Physiology of red and white blood cells

Blood is made up of plasma and formed elements, which are red blood cells, white blood cells and platelets. The red blood cells (erythrocytes) make up the vast majority of the cells present in the blood. Their principal function is the transport of oxygen from the lungs to the tissues and the transport of carbon dioxide from those tissues back to the lungs. This is due to the presence of haemoglobin, a protein that binds easily and reversibly with oxygen. The affinity of haemoglobin for oxygen changes under certain conditions allowing increased offloading of oxygen at the respiring tissues as required. White blood cells (leucocytes) form the body's defence against invading pathogens. They can be subdivided into granulocytes and agranulocytes, which have different mechanisms of attack against those pathogens.     

Physiology of red and white blood cells

Blood consists of formed elements (red blood cells, white blood cells and platelets) and plasma. Red blood cells (erythrocytes) account for 99.9% of cells. Their principal function is the transport of oxygen from the lungs to respiring tissues and carbon dioxide from tissues back to the lungs. This is achieved through the presence of haemoglobin, a conjugated metallo-protein. The affinity of haemoglobin for oxygen changes with a number of circumstances. At the partial pressure of oxygen (PO₂) in the alveoli (13 kPa) the binding of each oxygen molecule increases the affinity of haemoglobin, so aiding uptake of oxygen. At the low PO₂ in tissues, affinity is reduced, allowing the haemoglobin to offload more oxygen. This sigmoidal relationship is shifted to the right by a fall in pH or an increase in 2,3-diphosphoglycerate concentration or temperature. The role of white blood cells (leucocytes) is to defend the body against invading pathogens. Leucocytes are far less common than erythrocytes, although their numbers increase dramatically during an infection. Divided into granulocytes (neutrophils, eosinophils and basophils) and agranulocytes (monocytes and lymphocytes), leucocytes can recognize foreign material and either engulf cells or secrete membrane-disrupting chemicals that can destroy the organism. Lymphocytes play an important role in the immune response to disease, monitoring the internal environment and producing antibodies against pathogens.     

Physiology of red and white blood cells

Blood consists of formed elements (red blood cells, white blood cells and platelets) and plasma. Red blood cells (erythrocytes) account for 99.9% of cells. Their principal function is the transport of oxygen from the lungs to respiring tissues and carbon dioxide from tissues back to the lungs. This is achieved through the presence of haemoglobin, a conjugated metallo-protein. The affinity of haemoglobin for oxygen changes with a number of circumstances. At the partial pressure of oxygen (PO₂) in the alveoli (13 kPa) the binding of each oxygen molecule increases the affinity of haemoglobin, so aiding uptake of oxygen. At the low PO₂ in tissues, affinity is reduced, allowing the haemoglobin to offload more oxygen. This sigmoidal relationship is shifted to the right by a fall in pH or an increase in 2,3-diphosphoglycerate concentration or temperature. The role of white blood cells (leucocytes) is to defend the body against invading pathogens. Leucocytes are far less common than erythrocytes, although their numbers increase dramatically during an infection. Divided into granulocytes (neutrophils, eosinophils and basophils) and agranulocytes (monocytes and lymphocytes), leucocytes can recognize foreign material and either engulf cells or secrete membrane-disrupting chemicals that can destroy the organism. Lymphocytes play an important role in the immune response to disease, monitoring the internal environment and producing antibodies against pathogens.     

Detection of a vasoconstrictor factor in stroma-free haemoglobin solutions

Polymerised pyridoxylated haemoglobin solution (PPSFH) is a modified haemoglobin solution which has a normal oxygen carrying capacity, long half-life, and reasonable oxygen affinity, and is a leading candidate for use as an oxygen carrying blood substitute. Previous work has given indications that vasoactive factors may be present. A bioassay sensitive to vasoconstrictors was constructed. PPSFH prepared by chloroform extraction produced a mean pressure rise of 24.3 mm Hg. PPSFH prepared by a crystallisation method showed a mean rise of 2 mm Hg (p = 0.0004). Unmodified stroma-free haemoglobin (SFH) prepared from platelet- and white cell-free red blood cells showed a mean rise of 32.5 mm Hg. These data indicate that both PPSFH and SFH contain a vasoconstrictor factor which is of low molecular weight, is hydrophilic, and is derived from red blood cells.     

