Changes In Red Cell Volume Research Articles

Phenylephrine increases near-infrared spectroscopy determined muscle oxygenation during head-up tilt in men

Phenylephrine is an α-adrenergic agent and yet seems to increase near-infrared spectroscopy determined muscle oxygenation (SmO2) that reflects the ratio between oxygenated (O2Hb) and deoxygenated (Hb) haemoglobin/myoglobin. We examined whether the increase in SmO2 by phenylephrine reflects veno-constriction and to secure filling of the veins, subjects were exposed to head-up tilt (HUT). Phenylephrine (0.2 mg) was administered to 10 healthy males (24 years (22–27; median with interquartile range)) during 40° HUT with SmO2, O2Hb and Hb determined for the biceps brachii and vastus lateralis muscles. Changes in red cell volume within the thorax and thigh were evaluated by electrical admittance and brachial vein diameter determined by ultrasound. HUT accumulated blood in arms and legs as indicated by reduced thoracic and conversely enhanced thigh electrical admittance. Both over the arm and leg, HUT reduced SmO2 as a consequence of reduced O2Hb and increased Hb (p < .05). After 5 min HUT, phenylephrine increased MAP and total peripheral resistance, and both arm and thigh SmO2 increased due to a decrease in Hb and an increase in O2Hb. The results confirm that SmO2 decreases during HUT and demonstrate venous filling in the limbs. Furthermore, vasoconstriction during HUT is indicated by a decrease in O2Hb. Conversely, phenylephrine increased SmO2 likely illustrating increased muscle blood flow and venoconstriction as O2Hb increased while Hb was reduced.

Early Markers of Sickle Nephropathy in Children With Sickle Cell Anemia Are Associated With Red Cell Cation Transport Activity.

The early stages of sickle cell nephropathy (SCN) manifest in children with sickle cell anemia (SCA) as hyperfiltration and proteinuria. The physiological conditions of the renovascular system are among the most conducive to hemoglobin S polymerization in the body and will magnify small changes in red cell volume thus crucially modulating intracellular concentrations of hemoglobin S. This large cross-sectional study of children with sickle cell anemia measured glomerular filtration rates and microalbuminuria to report prevalence, clinical correlates and uniquely, association with key red cell cation transport mechanisms. One hundred and twelve patients (mean age 10.7 ± 4.1) were recruited. The prevalence of hyperfiltration and microalbuminuria was 98% and 15.1%, respectively. Glomerular filtration rates did not vary with age, but proteinuria became more prevalent with increasing age. Both features associated with markers of hemolysis, while elevated hemoglobin F was protective, but no association was seen with systolic or diastolic blood pressure. In multivariate analysis, both Gardos channel (β = 0.476, P < 0.001) and KCl co-transporter (KCC; β = −0.216, P = 0.009) activity, alongside age (β = 0.237, P = 0.004), remained independently predictive for microalbuminuria. Increased activity of Gardos channel and Psickle positively associated with microalbuminuria, while increased KCC activity associated with a reduction in microalbuminuria. This study demonstrates a direct link between the abnormally active red cell cation transport systems in sickle cell disease and sickle organopathy. Small variations in the activity of these transport mechanisms predict for SCN and measurement of them may help identify those at risk, while pharmaceutical manipulation of these excessively active systems may ameliorate their risk.

A study of changes in red cell volume and haemoglobin concentration during phlebotomy induced iron deficiency and iron repletion using the Technicon H1

The recently introduced Technicon H1 analyser uses an improved optical principle to measure the size and haemoglobin concentration of erythrocytes. We have made a serial study of ten patients undergoing phlebotomy to induce mild iron deficiency. The instrument showed the early development of anisohypochromia with subsequent fall in the mean cell haemoglobin concentration (MCHC). Cell volume was preserved until relatively late and during early iron deficient erythropoiesis cell volume would appear to be maintained at the expense of haemoglobin concentration. The Technicon H6000 (conventional technology) used in parallel produced contrasting results indicating anisomicrocytosis with preservation of cell haemoglobin concentration until relatively late. Five cases of severe iron deficiency treated with iron were similarly studied and showed comparable changes on both instruments, with characteristically bimodal cell volume histograms and large increases in red cell distribution width. Our results indicate that the new generation of instruments will generate red cell data of additional clinical value.

