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Mechanism for inhibition of renin release by acute plasma volume expansion in the dog.

Plasma volume expansion alters renal tubular sodium chloride transport and renal nerve activity. The purpose of this study was to determine the mechanism(s) for inhibition of renin secretion by acute volume expansion with albumin in the anesthetized dog. In dogs with a single intact kidney, albumin infusion decreased renin release by 86% and significantly increased renal blood flow, glomerular filtration rate, and sodium excretion. Albumin volume expansion inhibited renin secretion to a lesser extent in dogs with denervated filtering kidneys and in dogs with innervated nonfiltering kidneys. In dogs with denervated nonfiltering kidneys, albumin infusion did not change renin secretion. Comparable volume expansion was produced in all groups. Thus, inhibition of renin release by acute plasma volume expansion is dependent on both a renal tubular mechanism and the integrity of the renal nerves. Partial inhibition of renin release was observed with interruption of either one of the mechanisms, whereas interruption of both mechanisms totally abolished the effect of acute plasma volume expansion on renin secretion.

Albumins↗

Plasma volume in normal pregnant Nigerian primigravidae.

Plasma volume was measured in 10 non-pregnant, healthy nulliparous Nigerian and 30 normal primigravid Nigerians at various times of gestation by the Evans blue dye dilution technique. The mean plasma volume of 2098 ml for the non-pregnant Nigerians was statistically different (P less than 0.001) from values in non-pregnant caucasian primigravidae of comparable status. A mean maximum plasma volume increase of 1387 ml above non-pregnant value was found. Essentially, pregnancy imposed a much higher physiological load on Nigerian primigravidae compared to caucasian primigravidae. There was a significant negative correlation between plasma volume and packed cell volume (PCV) in pregnancy (r = -0.51, P less than 0.001), which may be related to excessive hemodilution in the primigravid Nigerian. Differences found may be due to geographical and/or racial factors.

Adolescent↗

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↗

An accurate method of plasma volume measurement by direct analysis of Evans blue spectra in plasma without dye extraction: origins of albumin-space variations during maximal exercise.

The Evans blue dye (EBD) dilution method, including a dye extraction step, is a standard way of measuring plasma volume. This report describes a new direct spectrophotometric method, which is simple and specific and avoids the dye extraction step. To begin with, all the contaminants which may appear during a plasma volume study were added to plasma samples, prior to the absorbance measurements. In this way we calculated correction factors for the haemolysis and the turbidity of the plasma samples, without dye. The study of the visible spectra showed that the correction factors could be obtained by measuring absorbances at only four visible wavelengths: 780, 720, 619 and 578 nm. The addition of various amounts of contaminants to dye-containing plasma samples allowed us to obtain precise values for the absorbance errors. The previously defined correction factors were then applied, and the residual absorbance errors were found to become nil. This spectrophotometric method can be used to check the efficiency of a dye-extraction procedure, as well as to study other biological fluids containing EBD. When used to analyse a chronological series of blood samples this method appeared to provide an effective way of simultaneously studying the processes of plasma volume concentration and albumin extravasation induced by maximal exercise.

Coloring Agents↗

Plasma volume, red cell volume, and thoracic duct lymph flow in hypothermia.

The effects of hypothermia on plasma volume (125I-albumin), red blood cell volume (51 Cr-RBC), and capillary permeability (thoracic duct lymph flow and protein concentration) were determined on dogs anesthetized with pentobarbital, paralyzed with succinylcholine, and mechanically ventilated. Red blood cell volume and plasma protein concentration did not change significantly after cooling. Reductions in plasma volume and total plasma proteins indicate that whole plasma was excluded from the effective circulating blood volume. Except for a lesser increase in hematocrit, chronically splenectomized dogs showed essentially the same changes as normal dogs in response to hypothermia. Following application of ice bags, there was a biphasic response in lymph flow. The early increase in lymph flow accompanying a slight decrease in plasma volume was attributable to transcapillary fluid loss into interstitial space, probably due to cold-induced sympathetic activity. The later decrease in lymph flow in hypothermia resulted from a decrease of lymph production secondary to a decrease in available capillary diffusion area. This decrease in lymph flows and the continued reduction in plasma volume suggest an intravascular sequestration of whole plasma.

Animals↗

Measurement of plasma volume in pregnancy.

