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Hypertonic saline resuscitation: saturated salt-dextran solutions are equally effective, but induce hemolysis in dogs.

Hypertonic saline, or saline-dextran resuscitation is normally achieved with an Na+ load of 4.8 to 7.2 mEq/kg given in a small volume (typically 4 to 6 ml/kg NaCl 7.5%). Na+ can also be administered saturated in a smaller volume, e.g., 1 to 1.5 ml/kg NaCl 25%, with similar results. Such reduction in administered volume would be an asset in prehospital trauma management. In the present experiments, severely bled (45 ml/kg) dogs were treated with one of three NaCl/dextran-70 solutions: S1, 25% NaCl + 24% dextran (1.5 ml/kg); S2, 15% NaCl + 14.4% dextran (2.5 ml/kg); S3, 7.5% NaCl + 6% dextran (5 ml/kg). S1, S2, and S3 were pump-infused in 10 min into a peripheral vein; S1 and S2 were also given into the right atrium. S1, S2, or S3 produced a number of similar responses irrespective of the route of administration; arterial pressure, cardiac index, and base excess reverted to near control levels, plasma Na+ was raised to 155-158 mEq/L, and 5-day survival was high and comparable. Plasma volume, and total and mean red cell volumes were similarly affected in all groups; however, peripheral injections of S1 and S2 induced severe hemolysis (plasma Hgb: 53 +/- 6 and 34 +/- 4 mg/dl, respectively), while right atrial S1 and S2 caused mild hemolysis (22 +/- 3 and 14 +/- 3 mg/dl, respectively). In contrast, S3 never induced hemolysis.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Low molecular weight heparin compared with dextran as prophylaxis against thrombosis after total hip replacement.

The effect of low molecular weight (LMW) heparin given once daily as prophylaxis against venous thrombosis was compared with that of dextran 70 in an open randomised trial of 100 patients undergoing elective total hip replacement. Four patients were withdrawn after randomisation and thus 96 were included in the final analysis. The development of thrombus was surveilled by the 125I fibrinogen test, and positive readings were verified by venography. Nine of 47 patients given LMW heparin developed thromboses (19%) compared with 18 of 49 given dextran (37%) (p = 0.09). Two further patients who received LMW heparin developed thromboses after leaving hospital (clinical signs became apparent on days 13 and 17, respectively), giving an overall rate of thrombosis in this group of 23%. Minor wound haematomas occurred in two of 47 in the LMW heparin group and three of 49 in the dextran group (4% and 6%, respectively), and blood loss, transfusion requirements, and reduction in postoperative haemoglobin concentration did not differ between the two groups. The studied LMW heparin given subcutaneously once a day was no less safe or effective than dextran in preventing thromboembolism after total hip replacement.

Aged↗

[Prevention of dialysis-induced leukopenia and hypoxemia by using low-molecular dextran].

In 10 patients with end stage renal failure on chronic haemodialysis the effect was studied of the low molecular dextran (filling the dialyser) on the peripheral blood leucocyte count and some gasometric and ventilatory parameters during and after haemodialysis (HD). When the dialyser was filled with dextran neither the leucocyte count nor the arterial PaO2 were altered but on the 10th minute of HD without dextran both those values fell. The decrease of the ventilation rate (VE), of the alveolar oxygen tension (PAO2) as well as of the index of oxygen utilisation (VIO2/VE) within the first hour of HD with or without dextran might be due to the absorption of the CO2 by dialysing fluid.

Adult↗

Hyperosmotic saline dextran for resuscitation from traumatic-hemorrhagic hypotension: effect on regional blood flow.

The macro- and microcirculatory effect of small-volume resuscitation with hyperosmotic-hyperoncotic solutions was analyzed in 21 anesthetized beagles subjected to standardized traumatic-hemorrhagic hypotension (laparotomy and exteriorization of the intestine; MAP 40 mmHg for 75 min). Primary resuscitation consisted of bolus infusion of 10% of the blood loss (approx. 4 ml/kg) of either hyperosmotic (7.2%) saline -HSS-, hyperoncotic (10%) dextran 60 -HDS-, or hyperosomotic-hyperoncotic saline dextran (10% dextran 60 in 7.2% saline; HHS). Within 5 min CO was restored and systemic pressure significantly increased. In the HHS-group nutritional blood flow (RBF, measured by radiolabeled microspheres phi 15 microns) in kidneys, gastric mucosa, small intestine, colon, and pancreas was completely restored, while RBF to the myocardium, brain, and skeletal muscles exceeded baseline values. Despite the identical response in central hemodynamics, RBF to gastric mucosa, intestine, pancreas, and kidneys was significantly lower in HSS-animals (P less than 0.05 vs. HHS). In contrast, in the HDS-group CO, splanchnic, myocardial, and renal blood flow remained significantly reduced (P less than 0.05 vs. HHS). Despite the normalization of cardiac output by small volumes of hypertonic solutions, 7.2% saline alone failed to fully restore RBF after protracted traumatic hemorrhage. For the concept of small-volume resuscitation, the hyperosomotic-hyperoncotic solution of 10% dextran 60 in 7.2% saline appears to be most effective to improve organ perfusion during the prehospital period of trauma patients.

