Dextran metabolism was evaluated in euvolemic and hemorrhaged rabbits following administration of a 7.5%NaCl/6% Dextran‐70 (HSD) solution. Control rabbits and those bled 8 ml/kg body weight were infused i.v. with 4 ml/kg of HSD or HSD containing 14 C‐Dextran‐70. Blood samples were withdrawn prior to and at times up to 96 hr after HSD infusion. Peak serum dextran concentrations were about 29% higher in hemorrhaged rabbits than in controls, yet serum dextran t 1/2 was similar in both groups. Molecular weight (MW) distribution of dextran in serum showed a slight shift toward a MW >70,000, consistent with excretion of lower MW forms in the urine. After 96 hr concentrations of 14 C‐Dextran were 20‐fold higher in liver from both groups of rabbits, in comparison to spleen, lung, and kidney. In addition, dextranase activity in liver was markedly higher than in the other tissues assayed. These studies indicate that dextran infused as HSD does not associate with any protein fractions, is found only in low concentrations in tissue, and has a serum half‐life adequate to serve as a useful plasma volume expander.

The introduction of a 7.5% hypertonic saline/6% dextran 70 (HSD) solution into clinical trials for the treatment of hypovolemic states, and the past concerns regarding the possible interference of dextran with blood serology, prompted us to investigate the effects of HSD on human red-cell typing and stability. HSD was evaluated with fresh and 35-day stored CPDA-1 red cells from 12 healthy donors. A 1:5 mixture of HSD to blood in vitro had no effect on ABO, Rh, and MN typing in both fresh and stored blood. HSD produced no significant lysis with fresh cells and a minimal level with stored blood. No evidence of metabolic or morphologic changes was seen after HSD treatment. The results of this study suggest that the clinical use of HSD for the treatment of hemorrhagic shock will not affect blood group determinations or red-cell stability from stored blood which may be infused after the HSD-treated patient is transported to a hospital.

: HSD is a resuscitative fluid which has shown great promise in experimental trials. However, clinical use of modern dextran solutions has been limited by concerns of anaphylactoid reactions. To assess the short term immunogenic response to HSD, analyses for total immunoglobulins, IgG, IgM, and C3 complement were performed on sera of hemorrhaged and euvolemic pigs receiving HSD (4 ml/kg) and euvolemic dogs infused with either 6% Dextran-70 in normal saline (Macrodex) or HSD 20 ml/kg). In swine, serum IgG, IgM, and total immunoglobulin titers were unchanged in response to hemorrhage and/or HSD infusion over the 120 hr experimental period. Total immunoglobulin titers were essentially unchanged in unhemorrhaged, HSD infused pigs over a three week period.

Dextran metabolism was investigated in ten hemorrhaged and seven euvolemic conscious swine. Chronically instrumented, splenectomized swine were subjected to a progressive fixed-volume hemorrhage (27 ml/kg over 45 min). Resuscitation with 4 ml/kg of a 7.5% NaCl/6% dextran 70 (HSD) solution was begun 5 min later. Blood and urine samples were drawn before and during hemorrhage, and at 15, 60, and 120 min following intravenous HSD infusion. Hemorrhage significantly reduced cardiac output (CO) and mean arterial pressure (MAP) and eliminated urinary flow. HSD administration to hemorrhaged pigs returned CO and MAP to control values and improved urinary flow. Creatinine clearance returned to prehemorrhage values. These parameters were not affected by HSD in nonhemorrhaged animals. Plasma dextran concentrations were 20-30% higher in hemorrhaged pigs compared with euvolemic swine. In additional studies, plasma t1/2 for dextran was 9.4 hr in hemorrhaged pigs (n = 3) compared to 10.8 hr in euvolemic animals (n = 2). These data show that HSD ameliorates the effects of hemorrhage on cardiovascular and renal function and suggest that plasma clearance of dextran may be affected by hemorrhage.

Dextran metabolism was investigated in ten hemorrhaged and seven euvolemic conscious swine. Chronically instrumented, splenectomized swine were subjected to a progressive fixed-volume hemorrhage (27 ml/kg over 45 min). Resuscitation with 4 ml/kg of a 7.5% NaCl/6% dextran 70 (HSD) solution was begun 5 min later. Blood and urine samples were drawn before and during hemorrhage, and at 15, 60, and 120 min following intravenous HSD infusion. Hemorrhage significantly reduced cardiac output (CO) and mean arterial pressure (MAP) and eliminated urinary flow. HSD administration to hemorrhaged pigs returned CO and MAP to control values and improved urinary flow. Creatinine clearance returned to prehemorrhage values. These parameters were not affected by HSD in nonhemorrhaged animals. Plasma dextran concentrations were 20-30% higher in hemorrhaged pigs compared with euvolemic swine. In additional studies, plasma t1/2 for dextran was 9.4 hr in hemorrhaged pigs (n = 3) compared to 10.8 hr in euvolemic animals (n = 2). These data show that HSD ameliorates the effects of hemorrhage on cardiovascular and renal function and suggest that plasma clearance of dextran may be affected by hemorrhage.

Abstract : Dextran metabolism was evaluated in euvolemic and hemorrhaged rabbits following administration of a 7.5% NaCl/6% Dextran-70 (HSD) solution. Control rabbits and those bled 8 ml/kg body weight were infused i.v. with 4 ml/kg of HSD or HSD containing c-Dextran-70. Blood samples were withdrawn prior to and 0.17, 0.5, 1, 2, 4, 6, 24, 48, 72, and 96 hours after HSD infusion. Although peak serum dextran concentrations were about 29% higher in hemorrhaged rabbits than in controls, in both groups of rabbits dextran was cleared from serum with a half-life of about 7.4 h. In addition, dextran was distributed throughout the blood volume and did not bind to serum proteins. At the end of the 96 h experimental period, concentrations of radiolabeled dextran were 20-fold higher in liver from both groups of rabbits, in comparison to spleen, lung and kidney. The c-dextran in liver was associated with the cytosolic fraction and was not associated with any membrane structures. Molecular weight distribution of the serum dextran revealed no significant metabolism over the 6 h post-infusion period assayed. After 96 h, radiolabeled dextran in liver showed some degree of metabolism and dextranase activity in liver was markedly higher than in the other tissues assayed.