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Hypertonic saline dextran resuscitation during the initial phase of acute endotoxemia: effect on regional blood flow.

BACKGROUND AND METHODS: Small-volume resuscitation by means of bolus application of hypertonic saline solutions has been demonstrated to restore central hemodynamics and regional blood flow in severe hemorrhagic and traumatic shock. The aim of this study was to elucidate the potential of this new concept for treatment of profound hypovolemia and microcirculatory deterioration associated with sepsis and endotoxic shock. In a porcine model of acute hyperdynamic endotoxemia (elicited by continuous iv infusion of Salmonella abortus equi endotoxin for 3.5 hrs), small-volume resuscitation applying hypertonic-hyperoncotic solutions was analyzed for its effect on central hemodynamics, oxygen delivery (Do2), and regional blood flow. Fluid therapy was initiated when the pulmonary artery occlusion pressure (PAOP) tended to decrease (at 43 to 52 mins of endotoxemia), and consisted of 4 mL/kg bolus infusion of either 7.2% sodium chloride, 10% dextran, or 10% dextran in 7.2% sodium chloride; thereafter, PAOP was maintained by controlled infusion of 6% dextran-60. In a control group, 6% dextran-60 was given without preinjection of hypertonic-hyperoncotic solutions. RESULTS: On small-volume resuscitation, cardiac index significantly increased within 5 mins in all groups, while mean arterial pressure remained unchanged. Fluid requirements were significantly reduced after small-volume resuscitation and the hyperdynamic circulatory state was maintained until the end of the observation period; Do2 as well as blood flow to heart, kidneys, and splanchnic organs remained high. CONCLUSION: Small-volume resuscitation by means of hypertonic saline-dextran proved the most effective, and seems to be an attractive supportive therapy to prevent microcirculatory failure in sepsis and endotoxemia.

Acute Disease↗

Effects on capillary fluid permeability and fluid exchange of albumin, dextran, gelatin, and hydroxyethyl starch in cat skeletal muscle.

OBJECTIVE: To evaluate the peripheral hemodynamic effects in a skeletal muscle in vivo model of the four commercially available colloid solutions, 20% human albumin, 6% dextran-70, 6% hydroxyethyl starch 200/0.5 (HES), and 3.5% urea-linked gelatin. DESIGN: Controlled laboratory study. SETTING: University research laboratory. SUBJECTS: Fifteen adult cats. INTERVENTIONS: The isolated, autoperfused, and denervated calf muscles of the cat hindlimb were placed in a plethysmograph. The colloids tested were given intra-arterially to the muscles in increasing rates of clinically relevant doses. MEASUREMENTS AND MAIN RESULTS: Arterial blood flow, arterial and venous blood pressures, total vascular resistance, tissue volume changes, and capillary filtration coefficient were measured before, during, and after the colloid infusions. The altered capillary filtration coefficient reflects a change in capillary fluid permeability. The capillary filtration coefficient was decreased by albumin and dextran, not affected by HES, and increased by urea-linked gelatin. Albumin induced transcapillary fluid absorption, gelatin induced transcapillary filtration, and no transcapillary fluid exchange was observed with dextran and HES. After discontinuation of the infusions, HES and gelatin induced a rebound transcapillary filtration. No such effect was seen after dextran and albumin. All colloids increased muscle blood flow. CONCLUSION: We conclude that capillary fluid permeability is decreased by albumin and dextran, unchanged by HES, and increased by gelatin. This and the differences in the rebound effect may contribute to the differences in the plasma volume expanding properties of the respective colloid. The increased blood flow induced by the colloids was more an effect of reduced vascular tone than of lowered blood viscosity.

Albumins↗

Effect of medium tonicity and dextran on neutrophil function in vitro.

BACKGROUND: Multiple investigations have demonstrated that hypertonic saline (HS) diminishes the response of polymorphonuclear leukocytes (PMNs) to stimulation. Recent meta-analysis suggests that hypertonic saline in dextran (HSD) is clinically superior to HS. No work to date has examined the effect of added dextran on this immunomodulatory property. METHODS: Human PMNs were exposed to media of varying osmolarity (220-360 mOsm/L) and stimulated with f-met-leu-phe with or without dextran present in the medium. Cell volume, respiratory burst, PMN aggregation, and beta(2)-integrin (CD18) expression were measured. RESULTS: Stimulation with f-met-leu-phe increased cell volume, respiratory burst, aggregation, and CD18 expression. The increases in cell volume, respiratory burst, and aggregation were significantly attenuated by exposure to hypertonic medium. The addition of dextran to the media did not change the results. CONCLUSION: The alterations in PMN function associated with HS are not changed or attenuated by the addition of dextran, suggesting that the clinically superior HSD may have effects similar to HS in mitigating the tissue damage associated with activated PMNs.

