Actively circulating blood volume in endotoxin shock measured by indicator dilution

To estimate the size of the actively circulating blood volume of splenectomized dogs during control conditions and after endotoxin infusion, the pattern of concentration changes of 51Cr-labeled erythrocytes and 125I-labeled albumin was monitored. A dual exponential equation was fitted to the data. The total red blood cell and albumin volumes of distribution were determined from the slow exponential disappearance curves. The active red blood cell and albumin volumes were 89.8 +/- 5.3% and 92.0 +/- 2.0% of the total volumes, respectively. After endotoxin shock (mean arterial blood pressure 49.1 +/- 17.8 mmHg) the active volumes fell to only 60.0 +/- 10.3% and 56.2 +/- 20.0% of the total volumes, respectively. The fast-mixing time constants were similar (3.1 +/- 1.4 min and 2.5 +/- 2.7 min, respectively) and did not change significantly during the endotoxin shock, indicating that the albumin tag mixed into its larger volume of distribution as rapidly as the cells mixed into their indicated volume. We conclude that 1) an active blood volume can be distinguished, 2) it decreases for both red blood cells and albumin in endotoxin shock, and 3) a major part of the "extravascular plasma volume," as estimated by albumin dilution, is in the actively circulating circulation.

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Importance of Monitoring the Circulating Blood Volume in Patients with Cerebral Vasospasm after Subarachnoid Hemorrhage

Neurosurgery ◽

10.1227/00006123-198111000-00004 ◽

1981 ◽

Vol 9 (5) ◽

pp. 514-520 ◽

Cited By ~ 52

Author(s):

Tadashi Kudo ◽

Shigeharu Suzuki ◽

Takashi Iwabuehi

Keyword(s):

Blood Cell ◽

Cell Volume ◽

Blood Volume ◽

Red Blood Cell ◽

Cerebral Aneurysms ◽

Neurological Deterioration ◽

Red Cell ◽

Dilution Technique ◽

Circulating Blood Volume ◽

Time Of Admission

Abstract We used the isotope dilution technique to monitor circulating blood volume (CBV) in three patients with ruptured cerebral aneurysms who developed pre- or postoperative ischemic symptoms that responded well to intravascular volume expansion therapy with blood transfusion and plasma expanders. In the first and second cases, predeterioration CBVs were obtained. Both of these patients showed hypovolemia and a decreased red blood cell volume at the time of neurological deterioration. A predeterioration CBV was not available for the third patient for comparison, but his red cell volume was also markedly decreased. Postrecovery CBVs were obtained in the second and third cases. Our data suggested that a depleted red blood cell volume was more responsible for neurological deterioration than was a lowered plasma volume. To prevent the occurrence of hypovolemia and anemia in aneurysm patients, we should monitor CBV not only at the time of neurological deterioration, but also at the time of admission and during the immediate postoperative period.

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Regulation of blood volume in lowlanders exposed to high altitude

Journal of Applied Physiology ◽

10.1152/japplphysiol.00118.2017 ◽

2017 ◽

Vol 123 (4) ◽

pp. 957-966 ◽

Cited By ~ 34

Author(s):

Christoph Siebenmann ◽

Paul Robach ◽

Carsten Lundby

Keyword(s):

Blood Cell ◽

High Altitude ◽

Cell Volume ◽

Blood Volume ◽

Plasma Volume ◽

Red Blood Cell ◽

Hemoglobin Concentration ◽

Circulating Blood Volume ◽

Oxyhemoglobin Saturation ◽

Physiological Relevance

Humans ascending to high altitude (HA) experience a reduction in arterial oxyhemoglobin saturation and, as a result, arterial O2content ([Formula: see text]). As HA exposure extends, this reduction in [Formula: see text] is counteracted by an increase in arterial hemoglobin concentration. Initially, hemoconcentration is exclusively related to a reduction in plasma volume (PV), whereas after several weeks a progressive expansion in total red blood cell volume (RCV) contributes, although often to a modest extent. Since the decrease in PV is more rapid and usually more pronounced than the expansion in RCV, at least during the first weeks of exposure, a reduction in circulating blood volume is common at HA. Although the regulation of hematological responses to HA has been investigated for decades, it remains incompletely understood. This is not only related to the large number of mechanisms that could be involved and the complexity of their interplay but also to the difficulty of conducting comprehensive experiments in the often secluded HA environment. In this review, we present our understanding of the kinetics, the mechanisms and the physiological relevance of the HA-induced reduction in PV and expansion in RCV.

