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Infusion of small volume of 7.5 per cent sodium chloride in 6.0 per cent dextran 70 for the treatment of uncontrolled hemorrhagic shock.

The effect of a solution of 7.5 per cent sodium chloride in 6.0 percent dextran 70 was studied in a rat model of uncontrolled hemorrhagic shock induced by partial resection of the tail of the rat. Fifty rats were randomly assorted into five groups of ten rats each. In group 1, uncontrolled hemorrhagic shock was induced by sharp resection of 10 per cent of the terminal portion of the tail of the rat. In group 2, uncontrolled hemorrhagic shock was treated with 5 milliliters per kilogram of 0.9 per cent sodium chloride. In group 3, uncontrolled hemorrhagic shock was treated with 5 milliliters per kilogram of 6 per cent dextran 70. In group 4, rats were treated with 5 milliliters per kilogram of 7.5 per cent sodium chloride, and in group 5, 5 milliliters per kilogram of 7.5 per cent sodium chloride in 6.0 per cent dextran 70 were infused. During the first five minutes, bleeding in rats in group 1 was 3.0 +/- 0.4 milliliters and the mean arterial pressure fell from 105 +/- 5 to 73 +/- 7 torr (p less than 0.001). In group 4, bleeding at 15, 30 and 60 minutes was 1.9 +/- 0.3 milliliters (p less than 0.02), 2.0 +/- 0.7 milliliters (p less than 0.04) and 2.4 +/- 1.1 milliliters (p less than 0.02), and in group 5, 2.5 +/- 0.6 milliliters (p less than 0.02), 2.2 +/- 0.6 milliliters (p less than 0.04) and 3.1 +/- 0.8 milliliters (p less than 0.04), respectively, compared with bleeding in group 1. Increased bleeding was followed by a fall in mean arterial pressure in groups 4 and 5 with a 60 per cent mortality rate (p less than 0.01) in both groups and respective, mean survival times of 135 +/- 29 and 144 +/- 26 minutes, which were significantly increased compared with group 1 (p less than 0.01 for both). The intravenous infusion of 6 per cent dextran 70 alone in group 3 resulted in delayed bleeding of 1.23 +/- 0.6 milliliters (p less than 0.04) after 180 minutes. It is concluded that infusions of small volume of 7.5 per cent sodium chloride or 7.5 per cent sodium chloride in 6.0 per cent dextran 70 solutions in rats in a state of uncontrolled hemorrhagic shock led to increased bleeding, decrease in mean arterial pressure and increased mortality.

Animals↗

Dextran and release of prostacyclin from ex vivo perfused rabbit arteries and veins.

The effects of dextran on the haemostatic system lead to prolongation of the bleeding time. To observe if the coating of endothelial cells by dextran influences the release of prostacyclin from the vessel walls in response to ex vivo perfusion, dextran 70 (1 g/kg b.w.) was given i.v. 15 min or 4 hours before excision of caval vein and aorta in rabbits, or was added to the perfusate. Vascular segments were perfused for 5 x 15 min, with the perfusate changed after each period and with arachidonic acid added on the last occasion. Prostacyclin was measured as its stable degradation product 6-keto-PGF1 alpha by radioimmunoassay. Arteries released more prostacyclin than did veins (p less than 0.01). Dextran given in vivo or ex vivo had no influence on release of prostacyclin from the walls of perfused arteries or veins. The anti-haemostatic properties of dextran 70, 1 g/kg b.w., thus do not seem to be mediated by prostacyclin release from vessel walls.

6-Ketoprostaglandin F1 alpha↗

Electron microscopic pathological patterns of alveolar septum in acute dextran-induced and alloxan-induced pulmonary edema in dogs.

