Large Vessel Hematocrit Research Articles

Dynamics of blood flow: modeling of the Fåhræus-Lindqvist effect.

To model the Fåhræus-Lindqvist effect, Haynes' marginal zone theory is used, following previous works, i.e., a core layer of uniform red blood cells (RBCs) is assumed to be surrounded by an annular plasma layer in which no RBCs are present. A simplified trial-and-error solution procedure is provided to determine the size of the core region and the hematocrit level in that zone in addition to the apparent viscosity, given the (upstream) large vessel hematocrit level and the average hematocrit level in the (downstream) small vessel. To test the model, a set of experimental data is selected to provide not only apparent viscosity data but also the average hematocrit levels in small tubes of different diameters. The results are found to support Haynes' marginal theory, with no fitting parameters used in the computations. Viscous dissipation is determined. The use of the mechanical energy balance is found to lead to results that are consistent with those based on the momentum balance, while leaving the average hematocrit level undetermined and required by either experimental data or an additional equation based on further theoretical work. The present analysis is used to model bifurcation using published empirical correlations quantifying the Fåhræus effect and phase separation. The model equations are extended to microvascular networks with repeated bifurcations.

Whole-body recruitment of glycocalyx volume during intravenous adenosine infusion

Adenosine-mediated recruitment of microvascular volume in heart and muscle has been suggested to include, in addition to vasodilation of resistance vessels, an increased accessibility of the endothelial glycocalyx for flowing plasma as a result of an impairment of its barrier properties. The aim of the current study was to investigate the effect of systemic intravenous administration of adenosine on the glycocalyx-dependent exclusion of circulating blood at a whole-body level. In anesthetized goats (N = 6), systemic blood-excluded glycocalyx volume was measured by comparing the intravascular distribution volume of the suggested glycocalyx accessible tracer dextrans with a molecular weight of 40 kDa (Dex-40) to that of circulating plasma, derived from the dilution of labeled red blood cells and large vessel hematocrit. Systemic glycocalyx volume was determined at baseline and during intravenous infusion of adenosine (157 ± 11.6 μg/kg min−1). Blood-inaccessible glycocalyx volume decreased from 458.1 ± 95.5 to 18.1 ± 62.2 mL (P < 0.01) during adenosine administration. While circulating plasma volume did not change significantly (617.1 ± 48.5 vs. 759.2 ± 47.9 mL, NS), the decrease in blood-excluded glycocalyx volume was associated with a decrease in Dex-40 distribution volume (from 1075.2 ± 71.0 to 777.3 ± 60.0 mL, P < 0.01). Intravenous administration of adenosine is associated with a robust impairment of whole-body glycocalyx barrier properties, reflected by a greatly reduced exclusion of circulating blood compared to small dextrans. The observed decrease in Dex-40 distribution volume suggests that the reduction in glycocalyx volume coincides with a reduction in tracer-accessible vascular volume.

Effect of acute hyaluronidase treatment of the glycocalyx on tracer-based whole body vascular volume estimates in mice

The endothelial glycocalyx forms a hyaluronan-containing interface between the flowing blood and the endothelium throughout the body. By comparing the systemic distribution of a small glycocalyx-accessible tracer vs. a large circulating plasma tracer, the size-selective barrier properties of the glycocalyx have recently been utilized to estimate whole body glycocalyx volumes in humans and animals, but a comprehensive validation of this approach has been lacking at the moment. In the present study, we compared, in anesthetized, ventilated C57Bl/6 mice, the whole body distribution of small (40 kDa) dextrans (Texas Red labeled; Dex40) vs. that of intermediate (70 kDa) and large (500 kDa) dextrans (both FITC labeled; Dex70 and Dex500, respectively) using tracer dilution and vs. that of circulating plasma, as derived from the dilution of fluorescein-labeled red blood cells and large-vessel hematocrit. The contribution of the glycocalyx was evaluated by intravenous infusion of a bolus of the enzyme hyaluronidase. In saline-treated control mice, distribution volume (in ml) differed between tracers (P < 0.05; ANOVA) in the following order: Dex40 (0.97 ± 0.04) > Dex70 (0.90 ± 0.04) > Dex500 (0.81 ± 0.10) > plasma (0.71 ± 0.02), resulting in an inaccessible vascular volume, i.e., compared with the distribution volume of Dex40, of 0.03 ± 0.01, 0.15 ± 0.04, and 0.31 ± 0.05 ml for Dex70, Dex500, and plasma, respectively. In hyaluronidase-treated mice, Dex70 and Dex40 volumes were not different from each other, and inaccessible vascular volumes for Dex500 (0.03 ± 0.03) and plasma (0.14 ± 0.05) were smaller (P < 0.05) than those in control animals. Clearance of Dex70 and Dex500 from the circulation was enhanced (P < 0.05) in hyaluronidase-treated vs. control mice. These results indicate that the glycocalyx contributes to size-dependent differences in whole body vascular distribution of plasma solutes in mice. Whole body vascular volume measurements based on the differential distribution of glycocalyx-selective tracers appear appropriate for the detection of generalized glycocalyx degradation in experimental animals and humans.