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.

Factors predicting loss and gain of red cell volume in cardiac surgery patients

Haemoglobin may be a poor indicator of changes in red cell volume (RCV) because of factors such as haemodilution. This study has been designed to analyse what peri-operative variables may be associated with loss or gain in RCV due to bleeding or transfusion. Prospective observational study. Single centre study based in a regional cardiac surgery centre. Twenty-nine elective adult cardiac surgery patients. Loss and gain of RCV were measured in theatre and for the first 24 h post-operatively. Patient and operative factors analysed were age, sex, height, weight, body surface area (BSA), induction haematocrit (Hct), estimated pre-operative RCV and antiplatelet therapy taken less than 7 days before operation, cardiopulmonary bypass (CPB) time, aortic occlusion time, minimum and maximum CPB temperatures and fluid administered. Age, sex, height, weight, BSA and induction Hct were found to predict red cell transfusion but not RCV loss. The total number of red cells transfused was significantly associated with RCV lost when expressed as a percentage reduction in the estimated pre-operative RCV but not the absolute RCV lost. Pre-operative RCV, as predicted by the variables outlined above, is more important than RCV lost in triggering red cell transfusion.

Commentary on Point-Counterpoint

This letter is in response to the Point:Counterpoint series “Positive effects of intermittent hypoxia (live high:train low) on exercise performance are/are not mediated primarily by augmented red cell volume that appeared in the November issue (vol. 99: 2053–2058, 2005; doi: 10.1152/japplphysiol

Counterpoint: Positive effects of intermittent hypoxia (live high:train low) on exercise performance are not mediated primarily by augmented red cell volume

To engage in this debate we will address the following questions: what is the change in performance after adaptation to living high and training low (LHTL); what physiological mechanisms could be responsible; what is the evidence that a change in red cell volume (RCV) is one such mechanism; and what

High predictive value of red cell volume measurement using carboxy-haemoglobin in a rabbit model of haemorrhage

We have studied the accuracy of blood volume measurements using carbon monoxide (CO)-labelled haemoglobin (COHb) injection and dilution (CO method) by comparing changes in red cell volume (RCV) measured using the CO method and 51Cr-labelled erythrocyte dilution (51Cr method) in a haemorrhage and infusion model in rabbits. RCV was measured repeatedly using the CO method at four different blood volume stages (stages I-IV). At stages I and IV, RCV was measured simultaneously using the 51Cr method. In comparing the sum of the circulating RCV and extracted RCV (SUM RCV) using the CO method, the values were almost equal and there were no significant differences between the values at the four stages. In comparing circulating RCV measured using the CO method and the 51Cr method, mean difference between the two methods was 0.80 (SD 0.76) ml kg-1 or 4.7 (4.6)%, and a positive correlation was observed (r = 0.91). We conclude that the CO method can be used to measure blood volume during perioperative periods in infants because it avoids use of a radioactive tracer, is simple and repeated measurements are possible.

First clinical implications of perioperative red cell volume measurement with a nonradioactive marker (sodium fluorescein).

