Evans Blue Dye Dilution Research Articles

Total Hemoglobin Mass Correlates with Peak Oxygen Consumption in Patients with Chronic Stroke

Background: The peak oxygen consumption (V.O2peak) and blood hemoglobin concentration [Hb] are lower in stroke patients than in age-matched healthy subjects. The ability of skeletal muscles to extract oxygen is diminished after stroke. We hypothesized that the oxygen extraction capacity of skeletal muscles in stroke patients depends on [Hb]. To test the hypothesis, we determined the relationship between V.O2peak and total hemoglobin mass (tHb-mass) in stroke patients. Methods: The subjects were 19 stroke patients (age: 74 ± 2, mean ± SD, 10 males) and 11 age-matched normal subjects (age 76 ± 3, 6 males). Plasma volume (PV) and V.O2peak were measured on the same day. PV was measured using Evans Blue dye dilution method. Blood volume (BV) was calculated from PV and hematocrit, while tHb-mass was estimated from BV and [Hb]. Each subject underwent cardiopulmonary exercise test on a bicycle ergometer using a V.O2peak respiratory gas analyzer. Results: There were no differences in age, height, and weight between the two groups. V.O2peak was lower in stroke patients than in the control. BV and tHb mass were not significantly different between the two groups, but [Hb] was significantly lower in stroke patients. In stroke patients, V.O2peak correlated significantly with tHb-mass (r = 0.497, p < 0.05), but not with BV. Conclusion: Our results suggested that low [Hb] seems to contribute to V.O2peak in stroke patients. The significant correlation between tHb-mass and V.O2peak suggested that treatment to improve [Hb] can potentially improve V.O2peak in stroke patients.

Modeling the Evans Blue Dilution Method for the Measurement of Plasma Volume in Small Animals: A New Optimized Method.

The measurement of plasma volume (Vp) in humans and animals is frequently performed by the Evans blue dye dilution method. However, after injection of Evans blue into the circulation, no steady state is observed because of delayed mixing and progressive leakage of dye out of vascular space. Various methods of calculation have been proposed, either with a single blood sampling 5-10min after dye injection (Single point method), or with extrapolation at time zero of a logarithmic decay (Log linear method). We propose a method based on a two-compartment hypothesis taking into account the initial mixing and the leakage phase in the time course of dye concentration. Nineteen Sprague-Dawley rats were studied in various conditions and blood sampling was performed before and 2, 4 and 6min after injection of 200μg Evans blue. A mathematical model was designed to describe the two-compartment hypothesis and allowed the calculation of Vp and Kout (rate of disappearance of dye from vascular space). A Bland and Altman representation evidenced an overestimation of Vp with previous methods and the great dispersion of results with the single point method, especially when using the 6min point. Calculation of Kout revealed more accurate with the model than the Log linear method, especially when the mixing rate is slow. We suggest using the two-compartment model to measure Vp with Evans blue technique in rats. This method also allows precise evaluation of the rate of dye leakage, which could be a good marker of vascular permeability to albumin.

Re-evaluation of Evans blue dye dilution method of plasma volume measurement.

To simplify the method of plasma volume measurement by Evans blue dye dilution we used, for the first time, the same venous site for injection of dye and collection of samples. In a series of 49 studies the dye decay between 10 and 35 min after injection was highly linear (r = 0.991 +/- 0.01), indicating that contamination of samples is very unlikely. We repeated the measurements after eight weeks in nine patients; the mean difference was 16.4 +/- 19.6 ml, indicating a high degree of reproducibility. We found that extrapolation of the dye decay curve to time zero is required for accurate estimates of plasma volume. There was good agreement between the estimates of plasma volume obtained by extrapolation from only three samples taken at 10, 20 and 30 min after dye injection with the results obtained using all six samples. We also found good agreement between the estimates of plasma volume obtained by using standard curves constructed from four standard dilutions of 1.25, 2.5, 5 and 10 mg/l and those obtained by the use of standard curves constructed from the blank and only one standard dilution of 10 mg/l. We therefore conclude that the Evans blue technique can be simplified with minimal loss of accuracy, by using only one venous site for injection and withdrawal, withdrawing only three samples between 10 and 30 min after injection and using a two point calibration line.