Development and validation of a mathematical algorithm for quantifying preoperative blood volume by means of the decrease in hematocrit resulting from acute normovolemic hemodilution

The interindividual variability of blood volume (BV) is high. The aim of this work was to use the decrease in large-vessel hematocrit (HK(LV)) during acute normovolemic hemodilution (ANH) as an instrument for estimating preoperative BV. In 39 patients, (Group 1) preoperative ANH was performed. Plasma volume, red cell volume, and HK(LV) were measured before and 30 minutes after ANH, respectively. In a retrospective analysis, a mathematical algorithm was developed for estimating BV before ANH by means of the measured changes in HK(LV) and the amount of blood removed during ANH. To validate the method prospectively, ANH was performed in an additional 10 patients (Group 2). Preoperative BV was estimated and measured in the same way as in Group 1. In Group 1, the mean difference between estimated and measured BV before ANH was 200 +/- 403 mL (5.14 +/- 10.12%; p > 0.05; r = 0.8). In Group 2, the estimated BV before ANH was 41 +/- 348 mL (-0.53 +/- 7.84%) lower than the measured BV (p > 0.05; r = 0.94). In this group, however, two patients with an extraordinarily small (2691 mL) and large (6172 mL) preoperative BV, respectively, were identified correctly by means of the algorithm. The changes in HK(LV) determined during ANH provide a good "bedside" estimation of preoperative BV.

Blood volume, colloid osmotic pressure and F-cell ratio in children with the nephrotic syndrome

The pathogenesis of edema in the nephrotic syndrome (NS) is classically explained by a decrease in blood volume secondary to low plasma colloid osmotic pressure () [1], resulting in stimulation of renal sodium reabsorption via neural [2] and endocrine [3] pathways. However, we have previously measured blood volume in a large group of adult nephrotic subjects and found values predominantly within the normal range [4]. Compensatory mechanisms such as a decrease in interstitial appear to play a major role in the defense of circulating blood volume in the NS [5]. Children with acute relapse of the NS often show symptoms such as abdominal pain, oliguria, cold extremities, anorexia and diarrhea that are rapidly ameliorated by infusing albumin, and hence are attributed to hypovolemia [6]. On the other hand, such albumin infusions are frequently complicated by hypertension, congestive heart failure and pulmonary edema [7]. Measurements of blood volume in nephrotic children are sparse. Both low and high volumes [8—10] have been suggested in preliminary reports. However, blood volume was usually computed from albumin distribution volume and hematocrit, which is relatively insensitive because the relation between whole-body hematocrit and largevessel hematocrit, the so-called F-cell ratio [11], is not constant between individuals. The F-cell ratio is sensitive to changes in distribution of the circulation between the microvasculature (where the hematocrit is low due to the Fahreus-Lindqvist effect) and the large vessels. Considering the large spontaneous variation found in blood volume measured by plasma volume and hematocrit in healthy adults [12] and children [131, it is questionable whether a decreased blood volume can actually be measured with this approach in nephrotic children. Simultaneous measurements of plasma volume and red cell volume, providing more reliable assessment of whole blood volume, are not available in normal children. Recently we found that children with or without symptoms of hypovolemia due to relapse of minimal change nephrosis had blood volumes that were not different from children in remission [14]. However, it is not certain whether the latter group have blood volumes that fall within the normal range, and can serve as a reference group. The