We measured red cell volume (RCV) with the nonradioactive marker sodium fluorescein (SoF) in 30 patients undergoing gynecological operations. Sixteen patients underwent preoperative isovolemic hemodilution (PIHD). RCV measurements were performed before and after PIHD and at the end of the operation. All RCVs were related to corresponding hematocrit (hct) levels. We report a simplified method for its clinical application by reducing the number of blood samples required. To validate our method, we compared RCV within the PIHD bags (bag RCV) with the difference of the patients' RCV before and after PIHD. Bag RCV obtained during PIHD (mean 399+/-81 mL) was measured with a precision of 4.2% by using SoF. There was a significant difference (mean 286+/-401 mL; P < 0.05) between intraoperatively estimated and measured blood loss. The blood loss tended to be underestimated and, in some cases, was underestimated or overestimated substantially. Preoperative and postoperative hct values only offered an imprecise estimation of the patients' RCV. We conclude that RCV measurement using SoF is a precise method for monitoring changes in RCV during PIHD and surgical operation. We measured red cell volume changes of 30 patients with the nonradioactive marker sodium fluorescein before and after hemodilution and postoperatively with a high precision. We frequently found large differences between intraoperatively estimated and measured blood loss. Preoperative hematocrit values offered an imprecise estimation of the patients' red cell volume.

First Clinical Implications of Perioperative Red Cell Volume Measurement with a Nonradioactive Marker (Sodium Fluorescein)

We measured red cell volume (RCV) with the nonradioactive marker sodium fluorescein (SoF) in 30 patients undergoing gynecological operations.Sixteen patients underwent preoperative isovolemic hemodilution (PIHD). RCV measurements were performed before and after PIHD and at the end of the operation. All RCVs were related to corresponding hematocrit (hct) levels. We report a simplified method for its clinical application by reducing the number of blood samples required. To validate our method, we compared RCV within the PIHD bags (bag RCV) with the difference of the patients' RCV before and after PIHD. Bag RCV obtained during PIHD (mean 399 +/- 81 mL) was measured with a precision of 4.2% by using SoF. There was a significant difference (mean 286 +/- 401 mL; P < 0.05) between intraoperatively estimated and measured blood loss. The blood loss tended to be underestimated and, in some cases, was underestimated or overestimated substantially. Preoperative and postoperative hct values only offered an imprecise estimation of the patients' RCV. We conclude that RCV measurement using SoF is a precise method for monitoring changes in RCV during PIHD and surgical operation. Implications: We measured red cell volume changes of 30 patients with the nonradioactive marker sodium fluorescein before and after hemodilution and postoperatively with a high precision. We frequently found large differences between intraoperatively estimated and measured blood loss. Preoperative hematocrit values offered an imprecise estimation of the patients' red cell volume. (Anesth Analg 1998;87:1234-8)

Redistribution of body fluids during postural manipulations

Inter-compartmental body-fluid distribution is contingent upon posture, exercise state and environmental temperature. This investigation aimed at quantifying the distribution of intra- and extravascular fluid volumes during postural manipulations. Fluid shifts were measured in eight males utilizing a simultaneous, radionuclide dilution technique, in which radioiodinated serum fibrinogen, radiochromated erythrocytes, radiobromine and tritiated water were used to measure plasma, red cell, extracellular and total body water volumes. Subjects were exposed to three postural changes [seated (control), supine and standing] for 30 min at an air temperature of 22.0 degrees C, with each posture separated by 30 min seated rest. Total body water content remained stable throughout postural changes (P = 0.842). Relative to seated volumes, BV increased by 89 mL when supine, and decreased by 406 mL while standing (P = 0.003), with such shifts being primarily a result of plasma movement (P = 0.011). Red cell volume changes were not significant. Vascular fluid lost during standing was filtered into the interstitial compartment (P = 0.014), with the extracellular and intracellular volumes remaining unaffected. (P = 0.271 and P = 0.800, respectively). These observations confirmed the influence of posture on inter-compartmental body-fluid distribution. The intravascular fluid loss when standing was caused by the filtration of plasma into the interstitium, while, during supine rest, intravascular volume increased, reflecting fluid flux from the interstitium to the circulation.

