant levels (16.5 +/- 1.60 ml/cm height) was present throughout pregnancy in 189 normal women, reaching 23.1 +/- 1.21 ml/cm at 33-36 weeks amenorrhoea. In another 40 initially normotensive pregnant women who developed hypertension, similar early volume expansion was followed by significant volume contraction in the third trimester, before evaluation of blood pressure in 29 (20.6 +/- 1.26 ml/cm), after it in 11 (18.6 +/- 1.27 ml/cm). Equivalent volume contraction was present in another 44 women studied only after hypertension developed in the third trimester. Oedema had no value as a clinical sign. In another 30 women with chronic hypertension, blood pressure was inversely related to plasma volume (r = 0.822) and to fetal growth (r = -0.710), which was directly related to plasma volume (r = 0.701). Plasma volume depletion plays a significant role in hypertension in pregnancy.

Blood Pressure