We studied the incidence of electron microscopic pathological patterns of the alveolar septum observed 30 min after induction of pulmonary edema by dextran-70 infusion (6 dogs, dextran group) and by alloxan injection (6 dogs, alloxan group). For comparable amounts of extravascular lung water in both dextran and alloxan groups, which were twice as much as control group (6 dogs), we characterized the pathological changes. The incidence of the electron microscopic pathological patterns that appeared in dextran group compared with that in control group was significantly high in terms of the widening of the interstitial space, dispersion and disarray of collagen fibrils, and erythrocytes in the interstitial space. The incidence in alloxan group compared with that in control group was significantly high in terms of the swelling of epithelial cells and endothelial cells as well as the widening of the interstitial space, and dispersion and disarray of collagen fibrils. We conclude that dextran causes interstitial changes exclusively and alloxan causes cellular changes primarily coupled with secondary interstitial changes in acute pulmonary edema.

Alloxan↗

Production of IgG antibodies and enhanced response of nude mice to DNP-AE-dextran.

DNP-AE-dextran, prepared by the binding of DNP-epsilon-aminocaproyl residues to animoethylated dextran (predominantly alpha-1,6-linked), induced a T-independent anti-DNP antibody response in mice. However, certain differences were observed between the response to this antigen in normal andnude mice. Thus, the antibody titers of nu/nu mice from day 10 to 38 after immunization were significantly higher than those of nu/+ controls. Furthermore, DNP-AE-dextran induced a weak secondary response in nu/+ but not in nu/nu mice. For both thymusless and normal mice the production of IgG in addition to IgM antibodies to DNP-AE-dextran could be established. The former included antibodies of the IgG1 subclass which were considered to be particularly thymus dependent (1). The higher response of nu/nu mice was reflected mainly in the increased production of IgG antibodies. Under the influence of a graft-vs-host reaction, a 10-fold increase in antibody titers to DNP-AE-dextran was observed, due entirely to an enhanced IgG response.

Animals↗

[Thrombosis prophylaxis with low doses of dextran 60 (author's transl)].

The antithrombotic effect of dextran 60 (Macrodex) was studied in a prospective, randomized trial on patients undergoing general surgery. 42 patients (group A) received 500 ml of dextran 60 intraoperatively, 49 patients (group B) received an additional dose of 100 ml dextran 60 on days 1 to 5 after operation. As tested by the 125-iodine-radiofibrinogen test 16 patients (38%) from group A, but only 2 patients (4%) from group B developed deep venous thrombosis. The difference between both groups is statistically highly significant (P less than 0,0005). The use of dextran for thromboprophylaxis was associated neither with hemorrhagic complications nor with anaphylactoid reactions. The fractionated application of a total of 1000 ml of dextran 60 resulted in a very efficient prophylaxis against deep venous thrombosis.

Aged↗

[Permeability of dextran-bound nuclease through the vascular barrier and tumor cell membrane].

Under study was the permeability of nuclease Ser marcescens, bound covalently by the method of diazocombinations with m-amino benzyloxymethyl-dextran of the molecular weight 20 000, 40 000, 60 000 via the vascular barrier and the membrane of tumor cells. It is shown that dextran-bound nuclease as well as the native enzyme would penetrate into the intacts cells of Ehrlich ascites carcinoma. The rate of the modified nuclease penetration is dependent on dextran molecular weight. Along with the native enzyme also nuclease bound to dextran of the molecular weight 20 000 and 40 000 penetrates the vascular barrier. The permeability of the vascular barrier for dextran-bound nuclease is found to be considerably higher in tumor-bearing animals than in intact ones.

Animals↗

[Pharmaco-physiologic correlations of iron-dextran complexes in laboratory animals].

