Calculated Blood Volume Research Articles

A pediatric trauma model of continuous hemorrhage

This report describes a new experimental model of hemorrhage in immature animals. Puppies were subjected to continuous hemorrhage equivalent to 1% of calculated blood volume per minute. In the control group there was no change in mean arterial pressure, central venous pressure, cardiac output, hematocrit, pH, or core temperature. In the experimental group the response to hemorrhage was gradual and in proportion to blood loss until 25% to 30% blood volume reduction. At this critical point, the fall in mean arterial pressure and cardiac output accelerated and death occurred. These observations suggest that the response to blood loss has break points beyond which sudden deterioration is rapid and dramatic. This model of hemorrhage should be useful for future study of the effects of treatment of hemorrhagic shock in immature subjects.

Liver function following hypovolemic hypotension in rats anaesthetized with halothane or enflurane

Rats which had approximately 25–30% of their calculated blood volume removed were exposed to halothane (1%) or enflurane (2%) in 33% oxygen for 30 min. Hepatic function was evaluated by determining, at various time intervals, serum activities of glutamic-oxalacetic and glutamic-pyruvic transaminase, acid phosphate and ∝-glutamyl-transpeptidase. In this model serum enzyme activities and animal mortality were significantly increased when hypovolemic hypotension was induced during halothane anaesthesia. The same events did not occur in bleeding animals anaesthetized with enflurane. The marked disparity in hepatic dysfunction and mortality between halothane and enflurane-anaesthetized rats during hypovolemic hypotension may be explained by the more pronounced decrease of oxygen available for the liver and production of reductive toxic intermediates in animals exposed to halothane.

Three Per Cent Dextran‐60 as a Plasma Substitute in Blood Component Therapy

Microaggregate-poor erythrocyte concentrate with 3% dextran-60 as a plasma substitute was compared with microaggregate-poor whole blood for replacement of intra-operative and immediately postoperative blood loss. Sixty patients undergoing total hip arthroplasty randomly received either of these two forms of therapy. In accordance with the clinical routine of our orthopedic department, an infusion of 500 ml of 6% dextran-70 (Macrodex) was given as thrombo-prophylaxis in both groups. Use of 3% dextran-60 as a plasma substitute in blood component therapy for surgical hemorrhage of up to 50% of the calculated blood volume caused no increase in bleeding tendency or frequency of postoperative hematoma compared with whole blood replacement. Plasma protein levels were low immediately postoperatively in patients given the dextran, but from the 4th postoperative day onward there was no difference between the groups. Applied in clinical practice, this would be efficient in saving plasma for other urgent purposes.

Midazolam pharmacodynamics and pharmacokinetics during acute hypovolemia.

This study was designed to test the hypothesis that acute hypovolemia would compromise the compensatory hemodynamic mechanisms to midazolam and decrease its metabolic clearance. Experiments were performed on seven chronically instrumented female beagle dogs. Animals received a single intravenous dose of midazolam, 10 mg/kg, 4 days apart during normovolemic (N) and hypovolemic (H) states in a random sequence. Hypovolemia was achieved by the withdrawal of 26 ml/kg of blood, equivalent to one-third of the calculated blood volume. Midazolam plasma concentrations were determined at 0.25, 0.5, 1, 2, 3, 4, 5, 6, 8, 10, and 12 h after midazolam injection. Elimination half-life (t 1/2 beta) was significantly longer and total clearance was significantly lower during H than during N. Initial distribution half-life, central compartment volume, total volume of distribution, and plasma protein binding were similar in both N and H states. Midazolam caused a significant decrease in systolic blood pressure (SBP) and an increase in heart rate (HR) during N, and produced significant decreases in SBP, diastolic blood pressure (DBP), and mean arterial pressure (MAP) during H. Midazolam led to similar per cent decreases in blood pressure and cardiac output in states N and H; however, the absolute values of blood pressure and cardiac output were significantly (P less than 0.001) lower in the hypovolemic state than in the normovolemic state. These data suggest that the hypotensive effects of midazolam, like those of other intravenous induction agents, could be potentiated by volume depletion.

Water and salt intake of wild rabbits (Oryctolagus cuniculus (L)) following dipsogenic stimuli.

