Evaluation of a Stroma-Free Hemoglobin Solution for Use as a Plasma Expander

Abstract

Plasma, dextran, and other preparations, although effective as plasma expanders, cannot carry oxygen and therefore are not as useful as whole blood for management of acute hemorrhage. Blood, on the other hand, has a limited storage time and must be typed and cross-matched prior to use. Hemoglobin in solution has several unique properties which could be desirable for treating hemorrhagic shock. In addition to its osmotic activity (tool wt 68,000), hemoglobin can transport and exchange oxygen and has the advantage of not requiring typing or cross-matching (1). Despite its potential, the use of hemoglobin solutions has not progressed past the animal experimentation stage because of reports of renal damage and methemoglobin formation following its administration (2--4).Recent studies strongly suggest that disseminated intravascular coagulation may play an important role in the pathogenesis of renal damage seen in shock, intravascular hemolysis, and other situations (5-8). It has also been dearly demonstrated that hemolyzed erythrocytes can initiate blood coagulation (9, 10) and that this coagulant activity is confined to erythrocyte stroma (11). With these observations in mind, it may be postulated that renal damage, following administration of hemoglobin solution, could be due to coagulant activity of red cell stromal contaminants. A stromalfree hemoglobin solution would therefore not have deleterious effects on renal function.It is the purpose of this report to describe a method for preparation ot large quantities of a hemoglobin solution which is rdativdy free of stromal particles or lipid and has no demonstrable coagulant activity. We also wish to report results of acute and chronic experiments which show distribution, excretion, oxygen-carrying capacity, and effect on renal function of this solution when it is administered to healthy mongrel dogs. Methods and MaterialsPreparation of Hemoglobin Sobut/on.--Erythroeytes were separated from outdated, human whole blood and washed three times with 1.6% saline. The washed cells were lysed by adding

Disposal of plasma heme in normal man and patients with intravascular hemolysis

“…4). Previous studies have shown that the liver is also the site of removal of protein-bound heme in animals (21,22) and of free and haptoglobin-bound hemoglobin in animals (35,43,48) and man (15,16 Reutilization of heme-iron (Fig. 4).…”

Artifical Blood

“…Their main known disadvantages are, reduced circulation half-life, haemodynamic and gastrointestinal perturbations, probably related to nitric oxide (NO) scavenging, free radical induction, and alterations of biochemical and haematological parameters (increase in liver enzyme levels, platelet aggregation) [1][2][3].…”

Tissue PO₂ during Reanimation with Hemoglobin Solutions

“…Stroma-free solutions of hemoglobin have been shown to be free of toxic effects such as deterioration of kidney function and coagulation disorders (Palani et al, 1975;Rabiner et al, 1967;Relihan and Litwin, 1973). The two major disadvantages are short intravascular persistence and high oxygen affinity (Sunder-Plassmann et al, 1975).…”