Investigated were the Bulgarian preparation dextrofer-100 (Pharmachim) and miofer-100 (Farbwerke, Hoechst, West Germany)--iron-dextran preparations with 100 mg Fe3+/cm3 each. Use was made of 62 domestic cats, 8 guinea pigs, and 18 albino rats. tI was found that the venous introduction of iron-dextran complexes into uretane-treated cats at rates of 100 to 500 mg Fe3+/kg body mass lowered the blood pressure by 10 to 65 per cent; the depressive effect was more strongly manifested with the use of miofer-100. At 100 mg Fe3+/kg and higher doses led to alfa-adrenolytic manifestations (an inverse effect of noradrenaline), and did not change the action of acetyl-choline, histamine, and serotonin. At venous injection the iron-dextran complexes diminished the amplitudes of the heart contractions (with cats in situ). With regard to the nervous-and-muscle condition these preparations were found to manifest an action that resembled that of curare (the effect produced by miofer was stronger). Dextrofer-100 in a five-fold application to guinea pigs at the rate of 0.2 cm3+ (= 20 mg Fe3+) blocked the sensibilizing action of horse serum--it gave protection from an aphylactic shock in about 70 per cent of the animals. In muscular application to albino rats with experimentally induced dextran edema this preparation manifested an antiedema action. The iron-dextran complexes lowered the contraction capacity of ileum sections (taken from guinea pigs) that was manifested under the action of serotonin and histamine.

Anaphylaxis↗

[Effect of a 3.6 o/o dextran Ringer acetate solution on moderately hypovolemic patients in intensive care].

The effects of 1000 ml 3.6% dextran Ringer's acetate solution (Mw 61,800; infusion time 60 min) on circulation, blood and plasma volume, blood viscosity and renal function parameters were investigated, the renal elimination of dextran also being measured. During the entire investigation period no significant alterations of cardiocirculatory parameters, blood and plasma volume and rheological properties of blood could be demonstrated, the same holding true for kidney function values. Dextran excretion was about 33% three hours after the end of infusion, reaching 51% of the whole amount given 21 hours later. It has to be assumed that mainly macromolecular dextran components of less efficiency are retained intravascularly. Taking into consideration the practically absent volume expanding effect - even at the end of infusion period - this dextran solution cannot be recommended as a blood substitute during acute hemorrhage or as an "expander" in other shock states.

Acetates↗

Analysis of the diversity of murine antibodies to dextran B1355. I. Generation of a larger, pauci-clonal response by a bacterial vaccine.

Mice immunized with a combination of dextran B1355 in adjuvant followed by three injections of 2 x 10(9) Escherichia coli B organisms produced an average of 14.5 mg/ml of anti-dextran antibodies. It was demonstrated that the stimulating effect of E. coli B was due to antigenic determinants cross-reactive with B1355 and not solely because of adjuvant properties of the organism. The anti-dextran antibodies were distributed among both 7S and 19S components. Isoelectric focusing of the 7S antibodies showed several spectrotypes of antibody, most of which were shared by the majority of the individual sera. The limited spectrotypic heterogeneity of the 7S antibodies was supported by idiotypic studies. Thus, a heterologous, anti-idiotypic serum, rabbit anti-M104, was prepared which distinguished between two closely related myeloma proteins, M104 and J558,with specificity for alpha-(1 leads to 3) dextran. This antiserum demonstrated that some, but not all, of the 7S and 19S anti-dextran antibodies possessed variable region determinants cross-reactive with M104.

Antibodies↗

Studies on mitogen activity of the dextrans.

The influence of dextrans of various molecule sizes on blastic transformation induced by Con A and PHA lectins was studied. It was found that particularly dextran of smaller molecule inhibits blastogenesis induced by Con A. The dextran of greater molecule is less so inhibitory. On the other hand, in the effect of dextrans on the induction provoked by PHA their stimulating component is rather pronounced. Discussing the obtained results it was pointed out that the dextrans depending on the molecule exhibit the affinity to lymphocyte receptors for lectins and both blocking and stimulating effects may be involved.

Cells, Cultured↗

Radioprotective effects of dextran sulphate in mice.

Influence of a single i.p. injection of dextran sulphate on radiosensitivity of mice was investigated. The administration of dextran sulphate 24, 48 and 72 hours prior to irradiation increased formation of endogenous colonies of the hemopoietic tissue on the surface of the spleen. DRF calculated from an equieffective exposure for 5 colonies was 1.96 when dextran sulphate was administered 24 hours before irradiation, and 2.25 when dextran sulphate was administered 72 hours before irradiation. The radioprotective effects of dextran sulphate were manifested also in the survival of animals exposed to lethal doses of short-termed as well as long-termed gamma radiation.

