Total body haematocrit iron kinetics and erythrocyte life span in pigeons (Columba livia)

1. The mean pigeon erythrocyte life span was found to be 17-25 days by Cr51-labeled erythrocytes and 21 +/- 3.4 days by iron kinetics. 2. Total red blood cell volume has been calculated by Cr51-labeled erythrocytes while total plasma volume was determined both by a dye method and iron kinetic data. From these results total blood volume and total body haematocrit were found to be 0.090 +/- 0.002 ml/g body wt and 36 +/- 4.3%, respectively. 3. Venous haematocrit, haemoglobin concentration, erythrocyte count, mean corpuscular haemoglobin concentration, plasma iron and red blood cell iron have also been measured. 4. A significant difference between total body and venous haematocrit and a short mean red blood cell life span, due to ageing and to random destruction of erythrocytes were shown. 5. The above observations are compared with analogous available data for human beings and their physiological significance is discussed.     

Discrimination between red blood cell and platelet components of blood clots by MR microscopy

Magnetic resonance imaging (MRI) of pulmonary emboli obtained ex vivo, verified by immunohistochemistry, showed that platelet layers display brighter signal intensity than areas containing predominantly red blood cells (RBC) in T (1)-weighted MRI. These results were surprising since platelets do not contain paramagnetic haemoglobin that would enhance magnetic relaxation. Our assumption was that the fibrin meshwork areas with entrapped RBC retain abundant extracellular space filled with serum, whereas platelets regroup into tight aggregates lacking serum, essentially mimicking solid tissue structure, rich with cellular proteins that enhance T (1)-relaxation. Our hypothesis was examined by MRI and NMR relaxometry of in vitro RBC suspensions and sedimented platelets, as well as by MRI of model clots and pulmonary emboli obtained ex vivo. Pure sedimented platelets exhibited shorter proton spin lattice relaxation times (T (1) = 874 +/- 310 ms) than those of venous blood of a healthy male with 40% haematocrit (T (1) = 1277 +/- 66 ms). T (1)-values of RBC samples containing high haematocrit (>/=80%) resembled T (1) of platelet samples. In T (1)-weighted spin-echo MRI echo time and repetition time (TE/TR = 10/120 ms) the ratio of signal intensities between a non-retracted whole blood clot (with a haematocrit of 35%) and a pure platelet clot was 3.0, and the ratio between a retracted whole blood clot with an estimated haematocrit of about 58% and a pure platelet clot was 2.6. We conclude that T (1)-weighted MRI can discriminate between platelet layers of thrombi and RBC-rich areas of thrombi that are not compacted to a haematocrit level of >/=80%.     

Extra-adipocyte leptin release in human obesity and its relation to sympathoadrenal function

The link between the human sympathoadrenalmedullary system and the adipocyte hormone leptin is controversial. We measured total and regional norepinephrine spillover, epinephrine secretion rate, and extra-adipocyte leptin release in 22 lean [body mass index (BMI) < 26] and 20 obese (BMI > 28) normotensive men who underwent arterial and central venous catheterization. Because plasma clearance of leptin is primarily by renal removal, for men at steady state we could estimate whole body leptin release to plasma from renal plasma leptin extraction. Whole body leptin release was 1,950 +/- 643 (means +/- SE) ng/min in obese men and 382 +/- 124 ng/min in lean men (P < 0.05). Total and renal norepinephrine spillover rates correlated directly with whole body leptin secretion rate. Leptin is released from multiple nonadipocyte sites, which we tested by use of simultaneous arteriovenous blood sampling. We found a surprisingly large contribution of brain leptin release to the plasma leptin pool, 529 +/- 175 ng/min (> 40% whole body leptin release), with greater leptin release in obese than in lean men, 935 +/- 321 vs. 160 +/- 59 ng/min (P = 0.045). In parallel with leptin measurements, we also quantified brain serotonin turnover and jugular overflow of neuropeptide Y (NPY). Brain serotonin turnover was higher in obese than in lean men, 227 +/- 112 vs. 21 +/- 14 ng/min (P = 0.019), as was overflow of NPY from the brain, 12.9 +/- 1.4 vs. 5.3 +/- 2.2 ng/min (P = 0.042). These results suggest that leptin is released within the brain and at an increased rate in obese humans, in whom activation of brain serotonergic and NPY mechanisms also exists.     

The effect of haemorrhage on erythropoietin concentration in the mature ovine fetus.

