Neurobehavior and neuron damage following prolonged exposure of silver nanoparticles with/without polyvinylpyrrolidone coating in Caenorhabditis elegans.

Silver nanoparticles (AgNPs) have become widespread in the environment with increasing industrial applications. But the studies about their potential health risks are far from enough, especially in neurotoxic effects. This study aimed to investigate the neurotoxic effects of longer-term exposure (prolonged exposure for 48 h and chronic exposure for 6 days) of 20nm AgNPs with/without polyvinylpyrrolidone (PVP) coating at low concentrations (0.01-10 mg·L-1 ) to Caenorhabditis elegans. The results suggested that exposure to AgNPs induced damage to nematode survival, with the longest and relative average life span reduced. Exposure to AgNPs caused neurotoxicity on locomotion behaviors (head thrashes, body bends, pharyngeal pumping frequency, and defecation interval) and sensory perception behaviors (chemotaxis assay and thermotaxis assay), as well as impaired dopaminergic, GABAergic, and cholinergic neurons, except for glutamatergic, based on the alters fluorescence intensity, in a dose- and time-dependent manner. Further investigations suggested that the low-dose AgNPs (0.01-0.1 mg·L-1 ) exposure raises receptors of GABAergic and dopamine in C. elegans at the genetic level, whereas opposite results were observed at higher doses (1-10 mg·L-1 ), which implied that AgNPs could cause neurotoxicity by impairing neurotransmitter delivery. The PVP-AgNPs could cause a higher fatality rate and neurotoxicity at the same dose. Notably, AgNPs did not cause any deleterious effect on nematodes at the lowest dose of 0.01 mg·L-1 . In general, these results suggested that AgNPs possess the neurotoxic potential in C. elegans and provided useful information to understand the neurotoxicity of AgNPs, which would offer an inspiring perspective on the safe application.

Assessment of Neurological Toxicity of Hydroxyethyl Starch 130/0.4 Injected in the Intrathecal Space in Rats.

Objective: Epidural blood patch is the procedure of choice to relieve postdural puncture headache. Hydroxyethyl-starch (HES) has been proposed as a patch in some circumstances such as in the case of hematological disease due to the theoretical risk of neoplastic seeding to the central nervous system. Acute neurological HES toxicity has been excluded by a previous animal study, but the long-term neurological toxicity has not been evaluated. Methods: Rats were randomly assigned to one of three groups: no intrathecal injection, 20 µL of intrathecal saline, or a 20-µL intrathecal HES (6% hydroxyethyl starch 130/0.4) administered via a cervical puncture. Clinical daily rat activity was measured before and after dural puncture by actinometry. The rats were killed at day 28, and the spinal cord was surgically removed and stained with hematoxylin-phloxine-saffron for gross and microscopic examination. Results: Eleven rats underwent dural puncture without injection, 11 were injected with normal saline, and 12 received intrathecal HES. No clinical or actimetric changes (total distance traveled, number of direction changes, and number of rearings) were observed up to one month after injection. Nonspecific histopathological changes were equally observed in all groups. Conclusions: The results of the current study indicate that intrathecal injection of HES in rats does not induce any clinical or histopathological evidence of long-term neuronal toxicity. Further safety studies in animals are warranted before HES might be considered a safe alternative to the classic epidural blood patch.

Sanguinate's effect on pial arterioles in healthy rats and cerebral oxygen tension after controlled cortical impact.