Respiration: gas transfer

Oxygen and carbon dioxide move passively between the alveoli and the pulmonary blood down concentration gradients, as described by Fick’s law of diffusion. Lungs are thin enough and offer a sufficiently large surface area for equilibrium to be achieved well before the blood has left them. As a result, the exchange of these gases is normally limited by the cardiac output. Both ventilation and perfusion of the lungs show gradients in the upright individual, with lower values at the apex than at the base. These gradients are caused by gravity, though the details of these effects differ between ventilation and perfusion. There is a ventilation-perfusion gradient down the lung, with the highest values at the apex; apical alveoli are over-ventilated and basal ones over-perfused. Such imbalances are normally minimized by local reflexes involving airway constriction (apex) and vascular constriction (base). One of the main functions of haemoglobin is to transport oxygen from the lungs to the tissues. The properties of this molecule are such that: small falls in the partial pressure of alveolar oxygen do not reduce the saturation of blood leaving the lungs; increased release of oxygen to the tissues is accomplished with small falls below the normal partial pressure of oxygen; and raised acidity and temperature in exercising tissues promote oxygen unloading. Haemoglobin is also involved in the carriage of carbon dioxide, directly (by the formation of carbaminohaemoglobin) and indirectly (by acting as a buffer for hydrogen ions produced during the formulation of carbaminohaemoglobin and by dissociation of carbonic acid formed at the erythrocyte membrane).     

Increased red cell 2,3-diphosphoglycerate levels in haemodialysis patients treated with erythropoietin

The efficacy of recombinant human erythropoietin (rHuEpo) forthe treatment of renal anaemia is well established. To assessthe effect of rHuEpo treatment on physical performance we evaluatedphysical working capacity, oxygen uptake and red cell 2,3diphosphoglycerate(DPG) values at rest and during and after exercise on a bicyclespiroergometer in eight chronically haemodialysed patients.Follow-up examination was carried out after a mean of 14 weeks(range 9–19 weeks), when mean haemoglobin had increasedfrom 7.8 to a stable value of 13.0 g/dl in response to rHuEpotreatment (P<0.001). Physical working capacity and oxygenuptake at the anaerobic threshold (4 rnrnol/l blood lactateconcentration) increased from 68±12 to 80±16 wattsand 0.95±0.14 to 1.10±0.20 l/min, respectively(P<0.01). DPG, which determines oxygen affinity to haemoglobinin red cells, increased by 13% from 13.7±1.5 to 15.5±2.2pmol/g Hb (P<0.05 ). With maximal exercise mean DPG valuessignificantly decreased to a much lower level without rHuEpotreatment than after correction of anaemia. Therefore rHuEpotreatment results both in better oxygen transport capacity andreduced intraerythrocytic oxygen affinity, which is followedby improved oxygen delivery to tissues per unit of haemoglobin.These effects may explain the improvement of exercise capacityobserved in dialysis patients after rHuEpo treatment.     

Extravasation of albumin in tissues of normal and septic baboons and sheep.

Extravasation of albumin was measured in the tissues of normal and septic baboons and sheep. A group of normal animals (4 baboons, 4 sheep) was anesthetized for 6 hr and then given radioactively labeled albumin and red blood cells intravenously. The labeled albumin and red blood cells were allowed to equilibrate for exactly 15 min, at which time the animals were deliberately killed. Volumes of distribution of labeled albumin and red blood cells were then determined in the lungs, heart, liver, spleen, brain, and skeletal muscle of the baboons and in the lungs, heart, liver, and spleen of the sheep. Another group of animals (6 baboons, 14 sheep) were made septic by infusing live Escherichia coli organisms. The animals were resuscitated and volumes of distribution of albumin and red blood cells determined as in the normal animals. The volume of distribution of albumin was greater than the volume of distribution of red blood cells in all tissues in both species, both in control animals and in septic animals, with the exception of the spleen and skeletal muscle of the baboons and the spleen of the sheep. That is, albumin extravasated readily in most of the tissues of the animals, even within only 15 min of equilibration. There was moderate but significant extravasation in the lungs, heart, and brain. There was marked extravasation in the liver. Extravasation tended to be more pronounced in the septic animals. With this extensive degree of albumin extravasation, administration of albumin to patients, especially septic patients, is unlikely to prevent edema except in the spleen and skeletal muscle.     