This study examines the response in plasma erythropoietin values to haemorrhage of 20% of the estimated blood volume in chronically cannulated ovine fetuses, of gestational ages 128-144 days. Blood samples were collected at 0, 2, 4, 6 and 24h with respect to the haemorrhage. In 5 control experiments there was no significant change in plasma erythropoietin concentration, across this time period, values being 6.1 +/- 2.3 and 6.4 +/- 2.4 mU/ml at 0 and 24h respectively. Values are mean +/- SEM. Haemorrhage reduced the haematocrit and haemoglobin values, significantly, to 83 +/- 6% and 85 +/- 4% (n = 5) of the initial value, respectively, but did not cause a statistically significant increase in plasma erythropoietin concentrations (7.2 +/- 2.4 and 20.7 +/- 8.2 mU/ml; P = 0.131). A larger degree of haemorrhage, in four fetuses reduced the haematocrit to 64 +/- 2.8% of initial, over 24-54h and increased erythropoietin values very significantly (from 11.9 +/- 3.6 to 91 +/- 8.3 mU/ml; P = 0.001).     

The importance of glucose for the freezing tolerance/intolerance of the anuran amphibians Rana catesbeiana and Bufo paracnemis

Several species of terrestrially hibernating frogs, turtles and insects have developed mechanisms, such as increased plasma glucose, anti-freeze proteins and antioxidant enzymes that resist to freezing, for survival at subzero temperatures. In the present study, we assessed the importance of glucose to cryoresistance of two anuran amphibians: the frog Rana catesbeiana and the toad Bufo paracnemis. Both animals were exposed to -2 degrees C for measurements of plasma glucose levels, liver and muscle glycogen content, haematocrit and red blood cell volume. Frogs survived cold exposure but toads did not. Blood glucose concentration increased from 40.35 +/- 7.25 to 131.87 +/- 20.72 mg/dl (P < 0.01) when the frogs were transferred from 20 to -2 degrees C. Glucose accumulation in response to cold exposition in the frogs was accompanied by a decrease (P < 0.05) in liver glycogen content from 3.94 +/- 0.42 to 1.33 +/- 0.36 mg/100 mg tissue, indicating that liver carbohydrate reserves were probably the primary carbon source of glucose synthesis whereas muscle carbohydrate seems unimportant. In the toads, the cold-induced hyperglycaemia was less (P < 0.05) pronounced (from 27.25 +/- 1.14 to 73.72 +/- 13.50 mg/dl) and no significant change could be measured in liver or muscle glycogen. Cold exposition had no effect on the haematocrit of the frogs but significantly reduced (P < 0.01) the haematocrit of toads from 20.0 +/- 2.1% to 5.8 +/- 1.7% due to a decreased red blood cell volume (from 1532 +/- 63 to 728 +/- 87 mm3). When toads were injected with glucose, blood glucose increased to levels similar to those of frogs and haematocrit did not change, but this failed to make them cryoresistent. In conclusion, the lack of cold-induced glucose catabolism may not be the only mechanism responsible for the freeze intolerance of Bufo paracnemis, a freeze-intolerant species.     

Distribution of antioxidants among blood components and lipoproteins: significance of lipids/CoQ10 ratio as a possible marker of increased risk for atherosclerosis.

Total CoQ10 levels were evaluated in whole blood and in plasma obtained from a group of 83 healthy donors. Extraction with light petroleum ether/methanol was more efficient, for whole blood, than the extraction which is often used for plasma and serum, i.e., ethanol hexane. An excellent correlation was present between plasma CoQ10 and whole blood CoQ10. CoQ10 is mainly associated with plasma rather than with cellular components. Positive, significant correlations were found between the LDL-chol/CoQ10 ratio and the total-chol/HDL-chol ratio, which is usually considered a risk factor for atherosclerosis. The proportion of CoQ10 carried by LDL was 58 +/- 10%, while the amount carried by HDL was 26 +/- 8%. In VLDL + IDL CoQ10 was 16 +/- 8%. The content of CoQ10 in single classes of lipoproteins is strictly correlated with CoQ10 plasma concentration. In a parallel study conducted on a population of diabetic patients (one IDDM group and one NIDDM) CoQ10 plasma levels were generally higher compared to the control group, also when normalised to total cholesterol. In particular the LDL fraction showed a CoQ10/chol ratio higher in NIDDM but not in IDDM patients, compared to controls. The CoQ10/triglycerides ratio was lower in NIDDM respect to controls and even lower in IDDM patients.     