Chronic vasodilation produces plasma volume expansion and hemodilution in rats: consequences of decreased effective arterial blood volume.

Plasma volume (PV) expansion is required for optimal pregnancy outcomes; however, the mechanisms responsible for sodium and water retention in pregnancy remain undefined. This study was designed to test the "arterial underfill hypothesis" of pregnancy which proposes that an enlarged vascular compartment (due to systemic vasodilation and shunting of blood to the placenta) results in renal sodium and water retention and PV expansion. We produced chronic vasodilation by 14 days administration of nifedipine (NIF; 10 mg·kg(-1)·day(-1)) or sodium nitrite (NaNO2; 70 mg·kg(-1)·day(-1)) to normal, nonpregnant female Sprague-Dawley rats. Mean arterial pressure, monitored by telemetry, was reduced by both NIF and NaNO2 but was unchanged in control rats. At day 14, vasodilator treatment lowered hematocrit and increased PV (determined by Evans blue dye dilution). Plasma osmolarity (Posm), sodium (PNa), and total protein concentrations all fell. These responses resemble the responses to normal pregnancy with hemodilution, marked PV expansion, and decreased Posm and PNa. Our previous work indicates a role of increased inner medullary phosphodiesterase-5 (PDE5) in the sodium retention of pregnancy. Here, we found that inner medullary PDE5A mRNA and protein expression were increased by both NIF and NaNO2 treatment vs. control; however, neither renal cortical nor aortic PDE5 expression was changed by vasodilator treatment. We suggest that a primary, persistent vasodilation drives increased inner medullary PDE5 expression which facilitates continual renal Na retention causing "refilling" of the vasculature and volume expansion.

Effect of reduced total blood volume on left ventricular volumes and kinetics in type 2 diabetes

Although impaired left ventricular (LV) diastolic function is commonly observed in patients with type 2 diabetes, it remains unclear whether the impairment is caused by altered LV relaxation or changes in LV preload. The purpose of this study was to examine the influence of LV function and LV loading conditions on stroke volume in men with type 2 diabetes. Cardiac magnetic resonance imaging scans were performed in eight men with type 2 diabetes and 11 non-diabetic men matched for age, weight and physical activity level. Total blood volume was determined with the Evans blue dye dilution technique. End-diastolic volume (EDV), the ratio of peak early to late mitral inflow velocity (E/A) and stroke volume were lower in men with type 2 diabetes than in non-diabetic individuals. Peak filling rate and peak ejection rate were not different between diabetic and non-diabetic individuals; however, men with type 2 diabetes had proportionally longer systolic duration than non-diabetic individuals. Heart rate was higher and total blood volume was lower in men with type 2 diabetes. The lower total blood volume was correlated with a lower EDV in men with type 2 diabetes. Men with type 2 diabetes have an altered cardiac cycle and lower end-diastolic and stroke volume. A lower total blood volume and higher heart rate in men with type 2 diabetes suggest that changes in LV preload, independent of changes in LV relaxation or contractility, influence LV diastolic filling and stroke volume in this population.

Effect of post-exercise sauna bathing on the endurance performance of competitive male runners