Sanguinate, a polyethylene glycol-conjugated carboxyhemoglobin, was investigated for cerebral vasoactivity in healthy male Sprague-Dawley rats (Study 1) and for its ability to increase brain tissue oxygen pressure (PbtO2) after controlled cortical impact (CCI) - traumatic brain injury (TBI) (Study 2). In both studies ketamine-acepromazine anesthetized rats were ventilated with 40% O2. In Study 1, a cranial window was used to measure the diameters of medium - (50-100µm) and small-sized (<50µm) pial arterioles before and after four serial infusions of Sanguinate (8mL/kg/h, cumulative 16mL/kg IV), volume-matched Hextend, or normal saline. In Study 2, PbtO2 was measured using a phosphorescence quenching method before TBI, 15min after TBI (T15) and then every 10min thereafter for 155min. At T15, rats received either 8mL/kg IV Sanguinate (40mL/kg/h) or no treatment (saline, 4mL/kg/h). Results showed: 1) in healthy rats, percentage changes in pial arteriole diameter were the same among the groups, 2) in TBI rats, PbtO2 decreased from 36.5±3.9mmHg to 19.8±3.0mmHg at T15 in both groups after TBI and did not recover in either group for the rest of the study, and 3) MAP increased 16±4mmHg and 36±5mmHg after Sanguinate in healthy and TBI rats, respectively, while MAP was unchanged in control groups. In conclusion, Sanguinate did not cause vasoconstriction in the cerebral pial arterioles of healthy rats but it also did not acutely increase PbtO2 when administered after TBI. Sanguinate was associated with an increase in MAP in both studies.

Neurotoxicity of intrathecal 6% hydroxyethyl starch 130/0.4 injection in a rat model.

Epidural blood patch is the gold standard treatment for post-dural puncture headache, although hydroxyethyl starch may be a useful alternative to blood if the latter is contraindicated. The aim of this experimental study was to assess whether hydroxyethyl starch given via an indwelling intrathecal catheter resulted in clinical or histopathological changes suggestive of neurotoxicity. The study was conducted in rats that were randomly allocated to receive three 10-µl injections on consecutive days of either saline or hydroxyethyl starch administered via the intrathecal catheter. Eight rats were given injections of saline 0.9% and 11 were given 6% hydroxyethyl starch 130/0.4 derived from thin boiling waxy corn starch in 0.9% sodium chloride (Voluven). Daily clinical evaluation, activity measured by actimetry and neuropathological analysis of the spinal cord were subsequently performed to assess for signs of neurotoxicity. No clinical or actimetric changes were observed in either group following intrathecal saline or hydroxyethyl starch administration. Histopathological examination showed non-specific changes with no differences between the two groups. This experimental study in the rat suggests that repeated intrathecal injection of hydroxyethyl starch is not associated with neurotoxicity.

Hydroxyethylstarch 200/0.5--the horse has bolted.

Hydroxyethylstarch (HES) 200/0.5 is associated with renal failure. Several studies have suggested that renal function is affected but the subsequent arguments leave the clinician in no man's land. A recent study in Critical Care by Simon and colleagues using a two hit animal model of shock demonstrates that the use of a higher molecular weight starch, HES 200/0.5, is associated with impaired renal function when compared with ringers acetate, gelatin or a lower molecular weight starch, HES 130/0.42. The authors conclude that both the lower molecular weight starch and the ringers acetate 'preserve renal function and attenuate tubular damage better than 10% hydroxyethylstarch 200/0.5 in saline'. Added to the previous evidence, the renal effects of HES200/0.5 are probably real. Many clinicians have already moved to the lower molecular weight starches on the basis of doubt rather than certainty, but this study tips the balance. The cause remains elusive and the lack of a mechanism should be seen as a problem.

Impairment of renal function using hyperoncotic colloids in a two hit model of shock: a prospective randomized study.