Adult↗

Scintigraphic diagnosis of gastrointestinal bleeding with 99Tcm-dextran.

Intravenously administered dextran is used clinically as a plasma expander. The aim of this study was to assess the use of 99Tcm-dextran in the diagnosis of gastrointestinal (GI) blood leaks. Twenty-one patients with GI blood loss underwent 99Tcm-dextran scintigraphy, 17 of whom were found to be positive. Pathologic or 99Tcm-RBC (red blood cell) blood pool correlation was possible in 15 cases, while 2 were unconfirmed. No case had a positive 99Tcm-RBC blood pool study and a negative 99Tcm-dextran study. Images obtained with 99Tcm-dextran were generally better than those with 99Tcm-RBC. This agent may have several other advantages over 99Tcm-RBC blood pool and 99Tcm-sulphur colloid scintigraphy for detecting GI blood loss.

Adult↗

Scintigraphic sentinel node detection in breast cancer patients: paired and blinded comparison of 99mTc dextran 500 and 99mTc phytate.

BACKGROUND: Breast cancer surgery has evolved towards minimizing morbidity, maximizing cure rates and stratifying treatments according to disease stage. Sentinel lymph node biopsy is becoming standard practice in most centres. However, no standard radiopharmaceutical exists. OBJECTIVES: To blindly compare 99mTc dextran 500 and 99mTc phytate in the scintigraphic detection of sentinel lymph nodes. Endpoints were the detection of axillary or internal mammary lymph nodes, number of lymph nodes detected, detectability in the first versus the second hour of evaluation and the relationship between rate of detection and age or body mass index. METHODS: Forty-six patients with histological diagnosis of early breast cancer, without previous surgical treatment, were enrolled in our study. Each patient underwent lymphoscintigraphy twice: on one day with 99mTc dextran 500 and on another day with 99mTc phytate. Images were acquired 1 h and 2 h after tracer administration. RESULTS: Eighty-eight lymphoscintigraphic studies were performed in 44 patients. On the first image (taken at 1 h), 34 patients from the 99mTc dextran group showed sentinel nodes compared with 28 positive examinations using 99mTc phytate (P = 0.113). On the second image (taken at 2 h) 39 patients from the 99mTc dextran group showed positive results compared to 30 positive examinations using 99mTc phytate (P = 0.036). There was no statistically significant correlation between the body mass index or age and the result of the lymphoscintigraphy. CONCLUSION: 99mTc dextran 500 is better than 99mTc phytate for use in a 2 h interval scintigraphic protocol because it demonstrates the sentinel node in a significantly higher number of patients and also showed more lymph nodes suitable for pathological examination.

Adult↗

The effect of dextran on microvascular thrombosis in an experimental rabbit model.

Although low molecular weight dextran is commonly utilized in clinical microsurgery, few experimental data are available documenting its efficacy. Bilateral 2-mm arterial inversion grafts were constructed in the femoral arteries of New Zealand White rabbits. The experimental group (n = 40 grafts) received a 5-day constant infusion of intravenous dextran 40 at 2.1 ml/hour, and the control group (n = 50 grafts) received no infusion. Whereas 85 percent (34/40) of the dextran grafts were patent at 1 week, only 48 percent (24/50) of the control grafts were patent (p = 0.0003). Scanning electron micrographs revealed a decrease in both platelet and fibrin deposition in the patent dextran arterial inversion grafts versus the patent control specimens. As a marked diminution in microvascular thrombosis was demonstrated at a clinically relevant dose, the continued use of intravenous dextran 40 in clinical microsurgery is supported by this study.

Animals↗

Plasma volume expansion and transcapillary fluid exchange in skeletal muscle of albumin, dextran, gelatin, hydroxyethyl starch, and saline after trauma in the cat.