Autotransfusion after open heart surgery: quality of shed mediastinal blood compared to banked blood

The need to conserve a patient's own blood and avoid homologous transfusion is now well recognized. Therefore, techniques designed to reduce requirements for homologous blood transfusions have been developed. One of the methods is autotransfusion of shed mediastinal blood after open-heart surgery. The objectives of the present study were to investigate osmotic fragility and oxygen transport capacity of shed mediastinal blood compared to patient blood and stored packed red blood cells (SAGM).
Shed mediastinal blood from ten consecutive patients undergoing elective cardiac surgery (coronary bypass grafting) was studied and compared to patient blood, 10 units of 3 weeks old and 10 units of 5 weeks old stored packed red blood cells (SAGM). Oxygen transport capacity was investigated by calculation of p50 for oxygen by use of the oxygen status algorithm (OSA 2.0) programme and measurement of 2,3-diphosphoglycerate (2,3-DPG) concentrations. The osmotic fragility was determined using increasing concentrations of saline.
2,3-DPG concentrations in shed mediastinal blood (5,3 mikromol/ml erythrocyte) were within the range measured in patient blood, but significantly higher than SAGM blood ( P <0.001). P50 for oxygen (3.5 kPa) in shed mediastinal blood was not significantly different compared to patient blood, but significantly higher ( P <0.01) compared with stored SAGM blood. The osmotic fragility in shed mediastinal blood was not significantly different compared to patient blood, but significantly lower ( P <0.001) than the osmotic fragility in stored SAGM blood. This suggests that red cells saved from shed mediastinal blood have better oxygen transport capacity and may have longer survival compared to stored blood.     

Is There a Role for Blood Substitutes in Civilian Medicine: A Drug for Emergency Shock Cases?

The oxygen carried inside plasma performs differently than the oxygen carried inside red cells. Only 0.13-0.3 mL of oxygen in 100 mL of blood is available inside plasma while 14-19 mL of oxygen is carried inside red cells. Thus, less than 5-8 mL of oxygen is available in the plasma of the entire body. When a patient develops hypovolemic shock, red cells are bypassed and are not perfused directly inside the tissues. However, plasma should reach such hypoxic tissues. Thus, an infusion of oxygen-carrying macromolecules in plasma with a hemoglobin concentration of only 6% and P50 value of 24 mm Hg should be therapeutically effective even if less than 100 mL of stabilized hemoglobin solution (conjugated hemoglobin of 90,000 Da with a molecular size of less than 10 nm or 0.01 microm) are infused under shock conditions. The basic physiology of oxygen-carrying macromolecules is described in detail, which is different from the oxygen carried inside the red cells and inside encapsulated oxygen-carrying particles (typically 250 nm or 0.25 microm). Thus, the oxygen-carrying macromolecues are extremely effective in the treatment of shock patients. In emergency cases, after the bleeding is controlled, a small infusion volume of oxygen-carrying macromolecules will supply sufficient oxygen to the hypoxic tissues and immediately improve the blood pressure of shock patients.     