Heart and spleen mass related to blood parameter changes after epinephrine injection

SummaryThe purpose of this study was to determine if splenic weight is correlated to changes in blood volume, haematocrit and haemoglobin concentration after epinephrine injection in horses. Ten mares, 5 racing type and 5 draft type, all over age 5 years were studied. Differences in plasma volume (PV), red cell volume (RCV), total blood volume (TBV) and venous haematocrit (PCV) were maximised by xylazine and epinephrine treatments to either sequester or mobilise the splenic RCV. Plasma volume was determined using an Evans Blue Dye (EBD) dilution technique, then used to calculate TBV and RCV. Horses were killed by captive bolt gun and exsanguination, and heart (HW) and spleen weights (SW) were recorded and expressed as a percentage of body weight (BW). Significant differences between breed types were found for changes in RCV and PCV between treatments. Analysis of variance found significant differences between breed types in HW/BW and SW/BW ratios. Regression analysis demonstrated a positive relationship between the change in RCV between treatments and SW/BW with significant differences (P &lt; 0.01) between breed types in this relationship. There was no relationship between changes in RCV or PCV and HW/BW.

Effect of leg exercise training on vascular volumes during 30 days of 6 degrees head-down bed rest.

Plasma and red cell volumes, body density, and water balance were measured in 19 men (32-42 yr) confined to bed rest (BR). One group (n = 5) had no exercise training (NOE), another near-maximal variable-intensity isotonic exercise for 60 min/day (ITE; n = 7), and the third near-maximal intermittent isokinetic exercise for 60 min/day (IKE; n = 7). Caloric intake was 2,678-2,840 kcal/day; mean body weight (n = 19) decreased by 0.58 +/- 0.35 (SE) kg during BR due to a negative fluid balance (diuresis) on day 1. Mean energy costs for the NOE, and IKE, and ITE regimens were 83 (3.6 +/- 0.2 ml O2.min-1.kg-1), 214 (8.9 +/- 0.5 ml.min-1.kg-1), and 446 kcal/h (18.8 +/- 1.6 ml.min-1.kg-1), respectively. Body densities within groups and mean urine volumes (1,752-1,846 ml/day) between groups were unchanged during BR. Resting changes in plasma volume (ml/kg) after BR were -1.5 +/- 2.3% (NS) in ITE, -14.7 +/- 2.8% (P less than 0.05) in NOE, and -16.8 +/- 2.9% (P less than 0.05) in IKE, and mean water balances during BR were +295, -106, and +169 ml/24 h, respectively. Changes in red cell volume followed changes in plasma volume. The significant chronic decreases in plasma volume in the IKE and NOE groups and its maintenance in the ITE group could not be accounted for by water balance or by responses of the plasma osmotic, protein, vasopressin, or aldosterone concentrations or plasma renin activity. There was close coupling between resting plasma volume and plasma protein and osmotic content.(ABSTRACT TRUNCATED AT 250 WORDS)

Influence of High and Low Sodium Dialysis on Blood Volume Preservation

Haemodialysis has a profound effect on fluid balance. Since fluid is initially withdrawn from the intravascular compartment, hypovolaemia is a frequent complication. A fluid shift from the overhydrated interstitium towards the intravascular compartment can counteract hypovolaemia. However, a fast decline in extracellular osmolality may cause an increase in the intracellular volume, reducing the available amount of fluid to compensate for the hypovolaemia. To overcome this problem, the use of alternating high and low sodium dialysate is advocated. In this study six patients were studied during standard haemodialysis (HD) and during dialysis with alternating high and low sodium dialysate (HLSD). Changes in intracellular fluid volume (IFV) and extracellular fluid volume (EFV) of tissue and blood were measured by means of a non-invasive electrical conductivity method. Changes in blood volume (BV) were studied by serial erythrocyte counts. Plasma sodium concentration was determined at regular intervals. The distribution volume of sodium during the high and low sodium episodes of HLSD was calculated according to a mathematical model. HLSD led to fluctations in plasma sodium concentration that induced changes in red cell volume, but not in IFV. Distribution of sodium was largely confined to blood. BV was better preserved during HLSD than during HD, probably due to a higher mean plasma sodium concentration. Postdialysis sodium concentration however, was not significantly different between HLSD and HD. These data suggest that the better BV preservation during HLSD results from an induced osmotic gradient across the capillary wall, rather than from an osmotic gradient across the cell membrane.

