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The effect of potato starch derived and corn starch derived hydroxyethyl starch on in vitro blood coagulation.

We have compared the effects of progressive in vitro haemodilution (30% and 60%) with potato starch derived hydroxyethyl starch and corn starch derived hydroxyethyl starch on blood coagulation in 80 patients using thrombelastography. Both solutions significantly compromised blood coagulation as evidenced by an increase in coagulation time and decrease in angle alpha, maximum amplitude and coagulation index (p < 0.05). Blood coagulation was more compromised during haemodilution with potato starch derived hydroxyethyl starch as compared with corn starch derived hydroxyethyl starch (p < 0.05). When taking the effect of haemodilution with 0.9% saline into account, haemodilution with both hydroxyethyl starch solutions also augmented clot lysis (p < 0.05), with potato starch derived hydroxyethyl starch having a greater effect than corn starch derived hydroxyethyl starch (p < 0.05). We conclude that potato starch derived hydroxyethyl starch compromises in vitro blood coagulation more than corn starch derived hydroxyethyl starch.

Adult↗

[Comparison of hydroxyethyl starch solutions derived from potato and corn starch] .

OBJECTIVE: The study was designed to investigate the effects of hydroxyethyl starch (HES) solutions derived from potato (p) compared to HES derived from corn (c) starch on the colloidosmotic pressure, plasma viscosity, and to measure the plasma and urine concentration. METHODS: After approval by the Ethics Committee, and having obtained informed consent, we recruited 20 patients undergoing lumbar disc surgery who received either 1000 ml of p-HES or c-HES (MW 200,000 DS 0.5) in a randomized, single-blind way. Colloidosmotic pressure, plasma viscosity and the plasma concentration were measured before and 30, 90, 240 min and one day after the infusion. Statistical analysis was performed using chi-square and Mann-Whitney test. There were no differences between the two groups in regard to demographics and anesthesia. RESULTS: Plasma viscosity and colloidosmotic pressure did not change significantly during that time. There were no differences in plasma concentration and excretion of both solutions. The peak plasma concentration was reached after 30 min in both groups (8.57 +/- 3.92 g/l c-group and 7.67 +/- 4.68 g/l p-group) and declined thereafter. Within 6 h 38% (c-group 23.0 +/- 3.2 g HES) and 28% (p-group 16.8 +/- 1.6 g HES) of the infused HES were found in the urine. 12 h later about 50% was excreted. CONCLUSION: The present study demonstrated that there was no clinically apparent effect on hematorheology and pharmacokinetics between these two solutions.

Adult↗

Mass spectrometry of partially methylated alditol acetates derived from hydroxyethyl starch.

The degradation and derivatization of hydroxyethyl starch to partially methylated alditol acetates (PMAAs) allows its detection by gas chromatography/mass spectrometry. The derivatization was performed by permethylation of the carbohydrate, hydrolysis of the permethylated polysaccharide, reduction of the resulting monosaccharides to alditoles and finally acetylation. A close similarity in the fragmentation of the PMAAs obtained was observed in both electron ionization (EI) and chemical ionization (CI) mass spectra owing to the comparable structures of the derivatives. CI measurements permitted the recognition of introduced hydroxyethyl groups in the glucose residues by detection of [M(+)+1]-60 signals. Investigations concerning the EI fragmentation schemes allowed secure determinations of monohydroxyethyl monosaccharides and differentiations between the possible positions (C-2, C-3 and C-6) of the substituted hydroxyethyl groups. Proposed generations of the main fragment ions are presented.

Gas Chromatography-Mass Spectrometry↗

Hydrophilic monolayer formation of adsorbed cationic starch and cationic hydroxyethyl cellulose derivatives on polyester surfaces.

Cationic starch, cationic cellulose derivatives, and hydrophobically modified cationic cellulose were physically adsorbed from aqueous solution onto oppositely charged hydrophobic polyester (poly(ethylene terephthalate)) fabric and nonwoven, and this resulted in hydrophilic surface properties. Surface coverage of the polysaccharides occurred primarily by strong electrostatic interactions, and the surface characteristics were evaluated by measuring the time required for a water droplet to be absorbed into the polyester material as well as by electron spectroscopy for chemical analysis (ESCA). From a comparison of the adsorption characteristics we assess the polysaccharide-dependent and substrate-dependent adsorption behavior and discuss the similarities and differences in the hydrophilic properties and wettability observed. In particular, the temperature of the cationic polysaccharide solutions in which the substrate was immersed, the configuration of the polymer in solution, and the presence of hydrophobic substituents on the cationic moiety have a considerable effect on the polysaccharide affinity and its adsorption on the surface, irrespective of the substrate type (fabric or nonwoven). We also evaluate the relative contribution of the polyelectrolyte molecular weight, concentration in solution, and degree of charge density along the polymer chain which determine the range of interactions and alter surface hydroplilicity dependent on the type of substrate.