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Influence of the spleen on blood volume and haematocrit in the brush-tailed possum (Trichosurus vulpecula)

Australian Journal of Zoology ◽

10.1071/zo9680603 ◽

1968 ◽

Vol 16 (4) ◽

pp. 603 ◽

Cited By ~ 12

Author(s):

TJ Dawson ◽

MJS Denny

Keyword(s):

Body Weight ◽

Blood Cell ◽

Blood Volume ◽

Plasma Volume ◽

Red Blood Cell ◽

Blood Cells ◽

Trichosurus Vulpecula ◽

Circulating Blood Volume ◽

Significant Function ◽

Blood Reservoir

The blood volume of T. vulpecula was measured and the influence of the spleen on the circulating blood volume investigated. The circulating blood volume of "normal" restrained animals was 57.4 � 3.19 ml, the plasma volume being 31.2 � 1.93 ml, and the red blood cell volume 26.2 � 2.08 ml per kilogram body weight. These values tended to be lower than those of eutherian mammals and it is suggested that this might be associated with a possible lower metabolic rate. The spleen was found to have a significant function as a blood reservoir. Measurement of volume of circulating red blood cells after injections of adrenaline (to cause splenic emptying) and chlorpromazine (to achieve maximum filling of the spleen) showed that the splenic reserve of erythrocytes was approximately 11.0 ml/kg body weight.

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Desensitization of Adrenaline-Induced Red Blood Cell H+ Extrusion in Vitro After Chronic Exposure of Rainbow Trout to Moderate Environmental Hypoxia

Journal of Experimental Biology ◽

10.1242/jeb.156.1.233 ◽

1991 ◽

Vol 156 (1) ◽

pp. 233-248 ◽

Cited By ~ 1

Author(s):

S. THOMAS ◽

R. KINKEAD ◽

P. J. WALSH ◽

C. M. WOOD ◽

S. F. PERRY

Keyword(s):

Rainbow Trout ◽

Blood Cell ◽

Red Blood Cell ◽

Whole Blood ◽

Inverse Correlation ◽

Adrenergic Stimulation ◽

Plasma Adrenaline ◽

Arterial Blood Gas ◽

Arterial Blood

The sensitivity of red blood cell Na+/H+ exchange to exogenous adrenaline was assessed in vitro using blood withdrawn from catheterized rainbow trout (Oncorhynchus mykiss) maintained under normoxic conditions [water PO2, (PwO2)=20.66 kPa] or after exposure to moderate hypoxia (PwO2=6.67-9.33 kPa) for 48 h, which chronically elevated plasma adrenaline, but not noradrenaline, levels. Peak changes in whole-blood extracellular pH over a 30 min period after adding 50–1000 nmoll−1 adrenaline were employed as an index of sensitivity; the blood was pre-equilibrated to simulate arterial blood gas tensions in severely hypoxic fish (PaO2=2.0 kPa, PaCO2=0.31 kPa). Blood pooled from normoxic fish displayed a dose-dependent reduction in whole-blood pH after addition of adrenaline. Blood pooled from three separate groups of hypoxic fish, however, displayed diminished sensitivity to adrenaline, ranging from complete desensitization to a 60%reduction of the response. Subsequent experiments performed on blood from individual (i.e. not pooled) normoxic or hypoxic fish demonstrated an inverse correlation between the intensity of H+ extrusion (induced by exogenous adrenaline addition) and endogenous plasma adrenaline levels at the time of blood withdrawal. However, acute increases in plasma adrenaline levels in vitro did not affect the responsiveness of the red blood cell to subsequent adrenergic stimulation. The intensity of H+ extrusion was inversely related to the PaO2in vivo between 2.67 and 10.66 kPa, and directly related to the logarithm of the endogenous plasma adrenaline level. The results suggest that desensitization of Na+/H+ exchange in chronically hypoxic fish is related to persistent elevation of levels of this catecholamine. This desensitization can be reversed in vitro as a function of time, but only when blood is maintained under sufficiently aerobic conditions.