Red cell volume changes monitored using a new 31P NMR procedure

The application of NMR spectroscopy to whole cell systems has provided considerable insight into a range of cellular phenomena. 3’P NMR is used routinely for the estimation of intracellular pH (I, 2) and in assessing the energy status of whole cell samples (3). ‘H NMR has been used to monitor a variety of membrane transport processes (4) as well as a number of intracellular reactions (5). The rates of reactions inside the cell depend upon the concentrations of enzymes, substrates, and effector molecules and these, in turn, are determined by the intracellular volume. Changes in cell volume have, for example, been shown to affect the glycolytic rate in the human erythrocyte, mainly by altering the intracellular concentration of ATP, a regulator of glycolysis (6). Therefore, in any study of intracellular reaction rates, an understanding of how (and why) the cell volume may be changing during a particular experiment is important. We present here results obtained using a method whereby time-dependent changes in red cell volume may be monitored using “P NMR. The method is based on the observed cell volume dependence of the chemical shift of the “P NMR signal to dimethyl methylphosphonate. It is applicable to high hematocrit cell suspensions and was used to monitor the decrease in erythrocyte volume that followed the addition of the potassium ionophore, valinomycin, to cells suspended in a low-potassium medium. Erythrocyte suspensions were prepared from fresh blood obtained from the Red Cross Transfusion Service, New South Wales, Australia. The cells were washed twice in isotonic saline (0.154 M NaCl, 4°C) then three times in Krebs bicarbonate buffer (7) equilibrated beforehand with Carbogen (Oz/COz ; 19: 1) to give a pH of 7.3. All 3LP NMR spectra were recorded at 162 MHz using a Bruker WM 400 spectrometer operated in the Fourier transform mode at 37°C. Broadband proton decoupling was used throughout the experiments and the sample tubes were spun at - 16 Hz. Chemical shifts are quoted relative to that of 85% (v/v) phos- phoric acid. Dimethyl methylphosphonate (DMMP; CH3PO(OCH3)2; Aldrich, Mich.) is a small, neutral molecule, readily miscible with water. The “P NMR spectrum of DMMP in saline solution appeared as a single resonance (6 = 39.4 ppm). The addition of whole cells to the solution caused the signal to split into two. Furthermore, as the average red cell volume was altered by varying the extracellular

Hydration and vascular fluid shifts during exercise in the heat.

This study examined the effects of hypohydration on plasma volume and red cell volume during rest in a comfortable (20 degrees C, 40% relative humidity) and exercise in a hot-dry (49 degrees C, 20% relative humidity) environment. A group of six male and six female volunteers [matched for maximal O2 uptake (VO2 max)] completed two test sessions following a 10-day heat acclimation program. One test session was completed when subjects were euhydrated and the other when subjects were hypohydrated (-5% from base-line body wt). The test sessions consisted of rest for 30 min in a 20 degrees C antechamber, followed by two 25-min bouts of treadmill walking (approximately 30% of VO2 max) in the heat, interspersed by 10 min of rest. No significant differences were found between the genders for the examined variables. At rest, hypohydration elicited a 5% decrease in plasma volume with less than 1% change in red cell volume. During exercise, plasma volume increased by 4% when subjects were euhydrated and decreased by 4% when subjects were hypohydrated. These percent changes in plasma volume values were significantly (P less than 0.01) different between the euhydration and hypohydration tests. Although red cell volume remained fairly constant during the euhydration test, these values were significantly (P less than 0.01) lower when hypohydrated during exercise. We conclude that hydration level alters vascular fluid shifts during exercise in a hot environment; hemodilution occurs when euhydrated and hemoconcentration when hypohydrated during light intensity exercise for this group of fit men and women.