INTRODUCTION: One of the therapeutic essentials in severe sepsis and septic shock is an adequate fluid replacement to restore and maintain circulating plasma volume, improve organ perfusion and nutritive microcirculatory flow. The type of solution to be used as a fluid replacement remains under discussion. The aim of the study was to evaluate the effects of clinically used fluid replacement solutions on renal function and inflammatory response. METHODS: A total of 23 anesthetized and ventilated female German Landrace pigs were investigated over 19 hours using a two-hit model that combined hemorrhagic and septic shock. The septic shock was induced using an Escherichia coli laden clot placed into the abdominal cavity. Infusions of 6% hydroxyethylstarch 130/0.42 in acetate (6% HES 130), 4% gelatin in acetate (4% gelatin) and 10% hydroxyethylstarch 200/0.5 in saline (10% HES200) compared to Ringer's acetate (RAc) were used for fluid replacement to maintain a central venous pressure of 12 mmHg. Ringer's acetate was also used in the sham-treated group (SHAM). RESULTS: At study end the cardiac output (10% HES200 143±48 ml/kgBW; 6% HES130 171±47 ml/kgBW; RAc 137±32 ml/kgBW; 4% gelatin 160±42 ml/kgBW), as well as mean arterial pressure did not differ between groups. N-acetyl-beta-D-glucosamidase was significantly higher in the hydroxyethylstarch 200 (157±115 U/g creatinine; P<0.05) group compared to hydroxyethylstarch 130 (24±9 U/g creatinine), Ringer's acetate (2±3 U/g creatinine) and SHAM (21±15 U/g creatinine) at the study's end. Creatinine significantly increased by 87±84 percent of baseline in the 10% HES200 group compared to RAc and 6% HES130. We demonstrated in the histology of the kidneys a significant increase in osmotic-nephrosis like lesions for 4% gelatin compared to RAc, 6% HES130 and SHAM. Urine output was lowest in the 10% HES200 and 4% gelatin group, however not significantly.Interleukin(IL)-6 levels were significantly elevated in the 10% HES200 group (3,845±1,472 pg/ml) two hours after sepsis induction compared to all other groups (6% HES130 1,492±604 pg/ml; RAc 874±363 pg/ml; 4% gelatin 1,623±1,242 pg/ml). CONCLUSIONS: Despite similar maintenance of macrocirculation 6% hydroxyethylstarch 130/0.42 and Ringer's acetate significantly preserve renal function and attenuate tubular damage better than 10% hydroxyethylstarch 200/0.5 in saline.

Acute normovolemic hemodilution can aggravate neurological injury after spinal cord ischemia in rats.

BACKGROUND: Acute normovolemic hemodilution (ANH) is currently performed during thoracoabdominal aortic surgery. However, the effects of ANH on spinal cord ischemic injury are currently unknown. Because hemodilution below a certain level of hematocrit (Hct) aggravates the neurological damage after cerebral ischemia, we hypothesized that ANH may increase neurological damage after spinal cord ischemia. The aim of these experiments was to determine the effects of ANH on spinal cord ischemic injury. METHODS: Thirty male Sprague-Dawley rats were randomly assigned to 1 of the following 3 groups: no hemodilution (group C), target Hct level of 30% (group HD30), and target Hct level of 25% (group HD25). ANH was performed upon withdrawal of blood and simultaneous replacement with the same volume with hydroxyethyl starch. Spinal cord ischemia and reperfusion were induced by using a balloon-tipped catheter placed in the descending thoracic aorta, and changes in mean arterial blood pressure were recorded. Neurological function of the hindlimbs was evaluated for 7 days and recorded using a motor deficit score (MDS) (0 = normal; 5 = complete paraplegia). The number of motor neurons within the spinal cord was counted after final MDS evaluation. RESULTS: Group HD25 developed hypotension during the latter part of the ANH procedure. Group C and group HD30 experienced 3 minutes of reperfusion hypotension, whereas 6 minutes of hypotension was observed in group HD25. Two rats in group HD25 died during the experimental period. Seven days after reperfusion, the MDS of group C, group HD30, and group HD25 was 1.0 (0.5-2.0), 1.0 (0.5-2.0), and 4.0 (2.8-4.2) (median [95% confidence interval]), respectively. Group HD25 showed significantly higher MDS compared with group C (corrected P = 0.0018; 95% CI for median difference = 1.0-3.5). Motor neuron numbers in the anterior horns of group C, group HD30, and group HD25 were 26.5 (25.0-27.5), 23.5 (22.0-26.5), and 12.5 (8.4-16.6) (median [95% CI]), respectively. Motor neuron numbers of group HD25 were significantly lower than those of group C (corrected P < 0.0001; 95% CI for median difference = 9.0-18.0). CONCLUSION: The results of the present study indicate that intraoperative ANH to an Hct of 25%, combined with coincident hypotension, caused a delayed recovery of baseline mean arterial blood pressure during the reperfusion period and aggravated neurological outcome after spinal cord ischemia.