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Modulation of endothelial nitric oxide synthase expression by red blood cell aggregation

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.00532.2003 ◽

2004 ◽

Vol 286 (1) ◽

pp. H222-H229 ◽

Cited By ~ 51

Author(s):

Oguz K. Baskurt ◽

Ozlem Yalcin ◽

Sadi Ozdem ◽

Jonathan K. Armstrong ◽

Herbert J. Meiselman

Keyword(s):

Nitric Oxide ◽

Blood Cell ◽

Red Blood Cell ◽

Cell Aggregation ◽

Shear Stresses ◽

Control Mechanisms ◽

Vascular Control ◽

Arterial Blood ◽

Rbc Aggregation ◽

Endothelial Nitric Oxide

The effects of enhanced red blood cell (RBC) aggregation on nitric oxide (NO)-dependent vascular control mechanisms have been investigated in a rat exchange transfusion model. RBC aggregation for cells in native plasma was increased via a novel method using RBCs covalently coated with a 13-kDa poloxamer copolymer (Pluronic F-98); control experiments used RBCs coated with a nonaggregating 8.4-kDa poloxamer (Pluronic F-68). Rats exchange transfused with aggregating RBC suspensions demonstrated significantly enhanced RBC aggregation throughout the 5-day follow-up period, with mean arterial blood pressure increasing gradually over this period. Arterial segments (≈300 μm in diameter) were isolated from gracilis muscle on the fifth day and mounted between two glass micropipettes in a special chamber equipped with pressure servo-control system. Dose-dependent dilation by ACh and flow-mediated dilation of arterial segments pressurized to 30 mmHg and preconstricted to 45–55% of the original diameter by phenylephrine were significantly blunted in rats with enhanced RBC aggregation. Both responses were totally abolished by nonspecific NO synthase (NOS) inhibitor ( Nω-nitro-l-arginine methyl ester) treatment of arterial segments, indicating that the responses were NO related. Additionally, expression of endothelial NOS protein was found to be decreased in muscle samples obtained from rats exchanged with aggregating cell suspensions. These results imply that enhanced RBC aggregation results in suppressed expression of NO synthesizing mechanisms, thereby leading to altered vasomotor tonus; the mechanisms involved most likely relate to decreased wall shear stresses due to decreased blood flow and/or increased axial accumulation of RBCs.

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An Assessment of the Differences in Erythropoiesis Between Transfused Males and Females with β Thalassaemia Major

Blood ◽

10.1182/blood.v124.21.4045.4045 ◽

2014 ◽

Vol 124 (21) ◽

pp. 4045-4045

Author(s):

Greg Hapgood ◽

Timothy Walsh ◽

Ronit Cukierman ◽

Eldho Paul ◽

Ken Cheng ◽

...

Keyword(s):