The physiological adaptations to sauna bathing could enhance endurance performance. We have therefore performed a cross-over study in which six male distance runners completed 3 wk of post-training sauna bathing and 3 wk of control training, with a 3 wk washout. During the sauna period, subjects sat in a humid sauna at 89.9+/-2.0 degrees C (mean+/-standard deviation) immediately post-exercise for 31+/-5 min on 12.7+/-2.1 occasions. The performance test was a approximately 15 min treadmill run to exhaustion at the runner's current best speed over 5 km. The test was performed on the 1st and 2nd day following completion of the sauna and control periods, and the times were averaged. Plasma, red-cell and total blood volume were measured via Evans blue dye dilution immediately prior to the first run to exhaustion for each period. Relative to control, sauna bathing increased run time to exhaustion by 32% (90% confidence limits 21-43%), which is equivalent to an enhancement of approximately 1.9% (1.3-2.4%) in an endurance time trial. Plasma and red-cell volumes increased by 7.1% (5.6-8.7%) and 3.5% (-0.8% to 8.1%) respectively, after sauna relative to control. Change in performance had high correlations with change in plasma volume (0.96, 0.76-0.99) and total blood volume (0.94, 0.66-0.99), but the correlation with change in red cell volume was unclear (0.48, -0.40 to 0.90). We conclude that 3 wk of post-exercise sauna bathing produced a worthwhile enhancement of endurance running performance, probably by increasing blood volume.

Hypervolemia of pregnancy is not maintained in mice chronically overexpressing angiotensinogen

Women who develop pre-eclampsia show significantly less hypervolemia of pregnancy, compared with controls. We have shown that chronically elevated angiotensinogen expression increases a woman's risk of developing pre-eclampsia. Our objective was to determine whether increased angiotensinogen expression is sufficient to cause failed hypervolemia. To isolate the effects of elevated angiotensinogen expression, we studied transgenic mice with either 2 or 3 copies of the murine angiotensinogen gene. Plasma volume was measured by Evans blue dye dilution, and kidney sections were immunostained for angiotensinogen and renin. Three-copy mice failed to maintain hypervolemia after midgestation (P < .01) and failed to up-regulate renin expression in the distal nephron, compared with 2-copy controls. Intrarenal angiotensinogen was up-regulated during pregnancy in both genotypes. Chronically elevated angiotensinogen expression is sufficient to cause failed hypervolemia of pregnancy. Whether this observation is related to failed up-regulation of distal tubule renin expression requires further study.

Short-term aerobic training and circulatory function in women: age and hormone-replacement therapy

The physiological basis of training responses in women, and particularly older women, is not well understood. Short-term aerobic training (STAT) was used to probe the effects of age and hormone-replacement therapy (HRT) on women's ability to rapidly change peak uptake ( VO(2max)), plasma volume and cardiac function. A total of 39 females participated in the STAT programme: 15 younger (Y; aged 19-29 years), 12 postmenopausal women undergoing HRT and 12 non-medicating postmenopausal (PM) women (aged 60-75 years). Training consisted of ten sessions of cycling over a 2-week period, which progressed in duration from 20 to 60 min and in intensity from 60-75% of maximum heart rate. Plasma volume (PV; as determined by Evan's Blue dye dilution), VO(2max) (cycle ergometry) and cardiac function (radionuclide ventriculography) were analysed using analysis of covariance or repeated measures ANOVA. All groups demonstrated similar increase in VO(2max) (Y, 13%; PM, 17%; HRT, 13%), but without a significant change in left-ventricular ejection fraction and diastolic function or volumes during supine exercise. PV expansion was observed among the Y group (7%; P <0.05) but not the PM group (2%; P >0.05) or women undergoing HRT (1%; P >0.05). Age and hormone-replacement status did not affect the magnitude of VO(2max) change. This study suggests that STAT improves VO(2max), independent of central adaptations.

Short-term aerobic training and circulatory function in women: age and hormone-replacement therapy