A search for the mechanism underlying the altered MCV in thyroid dysfunction: a study of serum and red cell membrane lipids.

The mean red cell volume (MCV) is increased in hypo- and decreased in hyperthyroidism but the underlying cause(s) is unknown. In view of the well recognised alterations in serum lipids in thyroid dysfunction, we have examined the possibility that a corresponding alteration in the amount or distribution of lipids in the red cell membrane may account for the red cell volume changes. Our findings however do not support this hypothesis.

Exercise responses in pregnant sheep: oxygen consumption, uterine blood flow, and blood volume.

In an attempt to explore the acute maternal responses to exercise we measured oxygen consumption, uterine blood flow, and blood volume in 13 chronically catheterized pregnant sheep at rest and while exercising on a treadmill. With maximal exercise O2 consumption increased 5.6 times, from a resting value of 5.8 +/- 0.3 (SE) to 32.1 +/- 2.8 ml X min -1 X kg -1, cardiac output increased 2.7 times, from 149 +/- 8 to 404 +/- 32 ml X min -1 X kg -1, and arteriovenous oxygen content difference increased 2.1 times, from 3.9 +/- 0.2 to 8.0 +/- 0.4 ml X dl -1. Total uterine blood flow decreased from a mean resting value of 292 +/- 6 to 222 +/- 19 ml X min -1 X kg fetus -1 near exhaustion during prolonged (40 min) exercise at 70% maximal oxygen consumption. Maternal blood volume decreased 14% (P less than 0.01) from 67.5 +/- 3.7 to 57.8 +/- 3.6 ml X kg -1 during this exercise period, with a 20% decrease in plasma volume without a change in red cell volume. We conclude that uterine blood flow decreases during maternal exercise. However, hemoconcentration helps to maintain a relatively constant oxygen delivery to the uterus.

Effects of red blood cell HCO3(-)/Cl- exchange kinetics on lung CO2 transfer: theory

A mathematical model has been used to study the influences of the kinetics of erythrocyte HCO3(-)/Cl-- exchange on CO2 elimination in the lung. In addition to the chloride shift, the model includes 1) CO2-H2CO3 hydration-dehydration reactions in plasma and erythrocytes; 2) CO2 reactions with hemoglobin; 3) O2 binding to hemoglobin; 4)buffering of H+ intra- and extracellularly; 5) red cell volume changes; and 6) diffusion of gases between alveoli and blood. Carbonic anhydrase activity was assumed to be available to plasma as it passes through the lung capillaries. The results show that a reduction of PHCO3(-) leads to a reduction in pulmonary CO2 elimination of up to 30%, whether or not carbonic anhydrase activity is available to plasma. Characteristic slow downstream pH and PCO2 changes predicted for each case may represent an explanation for the apparent discrepancy between in vivo and in vitro slow downstream pH changes reported previously. We conclude that red cell HCO3(-)/Cl- exchange partially limits CO2 elimination from blood in the lung and may have a major influence on capillary gas transfer when its speed is abnormally slow.

Improved stop-flow apparatus to measure permeability of human red cells and ghosts

An improved stop-flow apparatus has been designed and constructed to measure the permeability characteristics of human red cells, which can be inferred from the time course of red cell volume changes following a sudden change in cellular environment produced by a rapid mixing device. The improved apparatus is directly coupled to a computer which automates thesubtraction and averaging procedures that have been developed to minimize the noise generated in the system by the cessation of red cell forward motion when the flow is suddenly stopped. Real time data acquisition also makes it possible to increase the number of data points by an order of magnitude, thus improving accuracy significantly. The apparatus has been tested by measurements of the human red cel hydraulic permeability coefficient. Data are presented to validate the subtraction procedure. Experiments have also been carried out on red cell ghosts which indicate that the hydraulic conductivity of the ghost is similar to that of the undisturbed red cell.