The effects of colloid solutions on renal proximal tubular cells in vitro.

Renal failure is a common complication of critically ill patients. Colloids such as hydroxyethyl starch (HES), gelatin, or albumin are regularly used for intravascular volume resuscitation, but there are increasing reports about the nephrotoxic side effects of synthetic colloids in septic patients. Therefore, we investigated the influence of colloids (HES130/0.4 (Voluven®), gelatin (Gelafundin®), human albumin, and the crystalloid Sterofundin® ISO on cell viability of human proximal tubular (HK-2) cells. HK-2 cells were incubated with colloids (0.1%-4%) and with equivalent volumes of the crystalloid solution Sterofundin ISO. After 21 hours, cell viability of HK-2 cells was measured by EZ4U assay (dye XTT). Application of HES130/0.4 decreased cell viability significantly in a concentration-dependent manner (86.80% ± 10.79% by 0.5% HES down to 24.02% ± 4.27% by 4% HES). Human albumin (>1.25%) as well as gelatin (>1%) also showed deleterious effects on HK-2 cells. Interestingly, in lower concentrations, human albumin and the crystalloid solution Sterofundin ISO were cytoprotective in comparison with the NaCl control. In conclusion, synthetic and natural colloids showed a harmful impact on HK-2 cells in higher concentrations without any prior proinflammatory stimulus. HES130/0.4 exhibited the most distinctive harmful impact, whereas the application of crystalloid Sterofundin ISO revealed cytoprotective effects.

Renal effects of saline-based 10% pentastarch versus 6% tetrastarch infusion in ovine endotoxemic shock.

BACKGROUND: Conflicting data exist on the renal effects of hydroxyethyl starch (HES) preparations. The current study evaluates the effects of saline-based 6% HES 130/0.4, 10% HES 200/0.5, and a balanced isotonic crystalloid on renal function and microscopic changes in ovine endotoxemic shock. METHODS: Thirty sheep were subjected to endotoxin infusion (Salmonella typhosa) at incremental doses until mean arterial pressure was less than 65 mmHg. Animals were randomized to receive fluid resuscitation with saline-based 6% HES 130/0.4, 10% HES 200/0.5, or a balanced isotonic crystalloid (n = 10 each). Animals surviving the 12-h intervention period were anesthetized and killed. Kidney samples were taken for microscopic analyses. RESULTS: Endotoxemia was associated with hemoconcentration, protein extravasation, and arterial hypotension. Fluid resuscitation established a hypotensive-hyperdynamic circulation with increased cardiac index and oxygen delivery and decreased afterload. Diuresis was lowest in animals treated with 10% HES 200/0.5. In addition, plasma creatinine and urea concentrations increased in sheep treated with 10% HES 200/0.5 (1.2 +/- 0.1 and 19 +/- 2 mg/dl) when compared with the other two groups (0.9 +/- 0.1 and 15 +/- 1 mg/dl, 6% HES 130/0.4; 0.9 +/- 0.1 and 15 +/- 1 mg/dl, crystalloids; each P < 0.05). Electron microscopic tubular injury score was highest in sheep treated with 10% HES 200/0.5 (P < 0.001 vs. 6% HES 130/0.4). CONCLUSIONS: In ovine endotoxemic shock, saline-based 10% HES 200/0.5 was linked to impaired renal function and more pronounced tubular epithelial injury when compared with 6% HES 130/0.4 and balanced crystalloids.

rFVIIa and NN1731 reduce bleeding in hydroxyethyl starch hemodiluted rabbits.