OBJECTIVE: To compare 5% albumin, 6% dextran 70, 3.5% gelatin, 6% hydroxyethyl starch 130/0.4, and saline regarding their plasma volume expanding effect after a surgical skeletal muscle trauma and their simultaneous effects on transvascular fluid exchange in skeletal muscle. DESIGN: Controlled, prospective, randomized laboratory study. SETTING: University research laboratory. SUBJECTS: Thirty-six adult cats. INTERVENTIONS: Systemic arterial pressure and tissue volume variations of and blood flow to a surgically isolated and autoperfused calf muscle placed in a plethysmograph were recorded. Arterial and venous pressures to the muscle were kept constant. After preparation, plasma volumes were determined by a I albumin tracer technique just before and 3 hrs after a bolus infusion of the plasma expander (25 mL/kg). MEASUREMENTS AND MAIN RESULTS: Plasma volume was 20.9 +/- 2.9 mL/kg (n = 36) just before infusion of the plasma expander (normal plasma volume for the cat is 34-37 mL/kg). The remaining volume expansion of the infusion after 3 hrs was 6.8 mL/kg for albumin, 11.2 mL/kg for dextran, 1.8 mL/kg for gelatin, 2.2 mL/kg for hydroxyethyl starch, and 0.9 mL/kg for saline. Plasma volume decreased by 1.1 mL/kg when no solution was given (n = 6 per group). Colloid osmotic pressure was better preserved with dextran and albumin than with the other solutions. Albumin and dextran reduced muscle volume by absorption after 3 hrs, whereas the initial absorption turned to net filtration in the gelatin and hydroxyethyl starch groups. Saline infusion increased muscle volume by filtration for about 20 mins, followed by an approximately constant volume. CONCLUSION: The relatively poor plasma expansion for all solutions analyzed can most likely be explained by increased transcapillary leakage due to increased microvascular permeability following trauma. Under such circumstances, for equal volumes, plasma expansion was better preserved with 6% dextran 70 than with 5% albumin, which was better than 3.5% gelatin, 6% hydroxyethyl starch 130/0.4, and saline.

Animals↗

First use of hypertonic saline dextran in children: a study in safety and effectiveness for atrial septal defect surgery.

Hypertonic saline dextran (7.5% NaCl + 6% Dextran-70) has been used in adults in several studies and shown beneficial effects in hypovolemic shock, trauma, cardiogenic shock, and cardiac surgery. There have never been studies of this solution in children. This work studies its effect in children undergoing surgery for the correction of atrial septal defects. Twenty-five children underwent correction of atrial septal defect using cardiopulmonary bypass with bloodless priming. Children were divided in five groups and each received an incremental hypertonic saline dextran dose of 0.1, 0.5, 1.0, 2.0, and 4.0 mL/kg, 5 min before the beginning of cardiopulmonary bypass. Collected data were fluid balance, amount of bleeding, blood/derivative transfusion occurrence, plasma sodium, and hematocrit. Patients were divided into low-dose (0-1 mL/kg) and high-dose (2-4 mL/kg) groups. Analysis of variance was used to determine differences in blood loss between groups. The fluid balance and blood/derivative requirements were compared through Student's t test and Fisher's exact test (2-tail), respectively. All patients were discharged from hospital with corrected atrial septal defect. No hypertonic saline dextran-related complications occurred. There were no differences in the amount of bleeding. The high-dose group exhibited a significant decrease in fluid balance and in blood/derivative requirements in comparison with the low-dose group. In this study, the use of hypertonic saline dextran in the pediatric population submitted to cardiopulmonary bypass is safe and does not raise the amount of bleeding. Its effective doses produce negative fluid balance and reduce blood/derivative requirements.

Blood Loss, Surgical↗

In vitro release behavior of dextran-methacrylate hydrogels using doxorubicin and other model compounds.

In vitro drug release behavior of doxorubicin, Alizarin Red S, FITC-dextran from photocross-linked dextran-methacrylate hydrogel was studied. The effects of pH of media, degree of substitution (DS) of dextran-methacrylate hydrogel, and molecular weight of model compounds on their release profiles were investigated. Each model compound was successfully incorporated into dextran-methacrylate hydrogel matrix through photopolymerization of the hydrogel precursor. Delayed release of model compounds was observed with these hydrogels having a higher DS. Doxorubicin and Alizarin Red S showed pH-dependent release behavior because of the presence of ionizable groups in their structure. Different types of ionization of doxorubicin and Alizarin Red S resulted in more release into an acidic or alkaline media. As molecular weights of drugs increased, the total amount of released drug at the end of 240 hrs decreased significantly and reached a minimum level as the MW of drugs reached about 10,000. Release of these three model compounds followed simple Fickian diffusion at an early stage of release, i.e., cumulative release of model compounds was proportional to the square root of time. Dextran-methacrylate hydrogel effectively delayed and controlled the release of anticancer antibiotics, doxorubicin.

Acids↗

Gelation of Limulus lysate by synthetic dextran derivatives.