Wild rabbits trapped in their natural habitat and adapted to laboratory conditions were studied. Food, water and electrolyte (0.5 M-NaCl, 0.5 M-KCl, 0.25 M-MgCl2 and 0.25 M-CaCl2) consumption, urinary volume and sodium losses were monitored daily following stimuli which were found dipsogenic in other species. Water drinking was observed immediately after the intravenous injection of 1 M-NaCl (3 ml/kg), and following withdrawal of a mean of 13.9% of calculated blood volume. Daily intake of water decreased during intracerebroventricular (I.C.V.) infusion of 0.3 M-NaCl in artificial cerebrospinal fluid (c.s.f.), during I.C.V. infusion of 0.9 M-mannitol c.s.f., both at a rate of 17 microliters/h, following peritoneal dialysis with 5% (w/v) glucose solution, and during food restriction. Water intake was not affected following intravenous administration of acetazolamide (10 mg/kg). Daily intake of 0.5 M-NaCl solution was increased following peritoneal dialysis with 5% (w/v) glucose solution, which caused hyponatraemia, but not after haemorrhage which caused about the same sodium deficit as peritoneal dialysis, but as an isosmotic loss. Administration of two different angiotensin II analogues, systemically or I.C.V., failed to induce water drinking. However, urinary sodium excretion and intake of 0.5 M-NaCl were increased during the 5 days of I.C.V. infusion of angiotensin II (10 pmol/h). Infusion for 1 day of angiotensin II (500 pmol/h) led to increased urinary sodium excretion which was followed by increased intake. The intake of other electrolyte solutions was not significantly affected by any of the treatments detailed above. The mechanisms participating in initiation of thirst in wild rabbits are very sensitive to decrease in blood volume, in contrast to other species studied in laboratories. Angiotensin II at the doses and routes administered was not dipsogenic in wild rabbits. The increased intake of 0.5 M-NaCl solution observed during and after the long-term intraventricular administration of angiotensin II in the wild rabbit appears predominantly a response to sodium deficit caused by natriuresis. The persistence of appetite after the cessation of infusion is indicative of a residual effect on central mechanisms of salt appetite.

Immediate hemodynamic consequences of MAST inflation in normo- and hypovolemic anesthetized swine.

Use of the military antishock trouser (MAST) remains controversial in part because its mechanism(s) of action are poorly understood. We studied two aspects of the hemodynamic response to MAST inflation in 14 anesthetized swine. First, in six swine the relation that existed between inferior vena cava flow and aortic pressure/cardiac output was determined before and during inflation of the MAST, and then before and after removal of 30% of the calculated blood volume. Inflation of the MAST before hemorrhage had little effect on cardiac output but increased aortic pressure by 25%. Inflation of the MAST after hemorrhage increased cardiac output by 41% and increased aortic pressure by 62%. Three different inflation pressures were studied (40, 80, and 120 mm Hg) and were found to give equivalent results. Inflation of the MAST translocated about 3 ml/kg of blood to the heart. A second group of eight swine were instrumented so that the radiomicrosphere technique could be used to measure organ blood flow. Inflation of the MAST following hemorrhage increased coronary perfusion by 50% and cerebral perfusion by about one third. Flow to kidney, liver, and small intestine was not changed. We conclude that, in addition to tamponade of venous bleeding and the splinting of lower extremity fractures, use of the MAST might cause a clinically important increase in the perfusion of the heart and brain in some trauma patients.

Plasma and blood volumes in patients with the nephrotic syndrome.

In 88 patients with the nephrotic syndrome (NS) we estimated plasma volume (PV) with 131I-albumin (RISA) and calculated blood volume (BV) from PV and whole body hematocrit (Ht). To assess whether this method gives erroneously high values in the NS, the transcapillary escape rate of albumin (TER) and large vessel Ht/whole body Ht ratio (F-cell ratio) were measured in two subsets of these patients (n = 19 and 24, respectively). Although TER appeared to be increased and F-cell ratio slightly decreased in the NS as compared to normals, it could be calculated that overestimation of PV and BV from these sources will not exceed +/- 1%. Taking these errors into account PV and BV appeared normal or increased in the NS (62.8 +/- 9.6 and 94.9 +/- 15.1 ml/kg vs. 56.0 +/- 7.1 and 88.5 +/- 10.1 ml/kg lean body mass in 51 normal controls). We conclude that PV can be measured reliably in the NS with 131I-albumin, and that even after appropriate corrections are made, PV and BV are normal or increased in most patients with the NS.