1. Determination of the plasma volume in pregnant women is a useful research tool and may become an important clinical measurement. We used three methods to determine plasma volume using Evans Blue dye: (1) the 'usual' method, measuring serum absorbance at a wavelength of 610 nm, (2) a two-wavelength method, and (3) precipitation of non-albumin proteins by the addition of polyethyleneglycol before measuring serum absorbance at a wave-length of 620 nm. These were each compared with the standard 125I-human serum albumin method in 20 non-pregnant subjects. Subsequently, the polyethylene glycol method was considered the standard and the three Evans Blue dye methods were compared in 20 pregnant women. 2. In non-pregnant subjects mean plasma volumes did not differ significantly according to the method used. However, the limits of agreement with 125I-human serum albumin method were closest for the polyethyleneglycol method, for both clear and turbid sera. 3. In pregnant women, mean plasma volume values did not differ according to the Evans Blue dye method used, but the limits of agreement were significantly closer with the two-wavelength method than with the 'usual' method (P less than 0.05) largely owing to the effects of turbid sera. 4. These studies demonstrate that considerable error may occur when the Evans Blue dye concentration is determined in turbid sera by the 'usual' method. This can be overcome by the use of the two-wavelength method or the polyethyleneglycol method. The most accurate results will be obtained if the latter method is employed routinely to determine plasma volume in pregnant women.

Adult↗

Plasma volume expansion in early pregnancy.

OBJECTIVE: To determine the time course of plasma volume expansion in early pregnancy. METHODS: We prospectively measured plasma volume by Evans blue dye dilution during the menstrual (cycle day 2--3), follicular (cycle day 9--10), and luteal phases (cycle day urinary leutinizing hormone [LH] surge plus 9--10) of the menstrual cycle and at three additional time points (LH surge + 16 days, LH surge + 28 days, and LH surge + 70 days) in women achieving pregnancy. Twenty-one subjects were examined during 38 menstrual cycles to establish baseline menstrual cycle data. Ten subjects conceived within 1 year of menstrual cycle studies. All ten pregnancies were viable and reached the third trimester. Analyses used repeated-measures analysis of variance with P <.05 accepted for significance. RESULTS: Mean plasma volume was found to change significantly across the period of observation (P <.008) in those who conceived. Plasma volume at LH surge + 70 days (12 menstrual weeks, 2320 +/- 280 mL) was greater than either menstrual cycle estimates or early pregnancy estimates of plasma volume. There was no difference in plasma volume at LH surge + 16 days (2077 +/- 288 mL) or LH surge + 28 days (2010 +/- 271 mL) compared with menstrual cycle measurements during the menstrual phase (2156 +/- 292 mL), follicular phase (2036 +/- 280 mL), and luteal phase (2120 +/- 425 mL). There was no significant difference between those who conceived and those who did not in their mean menstrual cycle plasma volume. CONCLUSION: Plasma volume expansion in early human pregnancy cannot be identified until after the sixth menstrual week. By 12 menstrual weeks, plasma volume has expanded by approximately 14% +/- 12% (mean +/- SD) over follicular phase measurements.

Adult↗

Contracted plasma volume syndromes.

There is a wide range of disorders in which plasma volume may be contracted. This may either be due to a primary reduction in plasma volume, or secondary to a reduction in the volume of the vascular compartment. In the former there may be a salt and water deficit as the cause or a loss of plasma volume due to a capillary leak. Reduction of the vascular compartment is usually due to increased adrenergic activity reducing the circulatory capacitance volume. Plasma volume is reduced to compensate for the overfilling of the central circulation. The causes and clinical significance of plasma volume contraction are discussed, with particular emphasis on the pathophysiology and implications for therapy. The controversial subject of stress polycythaemia is addressed and a theoretical analysis of its pathophysiology presented.

Erythrocyte Indices↗

Angiotensinogen genotype and plasma volume in nulligravid women.