Impact of autotransfusion after coronary artery bypass grafting on oxygen transport

Background: Autotransfusion of shed mediastinal blood after coronary artery bypass grafting (CABG) has been shown to reduce the requirement for allogeneic blood. We have previously demonstrated in non-randomized studies that the oxygen capacity of shed mediastinal blood is similar to the patient's circulating blood and better than stored allogeneic blood. Therefore, we wanted to examine the influence of autotransfusion of shed mediastinal blood on oxygen transport capacity in patients undergoing CABG.
Methods: A prospective, randomized, controlled study involving 120 patients having elective, uncomplicated CABG was performed. The autotransfusion group received transfusion of shed mediastinal blood for 18 h. Both groups received allogeneic red cells if their hemoglobin concentration decreased below 5 mmol/L. Red blood cell 2, 3-diphosphoglycerate (2, 3-DPG) was measured preoperatively and at intervals up to the hospital discharged. Hemodynamic measurements as well as blood gas and hemoglobin measurements from samples of arterial and mixed venous blood were used for calculation of oxygen transport capacity.
Results: During the autotransfusion period only 2 patients (4%) in the autotransfusion group required allogeneic blood compared to 11 patients (20%) in the control group. The 2, 3-DPG levels in the autotransfusion group were unchanged before and after autotransfusion (4.4 vs. 4.3 umol/ml erythrocyte). In the control group, 2, 3-DPG levels decreased from 4.3 to 3.9 umol/ ml erythrocyte during the same period. There were no differences in the other measured parameters for oxygen transport capacity between the groups.
Conclusion: Autotransfusion of shed mediastinal blood conserves the 2, 3-DPG level of the red blood cells, while transfusion of stored blood leads to a decrease in 2, 3-DPG levels. Autotransfusion had no effect on hemodynamic parameters, oxygen delivery or oxygen extraction.     

The place for using erythrocyte substitutes in hemodilution: fluosol-DA and polymerized pyridoxylated hemoglobin

In conditions of limited haemodilution (haematocrit 0.25), an improvement in the rheological properties of blood and an increase in cardiac output allow increased perfusion of capillaries and maintenance of tissue oxygenation so long as normal circulating volume is maintained. However, some authors have suggested that blood substitutes enabling oxygen transport are necessary. The suitability of such substitutes depends on their physicochemical properties and, until now, only the use of haemoglobin solutions and fluorocarbon emulsions has been. The use of fluorocarbons requires respiration under hyperoxia or pure oxygen, which is a major limitation. Haemoglobin solutions suffer from inadequate concentration, short vascular persistence and too high an affinity for oxygen, but these deficiencies disappear with polymerized pyridoxylated haemoglobin. Though both types of preparation can keep animals alive with zero haematocrit for some time, their contribution to oxygenation goes down as the haematocrit goes up. According to Zander and Makowski [40]. the minimum acceptable amount of oxygen in the blood is reached with a haemoglobin concentration of 4.4 g X 100 ml-1 with a Po2 of 90 mmHg (12 kPa), and of 3.3 g X 100 ml-1 with a Po2 of 550 mmHg (73 kPa); these values correspond to a haematocrit close to 0.10. At this haematocrit and with a Po2 of 90 mmHg, a 70 g X l-1 haemoglobin solution contributes for 28% to the consumption of oxygen in baboons, while Fluosol DA 20, used at Po2 550 mmHg, takes care of 55% of this consumption. At higher haematocrits, it is not certain that these substitutions have a real advantage over the usual plasma expanders at normovolaemic haemodilution.(ABSTRACT TRUNCATED AT 250 WORDS)     