Effects of hypercapnia on the buffer capacity and haematological values in Salmo salar (L.)

The effects of high environmental carbon dioxide tension (PCO₂) on buffering status, pH, haematocrit, red blood cell (RBC) count, mean corpuscle volume (MCV), and chloride (Cl^–) distribution in the blood of young salmon were investigated after 30 min and 24 h. An increase in blood buffering capacity was observed after 24 h. As compared to the preacclimation situation, haematocrit, RBC, MCV and Cl^– content of the erythrocytes increased after 30 min but decreased if hypercapnia was sustained for 24 h. However the plasma bicarbonate (HCO₃) content increased over the whole experimental period. Plasma Cl^– content was decreased after 24 h, but the ratio of Cl^– between erythrocytes and plasma increased at the onset of hypercapnia, then remained unchanged during the rest of the investigation period.     

Interleukin-6 deficiency increases blood volume without altering body composition in young mice

This study was carried out to measure blood volume in interleukin-6 (IL-6) deficient and the wild type mice and to relate any differences to concomitant changes in body composition. Young animals (8-20 weeks of age) were used in this study. The red blood cell (RBC) and plasma volumes were measured by isotope-dilution using Cr(51)-labeled erythrocytes and I(131)-labeled human albumin injected simultaneously in each animal. Red blood cells and plasma volumes and hence total measured blood volume were significantly larger in the IL-6-deficient than in either male or female wild type mice. There were no differences in either whole body hematocrit or Fcells ratio. There were no differences in water, fat, protein and mineral content between the genotypes of either gender. Thus, IL-6-deficient mice at young age have a significantly greater blood volume than the wild type mice without concomitant changes in body composition. We suggest that the changes in blood volume may reflect a role for IL-6 in the regulation of the peripheral circulation.     

Plasma insulin concentrations during infusions of potassium and sodium chloride solutions into conscious splenectomized sheep

Haematocrit values, plasma osmolality and the plasma concentrations of sodium, potassium, chloride and insulin were measured in carotid arterial blood before, during and after intravenous infusion of NaCl (0.5 mol 1-1) and KCl (0.5 mol 1-1) at 2 ml min-1 for 105 min into six conscious splenectomized sheep. Hypertonic NaCl infusion was associated with a fall in haematocrit of 1.30 +/- 0.10% (P less than 0.001) and no consistent change in plasma insulin concentration occurred during this infusion. Hypertonic KCl infusion caused the haematocrit to increase by 1.70 +/- 0.39% (P less than 0.001) and the plasma insulin concentration to increase by 60.0 +/- 16.3 mu U ml-1 (P less than 0.01). It was concluded that this increase in insulin concentration was caused by elevation of the plasma potassium concentration and was not due to coincident increases in plasma chloride concentration or osmolality. Shrinkage of the extracellular fluid volume during KCl infusion made no major contribution to the increase in insulin concentration which was probably the result of increased release from the pancreas.     

Prostanoids contribute to cutaneous active vasodilation in humans

The specific mechanisms by which skin blood flow increases in response to a rise in core body temperature via cutaneous active vasodilation are poorly understood. The primary purpose of this study was to determine whether the cyclooxygenase (COX) pathway contributes to active vasodilation during whole body heat stress (protocol 1; n = 9). A secondary goal was to verify that the COX pathway does not contribute to the cutaneous hyperemic response during local heating (protocol 2; n = 4). For both protocols, four microdialysis fibers were placed in forearm skin. Sites were randomly assigned and perfused with 1) Ringer solution (control site); 2) ketorolac (KETO), a COX-1/COX-2 pathway inhibitor; 3) NG-nitro-L-arginine methyl ester (L-NAME), a nitric oxide synthase inhibitor; and 4) a combination of KETO and L-NAME. During the first protocol, active vasodilation was induced using whole body heating with water-perfused suits. The second protocol used local heaters to induce a local hyperemic response. Red blood cell flux (RBC flux) was indexed at all sites using laser-Doppler flowmetry, and cutaneous vascular conductance (CVC; RBC flux/mean arterial pressure) was normalized to maximal vasodilation at each site. During whole body heating, CVC values at sites perfused with KETO (43 +/- 9% CVCmax), L-NAME (35 +/- 9% CVCmax), and combined KETO/L-NAME (22 +/- 8% CVCmax) were significantly decreased with respect to the control site (59 +/- 7% CVCmax) (P < 0.05). Additionally, CVC at the combined KETO/L-NAME site was significantly decreased compared with sites infused with KETO or L-NAME alone (P < 0.05). In the second protocol, the hyperemic response to local heating did not differ between the control site and KETO site or between the L-NAME and KETO/L-NAME site. These data suggest that prostanoids contribute to active vasodilation, but do not play a role during local thermal hyperemia.     