Animals↗

Investigation on the dosage/efficacy relationship of iron dextran in veal calves.

The efficacy of a single dose of 800 mg resp. 1600 mg iron in the form of an intramuscularly administrable iron (III)-dextran complex (Anaemex, CAS 9004-66-4) has been tested. On 3 groups of 13 calves each, 0 ml (comparing group), 4 ml resp. 8 ml iron dextran 20% have been applied. All calves received iron-containing food during the test period of 10 weeks. At the beginning of the therapy, 5 weeks and 8 weeks after application, the parameters: weight, hemoglobin, erythrocytes, hematocrit, mean corpuscular hemoglobin (MCH), MCH concentration, mean corpuscular volume, plasma protein, fibrinogen, leukocytes and serum iron were measured. After 10 weeks the dead weight has been determined and the spleen of some calves tested histologically. The study shows that, by the administration of 1600 mg iron as a depot injection, a better growth results with the same quality of veal. The red-coloring of the veal was not significantly different from that of the comparing group. The histological findings show especially that the iron depots of the spleen were empty in all three groups and thereby in this collective no connection exists between the color of the veal and the tested dosage of iron dextran 20%. It is considered meaningful and economic to renounce in future the iron-containing food and in its place to apply intramuscular a single dose of 1600-2400 mg iron per calf. The results are compared with a study on full term infants, which has shown that a intramuscular single dose of 150 mg of iron as iron dextran at birth affords a nutritional advantage in iron status for up to 15 months.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

A comparison of TC7 and 32% dextran 70 for prevention of postoperative adhesions in hamsters.

Prevention of postoperative adhesion formation has received considerable attention by infertility specialists. Barrier methods and hydroflotation solutions are currently used for adhesion prevention. The present study compared the efficacy of TC7 and 32% dextran 70 in a hamster model. At laparotomy, 90 golden hamsters had a lesion created on the left uterine horn and repaired with absorbable suture. The first experiment used 3-0 chromic catgut suture in 43 hamsters; the second experiment used 5-0 polyglactin 910 suture in 47 hamsters. The animals were randomly divided into a control group (N = 25) which received no treatment, a TC7-treated group (N = 33), and a 32% dextran 70-treated group (N = 32). The animals were sacrificed between 10-14 days after laparotomy and adhesions were graded (0 = no adhesions; 3 = severe adhesions). TC7 had average adhesion scores of 1.91 for chromic catgut and 2.25 for polyglactin 910; 32% dextran 70 had average adhesion scores of 1.53 and 2.00, respectively. These scores were not different from the control average adhesion score of 1.80 for both chromic catgut and polyglactin 910. We conclude that TC7 and 32% dextran 70 do not appear to be effective agents for preventing postoperative adhesions in this animal model.

Animals↗

[Security evaluation of subcutaneous injection with water-based dextran-coated magnetic fluid].

Water-based magnetic fluid was synthesized by using 50% dextran 40,000 as coated reagent. The acute toxicity and irritant of the magnetic fluid injected into mice subcutaneous tissues were examined. The lethal dosage 50 of dextran-coated magnetic fluid was 4409.61 +/- 514.93 mg/kg. Twenty four h after subcutaneous injecting with 30 mg/0.3 ml dextran-coated magnetic fluid, no more inflammation than hemangiectasia and leucocytes infiltration had been seen in subcutaneous tissues, 72 h later the reaction phenomena disappeared. While, injection with 30 mg/0.3 ml water-based oleate sodium-coated magnetic fluid, ulceration and break-off of cutis had been seen in the seventh days. That is to say, the dextran-coated magnetic fluid was safe and well tolerate, however, the oleate sodium-coated magnetic fluid was not fit to subcutaneous injection.