OBJECTIVE: To determine if nonpregnant plasma volume is altered in women who are homozygous for the T 235 coding angiotensinogen allele, which predisposes women to an increased risk of preeclampsia. METHODS: We measured plasma volume by Evans blue dilution and analyzed it as a function of angiotensinogen genotype in 15 nulligravid women during midfollicular phase of 26 menstrual cycles. Eleven women were evaluated during two cycles, and four women were evaluated in one cycle. Fourteen women were white, and one was Asian. No subjects had illnesses or were taking medication. The range of body mass index (BMI [kg/m2]) was 20.2-31.0. Plasma volume (mL) was reported as plasma volume divided by BMI to control for variations in body sizes. Statistical analysis was performed by analysis of variance with post hoc testing using Fisher least significant difference test for multiple comparisons (P < .05 accepted for significance). RESULTS: Angiotensinogen genotype analysis showed five women homozygous for M 235, three women homozygous for T 235, and seven women who were heterozygous (MT 235). T 235 homozygotes had significantly lower plasma volume divided by BMI compared with women who were homozygous for M 235 and women who were heterozygous for MT 235 (mean + standard deviation [SD] [71.2 + 8.8, 86.6 + 5.2, 95.8 + 15.6, respectively, P < .05]). There was a tendency toward higher plasma volume in heterozygote MT 235 compared with homozygote M 235 carriers, but it was not statistically significant. CONCLUSION: We conclude that the homozygous T 235 coding angiotensinogen genotype is associated with reduced plasma volume in nulligravid women during the follicular phase of the menstrual cycle compared with M 235 homozygotes and heterozygotes. This association of the T 235 coding genotype might contribute to fetal growth restriction in preeclampsia.

Angiotensinogen↗

[Change of plasma volume on patients treated by induced hypertension therapy for vasospasm].

UNLABELLED: Plasma volume, central venous pressure and water balance of 24 patients were measured about 1st and 2nd week after early operation for the ruptured aneurysms. All of the patients had been treated by induced hypertension therapy for delayed vasospasm successfully. Plasma volume was measured by RI method using RISA. The average of plasma volume of 16 patients was 58.3 +/- 6.0 ml/kg. This group had 200 ml of 25% albumin every day. It was 48.2 +/- 6.2 ml/kg on 8 patients without albumin. The average of CVP was 11.3 +/- 2.2 cm on the albumin group. It was 5.3 +/- 1.5 cm on the other group. The value of plasma volume and CVP was higher statistically on the albumin group than the other group. Water balance was positive on about half of the albumin group. It was negative on the other group. Three patients of the albumin group had pulmonary edema. THE CONCLUSION: The state of patient's hydration is not hypovolemic, as far as the induced hypertension therapy is possible, even though patient's CVP is low and water blance is negative. Albumin lets the plasma volume increase easily. Therefore, the risk of pulmonary edema may rise when only unreliable CVP is used for the monitoring of plasma volume. Plasma volume measurement is indispensable to the monitoring of fluid management for vasospasm and plasma volume should be aimed at 55-60 ml/kg.

Adult↗

Concurrent expansion of plasma volume and left ventricular end-diastolic volume in patients after rapid infusion of 5% albumin and lactated Ringer's solution.

STUDY OBJECTIVE: To examine the effects of plasma volume expansion on plasma volume, left ventricular end-diastolic volume (LVEDV), and cardiac index (CI) after rapid fluid infusion, as knowledge of the degree of concordance between plasma and cardiac preload expansion could optimize LVEDV expansion without administering excessive fluid. DESIGN: Randomized, double-blinded study. SETTING: Academic community hospital. PATIENTS: 20 patients undergoing elective coronary artery bypass surgery. INTERVENTIONS: Patients were administered either 5% albumin (5 mL/kg) or lactated Ringer's solution (25 mL/kg) over 30 minutes, just before incision. MEASUREMENTS: Serial measurements of plasma volume, LVEDV by transesophageal echocardiography, and CI were recorded. MAIN RESULTS: Albumin expanded plasma volume and LVEDV to a similar degree (11.3% and 13.2%). In contrast, lactated Ringer's solution increased plasma volume more than LVEDV (21.7% vs 14.4%; P = 0.0005). Increased LVEDV significantly but poorly correlated with increased CI (r(2) = 0.2, P < 0.0001) for both fluids. However, LVEDV expansion was brief and returned to baseline or less within 30 minutes for both fluids despite continued plasma volume expansion and increased CI. Correspondingly, rates of decline from peak expansion were significantly faster for LVEDV than plasma volume expansion for both albumin (-1.9% + 1.9%/min vs -0.1% + 0.1%/min; P = 0.0008) and lactated Ringer's (-1.1% + 0.8%/min vs -0.4% + 0.2%/min; P = 0.006). CONCLUSIONS: Intravenous fluids increased LVEDV to a lesser extent and duration than did plasma volume expansion. Monitoring of LVEDV was a poor guide for fluid administration to maximize CI.

Aged↗

Plasma volumes, noradrenaline levels and renin activity during posture changes in end-stage renal failure.