Adsorption↗

Hydroxyethyl starch deferoxamine, a novel iron chelator, delays diabetes in BB rats.

Hydroxyl radicals (.OH) may contribute to beta cell death. Because iron catalyzes .OH production, we examined whether administration of a novel, long-acting iron chelator, hydroxyethyl starch-deferoxamine (HES-DFO) could prevent diabetes in spontaneously diabetic biobreeding (BB) rats. In our colony, a peripheral lymphocyte count (PBLC) < 4200 mm3 has an 88% positive predictive value for onset of diabetes mellitus (DM). Rats with PBLC < 4200 mm3 were randomized at 6 weeks of age to receive 50 mg/kg of HES-DFO (a high molecular weight hydroxyethyl starch-conjugated derivative of deferoxamine) or equimolar hydroxyethyl starch (HES) alone given intraperitoneally three times weekly until DM or 120 days of age. Administration of HES significantly decreased the incidence of IDDM to 57% as compared with the incidence of 87% in the lymphopenic unmanipulated BB rats in the colony (p < 0.01). Administration of HES-DFO further significantly decreased the incidence of IDDM to 31% as compared with the lymphopenic unmanipulated rats (p < 0.01). When analyzed by sex, 3 of 17 (18%) HES-DFO-treated males developed DM, versus 10 of 17 (58%) of HES-treated males (p < 0.05, chi square); 8 of 19 (42%) of HES-DFO-treated females developed DM, versus 11 of 20 (55%) HES-treated females (p = NS). There were no differences between the groups in (1) mean time of onset of DM, (2) serum iron levels at study entry and completion, (3) weekly hematocrits, (4) total lymphocyte counts; and (5) weekly weight gains.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Albumin and hydroxyethyl starch modulate oxidative inflammatory injury to vascular endothelium.

BACKGROUND: Human serum albumin is used clinically to maintain colloid osmotic pressure and is viewed to serve an antioxidant role in the vascular compartment via binding of redox-active metal complexes, transport of nitric oxide, and the oxidant-scavenging reactions of the single thiol of human serum albumin, cys34. Because of these potentially desirable adjunctive actions, we evaluated the purity and thiol redox state and compared the relative effects of clinically available 25% human serum albumin preparations with a starch-derived colloid, 6% hydroxyethyl starch, in in vitro models of inflammatory vascular injury. METHODS: Bovine aortic endothelial cell responses to chemical, enzymatic, and cell-derived reactive inflammatory mediators in the presence of human serum albumin or hydroxyethyl starch were assessed. RESULTS: The cys34 thiol of fresh human serum albumin preparations was 70-85% oxidized and contained a population of human serum albumin (approximately 25% of total) having the cys34 resistant to reduction by 2-mercaptoethanol and NaBH4. Treatment of bovine aortic endothelial cells with human serum albumin dose-dependently protected from HOCl-mediated 14C-adenine release, with this protective effect of human serum albumin not dependent on protein thiol status. Addition of human serum albumin to cell media provided no protection from the cytotoxic actions of peroxynitrite and xanthine oxidase-derived reactive species. Binding of activated polymorphonuclear leukocytes to bovine aortic endothelial cells was significantly amplified by hydroxyethyl starch and inhibited by human serum albumin administration. The binding of neutrophil-derived myeloperoxidase to bovine aortic endothelial cells, a mediator of multiple oxidative and nitric oxide-consuming reactions, was also inhibited by human serum albumin and enhanced by hydroxyethyl starch. CONCLUSIONS: Clinical human serum albumin preparations show modest intrinsic non-thiol-dependent antiinflammatory properties in vitro, a phenomenon that was not observed with hydroxyethyl starch.

Animals↗

Effect of intravenous administration of hydroxyethyl-starch-deferoxamine on oxygen-derived free radical generation in cancellous bone specimens obtained from dogs.

