PLASMA SUBSTITUTES 



67 



excreted was stored in unaltered form by the fixed 

 body phagocytes. Thrower & Campbell (104) gave 

 10 to 40 ml/kg of 3.5% PVP to rabbits. The rabbits 

 were killed in 14 to 28 days. No gross or significant 

 microscopic changes were seen. There was no evi- 

 dence of storage in the liver. Four patients given 500 

 to 1 500 ml of PVP showed at autopsy no changes 

 ascribable to P\T. About 75 % of the injected amount 

 could be recovered in the urine. If 500 ml of PVP 

 was infused intravenously, plasma levels were 3.5 g % 

 initially and 0.2 g % at the end of 50 hours. Gall and 

 associates (36) studied 22 patients who had received 

 a single infusion of looo ml of 3.5% or 4.5% PVP. 

 Liver biopsy specimens were obtained as controls 

 and after intervals of 1.5 to 13 months. Histologic 

 studies of the liver showed basophilic globular deposits 

 up to 50 micra in diameter. These were in the Kupff'er 

 cells or free in the sinusoids. There was occasionally a 

 mild inflammatory reaction in relation to these. 

 Deposits were seldom seen before 3 months from the 

 time of infusion, but almost uniformly after 6 months. 

 The histochemical studies were consistent with the 

 hypothesis that the material was PVP. Loeffler & 

 Scudder (68) gave carbon-14 tagged PVP to four 

 patients who died (from other causes) in 2 to 8 days. 

 One-third of this material was excreted in the urine 

 in 24 hours, and two-thirds in 48 hours. Small amounts 

 were excreted in the feces. The greatest amount of 

 the unexcreted portion was found in the kidneys, 

 liver, spleen, and lymph nodes. There was no histo- 

 logic evidence of damage caused by it. These patients 

 each received 540 ml of PVP (Macrose). Hueper (55) 

 gave rats and mice subcutaneous, intraperitoneal, 

 and intravenous PVP of molecular weight 20,000 to 

 300,000. In survival periods up to 24 months, tumors 

 of the lymphoid and reticuloendothelial tissues de- 

 veloped; also carcinomas of the uterus, skin, ovary, 

 and breast were found. The doses used were large and 

 would rarely be employed in man, except possibly in 

 the treatment of burns or nephrosis. The tumor 

 incidence, both malign and malignant, was 20 to 

 25% in rats. Frommer (35) gave low, medium, and 

 high molecular weight fractions of PVP to mice in 

 doses of 0.5 ml in a series of 20 injections totaling 10 

 ml. Changes occurred in the Kupffer cells and histio- 

 cytes of the periportal tissue. Some macrophages were 

 distended with vacuoles, giving them the appearance 

 of foam cells. Foam cell production seemed to be a 

 function of molecular size; the larger molecular 

 weights gave rise to many more foam cells than did 

 the lower weight in equivalent amount. A single 

 injection, equivalent to 20 to 25% of blood volume. 



did not produce hepatic changes. Stern (98) injected 

 3.5% PVP into mice. Storage of it or a derivative 

 was seen in the reticuloendothelial cells of the mouse. 

 Simultaneous administration of PVP and sulfonated 

 azo dyes led to renal excretion of dye and decrease 

 of dye storage in the reticuloendothelial system. 

 Polyvinylpyrrolidone given after the dye eluted it 

 from the reticuloendothelial cells. Polyvinylpyrroli- 

 done given before dye prevented its storage in the 

 reticuloendothelial cells. 



Altemeier and associates (3) studied the hepatic 

 storage of PVP in 25 patients receiving 1000 ml of 

 3.5% PVT (Macrose). The results were described 

 earlier in this chapter (36). Ravin and associates (87) 

 used PVP fractions tagged with P" and carbon-14 

 and showed that PVT is not metabolized to any 

 significant degree by rat, dog, or man. It does not 

 penetrate to the brain or fetus. The reticuloendothelial 

 system retains PVP with a molecular weight greater 

 than 110,000 for a long time, probably for years. 

 Polyvinylpyrrolidone with a molecular weight below 

 25,000 leaves promptly by way of the glomerulus 

 and is of little value as a plasma expander; that 

 below 40,000 can be excreted through the glomerulus 

 in a few days. The authors recommended PVP of 

 25,000 to 40,000 molecular weight with extremes of 

 20,000 to 70,000 molecular weight as plasma volume 

 expanders. These would expand plasma to 80 to 90 % 

 of infused volume at once and maintain 30 % expan- 

 sion at 1 2 hours. Sixty per cent of this molecular 

 weight PVP would be excreted in the urine in a few 

 days. The remainder would probably be totally 

 excreted in a year or more. 



Dexfrari 



Nelson & Lusky (8 1 ) gave rabbits i o ml/kg of 6 % 

 dextran (Macrodex) or 3.5% Periston (PVP) intra- 

 venously on 16 occasions over a 2-month period. No 

 systemic effects were seen. At autopsy the outstanding 

 observation was that of foam cells in the PVP group; 

 in the spleen these were J^ to 19 the entire organ. They 

 were also seen in moderate degree in lymph nodes, 

 bone marrow, and adrenal medulla; and to a lesser 

 extent in the lungs, liver, and thymus. In the dextran 

 animals changes were minor. Gray and associates (41) 

 studied the effect of dextran in starv-ed phlorhizinized 

 dogs. After infusing 200 ml of 6 % dextran the 24- to 

 48-hour post-infusion urine showed an increased 

 D/N ratio, suggesting metabolism of de.xtran to 

 glucose. These authors failed to find significant 

 excretion of dextran into the gastrointestinal tract in 