Animals↗

[The dynamics of 2',5'-oligoadenylate synthetase activity in the nuclear and cytoplasmic fractions of human fibroblasts treated by double-stranded RNAs, by their complexes with DEAE-dextran and by type-I recombinant interferons. The ratio of double-stranded RNA-activated and -nonactivated froms of the enzyme].

Novel original preparations of double-stranded RNAs (dsRNAs), i.e. larifan, ridostin and rifastin, and recombinant alpha 2- and beta-interferons promising for the clinical use were studied. The size and morphology of the dsRNAs in the preparation composition, the dynamics of their induction of interferon and the antiviral state in human fibroblasts and the effect of the DEAE dextran polycation on the activity of the dsRNAs were specified. For the first time the dynamics of 2',5'-oligoadenylate synthetase activity in the nuclei and cytoplasm of the human fibroblasts treated with the dsRNAs of different origin and their complexes with DEAE dextran was defined. To elucidate the specific features of the mechanism of antiviral action of dsRNAs and interferon, the relation of the 2',5'-oligoadenylate synthetase activity to dsRNAs was investigated. In the cells treated with dsRNAs and DEAE dextran there were an early activation of the enzyme and predominance of the enzyme activated forms requiring no addition of poly I.poly C to the reaction mixture. The results were indicative of possible intracellular activation of its isoforms, similar to that in the cells treated with interferon and contaminated with viruses. All the tested preparations of dsRNAs and interferons induced an increase in the activity of 2',5'-oligoadenylate synthetase both in the cytoplasm and the nuclei of human fibroblasts. The same ability was observed in DEAE dextran which is likely to be one of the causes of the increase in dsRNAs antiviral activity under its effect.

2',5'-Oligoadenylate Synthetase↗

Effect of intraperitoneal 32% dextran 70 on blood coagulation and serum electrolytes.

The most promising intraperitoneal agent for preventing adhesion formation is 32% dextran 70. To investigate its effect on blood coagulation and serum electrolytes, 22 women who required surgery for infertility were studied. No significant difference was seen in prothrombin time, partial thromboplastin time, platelet count or red-blood-cell indices between the dextran group (n = 12) and the control group (n = 10) on day 0 (before surgery) and postoperative days 1 and 3. In both groups the decrease in hematocrit and a proportionate decrease in serum albumin 24 hours after the operation suggested hemodilution. There was no further decrease in hematocrit on postoperative day 3. The dextran had no effect on serum electrolytes. These results suggest that intraperitoneal 32% dextran 70 does not impair blood coagulation and is not associated with an electrolyte inbalance.

Adult↗

The effect of dextran-40 on platelet adenosine triphosphate release in vitro.

Studies of dextran's effect on platelet function have revealed inconclusive results; some reports have suggested it acts as an aggregating agent, others as an inhibitor to aggregation. This study demonstrates the inhibitory effect of dextran (40,000 MW) on in vitro platelet adenosine triphosphate (ATP) release when stimulated by conventional aggregatory reagents. These data support inhibition of platelet surface phenomena, possibly involving receptor sites, rather than intracellular phenomena as the mechanism of dextran's anti-aggregatory effect. Significant inhibition occurs in vitro at dextran levels approximately twice that normally attained in vivo.

Adenosine Triphosphate↗

Sequences of variable regions of hybridoma antibodies to alpha (1----6) dextran in BALB/c and C57BL/6 mice.

The variable region sequences of light and heavy chains of three hybridoma antibodies to alpha (1----6) dextran, two from BALB/c and one from C57BL/6 mice, were determined by cloning and sequencing their cDNA. The three kappa-light chains are identical in nucleotide and amino acid sequences, except for the use of different J by BALB/c and C57BL/6; all three had the germ-line sequence of antibodies to 2-phenyloxazolone (20). Nevertheless, 2-phenyloxazolone BSA did not cross-react in gel with antidextrans, nor did dextran react with anti-2-phenyloxazolone ascitic fluids. The heavy chains differed, the BALB/c hybridomas having only three amino acid differences in CDR2 and two in CDR3; the C57BL/6 hybridoma differed throughout the variable region. All three VH are members of the J558 family. The three identical V kappa sequences suggest a significant role in dextran binding, with the differences in CDR of VH and the various J mini-genes of VL and VH being responsible for only fine differences in specificity. Alternatively, the role of V kappa might be minor, with most of the complementarity ascribable to VH. Additional sequences are needed to evaluate whether these data are typical of the repertoire of anti-alpha (1----6) dextran-combining sites.