Standard Deviation ◽

Blood Transfusion ◽

Blood Cell ◽

Blood Volume ◽

Red Blood Cell ◽

Reticulocyte Count ◽

Thalassemia Major ◽

P Value ◽

Red Cell ◽

Males And Females

Abstract Background: β thalassemia major results in ineffective erythropoiesis. Blood transfusion aims, in part, to suppress this and to limit morbidity from anaemia, bone marrow expansion and extra-medullary hemopoiesis (EMH), thereby increasing survival. According to current international guidelines, males and females are transfused equally. Aims: We sought to assess the adequacy of suppression of erythropoiesis in all 126 transfused adult (>18 years) males and females with β thalassemia major at our centre by: (1) assessing readily available pre-transfusion indices of erythropoiesis, including erythropoietin (EPO) levels; (2) determining the volume of blood transfused per kilogram (kg) and per calculated blood volume; and (3) assessing the incidence of para-spinal EMH masses based on magnetic resonance imaging (MRI). Methods: We analysed pre-transfusion (i.e., the day of transfusion) hemoglobin (Hb), reticulocyte count, red blood cell count (RCC), nucleated red blood cell (NRBC) count, EPO and ferritin levels in patients receiving stable, regular blood transfusion. Automated and manual NRBC and reticulocyte enumerations were performed. Blood volume was calculated using Nadler’s formula. MRI performed to assess cardiac function and hepatic and cardiac iron loading was reviewed for the presence of para-spinal EMH. Results: One hundred and sixteen adult patients (51 males and 65 females) provided pre-transfusion blood samples (Table 1). The 10 patients not included were either not available or declined testing. The mean pre-transfusion Hb was 98-99g/l with no difference between males or females (Table 2). Therefore, our data reflect long-standing adherence to current international transfusion recommendations. EPO levels and NRBC count (manual and automated) were significantly higher in males compared to females. RCC, reticulocyte count (manual and automated) and ferritin levels were not different between males and females. Males received less blood per kg of body weight and per calculated blood volume. The incidence of para-spinal EMH was 13% (14/110) and was significantly higher in males (11/50) compared to females (3/60)(22% versus 5%, respectively, (p = 0.01)). The incidence of splenectomy was higher in males. Conclusions: These findings confirm that erythropoiesis is not equally suppressed in males and females and that males are more prone to complications from being under-transfused with current transfusion practices. This work has major clinical implications for transfusion practices in the management of β thalassemia major. Abstract 4045. Table 1 Summary of patients included in the study Variable Overall Males Females p value Number 116 51 65 - Age (years) 39.3 ± 9.3 40.0 ± 9.6 38.8 ± 9.1 0.511 Weight (kg) 60.0 ± 11.6 64.9 ± 9.8 55.7 ± 12.4 < 0.0001 Height (cm) 159 ± 10.5 166 ± 8.3 153 ± 8.1 < 0.0001 Transfusion interval (weeks) 3.2 ± 0.6 3.2 ± 0.7 3.1 ± 0.5 0.168 No. RBC units per transfusion 3.03 ± 0.63 3.22 ± 0.76 2.89 ± 0.48 0.006 Estimated annual transfused volume (l) 13.5 (10.1-13.5) 14.0 (14.0-14.0) 14.0 (10.0-14.0) < 0.0001 Estimated annual transfused volume per kg (ml/kg) 215 (185-255) 202 (185-225) 225 (188-263) 0.028 Estimated patient blood volume (l) 3.79 ± 0.73 4.39 ± 0.50 3.32 ± 0.52 < 0.0001 Ratio of estimated annual transfused volume (l) per estimated patient blood volume (l) 3.33 (2.84-4.01) 2.98 (2.68-3.28) 3.79 (3.3-4.35) < 0.0001 Splenectomy 49.5% 61% 40% 0.031 Data are mean ± standard deviation, median (interquartile range) or percentage. Transfused volumes are calculated on the assumption that each unit contains 260ml red cells (Australia Red Cross Blood Service red cell unit mean volume = 259 ± 23ml). Nadler’s formula for total blood volume (TBV): men TBV (ml) = 604 + (367 x height3(m3)) + (32.2 x weight (kg)); women TBV = 183 + (356 x height3(m3)) + 33.1 x weight (kg)). Table 2. Laboratory indices of pre-transfusion erythropoiesis for all patients Variable Overall Male Female p value Hemoglobin (g/l) 98 ± 8.9 98 ± 9.9 99 ± 8.1 0.36 Red cell count (x 1012/l) 3.4 ± 0.35 3.45 ± 0.40 3.50 ± 0.32 0.46 Ferritin (mcg/l) 821 (604-1300) 754 (582-1139) 943 (639-1356) 0.11 Erythropoietin (mIU/ml) 58 (37-99) 72 (41-149) 52 (35-89) 0.006 Manual NRBC (number NRBC/100 WBC counted) 6 (1-54) 21 (2-98) 3 (1-28) 0.003 Automated NRBC (number NRBC/100 WBC counted) 5 (0-34) 17 (0-54) 1 (0-20) 0.014 Data are mean ± standard deviation or median (interquartile range). Disclosures No relevant conflicts of interest to declare.

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Comparison of the Terumo BCT MNC and Cmnc Protocols for Peripheral Blood Stem Cell Collections

Blood ◽

10.1182/blood.v128.22.5731.5731 ◽

2016 ◽

Vol 128 (22) ◽

pp. 5731-5731 ◽

Cited By ~ 2

Author(s):

Lindsey Westbrook ◽

Joseph Roig ◽

Neil Bagamasbad ◽

Reynold Dilag ◽

Melissa Nasser ◽

...

Keyword(s):

