A potential blood substitute from a tetronic polyol and a modified hemoglobin.

This investigation reports a new potential blood substitute. An acellular fluid is formed between a Tetronic polyol and a modified hemoglobin. It was possible to stabilize the hemoglobin with glutaric acid. The subsequent reaction with the alcohols of the Tetronic polyol resulted in a useful resuscitative fluid. Exchange transfusion experiments in rats was possible at the 75% replacement level with an excellent survival rate. This was apparently possible because of the effective transport properties of this material. Histological sections of the liver, kidney and lungs showed little or no permanent damage to the organs. The Tetronic polyol - modified hemoglobin complex was not excreted in the urine in contrast to the modified hemoglobin by itself and a solution of unmodified hemoglobin. These preliminary studies indicate that this combination of a polymer and modified hemoglobin has a potential use as a red cell substitute.

The erythrocyte sedimentation rates: some model experiments.

In order to obtain a better understanding of the erythrocyte sedimentation rate (ESR), several models are presented. The first directs attention to the importance of geometrical models to represent the structure of mixtures. Here it is our intention to understand the effect of the structure on the packing of red blood cells. In this part of the study, "Cheerios" (trademark General Mills) are used as a macroscopic model. It is interesting that a random sampling of "Cheerios" has the same volume distribution curve that is found for erythrocytes with a Coulter Sizing Apparatus. In order to examine the effect of rouleaux formation, the "Cheerios" are stacked one on top of another and then glued. Rouleaux of 2,3,4,5, 7 and 10 discs were used. In order to examine a more realistic biological model, the experiments of Dintenfass were used. These investigations were performed in a split-capillary photo viscometer using whole blood from patients with a variety of diseases. The novel part of this research is the fact that the work was performed at 1g and at near zero gravity in the space shuttle "Discovery." The size of the aggregates and/or rouleaux clearly showed a dependence upon the gravity of the experiment. The purpose of this model was to examine the condition of self-similarity and fractal behavior. Calculations are reported which clearly indicate that there is general agreement in the magnitude of the fractal dimension from the "Cheerios" model, the "Discovery" experiment with those determined with the automatic sedimentimeter. The final aspect of this work examines the surface texture of the sedimention tube. A series of tubes were designed with "roughened" interiors. A comparison of the sedimentation rates clearly indicates a more rapid settling in "roughened" tubes than in ones with a smooth interior surface.

The sedimentation potential and the boycott effect.

The sedimentation potential or the Dorn effect occurs when heavy particles fall in a liquid. An electrode near the bottom of the vessel acquires a potential difference with respect to another identical electrode placed near the upper surface of the solution. The Boycott phenomenon enhances the sedimentation in inclined vessels. In this investigation, fixed erythrocytes at 2-3% concentration were studied. The shapes include discs, oblate spheroids, spheres and spindles. From the sedimentation potentials, the zeta potentials were calculated and compared with those determined by laser Doppler velocity. By using a technique of reduced variables, it is shown that all of the data could be placed on a single curve, combining particle flexibility, shape, concentration and angle of inclination.

A blood substitute from hydroxyethyl starch and hemoglobin.

One method to increase the retention time of hemoglobin (Hgb) is to react it with a hydroxyethyl starch (HES) molecule. To examine this hypothesis, polymer-bound hemoglobin compounds were synthesized by the dialdehyde route. The electrophoretic mobility patterns indicate complete binding of the Hgb. Preliminary exchange-transfusion experiments in rates showed that they could survive for at least 10 h at Hct less than 10% when transfused with 6% HES-Hgb solutions. The retention time of the Hgb in the urine was increased to 12 h with these new polymers.

Mixtures of whole blood and hydroxyethyl starch--hemoglobin polymers.

This study examines some of the biophysical properties of mixtures of whole blood with 3 different hydroxyethyl starch-hemoglobin (HES-Hgb) polymer blood substitutes. The polymers have about a 3-fold range of number average molecular weight and intrinsic viscosity range. The range dependent rheologic studies with a 60 g/L of polymer solution showed that all 3 blood substitutes were very effective hemodiluents paralleling the hemorheologic properties of the starting HES polymers. The 2 higher molecular weight polymers enhanced the erythrocyte sedimentation rates (ESR) at an 8:1 blood to polymer dilution; however, the lowest molecular weight sample actually retarded the settling. The kinetics of malonamide-induced hemolysis indicated that these new polymers do not increase the rate of hemolysis but rather, offer some protection in a manner similar to stroma-free Hgb (SFH) solutions. The oxygen transport properties determined by biotonometry during an exchange transfusion showed that the P50 values decreased and were dependent upon the Hct. However, these samples were able to maintain rats at an Hct level of 10%.

Biophysical properties of resuscitation fluids.

The preliminary results of this study indicate that the biophysical characteristics of stroma-free hemoglobin solution (SFH) make it an extremely suitable blood substitute. At the concentration that is currently being considered as an infusing solution (70 g/L), it is a Newtonian fluid having a viscosity very similar to that of plasma. At this concentration, SFH also has very favorable hemodilution properties, as well as potential oxygen transport ability, which most expanders lack. There seems to be little interaction between the plasma proteins and SFH, as indicated from viscosity measurements. The osmotic behavior of SFH indicates that it approaches an ideal polymer-solvent system as illustrated by the small value of the second virial coefficient, especially when compared to other plasma substitutes. In mixtures with whole blood at a series of hematocrits, SFH seems to be hyperosmotic. This biophysical property could certainly have significance in patients with severe shock. SFH maintains the integrity of whole blood and does not initiate erythrocyte aggregation. The investigations of the erythrocyte sedimentation rate (ESR) in this study with SFH indicate the potential usefulness of SFH in maintaining stability of these systems, particularly during the treatment of shock. The transport properties of the red cell membrane are apparently not effectively altered by the presence of SFH. This has been illustrated in the hemolytic malonamide kinetic and osmotic fragility studies. Although the results are preliminary, it should be stressed that SFH may offer protection against hemolysis when used as a transfusion solution.