In nine normal subjects and nine patients with end-stage chronic renal failure (CRF) we studied the effect of prolonged (110 min) postural changes on the plasma volume, intrathoracic volume, plasma noradrenaline concentration, haemodynamic variables, and plasma renin activity (PRA). Upon standing, plasma volume decreased rapidly by about 11% in both groups as measured from the control volume and changes in haematocrit. This was accompanied by identical increments of plasma colloid osmotic pressure. The changes in intrathoracic volume (monitored by measurement of the electrical impedance of the thorax), as well as the alterations in plasma noradrenaline, blood pressure, and heart rate, were also comparable in the two groups. These similarities were in contrast with divergent responses of PRA. The increase in PRA on standing was significantly blunted in the CRF patients compared with the normal response (to 1.4 +/- 0.4 fold of the supine value in CRF v. 6.0 +/- 3.2 fold in the normals, P less than 0.0004). It is concluded that the attenuated increase in PRA upon standing in patients with CRF is not a consequence of diminished sympathetic stimulation or an altered response of the intravascular volume. Second, the unabated decrease in plasma volume upon standing pleads against a decrease of tissue compliance in CRF.

Adult↗

Persistent abnormalities in plasma volume and renal hemodynamics in patients with a history of preeclampsia.

OBJECTIVE: The objective was to test the hypothesis that women with a recent history of preeclampsia have abnormalities in renal hemodynamics and volume status. STUDY DESIGN: We studied a group of 26 primiparous women with history of preeclampsia and a group of 12 parous women with a history of uneventful pregnancies (control group). At least 4 months post partum we compared the following variables between these groups: effective renal plasma flow, glomerular filtration rate, plasma volume, plasma concentration of active renin, plasma concentration of angiotensin II, plasma concentration of aldosterone, and plasma concentration of atrial natriuretic peptide. RESULTS: Both plasma volume and plasma concentration of atrial natriuretic peptide were lower in the formerly preeclamptic group. Compared with the control subjects, the formerly preeclamptic group also had a lower effective renal plasma flow, a higher filtration fraction, and a higher renal vascular resistance. Intergroup differences in plasma concentration of active renin, plasma concentration of angiotensin II and plasma concentration of aldosterone were small and inconsistent. CONCLUSIONS: Women with history of preeclampsia are relatively hypovolemic and tend to have lower effective renal plasma flow and higher renal vascular resistance and filtration fraction than do control subjects. These findings support the hypothesis that otherwise healthy women with a history of preeclampsia show abnormalities in their volume status and renal hemodynamics, irrespective of their blood pressure.

Adult↗

The pattern of plasma volume changes in well-nourished and in food- or protein-restricted pregnant rats.

Plasma volume and plasma protein were measured on days 5, 12, 19, and 21 of gestation in rats fed 25% casein either ad libitum or 55% food restricted, or fed 6% casein ad libitum (protein restricted). Both forms of undernutrition prevented the large increase in plasma volume observed in well-fed rats by day 19. The pattern of plasma volume change, with maximum mean values on day 19 (compared to the other measurement days), was not altered by undernutrition. Differences in plasma protein concentration or total circulating protein did not explain plasma volume changes.

Animals↗

Clinical aspects of the control of plasma volume at microgravity and during return to one gravity.

Plasma volume is reduced by 10-20% within 24-48 h of exposure to simulated or actual microgravity. The clinical importance of microgravity induced hypovolemia is manifested by its relationship with orthostatic intolerance and reduced maximal oxygen uptake (VO2max) after return to one gravity (1G). Since there is no evidence to suggest that plasma volume reduction during microgravity is associated with thirst or renal dysfunctions, a diuresis induced by an immediate blood volume shift to the central circulation appears responsible for microgravity-induced hypovolemia. Since most astronauts choose to restrict their fluid intake before a space mission, absence of increased urine output during actual space flight may be explained by low central venous pressure (CVP) which accompanies dehydration. Compelling evidence suggests that prolonged reduction in CVP during exposure to microgravity reflects a "resetting" to a lower operating point, which acts to limit plasma volume expansion during attempts to increase fluid intake. In ground based and space flight experiments, successful restoration and maintenance of plasma volume prior to returning to an upright posture may depend upon development of treatments that can return CVP to its baseline IG operating point. Fluid-loading and lower body negative pressure (LBNP) have not proved completely effective in restoring plasma volume, suggesting that they may not provide the stimulus to elevate the CVP operating point. On the other hand, exercise, which can chronically increase CVP, has been effective in expanding plasma volume when combined with adequate dietary intake of fluid and electrolytes. The success of designing experiments to understand the physiological mechanisms of and development of effective counter measures for the control of plasma volume in microgravity and during return to IG will depend upon testing that can be conducted under standardized controlled baseline conditions during both ground-based and space flight investigations.