Increased left atrial pressure does not alter renal function in the conscious primate.

To study the functional role of the atriorenal reflex in the nonhuman primate, we chronically instrumented six Macaca fascicularis with left atrial snares and left atrial and aortic catheters. After inserting a bladder catheter, we determined hemodynamic and renal responses of the conscious chair-restrained monkey to increased left atrial pressure. In 23 snare experiments, no significant changes in renal or cardiovascular function were observed even though left atrial pressure increased from 6.5 +/- 3.3 to 16.2 +/- 3.4 mmHg. The animals were subjected also to blood volume expansion with isoncotic isotonic dextran solutions (+15% of calculated blood volume). They responded normally to this volume stimulus. Conscious dogs prepared in the same manner as the nonhuman primate exhibited diuresis in response to elevations of atrial pressure. We conclude that left atrial stretch receptors are not importantly involved in volume homeostasis in the nonhuman primate.

Effect of Clinical Bed Rest for Seven Days on Physical Performance

Twenty-two healthy men were confined to bed in a hospital ward (clinical bed rest) for one week. Variables related to physical fitness were measured before and immediately after the bed rest period, as well as one and three months thereafter. As a result of bed rest, maximal oxygen uptake, W170 and total Hb decreased to 94%, and calculated blood volume to 93% of the initial value. Hb concentration and Hct were unaltered. Thus, red cell and plasma volumes were proportionately reduced. No significant orthostatic dysfunction developed. The blood lactate peak at maximum work remained unchanged (14.0 mM/l). The resting exertion of noradrenaline decreased moderately during the bed rest period, whilst that of adrenaline was unchanged. Body weight decreased by a mean of 0.7 kg.

MICROCIRCULATORY CHANGES IN THE LUNG OF THE HYPOXIC AND HYPOVOLEMIC PUPPY AN ELECTRON MICROSCOPE STUDY

The effect of systemic hypoxemia and hypovolemia on pulmonary fine structure was studied and compared in 12 Labrador puppies 6 days to 3 weeks old. Central venous and arterial pressures were monitored and arterial pH, PCO2 and PO2 recorded serially. In 4 puppies lung biopsies were taken after a two hour period of breathing 7% oxygen. Four other puppies were made hypovolemic by acute hemorrhage of 50% of the calculated blood volume and lung biopsies taken after one hour. Four control puppies were maintained under anesthesia for two hours, breathing an atmosphere of 20% oxygen before lung biopsies were taken. Both hypoxemia and hypovolemia resulted in similar pulmonary ultrastructural changes. These changes which occurred more frequently in areas where the air spaces and blood vessels were expanded, were characterized by aggregation of platelets and leucocytes in the vascular space, focal endothelial cell disruption, interstitial edema and type I epithelial cell discontinuities with exudation of plasma into the alveolar air spaces.

Vacuum aspiration at therapeutic abortion: blood loss at operation in multigravid women.

Therapeutic abortion by vacuum aspiration in the first trimester was carried out on 129 healthy multigravid women. The loss of haemoglobin at operation was estimated and the volume of blood calculated. The figures were compared to those in a group of primigravid women earlier reported. Blood loss increases with gestational length. Blood loss at first trimester abortion is smaller in multigravid than in primigravid women. In multigravid women blood loss is not significantly influenced by the woman's age and the number of pregnancies.

Microcirculatory changes in the lung of the hypoxic and hypovolemic puppy: an electron microscope study.

The effect of systemic hypoxemia and hypovolemia on pulmonary fine structure was studied and compared in 12 Labrador puppies 6 days to 3 weeks old. Central venous and arterial pressures were monitored and arterial pH, PCO2 and PO2 recorded serially. In 4 puppies lung biopsies were taken after a two hour period of breathing 7% oxygen. Four other puppies were made hypovolemic by acute hemorrhage of 50% of the calculated blood volume and lung biopsies taken after one hour. Four control puppies were maintained under anesthesia for two hours, breathing an atmosphere of 20% oxygen before lung biopsies were taken. Both hypoxemia and hypovolemia resulted in similar pulmonary ultrastructural changes. These changes which occurred more frequently in areas where the air spaces and blood vessels were expanded, were characterized by aggregation of platelets and leucocytes in the vascular space, focal endothelial cell disruption, interstitial edema and type I epithelial cell discontinuities with exudation of plasma into the alveolar air spaces.