The Limulus test has been considered specific for the presence of bacterial endotoxins. To synthesize a simple model of endotoxin, palmitoyldextran phosphate was prepared by modification of dextran by palmitoylation and phosphorylation. The present studies indicated that a variety of polysaccharide derivatives, such as palmitoyldextran phosphate, palmitoyldextran, and dextran phosphate, give a positive Limulus test and show pyrogenic activity, except for low molecular dextran derivatives. On the other hand, polysaccharides, such as dextran, starch (soluble-, chitosan, xylan, and lentinan, were negative in these assays. The gelation reaction of Limulus lysate by modified dextran derivatives may depend on the molecular weight or modification of polysaccharides by palmitoylation and/or phosphorylation to a great extent.

Chemical Phenomena↗

The prolongation of local anaesthetic action with dextran. The effect of molecular weight.

Field blocks of the inguinal region were performed in two groups of patients, in one group using a mixture of 0.5% bupivacaine, 1:200 000 adrenaline and dextran 110 and in the second group using a mixture of 0.5% bupivacaine, 1:200 000 adrenaline and dextran 150; the study being performed in a double-blind fashion. The dextran 150 mixture produced a highly significant increase (p less than 0.01) in the duration of the block when compared with the dextran 110 mixture. The authors conclude that the use of dextran of increasing molecular weight increases the duration of action of local anaesthetics correspondingly.

Adjuvants, Anesthesia↗

Hapten inhibition and dextran anaphylaxis.

Hapten inhibition with dextran 1 has been used in Sweden since 1982 to prevent severe anaphylactic reactions to dextran. This has led to a reduction in the reports of severe reactions to dextran from 22 per 100,000 units of dextran used between 1975 and 1979, to 1.2 per 100,000 units between 1983 and 1985. The number of fatal reactions decreased from 23 to one. More than 600,000 units of dextran were used during each period.

Aged↗

Dextran sedimentation induces a difference in the percentage of hypodense eosinophils in peripheral blood between children with allergic asthma and healthy controls.

Considerable differences in the percentage of hypodense eosinophils in the peripheral blood of asthmatics have been reported by different investigators. In these previous studies dextran sedimentation was used for removal of erythrocytes prior to density centrifugation. We hypothesized that the sedimentation procedure might induce the presence of hypodense eosinophils in the peripheral blood of asthmatic patients. In order to test this hypothesis, we compared eosinophil density profiles from peripheral blood of children with asthma and of age-matched healthy controls, using different procedures. In the first method (direct method) blood samples were directly layered on a discontinuous Percoll gradient. Erythrocytes were removed by isotonic lysis. In the second method (dextran sedimentation) erythrocytes were removed by sedimentation with dextran prior to gradient centrifugation. Results of the direct method show no significant difference in percentage of hypodense eosinophils between children with asthma and healthy controls (9.19% and 6.84% respectively). However, after dextran sedimentation, children with asthma had a significantly higher percentage of hypodense eosinophils than healthy controls (15.40% and 8.84% respectively; P < 0.05). The percentage of hypodense eosinophils was correlated with the number of eosinophils and with the lung function, measured as the Tiffeneau index (FEV1/VC), in the whole group of subjects when the direct method was used. We conclude that an increased percentage of hypodense eosinophils is not present in the circulation of children with asthma, but can be induced in vitro by dextran sedimentation. Therefore, in vitro generation of hypodense eosinophils in the blood of patients with asthma seems to be related with the primed state of eosinophils.

Adolescent↗

Effect of the polymeric cryoprotectant dextran on fluid secretion in the isolated rabbit pancreas.

Physiological effects of the polymeric cryoprotectant dextran on an ion-transporting epithelium were investigated. In the isolated rabbit pancreas, dextran caused inhibition of fluid secretion and an increase of the concentrations of Na+, K+ and Cl-in the secreted fluid. Dextran did not affect the basal or pancreozymin-stimulated enzyme secretion. These effects of dextran can partially be explained by the fact that it is osmotically active and does not permeate through the epithelium. The effect of dextran on water transport can be compensated by lowering the ion concentrations in the solvent of the cryoprotectant. It is concluded that in cryoprotected ion-transporting epithelia the absolute ion concentration values obtained by X-ray microanalysis of frozen-hydrated specimens may not be completely correct, but that valid conclusions about intracellular ion distribution may still be drawn.

Animals↗

V and C gene contribution in creating anti-alpha-1,3 dextran antibodies in mice. I. Characteristics of Ig-lal prototype responses.