Stem Cell ◽

Blood Cell ◽

Blood Volume ◽

Mononuclear Cell ◽

Red Blood Cell ◽

Peripheral Blood ◽

Peripheral Blood Stem Cell ◽

Total Blood Volume ◽

Total Blood ◽

Run Time

Abstract Background: Terumo BCT recently offered a new method of peripheral blood stem cell (PBSC) collection using the Spectra Optia¨, an apheresis instrument. The new protocol includes a continuous mononuclear cell collection (CMNC) as opposed to an older version, the mononuclear cell collection (MNC), which involves an additional step where product pools through a cell separation insert. Our institution has used both methods and the purpose of this study was to compare the CMNC to the MNC protocol, including run times and PBSC product characteristics. Methods: A retrospective review and comparison of parameters from 120 collection procedures using the MNC insert and 60 collection procedures using the CMNC insert was done using the t-test. Data from patients/donors (including 20 allogeneic donors) as well as procedure details including run time, flow cytometry marker for stem cells (CD34)-positive (CD34+) throughput, CD34+ collection efficiency (CE%), platelet loss (plt loss/total blood volume [TBV]), and collection product characteristics were included in the analysis. Results: The MNC donor group included 12 allogeneic donors, which is comparable to the 8 allogeneic donors in the CMNC group. Donor weight and patient weight was not significantly different between the two groups. Pre-procedure laboratory values (WBC, percentage of lymphocytes [lymph%], percentage of monocytes [MNC%], and platelet count) were also similar between the two groups. Run time was found to be significantly shorter using the CMNC protocol compared to the MNC protocol. Product volume was also significantly lower in the CMNC group compared to the MNC group. Although the volume was lower, the CMNC product had significantly higher white blood cell count (WBC), MNC%, and lymph% when compared to the MNC product. The CD34+ throughput was significantly higher in the CMNC group than the MNC group. The CD34+ CE% was found to be slightly increased in the CMNC group, though not significantly. The platelet loss was nearly identical in both protocols when normalized for total blood volume. Product hematocrit (HCT%) was significantly higher using the CMNC protocol; however, the red blood cell volume never exceeded 20 mL due to the lower product volume with the CMNC protocol. The numerical results are summarized in the Table. Conclusion: The CMNC protocol collects a smaller volume of a purer product when compared to the MNC protocol with comparable platelet and red blood cell loss. Staff members who perform apheresis procedures are pleased by the shorter run time. Table Table. Disclosures Roig: Terumo BCT: Employment.

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Evaluation of cobalt as a performance enhancing drug (PED) in racehorses

Comparative Exercise Physiology ◽

10.3920/cep200001 ◽

2020 ◽

Vol 16 (4) ◽

pp. 243-252

Author(s):

K.H. McKeever ◽

K. Malinowski ◽

C.K. Fenger ◽

W.C. Duer ◽

G.A. Maylin

Keyword(s):

Adverse Effects ◽

Blood Cell ◽

Blood Volume ◽

Plasma Volume ◽

Red Blood Cell ◽

Jugular Vein ◽

Anaerobic Exercise ◽

Science Center ◽

Performance Enhancing ◽

A Performance

Cobalt is a required trace element in animals, but administration in excess is considered dangerous and potentially performance enhancing in equine athletes. This study seeks to determine if cobalt may actually act as a performance enhancing drug (PED) by altering biochemical parameters related to red blood cell production as well as markers of aerobic and anaerobic exercise performance. In addition, for adequate regulation of naturally occurring substances, such as cobalt, its distribution among the population must be defined. In order to identify this distribution, plasma Cobalt was determined from 245 Standardbred horses with no cobalt supplementation from farms in New York and New Jersey, including horses at the Rutgers University Equine Science Center. Samples were analysed by Inductively Coupled Plasma Mass Spectrometry. Seven healthy, race fit Standardbreds (4 geldings, 3 mares, age: 5±3 years, ~500 kg) were used for the PED experiment. An incremental graded exercise test (GXT) to measure maximal aerobic capacity (V̇O2max) and markers of performance, measurement of plasma volume and blood volume as well as the measurement of lactate, erythropoietin (EPO), and various blood haematological factors were determined 7 days prior to cobalt administration. Each horse was administered a sterile solution of cobalt salts (50 mg of elemental Co as CoCl2 in 10 ml of saline, IV) at 9 AM on three consecutive days via the jugular vein. Blood samples were obtained from the contralateral jugular vein before and at 1, 2, 4 and 24 h after administration. Plasma and blood volume were measured one day after the last dose of cobalt, and a post administration GXT was performed the next day. Horses were observed for signs of adverse effects of the cobalt administration (agitation, sweating, increased respiration, etc.). Plasma cobalt concentration increased from a pre-administration mean of 1.6±0.6 to 369±28 μg/l following 3 doses of the cobalt solution (P<0.05). This Co concentration was unaccompanied by changes in aerobic or anaerobic performance, plasma EPO concentration, plasma volume, resting blood volume, total blood volume, or estimated red blood cell volume (P>0.05). There were no observed adverse effects.

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