BACKGROUND: Colloid plasma expanders are used to maintain blood pressure and ensure tissue perfusion during hypovolemia, e.g., caused by traumatic bleeding. Although colloids stabilize the cardiovascular system, they can also potentially cause coagulopathy. Consequently, bleeding tendency may increase, as well as the associated risk of morbidity and mortality. Thus, there is a need for hemostatic treatment options for these patients. rFVIIa (NovoSeven, Novo Nordisk A/S, Bagsvaerd, Denmark) is a hemostatic agent that effectively controls bleedings in patients with inhibitor-complicated hemophilia. rFVIIa works by enhancing thrombin generation on the activated platelet surface at the site of injury, leading to the formation of a stable fibrin clot. NN1731 is an rFVIIa analog with increased hemostatic potential and is currently under clinical development. METHODS: In this study, the effect of rFVIIa and NN1731 on cuticle bleeding in rabbits 50% hemodiluted with hydroxyethyl starch (molecular weight ∼ 200,000) was tested. Cuticle bleeding was induced after a two-stage hemodilution procedure. After 5 minutes, the animals were treated with rFVIIa (2, 5, or 10 mg/kg), NN1731 (1 or 2 mg/kg), or vehicle, followed by 30 minutes of observation. RESULTS: Hemodilution caused a significant increase in bleeding time and blood loss. rFVIIa dose-dependently reduced bleeding time and blood loss, reaching statistical significance at 10 mg/kg. However, 2 mg/kg NN1731 reduced bleeding time and blood loss significantly and to a similar extent as 10 mg/kg rFVIIa. This increased hemostatic potential of NN1731 compared with rFVIIa and was confirmed by findings using thromboelastography on ex vivo hemodiluted whole blood. CONCLUSION: In summary, rFVIIa and NN1731 significantly and dose-dependently reduced bleeding in extensively hemodiluted rabbits.

Lyprinol (stabilised lipid extract of New Zealand green-lipped mussel): a potential preventative treatment modality for inflammatory bowel disease.

BACKGROUND: Lyprinol (Pharmalink International), the stabilised lipid extract of the New Zealand green-lipped mussel, is currently used to relieve symptoms of arthritis. We investigated the effect of pretreatment with Lyprinol (LYP) on experimentally induced inflammatory bowel disease (IBD) in mice. METHODS: Male C57BL/6 mice (aged 6 weeks) were gavaged daily for 13 days with (150 microl) olive oil (OO; n = 7), fish oil (FO; n = 8), or LYP (n = 8). Mice consumed 2% dextran sulfate sodium (DSS) for 6 days, starting on day 7. Body weight and disease activity index (DAI) scores were recorded daily. Colonic damage was determined by histopathology. Colonic inflammation was quantified by myeloperoxidase (MPO) activity. RESULTS: LYP treatment significantly (P < 0.05) reduced body weight loss, DAI scores, crypt area losses, and cecum and colon weights, compared with FO treatment. MPO activity was not significantly affected by any treatment. CONCLUSIONS: These findings provide preliminary evidence that Lyprinol may be potentially useful in ameliorating symptoms of IBD. The benefit, however, is unlikely to be due to the omega-3 fatty acid content. Dose-response evaluation of Lyprinol in experimental IBD is warranted.

Interaction of recombinant octameric hemoglobin with endothelial cells.

Hemoglobin-based oxygen carriers (HBOCs) may generate oxidative stress, vasoconstriction and inflammation. To reduce these undesirable vasoactive properties, we increased hemoglobin (Hb) molecular size by genetic engineering with octameric Hb, recombinant (r) HbßG83C. We investigate the potential side effects of rHbßG83C on endothelial cells. The rHbßG83C has no impact on cell viability, and induces a huge repression of endothelial nitric oxide synthase gene transcription, a marker of vasomotion. No induction of Intermolecular-Adhesion Molecule 1 and E-selectin (inflammatory markers) transcription was seen. In the presence of rHbßG83C, the transcription of heme oxygenase-1 (oxidative stress marker) is weakly increased compared to the two other HBOCs (references) or Voluven (control). This genetically engineered octameric Hb, based on a human Hb ßG83C mutant, leads to little impact at the level of endothelial cell inflammatory response and thus appears as an interesting molecule for HBOC development.

