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HANDBOOK. OF PHYSIOLOGY 



CIRCULATION I 



three dogs. Gray (39) showed that carbon- 14 dextran 

 was metabolized. It was broken down by the animal, 

 incorporated into the carbon pool, and distributed 

 throughout the body in the form of normal biochemi- 

 cal constituents. It appeared in lipids and amino 

 acids as early as the first day after administration. 

 Its metabolic half-life was 61 days in mice. This 

 author concluded that the possibility of de.xtran 

 retention in the body with adverse effects is unlikely. 

 Mowry & Millican (79) gave mice 6% dextran in- 

 travenously. The mice were sacrificed at intervals. 

 Histochemical tissue studies showed dextran widely 

 distributed in the blood, renal tubules, liver cells, and 

 reticuloendothelial system. In the hepatic cell cyto- 

 plasm the dextran appeared in 2 hours and was 

 maximal at 12 to 24 hours. None was seen in the 

 hepatic cells after i month. In the Kupffer cells, 

 dextran lasted longer and some was still present after 

 2 months. It also persisted in the phagocytes of 

 lymph nodes, spleen, pancreas, myocardium, fat, 

 lung, kidney, and skin. Hartman (47) gave 6% 

 dextran (CSC) to mice in seven intravenous injections 

 of 1.8 g/kg body weight each. This was shown to 

 produce retention in the lymph nodes, liver, kidneys, 

 and blood vessels. The liver cells showed granular 

 and vascular change, and the kidneys showed neph- 

 rosis. There were foam cells in the lung blood vessels 

 and in the lymph nodes. Most of these changes were 

 found to be reversible. Frawley and associates (34) 

 gave dextran (average mol wt 42,000) to 16 wounded 

 soldiers. The soldiers received i to 3 liters with an 

 average infusion rate of 500 ml in 2.7 hours. Six 

 hours after infusion 21% of the dextran was still in 

 the circulation and 45 'Jt of it had appeared in the 

 urine. At 72 hours 58 % of the dextran had appeared 

 in the urine. There was no significant difference in 

 the plasma disappearance curves of gelatin and 

 dextran in this study. Hehre & Sery (48) demonstrated 

 that an enzyme elaborated by certain gram negative 

 intestinal bacteria in man (Bacteroides group) is 

 able to cause breakdown of native and clinical 

 dextrans, releasing some as reducing sugar. The 

 importance of this mechanism in the metabolism of 

 dextran given to patients is unknown. Mowry and 

 associates (80), using a histochemical method, showed 

 a material believed to be dextran in the hepatic cells 

 and renal tubules of mice given CSC dextran 6 "^r in 



saline intravenouslv and sacrificed at 



hours. 



VVolman (117) compared the li\ers of mice injected 

 with clinical levan and clinical dextran. With dextran 

 there was found to be no increased liver glycogen and 

 most Kupffer cells were normal. Parn-nminosalic\'lic 



acid (PAS) positive granules were in the Kupffer 

 cells or in renal tubules, but most were free in the 

 blood vessels and between the cells. After clinical 

 levan there were found liver cell vacuoles which 

 stained like glycogen with aqueous PAS and which 

 were digested with saliva. Otherwise, the organ 

 changes were similar. The liver cell material was not 

 conclusively proved to be glycogen chemically, but 

 this was strongly suggested. If so, this may mean that 

 levan is metabolized more quickly than dextran and 

 thus a more desirable plasma expander. Terry and 

 associates (103) gave C'^-labeled dextran to dogs. 

 The average molecular weight was 30,000. With an 

 intravenous dose of 1 g/kg, plasma levels approached 

 zero at 70 hours. In 24 hours, 40 to 50% of the 

 dextran appeared in the urine by chemical tests, and 

 70% by carbon- 1 4 tests (the radioactive dextran 

 had a smaller molecular size). The amounts in the 

 plasma were negligible at 72 hours. The tissues 

 contained 5 to 10.79(1 of the dose at this time, mostly 

 in the liver, lymph nodes, adrenals, and spleen. In 

 72 hours the equivalent of 4.6 to 7.8% of the dextran 

 had appeared in expired air. The authors postulated 

 that, since C'^ carbon dioxide continues to appear in 

 expired air, all the dextran may be metabolized in 

 about 5 weeks. The liver was the only organ with PAS 

 positive diastase-resistant material in its parenchyma; 

 there was none in the kidneys. Bloom (11) gave 

 patients 30 g of dextran intravenously. The majority 

 of the excretable material was found in the urine 

 within 24 hours with a total of 42 '"[ over a 5-day 

 period. After a 30-gram infusion the plasma dextran 

 had disappeared by 5 days. No metabolic products 

 were identified in the blood and urine, although the 

 dextran remaining in the body was believed to be 

 metabolized slowly. Turner & Maycock (105) 

 studied the distribution of injected dextran in mice 

 given 360 mg of dextran per 100 g of mouse. About 

 half of this had left the body by 24 hours, 70 % by 7 

 days, and 80 % by 3 weeks. Lorenz, cited by Turner 

 (105), observed that mice given 60 mg of dextran 

 intravenously excreted 15 to 20% in the urine in 24 

 to 36 hours; 93 to 95% had left the body in 8 weeks. 

 Dextran was serologically but not chemically detect- 

 able in saline extracts of whole mouse after 32 weeks, 

 but not after i year. Bloom (12) treated 52 patients 

 in shock with dextran. When a hepatic vein was 

 catheterized, there was no evidence of dextran 

 removal by the liver. After 500 ml of 6 '^ dextran, 

 mean plasma levels were 726 mg 100 ml, falling 

 slowly to a mean of 88 mg at 96 hours. Most of the 

 urinarv excretion occurred in the first 48 hours and 