Red cell 2,3-diphosphoglycerate and oxygen affinity

The ease with which haemoglobin releases oxygen to the tissues is controlled by erythrocytic 2,3-diphosphoglycerate (2,3-DPG) such that an increase in the concentration of 2,3-DPG decreases oxygen affinity and vice versa. This review article describes the synthesis and breakdown of 2,3-DPG in the Embden-Meyerof pathway in red cells and briefly explains the molecular basis for its effect on oxygen affinity. Interaction of the effects of pH, Pco2, temperature and 2,3-DPG on the oxyhaemoglobin dissociation curve are discussed. The role of 2,3-DPG in the intraerythrocytic adaptation to various types of hypoxaemia is described. The increased oxygen affinity of blood stored in acid-citrate-dextrose (ACD) solution has been shown to be due to the decrease in the concentration of 2,3-DPG which occurs during storage. Methods of maintaining the concentration of 2,3-DPG in stored blood are described. The clinical implication of transfusion of elderly people, anaemic or pregnant patients with ACD stored blood to anaesthetically and surgically acceptable haemoglobin concentrations are discussed. Hypophosphataemia in association with parenteral feeding reduces 2,3-DPG concentration and so increases oxygen affinity. Since post-operative use of intravenous fluids such as dextrose or dextrose/saline also lead to hypophosphataemia, the addition of inorganic phosphorus to routine post-operative intravenous fluid may be advisable. Disorders of acid-base balance effect oxygen affinity not only by the direct effect of pH on the oxyhaemoglobin dissociation curve but by its control of 2,3-DPG metabolism. Management of acid-base disorders and pre-operative aklalinization of patients with sickle cell disease whould take account of this. It is known that anaesthesia alters the position of the oxyhaemoglobin dissociation curve, but it is thought that this is independent of any effects which anaesthetic agents may have on 2,3-DPG concentration. In vitro manipulation of 2,3-DPG concentration with steroids has already been carried out. Elucidation of the role of 2,3-DPG in the control of oxygen affinity may ultimately lead to iatrogenic manipulation of oxygen affinity in vivo.     

Haemoglobin hyperpolymers, a new type of artificial oxygen carrier -- the concept and current state of development

In the clinical setting, artificial oxygen carriers are needed when a patient has a tissue oxygen deficiency which he/she can not automatically compensate. There are two quite different situations where this might occur: (1) Heavy blood loss (e. g., following an accident) and (2) insufficient perfusion (e. g., as a result of arteriosclerosis or myocardial infarction) or anaemia, both without blood loss. In the first instance, an iso-oncotic oxygen-transporting plasma expander is required, whereas in the second instance a (hypo-oncotic) so-called blood additive is needed. This second type of situation also presents the greater range of very important indications. Experimental work has shown that, in comparison to erythrocytes, dissolved haemoglobin is able to release oxygen more rapidly (effective plasmatic transport), while at the same time also facilitating oxygen release from erythrocytes (mediator function). Blood additives occur naturally in lower forms of life (e. g., earthworm) where they can be found in the form of giant oxygen-carrying molecules. Using these natural forms as a basis, new oxygen-transporting blood additives were designed and developed (so-called haemoglobin hyperpolymers: HP (3)Hb) which exhibit a strong oxygen affinity (half saturation partial pressure p (50) = 16 Torr) and high cooperativity (n (50) = 2.1). One product has, up until now, been produced aseptically on a small technical scale and consists of highly purified, polymerised and pegylated porcine haemoglobin which is free of monomers and oligomers, with a mean molecular weight of approximately 800 kDa. It is sufficiently low in endotoxin (< 0,029 EU/mL), blood plasma compatible, and - at an effective concentration of 3 g/dL in blood plasma - causes only minor increases in oncotic pressure or viscosity. The product has a shelf-life of up to 2 years and is administered as a carbonyl derivative. Its half-life in the conscious rat is 30 h. This product was found to prevent death in rats where acute lung injury was induced using oleic-acid. In human self-experiments this product was repeatedly administered: No effects on blood pressure and heart rate, no increase in blood transaminase concentration and no immunological reaction were seen; the latter was also not found in selected sensitive mice. Furthermore, the blood additive is universally applicable as an oxygen transporter, since, when mixed with a conventional plasma expander, it can also be used to treat an oxygen deficiency occurring together with blood loss.     

Bovine haemoglobin is more potent than autologous red blood cells in restoring muscular tissue oxygenation after profound isovolaemic haemodilution in dogs

Purpose

This study compares the effects of stored red cells, freshly donated blood and ultrapurified polymerized bovine haemoglobin (HBOC) on haemodynamic variables, oxygen transport capacity and muscular tissue oxygenation after acute and almost complete isovolaemic haemodilution in a canine model.