Adaptation of marrow sinus wall to fluctuation in the rate of cell delivery: studies in rabbits after blood-letting.

The extent of marrow sinus wall coverage by perisinal adventitial cells was measured before and after removing 25% of the calculated blood volume in rabbits. A marked reduction in the area covered by adventitial cells was recorded coinciding with the early reticulocyte response to phlebotomy. In control animals, only scattered microfilaments were occasionally observed in the cytoplasmic process of adventitial cells. After phlebotomy, these filaments were more frequently observed and appeared as band-like structures, raising the possibility of an active role for perisinal adventitial cells in response to fluctuations in the magnitude of cell traffic. Perisinal adventitial cells may, therefore, translate the body's demand for cell delivery by regulating the rate of transmural cell migration from the marrow. Such an adaptive mechanism may depend on the incompleteness of the adventitial layer of the sinus wall and the absence of endothelial-adventitial cell junctions, permitting separation of the two layers of the wall, so that the reticulocyte can gain access to more endothelial surface and the pores.

Reduction in baroreflex cardiovascular responses due to venous infusion in the rabbit.

We studied reflex bradycardia and depression of mean arterial blood pressure (MAP) during left aortic nerve (LAN) stimulation before and after volume infusion in the anesthetized rabbit. Step increases in mean right atrial pressure (MRAP) to 10 mm Hg did not result in a significant change in heart rate or MAP. After volume loading, responses to LAN stimulation were not as great and the degree of attenuation was propoetional to the level of increased MRAP. A change in responsiveness was observed after elevation of MRAP by only 1 mm Hg, corresponding to less than a 10% increase in average calculated blood volume. after an increase in MRAP of 10 mm Hg, peak responses were attenuated by 44% (heart rate) and 52% (MAP), and the initial slopes (rate of change) were reduced by 46% (heart rate) and 66% (MAP). Comparison of the responses after infusion with blood and dextran solutions indicated that hemodilution was an unlikely explanation for the attenuation of the reflex responses. Total arterial baroreceptor denervation (ABD) abolished the volume-related attenuation was still present following bilateral aortic nerve section or vagotomy. It thus appears that the carotid sinus responds to changes inblood volume and influences the reflex cardiovascular responses to afferent stimulation of the LAN. On the other hand, cardiopulmonary receptors subserved by vagal afferents do not appear to be involved.

The haematological hazards of autotransfusion.

Fourteen heparinized dogs were autotransfused from 1-5 to 6 times calculated blood volume. Five animals retransfused 12 litres from an intraperitoneal bleed had marked decreases in all cellular elements, haematuria and a large (82 percent) drop in fibrinogen. All these animals died within 12 hours and post-mortem examination revealed evidence of disseminated intravascular coagulopathy. The dogs in which a smaller volume (3-6 litres) was recycled showed similar, but less devastating, changes. Haematocrit and platelet count dropped by a half and fibrinogen by 20 per cent. A leucocytosis of about 30 000/mm3 occurred within 24 hours. Autotransfusion of salvaged blood which was not allowed extravascular tissue contact significantly lessened these adverse effects. We conclude that the risk of cellular destruction and defibrination in large volume intra-operative autotransfusion is significant and must be weighed against its potential benefits in each case, and that red cell and platelet damage results primarily from extravascular tissue contact and is therefore unavoidable.

Influence of hemorrhage on adrenal secretion, blood glucose and serum insulin in the awake pig.

A study was performed to quantitate the adrenal medullary and cortical response to hemorrhage in awake animals bled at different rates and to relate these responses to simultaneous changes in blood glucose and serum insulin. A series of awake pigs were bled either slowly or rapidly of 30% of their calculated blood volume. Infusions of exogenous epinephrine were performed in an additional series of unbled animals and infusions of epinephrine plus hydrocortisone were similarly performed in an additonal series. Increase in blood glucose and epinephrine secretion rate following hemorrhage were found to be significantly dependent upon the rate of initial hemorrhage. Cortisol secretion was found to rise significantly during and following hemorrhage in both rapidly and slowly bled animals. Serum insulin levels remained at baseline levels during shock, despite the presence of significant hyperglycemia. In unbled animals infused with epinephrine at rates comparable to those measured in shock, elevations in blood glucose were markedly lower, shifting to the right of the dose-response curve during hemorrhage. Simultaneous infusions of cortisol and epinephrine resulted in a dose-response curve which did not differ significantly from that following infusion of epinephrine alone.