Amino Acid Sequence↗

Effect of dextran on factor VIII/von Willebrand factor structure and function.

Factor VIII/von Willebrand factor was analyzed before and after the infusion of 500 ml of Dextran 70 to normal volunteers. Factor VIII procoagulant activity, factor VIII related antigen and ristocetin cofactor activity showed a significant decrease, reaching after six hours the minimum level, which did not correlate with the hemodilution effect caused by dextran. Ristocetin-induced platelet agglutination (RIPA) in volunteers' platelet-rich plasma (PRP) did not show any significant change between preinfusion time and six hours after the infusion. Multimeric analysis of von Willebrand factor (vWF) showed a progressive decrease of all the multimers which was more pronounced in the largest multimers. No change was seen in the "triplet" structure of vWF. No effect was noticed when dextran was incubated "in vitro" either with PRP or platelet-poor plasma. The modification induced by dextran is close to the pattern seen in subtype Ib von Willebrand's disease.

Adult↗

Small-volume resuscitation with hypertonic saline dextran solution.

Small-volume hypertonic resuscitation has been proposed as an effective means for restoration of cardiovascular function after hemorrhage at the scene of an accident. We evaluated the cardiovascular, metabolic, and neurohumoral response of resuscitation after hemorrhage using 200 ml of 2400 mosm sodium chloride, 6% dextran 70. Unanesthetized adult sheep were bled to maintain mean arterial pressure at 50 mm Hg for 3 hours, shed blood volume = 42 +/- 7 ml/kg. The sheep were then treated with a single bolus infusion of hypertonic saline dextran (n = 7) or normal saline solution (control group, n = 7) and then observed for a 30-minute period of simulated patient transport during which no additional fluid was given. Hypertonic saline dextran caused rapid restoration of blood pressure and cardiac output within 2 minutes of infusion. Cardiac output remained at or above baseline level, while both O2 consumption and urine output increased to above baseline level during the 30 minutes of simulated patient transport. By comparison 200 ml of normal saline solution caused only a small increase in blood pressure and no improvement in cardiac output or oxygen consumption. After this 30-minute period, both groups were given lactated Ringer's solution as needed to return and maintain cardiac output at its baseline value. The volume of lactated Ringer's solution required to maintain cardiac output was less in the hypertonic group, 371 +/- 168 ml, only one sixth that of the control group, 2200 +/- 814 ml. In summary after 3 hours of hypovolemia, a small volume of hypertonic saline dextran, about 4 ml/kg, fully restored cardiovascular and metabolic function for at least 30 minutes and significantly lowered the total volume requirements of resuscitation.

Animals↗

[Immunochemical properties of immunoglobulin G conjugated with dextran].

Antigen-binding activity and effector functions of immunoglobulin G from horse and rabbit sera have been investigated, using hemagglutination, kinetic immune lysis, immune lysis in microplates and rosette-forming test with peritoneal mononuclear cells of mice, after their conjugation with dextran, MW 35-50 kD. The formation of conjugates of two types has been demonstrated: protein-dextran and protein-dextran-protein. It has been revealed that protein-dextran-protein conjugates have high specific antigen-binding activity, as compared to native IgG from rabbit sera specific for SRBC, while interactions with the complement system and Fc receptors is depressed.

Animals↗

Prevention of venous thrombosis after total hip arthroplasty. Antithrombin III and low-dose heparin compared with dextran 40.

The anticoagulant action of heparin is mediated through antithrombin III, and the postoperative decrease in the plasma concentration of antithrombin III may contribute to the relative ineffectiveness of prophylaxis with low-dose heparin in preventing venous thrombosis after total hip arthroplasty. We conducted a prospective, randomized trial to compare the effectiveness of a regimen of antithrombin III, given intravenously once daily, and low-dose heparin with a regimen of dextran 40, given intravenously, in preventing venographically documented venous thrombosis after total hip arthroplasty. The results demonstrated an incidence of venous thrombosis of 4.9 per cent in patients who received antithrombin III and heparin; this was significantly lower than the incidence (28.6 per cent) in patients who received dextran 40 (p less than 0.005). Venous thrombosis occurred only in patients who had total hip arthroplasty with a cemented prosthesis (fourteen of fifty-seven patients, or 24.6 per cent); none of the twenty-six patients in whom a non-cemented prosthesis was used had venous thrombosis (p less than 0.01). Of the patients in whom a cemented prosthesis had been inserted, the incidence of venous thrombosis was lower in those who were treated with antithrombin III and heparin (7.4 per cent) than in those who were treated with dextran 40 (40 per cent) (p less than 0.005). Postoperative levels of antithrombin III were maintained at more than 90 per cent of the baseline level in patients who received it; this was significantly higher than in patients who received dextran 40.(ABSTRACT TRUNCATED AT 250 WORDS)