Methods

Following randomization to one of three groups, 24 anaesthetized Foxhounds underwent isovolaemic haemodilution with 6% hetastarch to haematocrit levels of 20%, 15% and 10% before they received isovolaemic stepwise augmentation of 1 g · dl^?1 haemoglobin. In Group 1, animals were given autologous stored red cells which they had donated three weeks before. In Group 2, animals received freshly donated blood harvested during haemodilution. In Group 3, animals were infused with HBOC. Skeletal muscle tissue oxygen tension was measured with a polarographic 12 μ needle probe.

Results

In all groups, heart rate and cardiac index were increased with decreasing vascular resistance during haemodilution (P < 0.05). Haemodynamic variables showed a reversed trend during transfusion when compared to haemodilution but remained below baseline (P < 0.05). Arterial and venous oxygen content were changed in parallel to changes of haematocrit and haemoglobin concentrations but were lower in Group 3 than in Groups 1 and 2 (P < 0.05) during transfusion. In contrast, the oxygen extraction ratio was higher in Group 3 (59 ± 8%, P < 0.01) at the end of transfusion than in Group 1 (37 ± 13%) and 2 (32 ± 5%). In Group 3, mean tissue oxygen tension increased from 16 ± 5 mmHg after haemodilution to 56 ± 11 mmHg after transfusion (P < 0.01) and was higher than in Group 1 (41 ± 9, P < 0.01) and Group 2 (29 ± 11, P < 0.01). While in Group 3 an augmentation of 0.7 g · dl^?1 haemoglobin resulted in restoring baseline tissue oxygenation, higher doses of 2.7 g · dl^?1 and 2.1 g · dl^?1 were needed in Groups 1 and 2 to reach this level (P < 0.01).

Conclusion

The results show a higher oxygenation potential of HBOC than with autologous stored red cells because of a more pronounced oxygen extraction.     

Conditioning out‐of‐date bank‐stored red blood cells using a cell‐saver auto‐transfusion device: effects on numbers of red cells and quality of suspension fluid

We investigated the utility of a cell‐saver device for processing out‐of‐date red blood cells, by washing twenty bags of red blood cells that had been stored for between 36 and 55 days. The volume of recovered cells, and the characteristics of the suspension fluid, were measured before and after treatment. The ratio of free haemoglobin to total haemoglobin was up to 0.02 before processing, and up to 0.011 afterwards, changing by between ?0.013 and +0.003. This ratio met the current standard for free haemoglobin (less than 0.008 in more than 75% of samples), both before and after processing. Ninety‐three percent of red blood cells survived the process. Potassium ion concentration fell from above 15 mmol.l^?1 in all cases, to a mean of 6.4 mmol.l^?1 (p < 0.001). The pH rose to a mean value of 6.44 (p = 0.001). Lactate ion concentration fell to a mean value of 14 mmol.l^?1 (p < 0.001). Sodium ion concentration rose from a mean value of 93 mmol.l^?1 to a mean value of 140 mmol.l^?1 (p < 0.001). A useful proportion of out‐of‐date red blood cells remained intact after conditioning using a cell‐saver, and the process lowered concentrations of potentially toxic solutes in the fluid in which they were suspended.     

Red blood cell transfusion following burn

A severe burn will significantly alter haematologic parameters, and manifest as anaemia, which is commonly found in patients with greater than 10% total body surface area (TBSA) involvement. Maintaining haemoglobin and haematocrit levels with blood transfusion has been the gold standard for the treatment of anaemia for many years. While there is no consensus on when to transfuse, an increasing number of authors have expressed that less blood products should be transfused. Current transfusion protocols use a specific level of haemoglobin or haematocrit, which dictates when to transfuse packed red blood cells (PRBCs). This level is known as the trigger. There is no one 'common trigger' as values range from 6 g dl(-1) to 8 g dl(-1) of haemoglobin. The aim of this study was to analyse the current status of red blood cell (RBC) transfusions in the treatment of burn patients, and address new information regarding burn and blood transfusion management. Analysis of existing transfusion literature confirms that individual burn centres transfuse at a lower trigger than in previous years. The quest for a universal transfusion trigger should be abandoned. All RBC transfusions should be tailored to the patient's blood volume status, acuity of blood loss and ongoing perfusion requirements. We also focus on the prevention of unnecessary transfusion as well as techniques to minimise blood loss, optimise red cell production and determine when transfusion is appropriate.     