Distribution of body fluid and change of blood viscosity in broilers (Gallus domesticus) under high temperature exposure

This study was to observe the distribution of body fluid by measuring blood volume, extracellular and intracellular fluid volumes and total body water under heat exposure, in order to clarify the mechanism of decrease in whole blood viscosity of the heat-exposed broilers. Whole blood viscosity, haematocrit, plasma protein concentration, plasma osmolality and extracellular fluid volume decreased during high temperature exposure, while plasma and blood volumes increased. No significant changes were found in both intracellular fluid volume and total body water between thermoneutral and high temperature exposure. These results indicate the decreased whole blood viscosity is induced by a plasma volume expansion, in which water may come from the interstitial space and alimentary tract, under heat exposure.     

Measurement of parameters of cholic acid kinetics in plasma using a microscale stable isotope dilution technique: application to rodents and humans.

A stable isotope dilution method is described that allows measurement of cholic acid (CA) kinetics, that is, pool size, fractional turnover rate (FTR), and synthesis rate in mice, rats, and humans. Decay of administered [2,2,4,4-2H4]CA enrichment was measured in time in 50-microl plasma samples by gas-liquid chromatography/electron capture negative chemical ionization-mass spectrometry, applying the pentafluorobenzyl-trimethylsilyl derivative. The kinetic data expressed species-dependent differences. The CA pool sizes were 16.8 +/- 2.1, 10.6 +/- 1.2, and 2.4 +/- 0.7 micromol/100 g body weight for mice, rats, and humans, respectively. The FTR values were 0.44 +/- 0.03, 0.88 +/- 0.10, and 0.46 +/- 0.14 per day for mice, rats, and humans. The corresponding synthesis rates were 7.3 +/- 1.6, 9.3 +/- 0.1, and 1.0 +/- 0.2 micromol/100 g body weight per day. The human data agreed well with literature data obtained by conventional isotope dilution techniques. For rats and mice these are the first reported isotope dilution data. The method was validated by confirmation of isotopic equilibrium between biliary CA and plasma CA in the rat. Its applicability was demonstrated by the observation of increased CA FTR and CA synthesis rate in rats fed cholestyramine, which is known to increase fecal bile acid excretion. The presented stable isotope dilution method enables the determination of CA kinetic parameters in small plasma samples. The method can be applied in unanesthetized rodents with an intact enterohepatic circulation and may also be valuable when studying the development of human neonatal bile acid kinetics.     

Changes in plasma volume and haematocrit in intact and splenectomized sheep during feeding.

Changes in jugular haematocrit during daily 2-h feeding periods in trained sheep with and without spleens were compared with changes in the concentration of the plasma tracer radio-iodinated human serum albumin. Jugular haematocrit was increased by 16% in intact sheep and 9% in splenectomized sheep 20 min after they started to eat dry rations. The dilution of tracer in plasma, studied after mixing in the vascular system had been completed, showed four phases. Phase 1 was the rate of removal of tracer in the period before eating began. Phase 2 was the sudden increase in plasma radioactivity that occurred in the first 20 min of eating, indicating a loss of plasma from the circulation. Phase 3 was the decrease in tracer concentration during the remaining feeding period and phase 4 was a post-feeding phase, characterized by a slower rate of decrease of tracer than during phase 3, implying that there was significant recycling of tracer during this phase. The sudden increase in plasma radioactivity, initiated by the onset of feeding, represented a reduction in plasma volume of 10-12%. Minimum plasma volume coincided with peak haematocrit values. The reduced plasma volume accounted for the increased haematocrit in splenectomized sheep, but only accounted for about half of the increase in intact sheep. The residual increase in haematocrit in intact sheep was most likely the result of splenic contraction.     

