Distribution and Fate of Intravenously Administered Modified Human Globin and Its Effect on Blood Volume. Studies Utilizing I131 Tagged Globin 1

Abstract

The need for blood substitutes adequate to combat the fall in circulating volume in shock continues to stimulate search for high molecular weight compounds which might serve as plasma expanders. Globin, derived from human red blood cells, has been suggested for this purpose (1, 2). While considerable study with this substance is being pursued in various laboratories (1-7), there have been few published reports dealing with its use as a blood volume expander (1). METHODSThe present investigation was approached along two lines: 1) Study of the fate and distribution of globin. Plasma and urine were analyzed at frequent intervals following the intravenous administration of tracer doses of I' tagged globin accompanied by varying amounts of uniodinated globin. In vivo assay over the liver following the administration of the tagged globin was also performed in an attempt to localize the organ site of accumulation and breakdown. The disappearance rates of I" tagged globin and albumin from intramuscular, subcutaneous, and intracutaneous sites of injection were determined for the purpose of comparing vascular permeability to the two proteins.2) Blood volume studies with PU tagged erythrocytes were performed during and after the intravenous administration of infusions of 32 and 48 grams of globin. Radioiodinated proteinsModified human globin' was iodinated with a mixture of I" and I' at pH 8.0 according to the method of Pressman and Eisen (9) and then dialyzed against frequently changed

Insulin-I131 Metabolism in Human Subjects: Demonstration of Insulin Binding Globulin in the Circulation of Insulin Treated Subjects 1

“…Above this level the rate of insulin-I13' degradation decreases significantly, probably as a result of overloading of the insulin degrading mechanisms. A similar decrease in the rate of degradation of P" tagged globulin produced by overloading with large doses of stable globin has previously been reported (16). In the case of insulin, therefore, it appears as if the degradation reaction follows first order kinetics over a very wide range of insulin concentrations.…”

Nutritive Adequacy and Clinical Tolerance of Modified Human Globin 1

“…Human serum albumin given intravenously has a 50 per cent disappearance time of about five to ten days (17,18). In contrast, the half-life of globin is probably several hours as indicated in the present study and studies utilizing I'll tagged globin (16). Untoward reactions following globin infusions, although frequent in occurrence, were never severe nor harmful in the studies reported here.…”

“…globin. The rapid disappearance of infused globin from the blood has been noted by others (7,16). In contrast to this, following the daily administration of concentrated human serum albumin the level of albumin in the blood progressively rises and after cessation of administration there follows a slow and progressive decrease (17).…”

The Iodide Trapping and Binding Functions of the Thyroid

“…samples of packed erythrocytes, plasma and urine were counted in a well-type scintillation counter with a sensitivity of 1.00 X 106 counts per minute per,c I'l above a background of 200 counts per minute. PBI3s and iodide13 were determined separately utilizing the plasma/RBC ratio of 1131 as previously described (8,9).…”