A simple technique for the estimation of regional blood content in brain

A simple and inexpensive technique is described for the assessment of regional cerebral blood volume (CBV) using a color reaction based on the pseudoperoxidase activity of hemoglobin. Cryostat sections are placed on a commercially available reagent strip originally designed for quantitative estimation of blood content in urine. After melting of the brain section, a blue color reaction appears which is darker in areas with higher hemoglobin content. The image is analyzed by a computerized image-processing system and evaluated by standards prepared from brain homogenate with different hemoglobin content. From the optical density data, regional CBV is calculated with correction for the difference between microvascular and large vessel hematocrit. The method was validated by a radiolabel procedure. Values of regional CBV are reported in gray matter areas of control rabbits and in brains embolized by autologous clot. This simple inexpensive technique is a useful supplementary tool in multiparametric metabolic studies.

Deduction of pulmonary microvascular hematocrit from indicator dilution curves

We have developed a new model describing the relationship between plasma and red cell tracers flowing through the lung. The model is the result of an analysis of the transport of radiolabeled plasma albumin between two flowing phases and shows that differences between red cell and plasma tracer curves are related to microvascular hematocrit. The model was tested in an isolated, blood-perfused dog lung preparation in which we injected 51Cr-labeled red cells and 125I-labeled plasma albumin into the pulmonary artery. From the tracer concentration-time curves at the venous outflow, we calculated hr, the ratio of microvascular hematocrit to large-vessel hematocrit. In 18 baseline experiments, hr = 0.92 +/- 0.01 (mn +/- sem) at a blood flow rate of 10.7 +/- 0.3 ml s-1. We determined the effects of (a) glass bead embolization, (b) alloxan, and (c) lobe ligation on hr. Embolization attenuated the separation between plasma and red cells (increased hr), probably as a consequence of passive vasodilation. Alloxan enhanced separation of plasma and red cells (decreased hr), possibly as a result of arteriolar vasoconstriction. Ligation of a fraction of the perfused tissue at constant flow did not cause significant change in hr in the remaining perfused tissue. The model assumes that large-vessel transit times are uniform and that all dispersion occurs in the microvasculature. A theoretical analysis apportioning dispersion between large and small vessels disclosed that the error associated with these assumptions is likely to be less than 15% of the measured hr. We conclude from this study that the microvascular hematocrit model describes experimental plasma and red cell curves. The results imply that hr can be readily deduced from tagged red cells and plasma and can be accounted for in calculating permeability-surface area in diffusing tracer experiments.

Measurement of lung fluid volumes and albumin exclusion in sheep

A radioactive tracer technique was used to determine interstitial diethylenetriaminepentaacetic acid (DTPA) and albumin distribution volume in sheep lungs. 125I- and/or 131I-labeled albumin were injected intravenously and allowed to equilibrate for 24 h. 99mTc-labeled DTPA and 51Cr-labeled erythrocytes were injected and allowed to equilibrate (2 h and 15 min, respectively) before a lethal dose of thiamylal sodium. Two biopsies (1-3 g) were taken from each lung and the remaining tissue was homogenized for wet-to-dry lung weight and volume calculations. Estimates of distribution volumes from whole lung homogenized samples were statistically smaller than biopsy samples for extravascular water, interstitial 99mTc-DTPA, and interstitial albumin. The mean fraction of the interstitium (Fe), which excludes albumin, was 0.68 +/- 0.04 for whole lung samples compared with 0.62 +/- 0.03 for biopsy samples. Hematocrit may explain the consistent difference. To make the Fe for biopsy samples match that for homogenized samples, a mean hematocrit, which was 82% of large vessel hematocrit, was required. Excluded volume fraction for exogenous sheep albumin was compared with that of exogenous human albumin in two sheep, and no difference was found at 24 h.

Mechanisms underlying atriopeptin-induced increases in hematocrit and vascular permeation in rats.