Hämoglobinmodifikationen als sauerstofftransportierende Blutersatzmittel

Although the attempts to develop an oxygen-carrying alternative to red blood cells (RBC) have spanned the last 100 years, it has proven difficult to develop a clinically useful haemoglobin-based oxygen carrier. Four major problems have been shown to compromise the use of haemoglobin outside the RBC as an oxygen carrier: (1) the increased oxygen affinity due to the loss of 2,3-diphosphoglycerate; (2) dissociation into dimers and monomers with consequent renal and capillary loss of hemoglobin; (3) insufficient concentrations of prepared solutions under iso-oncotic conditions, and thereby reduced oxygen-carrying capacity; and (4) toxicity. Most of these limitations have been overcome by different modifications of haemoglobin, including pyridoxylation, intra- and intermolecular cross-linking, polymerisation, liposome encapsulation, conjugation to inert macromolecules, and genetic engineering. Questions of toxicity are not completely answered at present, especially with regard to renal toxicity, interactions with the nitric oxide system, and antigenicity. Therefore, the issues preventing clinical application are those of safety and not of efficacy of haemoglobin-based RBC substitutes. Potential clinical applications include fluid resuscitation, treatment of anaemia and ischaemia, support in extracorporeal circulation, and organ preservation. Based on promising and reproducible results obtained from animal studies, clinical phase I and II trials with newer haemoglobin solutions have been started in the United States. Substantial knowledge has been gained in the development, production, and evaluation of haemoglobin-based oxygen carriers during the past years. It will probably not take another century before oxygen-carrying RBC substitutes will become available for clinical use.     

Oxygen-Carrying Macromolecules: Therapeutic Agents for the Treatment of Hypoxia

Abstract: A stabilized form of hemoglobin as oxygen-carrying macromolecules was developed. It had an approximately 90,000 dalton molecular weight, and its intravascular half-life was 36 h. Its molecular size was less than 0.1 μ m. Its hemoglobin concentration was 6% and its P₅₀ value was 24 mm Hg. Oxygen carried inside plasma performs differently than oxygen carried inside red cells. Less than 0.3 cc of oxygen in 100 ml of blood is available in the plasma while 14–19 ml of oxygen is carried inside the red cells. Thus, less than 5 cc of oxygen is available inside the plasma of the entire body. When a patient develops hypovolemic shock, the red cells are bypassed and are not perfused directly inside the tissues. However, the plasma should reach hypoxic tissues. Thus, infusion of oxygen-carrying macromolecules into the plasma should be therapeutically effective even when infusing less than 100 ml of stabilized hemoglobin solution under shock conditions. The basic physiology of oxygen-carrying macromolecules is described in detail, which is different from the physiology of oxygen-carrying red cells.     

The function of red blood cells under open-heart surgery with extracorporeal circulation without donor blood]

In 18 patients scheduled for open-heart surgery with extracorporeal circulation without donor blood, P50, 2, 3-DPG, intracellular sodium and potassium in red blood cells, and erythrocyte deformability were measured for the purpose of investigating the influence of severe hemodilution on oxygen transport and function of red cells. P50 and 2, 3-DPG in red cells showed no significant changes until the end of cardiopulmonary bypass (CPB). At the end of operation, 2, 3-DPG content decreased significantly without a significant change of P50. This is probably due to the rightward shift of oxyhemoglobin dissociation curve as compensation for the hemodilution without donor blood. On the first postoperative day, P50 value and 2,3-DPG content decreased significantly but returned to previous values on the second day. As the result of changes of red cell sodium contents and deformability, erythrocyte morphology recovered soon after the end of CPB, but the membrane function of red cells was restored a few days later. In conclusion, oxygen transport in red cells may be disturbed after open-heart surgery with extracorporeal circulation without donor blood.