Adaptation, Physiological↗

Thiazide induced hypotension: the role of plasma volume reduction and the urinary kallikrein system.

The hypotensive response the thiazide diuretics was studied in 15 males with moderate essential hypertension and correlated with serial changes in plasma volume, weight, plasma renin activity, urinary aldosterone, and urinary kallikrein, both total and activity. A greater than 10 mmHg fall in mean arterial pressure after four weeks of treatment defined the responders to therapy (n = 10) while all others were considered non-responders (n = 5). In responders, the fall in mean arterial pressure was accompanied by sustained reduction in plasma volume and weight. No sustained fall in plasma volume was noted in non-responders. Plasma renin activity and urinary aldosterone excretion increased in responders but not in non-responders. Urinary kallikrein, both total and active, increased in the responders but remained unchanged in the non-responders. The results are consistent with the hypothesis that a sustained reduction in plasma volume is necessary for the maintenance of a hypotensive response to thiazides. Stimulation of the renal kallikrein-kinin system may be necessary to balance the antinatriuretic and pressor effects of the renin-angiotensin-aldosterone system. If unopposed, this system would return plasma volume and blood pressure to pretreatment levels.

Aldosterone↗

Formerly preeclamptic women with a subnormal plasma volume are unable to maintain a rise in stroke volume during moderate exercise.

INTRODUCTION: In formerly preeclamptic women with a low plasma volume, the recurrence rate of preeclampsia is higher than in women with a normal prepregnant plasma volume. In a recent study, we demonstrated that the low plasma volume subgroup also had a subnormal venous capacitance. In the present study, we determined the impact of subnormal plasma volume on the hemodynamic response to moderate exercise. PATIENTS AND METHODS: We performed this study in the follicular phase of the menstrual cycle, in 31 formerly preeclamptic women with a subnormal plasma volume (low-PV) and eight parous controls. The exercise consisted of 60 minutes of cycling in the supine position at 35% of the individualized maximum capacity. Before, during, and after cycling, we measured the percentage change in heart rate, stroke volume, and cardiac output. Before and after exercise, we measured the effective renal plasma flow (ERPF, para-amino-hippurate [PAH] clearance), glomerular filtration rate (GFR, inulin clearance), circulating levels of alpha-atrial natriuretic peptide (alpha-ANP), and active plasma renin concentration (APRC). RESULTS: The response to exercise of formerly preeclamptic women with a subnormal plasma volume differed from that in controls by a lack of rise in stroke volume, a smaller rise in cardiac output and alpha-ANP, and a greater fall in GFR. The responses in heart rate, ERPF, and APRC did not differ between the two groups. CONCLUSION: The response to moderate exercise of formerly preeclamptic women with a subnormal plasma volume differs from that in healthy parous controls with a normal plasma volume and suggests a lower capacity to raise venous return in conditions of a higher demand for systemic flow. The lower capacity to raise venous return in these conditions is associated with more cardiovascular drift. The physiologic consequence is a lower aerobic endurance performance during moderate exercise.

Adult↗

Plasma volume determination in normal and preeclamptic pregnancies.

To determine the clinical usefulness of plasma volume determinations, we measured plasma volume serially throughout pregnancy with the use of the Evans blue dye-dilution technique in 20 subjects with normal pregnancies. In comparison, four preeclamptic subjects were studied. In preeclamptic subjects compared to normal subjects, plasma volume was reduced (1763 +/- 216 versus 2345 +/- 198 ml/m2, p less than 0.001). Two normotensive subjects who subsequently developed preeclampsia had reduced plasma volumes prior to the onset of hypertension as compared to volumes in those who remained normotensive (1918 +/- 86 versus 2345 +/- 198 ml/m2, p less than 0.01). Those subjects who were delivered of infants who were small for gestational age had significantly reduced plasma volumes compared to volumes of those who were delivered of infants who were appropriate for gestational age (1950 +/- 333 versus 2237 +/- 259 ml/m2, p less than 0.05), but this was true only among gravid women with pregnancies complicated by preeclampsia. We conclude that failure of plasma volume expansion is associated with the development of preeclampsia and also intrauterine fetal growth retardation in preeclamptic subjects.

Birth Weight↗