The physiological basis of training responses in women, and particularly older women, is not well understood. Short-term aerobic training (STAT) was used to probe the effects of age and hormone-replacement therapy (HRT) on women's ability to rapidly change peak uptake (VO2max), plasma volume and cardiac function. A total of 39 females participated in the STAT programme: 15 younger (Y; aged 19–29 years), 12 postmenopausal women undergoing HRT and 12 non-medicating postmenopausal (PM) women (aged 60–75 years). Training consisted of ten sessions of cycling over a 2-week period, which progressed in duration from 20 to 60min and in intensity from 60–75% of maximum heart rate. Plasma volume (PV; as determined by Evan's Blue dye dilution), VO2max (cycle ergometry) and cardiac function (radionuclide ventriculography) were analysed using analysis of covariance or repeated measures ANOVA. All groups demonstrated similar increase in VO2max (Y, 13%; PM, 17%; HRT, 13%), but without a significant change in left-ventricular ejection fraction and diastolic function or volumes during supine exercise. PV expansion was observed among the Y group (7%; P&lt;0.05) but not the PM group (2%; P&gt;0.05) or women undergoing HRT (1%; P&gt;0.05). Age and hormone-replacement status did not affect the magnitude of VO2max change. This study suggests that STAT improves VO2max, independent of central adaptations.

Relationship between body composition, blood volume and maximal oxygen uptake.

It has long been known that body mass and, more specifically, lean body mass are strongly correlated with maximal oxygen uptake (VO2max) in man and animals. However, there are no data to date describing this phenomenon in the horse. The purpose of this paper is to examine the relationship between body composition and VO2max in the horse. Twenty-three healthy and unfit Standardbred mares performed an incremental exercise test (GXT) to measure VO2max. Rump fat thickness (RTH), a measure of fat covering, was measured using B-mode ultrasound. Plasma volume, total blood volume and red cell volume were determined, using the Evan's Blue dye dilution technique and packed cell volume. VO2max was correlated with body mass (r = 0.541; P<0.01) and exercise haematocrit (exHCT; r = 0.407; P<0.05) but not RTH or the other haematological variables. To eliminate the influence of body mass on the individual variables, a regression analysis was performed on the mass-residuals of VO2max, RTH, plasma volume and exHCT. The residuals of VO2max were correlated negatively with the residuals of RTH (r = -0.687; P = 0.0003) and positively with the residuals of exHCT (r = 0.422; P = 0.045) but not plasma volume. VO2max could be predicted from a linear combination of the residuals of RTH and exHCT (r = 0.767; P<0.0001). These data indicate that VO2max in the horse is significantly related to fat-free mass (FFM), independent of body mass. Red blood cells from the splenic reserve constitute an important factor in the horse's ability to achieve a high VO2max. Therefore, lean body mass may be a more appropriate basis for assessing metabolic function in the athletic horse.

Changes in circulating blood and plasma volume after hemoglobin-based oxygen carrier infusion and additional infusion of colloid solutions.

The aim of this study was to investigate the changes in circulating blood volume (CBV) after infusions of Hemoglobin glutamer-200 (bovine; Hb-200) in combination with 6% hetastarch in an animal model of acute posthemorrhagic anemia. Fifteen rabbits with a mean body weight of 2.2 +/- 0.2 kg were studied. After determination of the circulating plasma volume (CPV) and CBV, one third of the CBV was withdrawn via an arterial catheter. An equal volume of Hb-200 was then infused in the 5 animals in study group 1. In the remaining 10 animals, the same volume of 6% hetastarch solution was infused. Fifteen minutes after completion of the infusion, an additional infusion of 6% hetastarch at a dose equal to one third of the baseline CBV was performed in study group 1 and the control group. In study group 2, equal volumes of Hb-200 were infused. CPV measurements were performed at baseline, after hemorrhage, 5 and 15 minutes after volume replacement, and 1 and 15 minutes after hypervolemic hemodilution using the Evans blue dye dilution technique. The mean baseline CPV value was 53.4 +/- 1.1 mL/kg. The mean CBV at baseline was 90.8 +/- 4.9 mL/kg. After one third of the CBV was withdrawn, no differences in CBV or CPV were observed between the three groups. Replacement of one third of the CBV with Hb-200 significantly increased the CPV (73.7 +/- 1.8 mL/kg) when compared with the baseline level (53.5 +/- 1.8 mL/kg; n = 5; P < 0.05). The difference between the groups was first observed 15 minutes after infusion. CPV was significantly higher in study group 1 (87.0 +/- 2.2 mL/kg) compared with the other groups (80.2 +/- 2.6 mL/kg in the control group and 79.5 +/- 3.6 mL/kg in study group 2). After a second transfusion, the differences between the groups became more prominent. Study group 2 demonstrated the highest CPV and CBV. The two study groups demonstrated a statistically significant increase in circulating volumes compared with the control group. The magnitude of this difference was lower than expected based on in vitro colloid osmotic pressure measurements.