The ability of IV administered hydroxyethyl-starch-deferoxamine to attenuate radical production in freshly procured cancellous bone specimens was investigated, using spin-trapping and electron spin resonance (ESR) techniques. A core cancellous bone specimen 10 mm long and 5.6 mm in diameter was obtained, using aseptic technique, from the proximal portion of the humerus of 30 adult mixed-breed dogs. After procurement of the initial bone specimen, 10 dogs received a 10% solution of hydroxyethyl-starch-deferoxamine in 0.9% NaCl (50 mg/kg of body weight, IV), 10 dogs received an equivalent volume (5 ml/kg, IV) of a 10% solution of hydroxyethyl-starch in 0.9% NaCl, and 10 dogs received 0.9% saline solution (5 ml/kg, IV). A second core cancellous bone specimen was obtained from the contralateral humerus of each dog 45 minutes after treatment. All specimens were individually incubated in the spin trap alpha-phenyl-N-tert-butylnitrone in Eagle's minimum essential medium, at 26 C for 45 minutes, then were frozen at -20 C until they were prepared for analysis by ESR spectroscopy. Each specimen was thawed, homogenized, and extracted in a low-dielectric organic solvent prior to obtaining an ESR spectrum, which was analyzed for hyperfine splitting constants for radical identification. Each first-derivative spectrum was digitally double-integrated to obtain an area; these areas were used to compare intensities of the spin adducts. Difference in the area obtained before and after treatment for each dog was expressed as a ratio of that dog's pretreatment area ([pretreatment - posttreatment])/pretreatment).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Attenuation of shock-induced hepatic microcirculatory disturbances by the use of a starch-deferoxamine conjugate for resuscitation.

OBJECTIVE: To determine the effects of a hydroxyethyl starch-deferoxamine conjugate on hepatic microcirculation in an isobaric, anesthetized rat model of hemorrhagic shock and asanguineous resuscitation. DESIGN: Prospective, randomized, controlled study. SETTING: Laboratory at a university hospital. SUBJECTS: Twenty-three female, inbred Lewis rats (190 to 215 g). INTERVENTIONS: After anesthesia (pentobarbital-sodium; 50 mg/kg), tracheotomy, and cannulation, animals were assigned to a hemorrhagic shock (mean arterial pressure at 40 +/- 3 mm Hg for 45 mins) or a time-matched sham protocol. Rats in the shock groups received either hydroxyethyl starch or a starch-deferoxamine conjugate for resuscitation. Liver microcirculation was assessed in vivo 60 mins after onset of volume therapy by epifluorescence microscopy. MEASUREMENTS AND MAIN RESULTS: Conventional resuscitation with the starch-vehicle failed to restore sinusoidal blood flow compared with either time-matched controls (71% of control value; p < .01) or the starch-deferoxamine-treated animals (89% of control value; p < .05 compared with starch-vehicle), although a comparable restoration of central hemodynamics was achieved with both starch preparations. Additionally, treatment with the starch-deferoxamine conjugate resulted in a significant attenuation of sinusoidal leukocyte margination (sham 72.4 +/- 11.0/mm2; starch-vehicle 194.5 +/- 19.0/mm2 [p < .01 compared with controls]; starch-deferoxamine conjugate 135.9 +/- 12.1/mm2 [p < .02 compared with sham and starch-vehicle]). CONCLUSIONS: Asanguineous resuscitation with conventional hydroxyethyl starch failed to restore hepatic microvascular blood flow, despite otherwise effective resuscitation. In contrast, the starch-deferoxamine conjugate improved volumetric blood flow and attenuated leukocyte margination in hepatic sinusoids compared with starch-vehicle, suggesting involvement of iron-dependent, oxygen-derived radicals in shock-induced hepatic microcirculatory disturbances.

Animals↗

Rheology of hydroxyethylated starch aqueous systems. Analysis of gel formation.

This paper reports dynamic viscoelastic and steady shear measurements of aqueous solutions of two commercial hydroxyethyl ethers of potato starch, allowing us to define three different viscoelastic regions, depending on the polymer concentrations. The fluid-like zone (I) corresponds to a homogeneous solution, free of associations between chains, where the linear viscoelastic model can be applied; the fluid-gel transition zone (II) is associated with the rheology of complex systems which possess intermolecular specific interactions; and the gel-like zone (III) involves a network formation giving rise to a gel. The reversibility of the hydrogels was studied by means of steady/dynamic transient experiments allowing breakdown of the gel network and analysis of rehealing. Comparing the elastic moduli of the starch derivative gels leads us to assume that the functionality depends on the capacity to form hydrogen-bonding associations between polymer chains.

Elasticity↗

Rapid screening of plasma volume expanders in urine using matrix-assisted laser desorption/ionisation time-of-flight mass spectrometry.