Animals↗

[The effects of 500 ml 10% hydroxyethyl starch 200/0.5 and 10% dextran 40 on blood volume, colloid osmotic pressure and renal function in human volunteers (author's transl)].

The effects of administration of a new, middle-molecular 10% hydroxyethyl starch 200/0.5 (HAES-steril) were compared to 10% dextran 40 (Rheomacrodex) in 20 hypovolaemic volunteers after withdrawal of 400 ml blood. The total increase of blood volume after 500 ml of 10% hydroxyethyl starch 200/0.5 was 10.19 +/- 1.1 ml/kg (754 ml), after 500 ml of 10% dextran 40 14.10 +/- 1.1 ml/kg (1032 ml), which was significantly higher (p less than 0.01) and in correspondence with the known volume expanding properties of 10% dextran 40. The volume effect after administration of both substances was stable, as demonstrated by the ability to compensate the loss of 400 ml blood for more than 8 hours. The maximal increase of the colloid osmotoc pressure after 10% hydroxyethyl starch 200/0.5 was 5.3 +/- 0.2 mm Hg, after 10% dextran 40 7.2 +/- 0.4 mm Hg and paralleled the increase of the blood volume. After 10% hydroxyethyl starch 200/0.5 an increase of serum amylase was observed. This hyperamylasemia is caused by the formation of a high molecular hydroxyethyl starch-amylase complex, which cannot be eliminated easily. Urinary volume and endogenous creatinine clearance were increased by administration of both colloids. After dextran 40 a pronounced increase of the urinary viscosity occurred.

Adult↗

Prolonged local analgesia for inguinal herniorrhaphy with bupivacaine and dextran.

In a randomised double-blind trial 40 patients undergoing unilateral inguinal herniorrhaphy were each locally anaesthetised with one of a series of 8 solutions. These contained bupivacaine, both with and without adrenaline, mixed with an equal volume of dextran 40, dextran 70, dextran 110, or saline. Significant prolongation of local analgesia was achieved with high-molecular-weight dextran and this was most consistently obtained when the solution used contained adrenaline. The possible influence of the pH of the solutions used, together with the ways in which dextran may affect the duration of action of bupivacaine are discussed.

Anesthesia, Local↗

Role of self carriers in the immune response and tolerance. VIII. Suppression of the MOPC-104E idiotypic response by idiotype-modified self, but not by dextran-modified self.

We have investigated the suppression of the anti-dextran B1355S immune response using our model of modified self. The anti-dextran response is idiotypically well defined in BALB/c mice. This system enables us to examine the contribution of various predominant idiotypes to the antibody response under conditions of suppression by antigen or by idiotype-specific suppressor cells. Our results demonstrate that the total anti-dextran response can be inhibited by pretreatment of animals with dextran-coupled syngeneic spleen cells; however, the representation of major idiotypes constituting this response are not reduced in percentage. In contrast, pretreatment of mice with MOPC-104E-coupled spleen cells leads to a specific suppression of the private IdI-104E idiotype. The total anti-dextran response remains unchanged, as well as proportions of other major idiotypes known (IdI-588 and IdX). This suppression is mediated by Thy-1.2+, Lyt-2.2+ T cells, as demonstrated by adoptive transfer assays. This system will allow the molecular dissection of the regulation of an idiotypically well-defined system for the suppression by either antigen- or idiotype-specific suppressor T cells.

Animals↗

High molecular weight dextran--effect on adhesion formation and peritonitis in rats.