Antithrombin III↗

Properties of chymotrypsin bound covalently to dextran.

The kinetic properties dextran-chymotrypsin conjugate were studied by means of low molecular weight substrates. It was found that KM, kcat and kcat/KM of dextran chymotrypsin for the hydrolysis of benzoyl-L-tyrosine-ethyl-ester did not differ substantially from those of the free enzyme. However, the data found for kcat of dextran-chymotrypsin and free chymotrypsin assayed for the hydrolysis of three tripeptidyl-p-nitroanilide D-Arg-Val-Trp-pNA, D-Arg-Val-Tyr-pNA, Z-Phe-Pro-Phe-pNA, were definitely different. The inhibition of the modified chymotrypsin with soybean trypsin inhibitor was found to be less pronounced than that with the free enzyme. The effect of potassium and magnesium salts on the inactivation of both enzymes was also studied. The effect of dextran matrix on the catalytic properties and the conformational stability of modified chymotrypsin is discussed.

Animals↗

Effects of intraocular pressure change on movement of FITC-dextran across vitreous-aqueous interface.

In an attempt to study the effect of change in the intraocular pressure (IOP) on the status of the vitreous-aqueous interface, the effect of topical bunazosin was studied in the rabbit eye using the new Johnson-Maurice method. This entails an intravitreal injection of FITC-dextran and measurements of its concentration changes in the anterior chamber many days after the injection. Repeated instillations of bunazosin solution reduced the IOP by about 5 mmHg, without changing the aqueous flow rate as determined by the method of fluorometry. On the other hand, the FITC-dextran concentration in the anterior chamber increased, indicating that the movement of FITC-dextran from the vitreous into the aqueous was greater when the IOP was lowered. This increase in the FITC-dextran movement into the anterior chamber was thought to be mainly attributable to an increase in the anteriorly directed fluid movement across the vitreous-aqueous interface. The increase in the fluid movement was estimated to be about 1.3 microliter/hour. This study suggested that a reduction in the IOP generated a small fluid flow from the vitreous into the aqueous, and that the new Johnson-Maurice method can be a useful means for noninvasive investigations of the physiology of the vitreous-aqueous interface.

Adrenergic alpha-Antagonists↗

Daflon 500 mg depresses bradykinin-ischemia-induced microvascular leakage of FITC dextran in rat cremaster muscle.

We studied the in vivo effects of Daflon 500 mg on transvascular movement of macromolecules induced by bradykinin (BK) and ischemia. The experimental preparation involved the rat cremaster muscle. The muscle was fashioned as a single bag (new procedure), placed in a transparent chamber and superfused with a bicarbonate buffer solution equilibrated with a 5% CO2 95% N2 gas mixture in order to obtain pH 7.40, PCO2 = 40 mmHg, PO2 = 20-40 mmHg and thermostated at 35 degrees C. FITC-Dextran 150 (MW 150,000) was injected i.v. as a macromolecular tracer. BK was added to the buffer solution at the concentration of 2 micrograms/ml five minutes after a control period of 60 minutes. Ischemia was performed during 60 min by a clamp positioned on the main artery of the cremaster muscle. Animals treated with Daflon 500 mg (100 mg/kg) 18 and 2 hours before experiments showed a significant reduction in FITC-Dextran 150 leakage in both BK and ischemia protocols. Leakage of FITC-Dextran 150 started 2-3 min after application of BK in the two animal groups but the response was less important (+ 270%) and the preparation returned to control appearance after 40 min in the treated rats in contrast with control rats (+ 450% and 70 min). The amplitude of FITC-Dextran 150 leakage was identical just one hour after ischemia in the two animal groups, but microvascular permeability returned to basal state in treated animals (30 min), a fact non observed in non treated animals. These data demonstrate the protective effect of Daflon 500 mg on the microvascular muscle network in vivo.

Animals↗