The use of plasma volume expanders, especially those based on chemically modified polysaccharides such as hydroxyethyl starch, has found its way from the medical field to the athletic community in the everlasting drive for performance enhancement. As such, plasma volume expanders have been placed on the list of banned substances by the International Olympic Committee, and in turn require accurate and sensitive analytical tools for their detection in complex biological matrices. Here we present a relatively straightforward method for the detection of polysaccharide-based plasma volume expanders (PVE) in urine, based on the carefully controlled partial acid hydrolysis of urine (20 microL) in a total volume of 500 microL 4 M trifluoroacetic acid. Following the incubation (30 min at 100 degrees C) an aliquot of the hydrolysate is dried, re-suspended in the analytical matrix (e.g. 2,5-dihydroxybenzoic acid) and examined by matrix-assisted laser desorption/ionisation time-of-flight mass spectrometry (MALDI-TOFMS). The obtained mass spectrometric profile reveals a high number of characteristic peaks in the mass range between 500 and 3000 Da, a region that in urine samples devoid of PVE appears relatively clean, and thus allows the unambiguous identification of the presence of such PVE. This approach is fast (the mass profile can be obtained within 90 min), highly sensitive (the effective sample amount on the MALDI target is equivalent to 100 nL urine), needs little sample handling (four steps), requires no derivatisation and is devoid of interference from other biomolecules. The approach has been worked-out for hydroxy ethyl starch but can be applied to other polymer-derived plasma expanders such as dextran and probably the newly developed acetyl starch.

Doping in Sports↗

[Hydroxyethyl starch accumulation in the skin with special reference to hydroxyethyl starch-associated pruritus].

BACKGROUND AND OBJECTIVE: Hydroxyethyl starch (HES) is a colloidal infusion fluid that has for a long time been used in emergency situations and to improve impaired blood perfusion. In the last few years there have been numerous reports about treatment resistant pruritus, often persisting for months, after HES infusion. We investigated the intracellular uptake of HES in the skin, special attention being focused on associated pruritus. PATIENTS AND METHODS: Skin biopsies were obtained from 120 patients (120 men, 35 women) and examined immunohistochemically and for their ultrastructure. Three patients had received various HES preparations, while 22 had been given dextran. Five patients who had received no infusions served as controls. RESULTS: All patients given HES had lysosomal deposits in the histiocytes, some of them also in cutaneous epithelium and endothelium. The extent of lysosomal storage correlated with the amount of infused HES and the interval between biopsy and last HES infusion. Consecutive biopsies in some cases demonstrated a definite decrease over the years of HES deposits in the vacuoles. This suggests that HES is regularly metabolized in the skin. Pruritus after high cumulative doses of HES was closely correlated with HES deposition in cutaneous nerves. CONCLUSIONS: These results emphasize the need for starch derivatives that can be better metabolized and for better adapted infusion schedules to reduce the high incidence of pruritus.

Adolescent↗

[The role of infusion fluids and blood derived preparations during the perioperative period].

The treatment with infusion fluids in perioperative period is a basic therapeutic method. Depending on clinical situation, the doctor has various fluids available, both blood-replacing, and blood-derived. The number of crystaloid and colloidal fluids used has been systematically growing in two last decades. Ever more importance, beside the 0.9% NaCl solution and Ringer's solution used, is gaining 7.5% NaCl solution and hydroxyethyl starch solutions. The production of hydroxyethyl starch solutions in Poland has created an alternative to the use of dextran and gelatin solutions. The change towards treatment with blood components has caused the change of the strategy of therapeutic management of patients used as yet. For compensation of oxygen demand during blood loss, erythrocyte concentrate is commonly used. Such management requires blood-clotting factor monitoring. Hypofibrinogenaemia develops earlier than deficiencies of the remaining blood-clotting factors and later than thrombocytopenia. The use of fresh frozen plasma (FFP) is the first step in the treatment of pathological bleeding in surgically treated patients. The occurrence of thrombocytopenia shows great individual variability. Thrombocyte concentrate transfusion should be performed after laboratory determination of thrombocyte count.

Fluid Therapy↗

[Intravascular persistence, tissue storage and excretion of hydroxyethyl starch (HAS)].

Hydroxyethyl starch is a derivative of amylopectin, the branched glycogen-like alpha-1,4-glucose polymer, the amylase hydrolysis of which is retarded by hydroxyethylation. If 70 to 90 per cent of the glucose polymer units contain hydroxyethyl groups, the intravascular persistence and urinary excretion of hydroxyethyl starch of a molecular weight of 435,000 is similar to that of Dextran 70. Hydroxyethyl starch and Dextran 70 are stored briefly in reticuloendothelial and hepatic cells, and cause swelling and vacuolation of renal tubules with little alteration of renal function. Elimination of hydroxyethyl starch from sites of tissue storage is much faster than elimination of the non-metabolized polymers acacia and polyvinylpyrrolidone. The distribution and excretion kinetics of hydroxyethyl starch are thus appropriate for a plasma substitute.