Infusion of atriopeptin into humans and animals induces diuresis, natriuresis, hemodynamic changes, and an increase in arterial hematocrit. The objective of the present study was to elucidate the mechanism(s) responsible for the increase in hematocrit in rats given atriopeptin-24 (AP-24). Infusion of AP-24 for 30 minutes increased large vessel and total vascular hematocrits by 10-15% while decreasing microvascular hematocrits by 9-26% in numerous tissues. Regional vascular permeation by [131I] bovine serum albumin was markedly increased (2-5.6-fold) in many tissues, consistent with a 16% decrease in plasma volume. AP-24 infusion had no effect on extracellular fluid volume or the volume of circulating red cells. Vascular resistance was decreased and was associated with a significant increase in blood flow in many, but not all, tissues. In the atrium and in the small and large intestine the percentage decrease in microvascular hematocrit exceeded the increase in blood flow. These observations indicate that the increase in large vessel hematocrit induced by AP-24 infusion 1) is accompanied by a decrease in (microvascular) hematocrit in many tissues, 2) reflects an increase in overall (i.e., total vascular hematocrit), and 3) is the consequence of a decrease in plasma volume resulting from a marked increase in the rate of vascular permeation by plasma constituents in multiple tissues.

Correction for intravascular activity in the oxygen-15 steady-state technique is independent of the regional hematocrit.

The oxygen-15 steady-state technique to measure the regional cerebral metabolic rate for oxygen requires a correction for the nonextracted intravascular molecular oxygen-15. To perform this correction, an additional procedure is carried out using RBCs labeled with 11CO or C15O. The previously reported correction method, however, required knowledge of the regional cerebral to large vessel hematocrit ratio. A closer examination of the underlying model eliminated this ratio. Both molecular oxygen and carbon monoxide are carried by RBCs and are therefore similarly affected by a change in hematocrit.

Distortion of calculated whole-body hematocrit during lower-body immersion in water

We found a difference between the venous hematocrits of immersed and nonimmersed arms during immersion of the lower body in cold water but not during a comparable exposure to warm water. Fourteen healthy men were exposed to three different experimental conditions: arm immersion, body immersion, and control. The men always sat upright while both upper extremities hung vertically at their sides. During arm immersion, one forearm was completely immersed for 30 min in either cold water (28 degrees C, n = 7) or warm water (38 degrees C, n = 7). This cold-warm water protocol was repeated on separate days for exposure to the remaining conditions of body immersion (immersion of 1 forearm and all tissues below the xiphoid process) and control (no immersion). Blood samples were simultaneously drawn from cannulated veins in both antecubital fossae. Hematocrit difference (Hct diff) was measured by subtracting the nonimmersed forearm's hematocrit (Hct dry) from the immersed forearm's hematocrit (Hct wet). Hct diff was approximately zero when the men were exposed to the control condition and body immersion in warm water. In the remaining conditions, Hct wet dropped below Hct dry (P less than 0.01, 3-way analysis of variance). The decrements of Hct diff showed there were differences between venous hematocrits in immersed and nonimmersed regions of the body, indicating that changes of the whole-body hematocrit cannot be calculated from a large-vessel hematocrit soon after immersing the lower body in cold water.

Splenic storage volume in the unanesthetized resting beagle.

Determination of the dog's splenic storage volume without surgical procedures requires measurement of both circulating and total red cell volumes. The estimation of circulating red cell volume by radioisotope techniques is impeded by the rapid uptake of tagged cells in the spleen. The circulating cell volume might be calculated from plasma volume and large vessel hematocrit, provided that the latter is corrected for the unequal distribution of red cells in the circulatory system. However, the correction factor can only be estimated in the splenectomized dog. We describe here a method to determine the factor in the intact dog, "physiologically splenectomized" by the severe exercise. The values obtained by this method slightly exceed those in the resting dog, as shown by studies in splenectomized exercising beagles in which splenic function was simulated by infusion of packed cells. The method was tested in beagles exercised by swimming and treadmill running and it was concluded that in the unanesthetized resting beagle about one-third of all erythrocytes is stored in the spleen. Labeled cells are equilibrated with about one-half of the splenic storage volume within 10 min after their injection. During maximal exertion the mean increase in large vessel hematocrit was 38.6 +/- 3.3%, the mean decrease in plasma volume 13.6 +/- 1.7% and the mean increase in plasma osmolarity 2.8 +/- 0.9% (percentages of control values).