Comparison of 7.5% NaCl/6% dextran-70 resuscitation of hemorrhage between euhydrated and dehydrated sheep.

7.5% NaCl/6% dextran-70 (HSD) has been shown to be an effective, small volume resuscitation fluid following hemorrhage (HEM) in euhydrated (E) sheep. However, there is controversy whether hypertonic solutions would be effective in dehydrated (D) animals. Therefore, we used two groups (E and 4 days D) of chronically instrumented ewes to evaluate the responses to HSD following HEM. All sheep were bled and maintained at 50 mmHg mean arterial pressure (MAP) for 2 h, then resuscitated with a 4 mL/kg bolus of HSD. Dehydration did not affect baseline MAP, heart rate (HR), or total peripheral resistance (TPR), whereas cardiac output (CO: E, 5.28 +/- .31; D, 4.00 +/- .31 L/min), stroke volume (SV: E, 61 +/- 4; D, 44 +/- 4 mL/beat), urine flow rate (V: E, .51 +/- .11; D, .34 +/- .07 mL/min), and sodium excretion (UNa V: E, 22 +/- 8; D, 6 +/- 2 microEq/min) were reduced and plasma sodium (PNa: E, 150 +/- 3; D, 157 +/- 2 mEq/L) and protein (PTP E, 7.8 +/- .1; D, 8.8 +/- .6 g/dL) were elevated. The only difference between groups during HEM were HR (E, 98 +/- 8; D, 150 +/- 17 bpm), SV (E, 31 +/- 3; D, 14 +/- 2), and TPR (E, 23 +/- 2; D, 32 +/- 3). Resuscitation with HSD restored MAP (E, 92 +/- 3; D, 92 +/- 2), CO (E, 6.2 +/- .3; D, 4.2 +/- .2), and TPR (E, 15 +/- 1; D, 23 +/- 1) to baseline values. SV was increased above hemorrhage values but was not restored to baseline values in either group (E, 50 +/- 7; D, 27 +/- 3). HR increased further following HSD (E, 143 +/- 11; D, 158 +/- 5). PNa was raised 10 and 16 mEq/L in the E and D sheep, respectively, following HSD infusion, but no adverse effects associated with elevated PNa were observed in either group. Thus, HSD was effective in restoring MAP, CO, and TPR to baseline values in D sheep but it was at the expense of a lower SV and a higher HR than in E sheep.

Peritoneal accumulation of infused stroma-free hemoglobin. Potential toxicity of an oxygen-carrying substitute.

The efficacy of stroma-free hemoglobin (SFH) as an oxygen-carrying red blood cell substitute in shock and trauma remains inconclusive. A major problem is the retention of sufficient intravascular persistence. The sites and mechanisms for clearance of SFH or its chemically modified variants are not well characterized. Capillary leakage has been reported. Any significant leak into the peritoneal cavity may be toxic, especially if bacteria are present. The present study quantitates peritoneal accumulation of SFH and chemically modified adenosine triphosphate (ATP)-SFH following a 50% exchange transfusion in rats. m-Dansyl cadaverine, an endocytotic blocking agent, was studied for its ability to alter accumulation of hemoglobin in the peritoneum. Differences in renal clearance corresponded to differences in vascular halflife of SFH (90 minutes) and ATP-SFH (210 minutes). Peritoneal leakage was not related to vascular persistence. We found that MDC significantly decreases the peritoneal accumulation of ATP-SFH but not that of SFH. We also noted that MDC neither inhibits nor alters renal clearance of either hemoglobin variant. Total peritoneal leakage is, at most, 4% of infused SFH at four hours. Molecular size and charge might be factors important in hemoglobin transport from the vasculature to the peritoneum.

Adverse reactions to plasma volume expanders.