To evaluate the effect of 32% dextran 70 instillation on intra-abdominal adhesion formation and intestinal leaks, 100 animals were prospectively, randomly, and blindly treated with a sham laparotomy (n = 10), sham plus 5 ml dextran (10), intestinal abrasion plus 2 ml (20) or 5 ml (20) of dextran or saline, or intestinal division and anastomosis plus 2 ml (20) or 5 ml (20) of dextran or saline. Autopsies were performed on the animals without knowledge of treatment group at the time of death or sacrifice at 2 weeks. Adhesions were graded 0 to 3, anastomoses were examined for leaks, and the peritoneal cavity was searched for abscesses or peritonitis. Anastomosis produced more severe adhesions than abrasion. Dextran significantly (P greater than 0.01) reduced adhesion formation but resulted in peritonitis (5/40) rather than abscess (7/40) as seen with saline.

Animals↗

Tissue blood flow and blood flow distribution after administration of dextran 70, dihydroergotamine and their combination. A study in dogs using the radioactive microsphere technique.

The radioactive microsphere technique was used to measure tissue blood flow after administration of dextran 70 and dihydroergotamine, both separate and in combination, in normotensive dogs. Dextran 70 increased cardiac, output and tissue blood flow to most organs. Unchanged blood flow after dextran 70 to CNS, liver (hepatic artery blood flow), adrenals, genitals, uterus and lungs (bronchial artery and arteriovenous shunts) was found. Dihydroergotamine administration did not alter cardiac output. Tissue blood flow to pancreas and thyroid was reduced and CNS-tissue blood flow increased. Heart tissue blood flow was unaffected. When dihydroergotamine was given after dextran 70 had been infused, tissue blood flow returned to baseline values--except for pancreas and thyroid, where tissue blood flow was reduced, and CNS-tissue, where blood flow was increased. When dextran 70 was infused after dihydroergotamine, cardiac output and tissue blood flow remained mainly unchanged.

Animals↗

Characterization of the enhanced paw edema response to carrageenan and dextran in 2,3,7,8-tetrachlorodibenzo-p-dioxin-treated rats.

Rats pretreated with 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD, 10 micrograms/kg) are supersensitive to the edemagenic effects of carrageenan and dextran as indicated by the increased potency of these irritants in TCDD-treated animals compared to controls. This effect of TCDD was characterized using indomethacin, dexamethasone and a combination of cyproheptadine and pyrilamine as inhibitors of edema formation. Because TCDD increases the potency of carrageenan and dextran, it was necessary to select appropriate doses of the edemagenic irritants in order to evaluate the effect of edema inhibitors properly. At low and moderate irritant doses, TCDD-treated and control rats exhibited similar responses to inhibitory agents, suggesting that the mechanisms by which carrageenan and dextran produce edema involve the same mediators in control and TCDD-treated animals. The effect of TCDD on edema induced by bradykinin, histamine, prostaglandin E2 and serotonin, substances which are postulated endogenous mediators of carrageenan-, dextran- and/or compound 48/80-induced edemas, was also examined. Inasmuch as TCDD increased the edemagenic potency of bradykinin and histamine, but not that of prostaglandin E2 or serotonin, it was concluded that TCDD enhances carrageenan-, dextran- and compound 48/80-induced edema formation by augmenting the edemagenic activities of bradykinin and histamine. It is postulated that the mechanism of enhancement may involve TCDD-induced potentiation of the ability of bradykinin and histamine to stimulate phospholipase activity in vascular endothelial cells.

Animals↗

[Autopsy findings in a case of fatal dextran reaction (author's transl)].

A report of fatal dextran reaction is presented. A patient who had had a stable circulatory status developed massive systemic venous congestion and irreversible cardiac arrest after receiving an infusion of approximately 50 ml of dextran solution. Autopsy showed total occlusion of the pulmonary circulation as a result of precipitation of the dextran-blood mixture. Similar occlusion was demonstrated in capillaries in the kidneys, spleen and cardiac musculature. Death occurred during acute, right-sided heart failure. Pathogenetically a type III allergic reaction with precipitation of antigen antibody complexes in the presence of excess antibody is suspected. In cases such as this one, with no history of prior exposure to dextran, sensitization may have occured with a substance sharing antigenic properties with dextran.

Aged↗