Effects of large volume-hemodilution perfusion on plasma volume, plasma proteins and plasma electrolytes in neonatal piglets.

Two groups of 15 neonatal piglets underwent arteriovenous perfusion with the chest closed, at normothermia and without an oxygenator in the system until complete mixing of the blood and priming fluid was accomplished. The extracorporeal circuit was primed in one group with a warm (38 °C) buffered Ringer-lactate solution, and in the second group with an equally warm buffered solution of 2% Rheomacrodex in Ringer-lactate. The priming volumes of the perfused animals were individually tailored to result in a mixed (blood and priming solution) hematocrit of 22%. A control group of 15 piglets underwent the same surgical procedures but were not perfused. Large vessel hematocrit, plasma volume, the five major plasma protein components, plasma electrolytes and plasma osmolarity were measured before perfusion, immediately after and every 8 h for a period of 24 h. During perfusion, plasma volume, erythrocytes, and proteins were lost from the circulation. Plasma osmolarities showed larger fluctuations in the Rheomacrodex group than in the Ringer-lactate group. The neonatal pig is able to cope with large volume hemodilution resulting in a hematocrit of 22%. It shows a well-developed regulatory mechanism to counteract plasma volume and plasma protein losses; the replenishment of plasma volume and restoration of each major circulating plasma protein fraction, except γ-globulin, are accomplished in about 24 h. The restoration of plasma volume occurs faster than the restoration of plasma proteins, but when dextran is present the reverse is the case. Since the restoration of plasma volume, plasma proteins, and red blood cells do not show the same patterns, sequestration of whole blood is unlikely. 2% Rheomacrodex in Ringer-lactate appears to enhance protein restoration considerably.

Serial measurements of total blood volume in patients on maintenance hemodialysis.

In 10 patients on maintenance dialysis red cell and plasma volumes (PV) were measured before and after dialysis and several times during the next 3 days in order to establish the usual pattern of intravascular variation associated with this treatment and to determine whether there was a correlation with dialysis induced untoward effects. PV decreased from 23.7 +/- 1.5 before to 20.7 +/- 1.5 ml/cm body height immediately after dialysis. Unexpectedly it was even significantly lower 16 h after (20.1 +/- 1.4 ml/cm). Nevertheless, undesired dialysis symptoms had disappeared by that time indicating that they had not been caused by a reduction in PV or that the patients had adapted to it. Changes in PV correlated better with changes in hematocrit (r = 0.89) than with changes in body weight (r = 0.60). Therefore careful determination of the large vessel hematocrit offers a reliable estimation of blood volume variations over short periods.

Intrinsic plasma volume deficits in patients with coronary artery disease. Effects of myocardial revascularization.

Plasma volumes, red blood cell volumes, large vessel hematocrit readings, and total blood volumes were measured before operation, immediately after operation, and four to six months later in 12 patients with coronary artery obstruction, disabling angina, and normal left ventricular function. There were significant plasma volume deficits in all patients before and six months after operation despite complete amelioration of angina and replenishment of the plasma volume immediately after surgery. The importance of recognizing possibly significant preoperative oligemia in patients undergoing coronary revascularization is emphasized.

Critical evaluation of methods for determination of blood volume in the dog.

In 7 mongrel dogs a total of 202 measurements of blood volume were performed according to three different methods (RIHSA, Cr51, double-isotope method). Careful weighing of tracers and samples proved to be essential for correct measurements. Large vessel hematocrit values obtained by centrifugation and by the distribution of RIHSA in whole blood and in plasma were essentially equal. The disappearance rate of RIHSA averaged 10% per hour, while that of Cr51 differed significantly between dogs with and without saline infusion (20.9 and 13.7% per hour respectively). Values of blood volume for the fasting conscious dog averaged 80 ml/kg of BW with no significant difference between the three methods of determination. The correlation between blood volumes obtained by synchronized determination with Cr51 and RIHSA was rather weak (r=0.7143, standard deviation of the mean error ±14.3%). In agreement with this, the rate offcells showed a large scatter of ±7 and ±10% respectively for the two groups. It was demonstrated that the decrease of activity of Cr51 in the circulating blood due to the uptake of tagged red cells by the spleen is not linear, as initially supposed, but follows an exponential function, resulting in an error in the measurement of red cell volume of +10 and +13% respectively.