Animals↗

Moderately severe anaphylactoid reaction to pentastarch (200/0.5) in a patient with acute severe asthma.

The use of synthetic colloids for resuscitation and volume replacement is common in the intensive care unit. Although adverse reactions have been reported to colloid solutions, the incidence of severe reactions to the starch derivatives is low. We report a case of an anaphylactoid reaction to pentastarch (200/0.5) in a young asthmatic who received it as a fluid challenge in the intensive care unit. The pathogenesis and implications of such a reaction in an asthmatic are discussed.

Adult↗

Mechanism of systemic vasodilation during normovolemic hemodilution.

In the nonfailing heart, normovolemic hemodilution increases cardiac output and decreases total peripheral resistance (TPR). Putative mechanisms mediating the decrease in TPR include reflex vasodilation and changes in the local regulation of blood flow. Our objectives were to determine whether ablation of reflex neural mechanisms or the inhibition of nitric oxide (NO) synthase, the enzyme responsible for the synthesis of the endothelium-derived relaxing factor (EDRF-NO), modulates the systemic vasodilator response to normovolemic hemodilution. Three groups of male Sprague-Dawley rats were subjected to acute normovolemic hemodilution, which was achieved by exchanging a volume of blood equivalent to 3.8% of body weight with hydroxyethyl starch. Hemodilution increased cardiac output and decreased TPR. Subsequent administration of the NO synthase inhibitor, L-nitroarginine (LNA), returned both cardiac output and TPR to control values. Pretreatment with LNA prior to hemodilution increased TPR, an effect that was partially reversed by the NO donor, sodium nitroprusside. In this setting, hemodilution failed to decrease TPR. After spinal cord destruction by "pithing," hemodilution decreased TPR to the same extent as that observed in intact rats. This hemodilution-induced decrease in TPR was abolished by the subsequent administration of LNA. These results indicate that neural reflexes do not modulate the systemic vascular response to hemodilution. Moreover, the systemic vasodilator response to hemodilution is abolished after inhibition of endogenous NO synthesis.

Amino Acid Oxidoreductases↗

Cardiopulmonary bypass alters vasomotor regulation of the skeletal muscle microcirculation.

BACKGROUND: Cardiopulmonary bypass (CPB) is associated with alterations in the regulation of organ perfusion and vascular permeability. The purpose of this study was to examine the effects of hypothermic CPB on the regulation of the skeletal muscle microcirculation and the modulating influence of the priming solution. METHODS: Sheep were placed on hypothermic CPB with a prime of either Pentastarch hydroxylethyl starch (HS) solution (n = 7), a solution in which HS is conjugated with deferoxamine (n = 7), or Ringer's lactate solution (n = 7). Sheep were placed on hypothermic CPB (27 degrees C) for 90 minutes while the heart was protected with cold blood cardioplegia. Sheep were then separated from CPB and perfused for an additional 3 hours off CPB. Hemodynamics and total water content were measured. RESULTS: In vitro relaxation responses of gracilis muscle arterioles (70 to 180 microns) to the endothelium-dependent agent acetylcholine, the endothelium-independent cyclic GMP-mediated vasodilator sodium nitroprusside, the beta-adrenergic agonist isoproterenol, and the adenylate cyclase activator forskolin were studied. No statistically significant hemodynamic differences were observed between groups. However, weight gain was significantly less when the priming solution was HS or HS-deferoxamine compared to when Ringer's lactate was used. Skeletal muscle arteriolar relaxations to the endothelium-dependent vasodilator acetylcholine and the beta-adrenergic agonist isoproterenol were impaired after CPB in the HS and Ringer's lactate groups. Acetylcholine response was preserved in the HS-deferoxamine group, whereas the response to isoproterenol remained impaired. The responses to sodium nitroprusside and forskolin were similar in all groups. CONCLUSIONS: Skeletal muscle microvascular endothelium-dependent relaxation and beta-adrenergic relaxation are reduced after CPB using either a crystalloid or HS prime. Skeletal muscle microvascular endothelial dysfunction may be attributable to oxygen-derived free radical-mediated injury, whereas altered beta-adrenergic regulation is attributable to mechanisms other than the generation of oxygen-derived free radicals during CPB.

Acetylcholine↗