Effect of Low Molecular Dextran on Total Liver Blood Flow in Hemorrhagic Shock

Hemorrhage amounting to 40% of the calculated blood volume in dogs produced a fall in systemic blood pressure to a level of approximately 50 mm Hg. This was associated with a decline of total liver blood flow of about 60% of normal. Infusion of low molecular dextran (LMD) or saline of a volume, corresponding to 1/7 of the volume of blood taken out, increased the total liver blood flow. This increase was much more pronounced in the LMD group, maybe due to the ability of LMD to simultaneously increase systemic blood pressure, decrease blood viscosity and disaggregate red blood cells in the microcirculation.

Autotransfusion in the subhuman primate

In the subhuman primate, autotransfusion of up to four times the calculated blood volume has been achieved with a commercially available system without significant development of microaggregates or pulmonary dysfunction when the animal has been adequately heparinized and maintained normotensive. These findings correlate clinical results achieved in elective autotransfusion carried out with systemic heparinization. Persons subjected to trauma and shock may be more susceptible to platelet aggregation, microembolization, and pulmonary insufficiency. Although these sequelae may occur after autotransfusion, they are not necessarily caused by autotransfusion of even massive proportions.

High energy phosphate compounds in adipose tissue: the effect of hemorrhage.

AbstractThe levels of ATP and CP in gastrocnemius muscle and inguinal subcutaneous adipose tissue of cats were measured before and after withdrawal of 25–45 per cent of the calculated blood volume and after retransfusion of the shed blood. Resting values were in skeletal muscle: ATP‐6.77±0.49 μmol/g tissue, CP‐17.35 ±1.31 μmol/g tissue (mean ± S.E.), and in adipose tissue: ATP 86.7 ±18.1 and CP 132.8± 8.5 nmol/g. Within 10 min after withdrawal of blood, muscle high energy phosphate levels were unchanged whereas adipose tissue CP and ATP levels had dropped to 20 and 48 per cent of control, respectively. Later during the hypotensive period, skeletal muscle levels also fell. Following retransfusion of the shed blood, adipose tissue levels remained low, whereas skeletal muscle levels returned towards control. The results demonstrate that the high energy phosphate levels are more severely decreased in adipose tissue than in skeletal muscle following bleeding in cats, and that the fall is not reversible in adipose tissue in contrast to muscle. The results are compatible with the idea that adipose tissue is one of the organs in which irreversible changes following hemorrhage are manifested.

Angiotensin II-like activity in circulating arterial blood in immature and adult rabbits.

1. Angiotensin II-like activity was estimated from the contraction of the rat ascending colon superfused with arterial blood in an extracorporeal circuit. The colon was calibrated by infusion of synthetic angiotensin II amide (Hypertensin, CIBA Ltd).2. Resting levels of angiotensin II-like activity were obtained by comparison of the length of a rat colon preparation superfused alternately with blood from an intact and from a nephrectomized rabbit.3. The resting levels of angiotensin II-like activity reached a maximum value of about 1.6 ng/ml. at 10-14 days of age, and thereafter declined to the adult value of 0.23 ng/ml. Rabbits of less than 100 g body weight had resting levels in the same range as adults.4. Removal of 25% of the calculated blood volume induced five times greater increments in arterial angiotensin II-like activity in immature than in adult rabbits (1.68 +/- 0.26 S.E. of mean ng/ml. compared with 0.34 +/- 0.08 S.E. of mean ng/ml.).5. No evidence was obtained that the high levels of angiotensin II-like activity encountered in immature rabbits were attributable to a slower rate of inactivation of angiotensin by tissues.6. The pronounced activity of the renin-angiotensin system demonstrated by these experiments in immature rabbits especially during haemorrhage is consistent with the suggestion that this system is of particular importance in cardiovascular control in early life.