Clinical effects of thigh cuffs during a 7-day 6° head-down bed rest

Thigh cuffs are used by Russian cosmonauts to limit the fluid shift induced by space flight. A ground simulation using the head-down bed rest (HDBR) model was performed to assess the effects of thigh cuffs on clinical tolerance and orthostatic adaptation. 8 male healthy volunteers (32.4±1.9 years) participated twice in a 7-day HDBR — one time with thigh cuffs (worm daily from 9 am to 7 pm) (TC) and one time without (WTC). Orthostatic tolerance was assessed by a 10 minute stand test and by a LBNP test (5 min at −15, −30, −45 mmHg) before (BDC-1) and at the end of the HDBR period (R+1). Plasma volume was measured before and at the end of HDBR by the Evans blue dye dilution technique. Thigh cuffs limits headache due to fluid shift, as well as the loss in plasma volume (TC: −5.85±0.95%; WTC: −9.09±0.82%, p<0.05). The mean duration of the stand test (R+1) did not differ in the two group (TC 7.1±1.3 min; WTC 7.0±1.0 min). The increase in HR and decrease in diastolic blood pressure were slightly but significantly larger without thigh cuffs. Duration of the LBNP tests did not differ with thigh cuffs. Thigh cuffs limit the symptoms due to fluid shift and the loss in plasma volume. They partly reduced the increase in HR during orthostatic stress but had no effect on duration of orthostatic stress tests.

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.

Plasma Volume Expansion in Early Pregnancy

In Brief 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. Plasma volume expansion in pregnancy can be detected 12 weeks after the last menstrual period but not at 6 weeks.

A novel approach to measuring circulating blood volume: the use of a hemoglobin-based oxygen carrier in a rabbit model.

Hemoglobin-based oxygen carriers (HBOC) may be ideal for monitoring circulating plasma volume (CV-P) and circulating blood volume (CV-B). We used an HBOC (Hemoglobin glutamer-200 [bovine], Oxyglobin; Biopure, Cambridge, MA) as an indicator for relative CV-B in the rabbit model. Accuracy of the technique was determined by comparison with the Evans blue dye (EBD) dilution technique in 19 anesthetized female New Zealand rabbits weighing 2.0 to 10.6 kg. The measurements were performed at baseline, after hemorrhage (1/3 of CV-B), normovolemic hemodilution (replacement of 1/3 CV-B by Hextend; Abbot Laboratories, North Chicago, IL), and hypervolemic hemodilution (additional infusion of Hextend(R) in a volume equal to 1/3 of CV-B). Hemoglobin concentration was measured by using a HemoCue photometer (HemoCue AB, Angelholm, Sweden). EBD concentration was analyzed by using linear regression to estimate Time 0 concentration; Time 0 was defined as EBD injection time. The difference between CV-P values determined by EBD and HBOC dilution was independent from the magnitude of the CV-P value. The relative bias was 1.29 mL, and the precision (one SD) was 2.82 mL. The difference did not reach statistical significance. Circulating plasma and blood volumes can be accurately estimated by plasma hemoglobin concentration measurements by using hemoglobin-based oxygen carrier infusion.

Increased albumin and fibrinogen synthesis in hemodialysis patients with normal nutritional status.