Plasma volume expanders are effective in the restoration of blood volume. All the available plasma volume expanders may rarely induce anaphylactoid reactions, although such reactions are extremely uncommon in shocked patients. The reactions are caused by different mechanisms depending on the solution, and there is little evidence that IgE antibodies are involved. In addition to these reactions, effects on haemostasis and renal function may occur, and the persistence of hydroxyethyl starch in the body has led to concern about its potential role as a carcinogen, although there is no evidence to suggest that this has occurred.

Amelioration of nephrotoxicity associated with synthetic oxygen transport media.

Use of synthetic oxygen transport media offers the potential advantages of reducing requirements for coadministration of blood products and oxygen at the scene of mass casualty situations. Previous studies have shown perfusions of isolated kidneys with stroma-free hemoglobin (SFH) to be physiological while those with Fluosol-DA (20% FDA) have been associated with low glomerular filtration rate, urinary flow rate, and fractional reabsorption of sodium and potassium (FrNa+ and FrK+). In the present studies, perfusions with SFH/FDA mixtures showed normal glomerular filtration rate, a 50% lower urinary flow rate, and FrNa+ values 3% to 5% higher than SFH controls. Compared with 20% FDA perfusions, nephrotoxic effects of SFH/FDA combinations were moderate. Compared with SFH/FDA mixtures, perfusion with 20% FDA showed lower urinary flow and glomerular filtration rates. Ultrastructural assessment of glomerular filter revealed that FDA emulsion particles were adherent to epithelial podocytes. We conclude that resuscitation with a mixture of SFH and FDA may ameliorate the previously reported nephrotoxicity associated with the use of FDA alone.

Action of hydroxyethyl starch (HES) on the activity of plasmatic clotting factors.

Studies were carried out on the effects of different doses of hydroxyethyl starch 200/0.5 (HES) on plasma clotting factors in dogs, as an animal model for the human clotting system. In 8 German shepherd dogs 15% of the total blood was isovolemically substituted either by Ringer's solution with lactate alone (controls) or with 0.6, 1.3, 1.9, 2.5 g HES/kg b.w. Immediately after the infusion, the HES concentration in the recipients' plasma amounted to 8 mg/ml up to 38 mg/ml. In the following 6 h, the HES decreased to 25% in each case. It was found that the higher the plasma HES content was, the lower the haematocrit. Neither the thrombin-nor the batroxobin-time showed any significant change, irrespective of the plasma HES concentration. The prothrombin-time was decreased directly after the infusion in parallel to the haematocrit. The single clotting factors FI, FII, FV, FVII, FVIII, FX, and FXII behaved approximately in the same way: their activities directly after infusion, but also 6 h later, were lowered in proportion to the amount of HES infused. The loss of factor activity correlated with the volume-expanding effect of HES shortly after the infusion, but not 6 h later. It is concluded that there are two different modes of HES action on clotting factors: the dilution by plasma volume expansion and a non-dilutional action. Cautious handling might be required in patients with clotting disturbances as well as in long-term treatment.

[Hydroxyethyl starch]. / Les hydroxyéthylamidons.

OBJECTIVE: The purpose of this review is to draw up a statement on current knowledge available on the more recent hydroxyethyl starch (HES). DATA SOURCES: References were obtained from computerized bibliographic research (Medline), recent review articles, the library of the service and personal files. STUDY SELECTION: All categories of articles on this topic have been selected. DATA EXTRACTION: Articles have been analysed for biophysics, pharmacology, toxicity, side effects, clinical effects and using prospect of HES. DATA SYNTHESIS: The first HES was made available in the United States in 1970. The development of a new generation of HES restarted the discussion on clinical interest and the limits in the use of these macromolecules. This interest is also strengthened today by the recent data attached to plasma substitution in intensive care or perioperative resuscitation. The interest for crystalloids and colloids is still widely debated, and among the latter, the relative interest of the HES last generation compared to older ones. Recent HES development is in line with a decrease molecular weight, change rate molar substitution and to amend the glucose to hydroxyethyl report. The ultimate goal is to reduce the side effects of these molecules preventing their use. Side effects are dominated by haemostasis and renal dysfunction. The latest developments are the so-called HES "balanced" solutions.