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Methods and MaterialsPreparation of Hemoglobin Sobut/on.--Erythroeytes were separated from outdated, human whole blood and washed three times with 1.6% saline.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
Hemolytic plasma transfusion reactions were produced in six Macaca irw monkeys. The plasma for these transfusions was obtained from alloimmunized animals with amlutinins of high titu and, in some cases, hemolysins directed against the recipients' red blood cells. The transfusion reactions were characterized by varying degrees of intravaacular hemolysis, hemoglobinemia and hernoglobmuria, and disseminated intravascular coagulation accompanied by marked falls in Factors VIII and V, and fibrinogen. Shortening of euglobulii clot lysis time was seen in three animals.Two animals died and had fibrin thrombi in renal glomeruli, myocardial veins, pulmonary arteries, and hepatic sinusoids.
Ten randomly selected cynomolgus monkeys were each given an intramuscular injection of a mixture of isologous red cells suspended in complete Freund's adjuvant. After 6 weeks a second injection of red cells in incomplete Freund's was given and thereafter intravenous booster injections of red cells in isotonic saline were used. Antibody titres were determined with serial crossmatches at 37"C, 4"C, and with rabbit antimonkey serum. All animals developed antibody to at least one and several against all four immunizing red cells. Haemolysins were seen frequently.Transfusion reactions followed intravenous injections of incompatible 51 Crlabelled red cells. Major reactions occurred in five of seven animals and consisted of complete destruction of infused cells within 5 min, haemoglobinuria, haemoglobinaemia, oliguria, anuria in one case, and the disseminated intravascular coagulation syndrome in three cases. The remaining two animals had mainly extravascular destruction of the transfused red cells and exhibited no coagulation changes.
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