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Methods and MaterialsPreparation of Hemoglobin Sobut/on.--Erythroeytes were separated from outdated, human whole blood and washed three times with 1.6% saline.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
Synthetic mixtures of galacturonic acid, galactose, and rhamnose have been quantitatively resolved. Overall concentrations as low as 21 y per ml. were used. The color produced by the reaction of di-, tri-, or tetragalacturonic acid with anthrone obeys Beer's law, at least up to 200 y per 6 ml.; the quantity of color is pro-
Molecular weight, titration, and elemental analytical data led to (Ci2H]6Oi6NS2Na3)20 for the molecular formula of sodium heparinate. Six to seven equivalents of sulfate per mole of heparin were found, which were not an integral part of the heparin molecule. After conversion of sodium heparinate to heparinic acid, titration data indicated forty ionizable sulfate groups, twenty ionizable carboxyl groups, and one ionizable amino group per mole. These values indicate that there were no diester sulfate linkages in the heparinic acid. Although the possibility of one -NH-S02-O-• cross linkage per mole of sodium heparinate has not been excluded by the present findings, it seems improbable. Unequivocal stoichiometric evidence
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