Studies of Dextrans of Various Molecular Sizes

Dextran metabolism following infusion of 7.5% NaCl/6% dextran‐70 to euvolemic and hemorrhaged rabbits

“…This reflects its major route of metabolism in the first hours following its infusion. In the present study, approximately 25 to 30% of the administered dextran was excreted in urine in 24 hr; slightly less than 31-47% previously reported for Dextran-60 and -70 [Thoren, 1980;Arturson and Wallenius, 1964b;Howard et al, 1956;Harrison, 19541. Thus, if renal function is not impaired by an induced hypovolemic state or is corrected following resuscitation [Dubick et al, 19891 it seems reasonable to assume that dextran turnover would be similar in both groups of rabbits. It should be mentioned that some authors reported that dextran clearance followed a biphasic pattern [Emmrich et al, 19771. In these situations it appeared that the first phase mainly represents renal clearance, while the second phase presumably denotes dextran distribution and metabolism in tissues [Gray, 19531. It is reported that dextran metabolism is a slow process [Gruber, 19691 and is insignificant with respect to the rate of renal clearance.…”

“…In the first 24 hr, the change in serum dextran concentrations over time was best described by a one-compartment model and is consistent with the observation that dextrans distribute rapidly following i v administration [Gruber, 1969] These data indicated that the serum tI,2 of Dextran-70, administered as HSD, was about 7 hr and is consistent with tI,2 of 6 2 hr following administrationi of Dextran-60 in young children [Anurson et al , 1966] However, the value is lower that the > 12 hr reported in normal adults following infusion of dextrans with molecular weights of 55,000 to 69,000 [Arturson and Wallentus, 1964aj It should be noted that HSD diffeis from early cliutcal Dextran-70 in that its molecular weight range is narrower, ranging from 20,000 to 100,000 compared to 25,000 to 200,000, and this may account, at least tn part, for the differences tn serum t,, 2 observed Although the t,, 2 of dextran in serum was similar in both groups of rabbits, it appeared that dextran clearance was about 21% slower in hemorrhaged animals than thetr euvolemc counterparts As a plasma volume expander, infusion of dextran causes a hemodilution that is a function of the dextran dose and time after infusion Previous reports discussing pharmacokinettes of plasma volume expander [Mishler, 1984, Klotz and Kroemer, 19871 have not dealt with differential volume expansion as observed in euvolemic vs hemorrhaged animals nor have they discussed possible difficulty in data interpretation as volume expansion changes over time Nevertheless, it is clear that conventional pharmacokinctic analysis cannot be strictly applied to plasma volume expanders that are heterogeneous in molecular size, such as dextrans and hydroxyethyl starch [Klotz and Kroemer, 1987, Yacobi et al , 19821 As previously mentioned, studies with othe clinical dextrans indicate that initially, dextrans are primarily cleared through the kidney [Arturson and Wallenius, 1964b, Arturson et al , 19641 This reflects its major route of metabolism m the first hours following its infusion In the present study, approximately 25 to 30% of the administered dextran was excreted in urnie in 24 hr, slightly less than 31-47% previously reported for Dextran-60 and -70 [Thoren, 1980, Arturson and Wallenius, 1964b, Howard et al , 1956, Harrison, 1954 Thus, if renal function is not impaired by an induced hypovolemic state or is corrected following resuscitation [Dubick et al , 1989] it seems reasonable to assume that dextran turnover would be similar in both groups of rabbits It should be mentioned that some authors reported that dextran clearance followed a biphasic pattern [Emmrich et al , 19771 In these situations it appeared that the first phase mainly represents renal clearance, while the second phase presumably denotes dextran distribution and metabolism in tissues [Gray, 1953] It is reported that dextran metabolism is a slow process [Gruber, 1969] and is insignificant with respect to the rate of renal clearance However, this metabolism plays a more important role after low molecular weight components of dextran are excreted Therefore, in the context of HSD as a resuscitation fluid ...…”

Treatment of Shock with Dextrans and Gelatins

“…During the Fifties, the enhanced bleeding tendency caused by infusions of clinical dextran was recognized in several countries [1,2,3,4,16,27,30,36,49,94,95,99,100,117,138,181,218]. One liter of the 6% solution then available, the weight average of which varied between 50,000 and 90,000, sufficed to prolong the bleeding time significantly in close to 50% of the recipients.…”

“…One liter of the 6% solution then available, the weight average of which varied between 50,000 and 90,000, sufficed to prolong the bleeding time significantly in close to 50% of the recipients. The maximum effect did not coincide with the peak concentration of dextran in the blood, but manifested itself 6 to 9 h after the infusion [2,3,36,95,117]. Blood loss from standardized experimental and clinical wounds (dermatome incisions) increased significantly following the adminis tration of 1500-2000 ml of clinical dextran [3,16,100,218].…”

Molecular composition of transfusion dextran. A report to the Medical Research Council's Blood Transfusion Research Committee.

“…The corresponding changes in intrinsic viscosity have been calculated and are shown in Table I. The persistence in the human circulation of dextrans of various molecular weights was measured by Howard et al (1956), who found little difference between fractions of average molecular weight 194,000, 255,000, and 412,000. The top 30% of dextran B.P.…”