Central venous pressure and plasma arginine vasopressin in man during water immersion combined with changes in blood volume

To investigate the influence of central venous pressure (CVP) changes on plasma arginine vasopressin (pAVP), 8 normal male subjects were studied twice before, during and after immersion to the neck in water at 35.1 degrees +/- 0.1 degrees C (mean +/- SE) for 6 h. After 2 h of immersion, blood volume was either expanded (WIEXP) by intravenous infusion of 2.0 1 of isotonic saline during 2 h or reduced by loss of 0.5 1 of blood during 30 min (WIHEM). The two studies were randomised between subjects. WIEXP increased CVP, systolic arterial pressure (SAP), diuresis, natriuresis, kaliuresis and osmolar clearance compared to WIHEM while haematocrit, haemoglobin concentration and urine osmolality decreased. Heart rate, mean arterial (MAP) and diastolic arterial pressure, plasma osmolality, plasma sodium, plasma potassium and free water clearance did not differ significantly in the two studies. pAVP was significantly higher after 6 h in WIHEM than after 6 h in WIEXP (2.0 +/- 0.2 vs. 1.6 +/- 0.2 pg X ml-1, mean +/- SE; P less than 0.05). pAVP values were corrected for changes in plasma volume due to infusion in order properly to reflect AVP secretion. In conclusion, there was a weak, but significant, negative correlation between CVP and pAVP during the two studies, while during recovery from WIHEM and WIEXP decrements in SAP and MAP correlated significantly and strongly with increases in pAVP. It is therefore concluded that it is the arterial baroreceptors rather than the cardiopulmonary mechanoreceptors which are of importance in AVP regulation in man.     

A comparison of chloride, bromide, and sucrose dilution volumes in neonatal pigs

Use of 36Cl, 82Br, and [3H]sucrose to estimate extracellular water volume was evaluated in 14 piglets (7-14 days old). 36Cl and 82Br were distributed in approximately the same volume, but a period of 5-6 hr after injection was required to reach equilibrium in the neonatal pig. Dilution volumes calculated before equilibration (2-5 hr) for 36Cl (326 +/- 11 ml/kg) and 82Br (328 +/- 13 ml/kg) were different from equilibration (6-8 hr) phase volumes (356 +/- 13 ml/kg and 355 +/- 13 ml/kg, respectively; P less than 0.001). A 3-hr sample estimated the same volume distribution calculated by extrapolation of the 6- to 8-hr period because of the relationship between the two slopes of the plasma clearance curves. After the 82Br and 36Cl had achieved equilibration, each was distributed in a volume equivalent to total body chloride space (362 +/- 29 ml/kg) measured by neutron activation; no statistical differences were found (P = 0.6). The early equilibration phase measured a 10% smaller, faster exchangeable fraction of total body Cl. Sucrose dilution volume (332 +/- 19 ml/kg) required multiple plasma samples for extrapolation and measured a dilution volume 7% smaller (P less than 0.05) than total body chloride space.     

Characterization of a new double-filament model of focal cerebral ischemia in heme oxygenase-2-deficient mice

Variations in vascular anatomy in knockout mouse strains can influence infarct volume after middle cerebral artery (MCA) occlusion (MCAO). In wild-type (WT) and heme oxygenase-2 gene-deleted (HO2-/-) mice, infarcts were not reproducibly achieved with the standard intraluminal filament technique. The present study characterizes a double-filament model of MCAO, which was developed to produce consistent infarcts in both WT and HO2-/- mice. Diameters of most cerebral arteries were similar in WT and HO2-/- mice, although the posterior communicating artery size was variable. In halothane-anesthetized mice, two 6-0 monofilaments with blunted tips were inserted into the left internal carotid artery 6.0 and 4.5 mm past the pterygopalatine artery junction to reside distal and proximal to the origin of the MCA. The tissue "volume at risk" determined by brief dye perfusion in WT (59 +/- 2% of hemisphere; +/-SE) was similar to HO2-/- (62 +/- 4%). The volume of tissue with cerebral blood flow <50 ml.min(-1).100 g(-1) was similar in WT (35 +/- 9%) and HO2-/- (36 +/- 11%) during MCAO and at 3 h of reperfusion (<2%). After 1 h MCAO, infarct volume was greater in HO2-/- (44 +/- 6%) than WT (25 +/- 3%). After increasing MCAO duration to 2 h, the difference between HO2-/- (47 +/- 4%) and WT (36 +/- 3%) diminished, but infarct volume remained substantially less than the volume at risk. Infusion of tin protoporphyrin IX, an HO inhibitor, during reperfusion after 1 h MCAO increased infarct volume in WT but not significantly in HO2-/- mice, although infarct volume remained less than the volume at risk. Thus greater infarct volume in HO2-/- mice is not attributable to a greater volume at risk, lower intraischemic blood flow, or poor reflow, but rather to a neuroprotective effect of HO2 activity. The double-filament model may be of use as an alternative in other murine knockout strains in which the standard filament model does not yield consistent infarcts.     