This study compared the rates of whole-body proteolysis and of albumin and fibrinogen synthesis of seven hemodialysis patients (HD) with those of seven normal matched control subjects (C). HD patients had a normal nutritional and inflammatory status and serum albumin levels >3.5 g/dl. Endogenous leucine flux, albumin and fibrinogen fractional synthesis rate (FSR), and absolute intravascular synthesis rate (ASR) of albumin and fibrinogen all were evaluated by a primed/continuous infusion of 5,5,5-D3-L-leucine. Plasma volume was determined by the Evans blue dye dilution method. Endogenous leucine flux was significantly increased in HD (2.64 +/- 0.08 micromol/kg per min) compared with C (2.17 +/- 0.07 micromol/kg per min, P: < 0.05). Serum albumin concentrations were similar in HD and C. Plasma fibrinogen levels were significantly increased in HD compared with C (P: < 0.05). Plasma volume was greater in HD than in C (P: < 0.05). As a result, total intravascular pool of both albumin (141 +/- 7 versus 114 +/- 3 g/1.73 m(2), P: < 0.05) and fibrinogen (11.7 +/- 1 versus 6.7 +/- 0.5 g/1.73 m(2), P: < 0.05) were greater in HD than in C. Albumin FSR was not statistically different in HD and C. However, albumin ASR was significantly increased in HD than in C (13.7 +/- 2 versus 10.3 +/- 1 g/1.73 m(2) per d, P: < 0.05). Similarly, FSR of fibrinogen did not differ in HD and C groups, whereas ASR of fibrinogen was significantly higher in HD than in C (3.31 +/- 0.6 versus 1.94 +/- 0.3 g/1.73 m(2) per d, P: < 0.05). In summary, normoalbuminemic HD patients have an increased intravascular pool with a greater absolute synthesis rate of both albumin and fibrinogen and an increased rate of whole-body leucine flux.

High dose angiotensin-converting enzyme inhibition prevents fluid volume expansion in heart transplant recipients

OBJECTIVESWe sought to test the hypothesis that plasma volume (PV) expansion in heart transplant recipients (HTRs) is caused by failure to reflexively suppress the renin-angiotensin-aldosterone (RAA) axis.BACKGROUNDExtracellular fluid volume expansion occurs in clinically stable HTRs who become hypertensive. We have previously demonstrated that the RAA axis is not reflexively suppressed by a hypervolemic stimulus in HTRs.METHODSPlasma volume and fluid regulatory hormones were measured in eight HTRs (57 ± 6 years old) both before and after treatment with captopril (225 mg/day). Antihypertensive and diuretic agents were discontinued 10 days before. The HTRs were admitted to the Clinical Research Center (CRC), and, after three days of a constant diet containing 87 mEq/day of Na+, PV was measured by using the modified Evans blue dye dilution technique. After approximately four months (16 ± 5 weeks), the same HTRs again discontinued all antihypertensive and diuretic agents; they were progressed to a captopril dose of 75 mg three times per day over 14 days, and the CRC protocol was repeated.RESULTSCaptopril pharmacologically suppressed (p < 0.05) supine rest levels of angiotensin II (−65%) and aldosterone (−75%). The reductions in vasopressin and atrial natriuretic peptide levels after captopril did not reach statistical significance. The PV, normalized for body weight (ml/kg), was significantly reduced by 12% when the HTRs received captopril.CONCLUSIONSExtracellular fluid volume is expanded (12%) in clinically stable HTRs who become hypertensive. Pharmacologic suppression of the RAA axis with high-dose captopril (225 mg/day) returned HTRs to a normovolemic state. These findings indicate that fluid retention is partly engendered by a failure to reflexively suppress the RAA axis when HTRs become hypervolemic.

TWELVE WEEKS OF ENDURANCE TRAINING DOES NOT INDUCE HYPERVOLEMIA IN ELDERLY MALES

1948 The aim of this study was to investigate the time course of blood volume changes during a 12 wk endurance training programme in elderly males. Fourteen men (68 ± 2 yr) trained 3 days per wk for 30 min on a cycle ergometer at 70% V̇O2peak. Peak oxygen consumption and blood volume were reassessed every 4 wk. Blood volume was measured using the Evans Blue dye dilution method. Results: (Table)TableDespite a significant increase in V̇O2peak, the present study found no significant change in blood volume. These results indicate that a 12 wk endurance training programme does not induce hypervolemia in healthy elderly males. Supported by The National Health and Medical Research Council of Australia.