The light (L) and heavy (H) chain and the antigenic, idiotypic (Id) composition of the antibody (Ab) plaque-forming cells (PFC) and serum Ab specific for alpha-1,3 dextran have been characterized in Ig-lal BALB/c prototype mice, in Ig-la- [30] mice, and in BALB/c congenic and recombinant strains. Four distinct Ab Id specificities were identified by using criteria of Id relatedness to three Id-distinct, alpha-1,3 dextran-binding BALB/c myeloma proteins (MP), all associated, in the Ig-lal mice with the lambda (lambda) chains: a major, common IdX in 40--90% of the molecules; three minor, individual IdI in 1--49% of the molecules; and a fifth, Id-undefined one. These specificities were expressed at the PFC and serum level in the mu and gamma isotypes. A minor, kappa (kappa), Id-negative Ab was discerned only at the PFC level. The Ig-la- CBA and C3H mice responded with anti-alpha-1,3 dextran, kappa Id-negative Ab. The BALB/c, congenic strain CB20 (BALB/c Ig-lb, carrying the C57Bl/Ka, Ig-lb variable H (VH) gene complement and CH phenotype, made anti-alpha-1,3 dextran kappaId-negative Ab of the Ig-lb prototype. The recombinant BAB/14, carrying in the C57Bl/Ka CH-Ig-lb phenotype the BALB/c Ig-lal VH gene(s) controlling anti-alpha-1,3 dextran lambda Ab responsiveness and Id specificity (VH-DEX+), express the BALB/c lambdaId repertoire.

Animals↗

Genetic analysis of the low responsiveness to dextran B512 in CBA/N and C57BL/10ScCr mice.

CBA/N and C57BL/10ScCr mice are low responders to the antigen dextran B512. This is due to the Xid gene in CBA/N mice and to unknown genes in C57BL/10ScCr mice, although this strain is unresponsive to lipopolysaccharide (LPS) due to a defective gene in the fourth chromosome. The female F1 hybrids (C57BL/10ScCr X CBA/N) and (CBA/N X C57BL/10ScCr) were low responders to dextran, although the Xid gene is not expressed in these hybrids, indicating lack of genetic complementation. In contrast, female F1 hybrids between the dextran high-responder strains CBA or C57BL/10 as one parental strain and the low-responder strains CBA/N or C57BL/10ScCr as the other parental strain, respectively, were responders to dextran. The C57BL/10ScCr mice did not appear to have an X-linked gene determining low responsiveness to dextran. The findings suggest that the only defect in CBA/N mice cannot be the Xid gene and the only defect in C57BL/10ScCr mice cannot be the gene determining unresponsiveness to LPS.

Animals↗

Role of antigen in the regulation of the immune response to dextran B512.

Dextranase mixed with dextran in vitro or injected into mice before the antigen abolished the immunogenicity of both thymus-dependent and thymus-independent forms of dextran. Dextranase could degrade dextran in vivo even when given 6-15 days after the antigen. Dextranase injected after the antigen suppressed the immune response when given 24 h, but not 48 h, after the antigen, indicating that the antigen must interact with the immune system for 48 h to initiate a response. Thereafter , the B cells are independent of further antigen stimulation. The induction of autoanti -idiotypic anti-dextran antibodies was abolished if dextranase was given 24 h, but not 48 h, after the antigen, indicating that anti-idiotypic antibodies can be induced in the absence of antigen or immune complexes once anti-dextran antibodies have been synthesized.

Antibody Formation↗

Effect of dextran on fibrinolysis inhibition activity in the blood after major surgery.

Patients undergoing total hip replacement surgery were given 500 ml of 6% dextran 70 or 5% albumin by intravenous infusion on the third postoperative day when the post-traumatic fibrinolysis inhibition has reached its maximum. The large increase in the fibrinolysis inhibition activity measured by a clot-lysis system was counteracted by the infusion of dextran, whereas the albumin infusion had no such effect. The plasma concentration of antiplasmin (chromogenic substrate assay) and the immunologically determined plasma levels of the primary fibrinolysis inhibitor (alpha2-antiplasmin), alpha2-macroglobulin, alpha2-antitrypsin and plasminogen were not changed after the infusion of dextran. It is hypothesized that dextran exerts its effects partly by interfering with the interaction between the primary fibrinolysis inhibitor, fibrin and plasmin(ogen) and by enhancing the activation rate of plasminogen. This observed effect of dextran may be of importance in the prevention of deep venous thrombosis and pulmonary embolic complications, as well as pulmonary microembolism.

Aged↗