Blood-Volume Determination with Evans Blue Dye in Foals

The rate of disappearance of Evans blue dye from the blood after an intravenous injection was studied in young foals, between 4 and 105 days of age. This was found to be age dependant, especially during the first month, the initial dye disappearance being much faster than in the adult horse. This would mean an overestimation of plasma volume, using the single sampling technique, of about 5% during the first day of life, i.e. negligible from a practical point of view considering the standard error of estimation. The effect of exercise on the venous haematocrit was studied, too, in foals less than 3 months of age. There was a significant difference between mean values before and after exercise, and this difference seemed to increase with age, indicating an increasing erythrocytestoring capacity of the spleen. This means that even in young foals, the splenic function should be considered when determining the total blood volume from the plasma volume and the venous haematocrit.     

Continuous monitoring of blood volume changes in humans

The mass density of antecubital venous blood was measured continuously for 80 min/session with 0.1 g/l precision at a flow rate of 1.5 ml/min in six male subjects. Each person participated in two different sessions with the same protocol. To induce transvascular fluid shifts, the subjects changed from sitting to standing and from standing to supine positions. There was transient blood density shifts immediately after postural changes, followed by an asymptotic approach to a new steady-state blood density level. Additional deviations from a simple time course were regularly observed. Blood density increased by 3.5 +/- 1.4 (SD) g/l when standing after sitting and decreased by 5.0 +/- 1.2 g/l while supine after standing. The corresponding half time of the blood density increase was 5.6 +/- 1.4 min (standing after sitting) and 6.9 +/- 3.1 min (supine after standing) of the blood density decrease. Erythrocyte density was calculated and did not change with body position. Whole-body blood density was calculated from plasma density, hematocrit, and erythrocyte density, assuming an F-cell ratio of 0.91. Volume shifts were computed from the density data; the subject's blood volume density decreased by 6.2 +/- 1.2% from sitting to standing and increased by 8.5 +/- 2.1% from standing to supine. Additional discrete plasma density and hematocrit measurements gave linear relations (P less than 0.001) between all possible combinations of blood density, plasma density, and hematocrit.(ABSTRACT TRUNCATED AT 250 WORDS)     

Vitamin C in mouse and human red blood cells: an HPLC assay

Although vitamin C (ascorbate) is present in whole blood, measurements in red blood cells (RBCs) are problematic because of interference, instability, limited sensitivity, and sample volume requirements. We describe a new technique using HPLC with coulometric electrochemical detection for ascorbate measurement in RBCs of humans, wild-type mice, and mice unable to synthesize ascorbate. Exogenously added ascorbate was fully recovered even when endogenous RBC ascorbate was below the detection threshold (25 nM). Twenty microliters of whole blood or 10 μl of packed RBCs was sufficient for assay. RBC ascorbate was stable for 24h from whole-blood samples at 4°C. Processed, stored samples were stable for >1 month at -80°C. Unlike other tissues, ascorbate concentrations in human and mouse RBCs were linear in relation to plasma concentrations (R=0.8 and 0.9, respectively). In healthy humans, RBC ascorbate concentrations were 9-57 μM, corresponding to ascorbate plasma concentrations of 15-90 μM. Mouse data were similar. In human blood stored as if for transfusion, initial RBC ascorbate concentrations varied approximately sevenfold and decreased 50% after 6 weeks of storage under clinical conditions. With this assay, it becomes possible for the first time to characterize ascorbate function in relation to endogenous concentrations in RBCs.     

Ethacrynic Acid in Blood Transfusion—its Effects on Plasma Volume and Urine Flow in Severe Anaemia in Pregnancy

Thirty grossly anaemic pregnant Nigerian women with venous haematocrit levels varying between 6 and 17%, had their plasma volumes estimated by the Evans blue dye dilution technique, both before and immediately after direct transfusion of packed blood cells. Parenteral ethacrynic acid was added to the blood for transfusion in 20 patients, seven of whom were in anaemic heart failure on admission. Ethacrynic acid used in this way was successful in the prevention of acute pulmonary oedema, and it produced acute diuresis as well as a reduction of plasma volume in the majority of cases. This technique of direct transfusion with ethacrynic acid is simple, and it may well replace exchange transfusion as a means of treating patients with anaemic heart failure.