Effects of moderate exercise training on plasma volume, baroreceptor sensitivity and orthostatic tolerance in healthy subjects.

The effect of physical training on an individual's ability to withstand an orthostatic stress is unclear. This study was undertaken to determine the effects on orthostatic tolerance in healthy volunteers of training at a level appropriate for unfit subjects and cardiorespiratory patients. In 11 asymptomatic, untrained subjects the following assessments were made: plasma volume by Evans Blue dye dilution and blood volume derived from haematocrit; carotid baroreceptor sensitivity from the slope of the regression of change in cardiac interval against pressure applied to a neck chamber; orthostatic tolerance as time to presyncope in a test of head-up tilting combined with lower body suction; exercise test relating heart rate to oxygen consumption. Subjects were then given a training schedule (5BX/XBX, Royal Canadian Air Force) involving 11-12 min of mixed exercises per day until an age/sex related 'target' was reached. Following training all subjects showed evidence of improved fitness, seen as decreases in heart rate at an oxygen uptake (Vo2) of 1.5 1 min-1 and in the elevation of the regression line between heart rate and Vo2. All also had increases in plasma and blood volumes and decreases in baroreceptor sensitivity. Seven of the subjects showed increases in orthostatic tolerance. Improvement in orthostatic tolerance was related to a low initial tolerance, and was associated with increases in plasma volume and decreases in baroreceptor sensitivity. These results show that moderate exercise training increases orthostatic tolerance in subjects who do not already have a high initial tolerance and suggest that training may be of value in the management of untrained patients with attacks of syncope due to orthostatic intolerance.

Cardiac Output Responses During Exercise in Volume-Expanded Heart Transplant Recipients

The mechanisms responsible for immediate adjustments in cardiac output at onset of exercise, in the absence of neural drive, are not well defined in heart transplant (HT) recipients. Seven male HT recipients (mean ± SD 57 ± 6 years) and 7 age-matched sedentary normal control subjects (mean age 57 ± 5 years) performed constant load cycle exercise at 40% of peak power output (Watts). Cardiac output and plasma norepinephrine were determined at rest and every 30 seconds during the first 5 minutes of exercise and at minutes 6, 8, and 10. All subjects were admitted to the General Clinical Research Center for determination of plasma volume. After 3 days of equilibration to a controlled and standardized diet, plasma volume was measured using a modified Evans Blue Dye (T-1824) dilution technique. Heart rate at rest was higher in the HT group (105 ± 12 vs 74 ± 6 beats/min), but during submaximum exercise, heart rates in the control group increased more rapidly (p ≤0.05) and to a greater magnitude (54 ± 7% vs 17 ± 4% above rest). Stroke volume at rest was lower in HT recipients (45 ± 4 vs 68 ± 9 ml) but was significantly augmented immediately after onset of exercise (30 seconds) and the relative increase was greater than controls at peak exercise (61% vs 38% greater than baseline). Cardiac output at rest was within the normal range in both groups (4.58 ± 0.27 vs 4.94 ± 0.40 L/min). Relative increases in cardiac output were similar (p ≥0.05) for the HT (106 ± 12%) and control groups (97 ± 10%). Plasma norepinephrine did not become significantly greater than resting values until approximately 4 minutes after onset of exercise in both groups. Blood volume, normalized for body weight, was 12% greater in the HT group. Thus, HT recipients with expanded blood volume (12%) augment stroke volume immediately after the onset of exercise. Plasma norepinephrine levels contribute negligibly to the rapid adjustment in cardiac output. Rather, we speculate that abrupt on-transit increases in stroke volume are due to augmented venous return, secondary to expanded blood volume.