Effects of Hyperbaric Oxygen, THAM and Antibiotics on Experimental Burns in Rats

After an experimental burn covering 30% of the body surface, rats were treated by an association of HBO, THAM, and penicillin-colimycin. The following parameters were measured on the 3rd, 8th, 24th hour and the 3rd and 7th day: total body water (TBW), circulating blood volume, large vessel hematocrit, circulating red cell volume, circulating plasma volume, plasma sodium and potassium concentrations, pH and pCO2 and PO2. The results were compared to those found in control burned rats. Despite early changes, the treated animals had an accelerated recovery of their biological parameters.

Circulatory volume changes associated with chronic sepsis

1. 1. Total blood volume, red blood cell mass, plasma volume, total serum protein, serum albumin, total body hematocrit, and large vessel hematocrit were studied in relation to the surgical treatment of young male patients with chronic septic states and weight loss due to primary intra-abdominal illnesses and to acute trauma sustained in the Republic of Vietnam. Marked reduction in red blood cell mass, total body hematocrit, and serum albumin was found with relatively minor deficits in total serum protein, large vessel hematocrit, total blood volume, and plasma volume. 2. 2. Antibiotic therapy based on appropriate cultures and transfusion with whole blood and packed red cells was employed liberally in sustaining these patients and preparing them for definitive surgical treatment. 3. 3. Recovery in these patients is dependent on adequate debridement of all infected tissues and drainage of abscesses. 4. 4. The abnormalities noted herein disappear once definitve surgical therapy has taken place. 5. 5. Despite conflicting statements in the surgical literature, we believe that this study supports the liberal use of preoperative transfusion therapy to correct the red blood cell deficit. With this program of measured replacement based on calculated normal values for the patients' normal weight, no untoward effects were noted and the incidence of marked operative hypotension and cardiac arrest was greatly reduced.

Effect of induced respiratory acidosis on the circulating blood volume in normal dogs

1. 1. The effect on the circulating blood volume of an acute increase in the fractional concentration of inspired carbon dioxide (respiratory acidosis) without a concomitant decrease of inspired concentration of oxygen was studied in anesthetized dogs. 2. 2. A gas mixture containing 5 per cent carbon dioxide and 21 to 23 per cent oxygen was administered to anesthetized dogs for four hours. Red blood cell volume, large vessel hematocrit, arterial pH, carbon dioxide pressure, oxygen pressure, and serum electrolytes were measured. 3. 3. Our results indicate that moderate to severe respiratory acidosis in the presence of normal oxygenation does not alter circulating blood volume significantly in anesthetized mongrel dogs.

Studies of the bodyhematocrit phenomenon: dynamic hematocrit of a large vessel and initial distribution space of albumin and fibrinogen in the whole body.

Larsen, O. A. Studies of the Bodyhematocrit Phenomenon: Dynamic Hematocrit of a Large Vessel and Initial Distribution Space of Albumin and Fibrinogen in the Whole Body. Scand. J. clin. Lab. Invest. 22, 189-195, 1968.By measuring the mean circulation times of 125I-labelled albumin and 51Cr-labelled red cells from the femoral vein to the pulmonary artery it has been shown that the dynamic hematocrit of this vascular area is 99 per cent of the hematocrit determined by centrifugation of a venous blood sample. It is therefore possible for all practical purposes to regard the centrifuge hematocrit as equal to the dynamic hematocrit in a large vessel.The distribution volume of T-1824 and 131I-labelled fibrinogen has been determined simultaneously in 10 patients. T-1824 space exceeded fibrinogen space by 6.4 per cent. The explanation for the difference between the bod yhematocrit and the large vessel hematocrit appear to a major degree to be due to a low intravascular hematocrit caused by a more rapid passage of the red cells than of the plasma through the microvasculature and to a lesser degree to the fact that the normally used plasma indicators overestimate the plasma volume.