Effects of Hextend hemodilution on plasma coagulation kinetics in the rabbit: role of factor XIII-mediated fibrin polymer crosslinking

BACKGROUND: Hydroxyethyl starch administration has been associated with decreases in hemostasis and has recently been demonstrated to decrease fibrinogen (FI)-thrombin-(FIIa)-Factor XIII (FXIII) interactions in vitro in human plasma. Thus, the purpose of the present study was to determine the effect of in vivo hemodilution with Hextend (6% hydroxyethyl starch, mean molecular weight 450 kDa) on plasma coagulation kinetics. MATERIALS AND METHODS: Eight male, New Zealand White rabbits were intravenously administered with 20 ml/kg of Hextend. Citrated plasma was obtained before, 1 min after, and 1 h after hemodilution. Thrombelastographic analyses were performed, with clot initiation (R, sec), clot propagation (alpha, degrees), and clot strength (shear elastic modulus, G, dynes/cm(2)) determined over 20 min. Samples were celite-activated and had either with addition or without additions of FI, FIIa or activated FXIII (FXIIIa) to restore protein content to prediluted values. RESULTS: There was no significant difference in R values observed before (229 +/- 30), 1 min after (241 +/- 54), and 1 h after (214 +/- 42) hemodilution. Prediluted alpha values (75.2 +/- 1.9) were significantly decreased 1 min (53.3 +/- 5.9) and 1 h after hemodilution (56.1 +/- 10.2). Prediluted G values (1,992 +/- 434) were significantly reduced 1 min (532 +/- 195) and 1 h after (630 +/- 297) hemodilution. FI, FIIa, and FXIIIa addition significantly decreased R values after hemodilution. alpha and G values were significantly improved by FI and FXIIIa after hemodilution. FIIa addition did not significantly affect alpha or G. CONCLUSIONS: Hextend hemodilution in rabbits maintains clot initiation by diminishing both FIIa-FI and FXIIIa-fibrin interactions, whereas clot propagation and strength were reduced by diminished FXIIIa-fibrin interactions.     

Blutglucose und Seruminsulin nach oraler Applikation von Glucose und Stärkesirup in unterschiedlicher Dosierung

Zusammenfassung Bei 6 Gruppen stoffwechselgesunder Personen (8–14 Probanden pro Gruppe) wurden orale Belastungen mit 50 g, 100 g oder 200 g Glucose bzw. Stärkehydrolysat durchgeführt. Die Blutglucoseveränderungen waren von der Art und der Menge der verabreichten Kohlenhydrate weitgehend unabhängig. Bei den Seruminsulinwerten war dagegen eine deutliche Beziehung zur verabreichten Kohlenhydratmenge vorhanden. Nach 50 g Kohlenhydraten betrug der Anstieg des Seruminsulins etwa 50 E/ml, nach 100 g Kohlenhydraten etwa 90 100 E/ml. Eine weitere Erhöhung der verabreichten Kohlenhydratmenge bewirkt zwar keine weitere Steigerung der Maximalwerte, jedoch war die Normalisierung der Seruminsulinwerte stark verzögert. Aus dem Verhalten der Seruminsulinwerte nach Verabreichung großer Kohlenhydratmengen kann geschlossen werden, daß trotz Normalisierung der Blutglucosewerte die Glucoseresorption nach 120 min noch nicht abgeschlossen ist. 100 g Glucose oder Stärkesirup sind nach diesen Ergebnissen für die orale Belastungsprobe zu diagnostischen Zwecken besser geeignet als 50 g Kohlenhydrate. Erst bei Einnahme von 100 g Kohlenhydraten wird die Insulinsekretion ausreichend stimuliert, was besonders für den wichtigsten Zeitpunkt der Untersuchung — zwei Stunden nach Einnahme der Kohlenhydrate von wesentlicher diagnostischer Bedeutung ist.

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Blood glucose and serum insulin after oral loading with glucose and starch syrup in varying doses

Summary 6 groups consisting of 8–14 healthy control persons received 50 g, 100 g or 200 g of glucose or of a starch-hydrolyzate preparation by mouth. Blood sugar changes were largely independent of the type or amount of carbohydrate given. Serum insulin values, however, showed a definite correlation with the amount of ingested carbohydrate. After 50 g of carbohydrate the rise of serum insulin was about 50 U/ml; after 100 g of carbohydrate it reached 90–100 U/ml. There was no further rise of maximal values after ingestion of larger amounts of carbohydrate, but the normalization of insulin levels was markedly delayed. From the pattern of serum insulin levels after ingestion of large amounts of carbohydrates, it can be concluded that glucose absorption is not finished at 120 min despite normal blood glucose values. As indicated by these results, 100 g of glucose or starch-syrup is better suited for diagnostic purposes than is 50 g of carbohydrates. Only the ingestion of 100 g of carbohydrates stimulates insulin release sufficiently, which is of special diagnostic interest for the most significant interval of the test, i.e. 2 h after ingestion of the carbohydrate load.

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Glucose sanguin et insuline sérique aprés charge orale de glucose et de sirop d'amidon à différentes doses

Résumé 6 groupes de 8–14 sujets en bonne santé ont reu 50 g,ç 100 g ou 200 g de glucose ou d'une préparation d'hydrolysat d'amidon par voie orale. Les modifications de la glycémie étaient largement indépendantes du type ou de la quantité d'hydrates de carbone administrés. Les valeurs de l'insuline sérique, par contre, montraient une corrélation nette avec la quantité d'hydrates de carbone ingérés. Aprés 50 g d'hydrates de carbone, l'augmentation de l'insuline sérique était environ de 50 U/ml; aprés 100 g d'hydrates de carbone, elle atteignait 90–100 U/ml. Il n'y avait pas d'autres augmentations des valeurs maximales aprés ingestion de quantités plus grandes d'hydrates de carbone, mais la normalisation des taux d'insuline était nettement retardée. A partir du comportement des taux d'insuline sérique aprés ingestion de grandes quantités d'hydrates de carbone, on peut conclure que la résorption du glucose n'est pas terminée à 120 min malgré des valeurs normales de glucose sanguin. Comme l'indiquent ces résultats, 100 g de glucose ou de sirop d'amidon conviennent mieux à des buts diagnostiques que 50 g d'hydrates de carbone. Seulement l'ingestion de 100 g d'hydrates de carbone stimule suffisamment la sécrétion d'insuline, ce qui est d'un intérêt diagnostique spécial pour le moment le plus important du test, c'est-à-dire 2h aprés l'ingestion d'une charge d'hydrates de carbone.

     

Ascites als Komplikation hepatischer Speicherung von Hydroxyethylstärke (HES) bei Langzeitdialyse

Summary Three adult dialysis patients developed ascites after having received repeatedly the plasma substitue hydroxyethyl starch (HES 40/0.5). In two cases (total dose 180, and 330 g HES, respectively) the ascites was reversible after discontinuation of the HES administration. In the third case (total dose 915 g HES) the ascites could be controlled only by implantation of a Denver shunt. In this latter case it was shown by histological, electron microscopical, and biochemical findings that the ascites was caused by hepatic sinusoidal obstruction due to an extreme storage of HES in the sinusoidal lining cells. Additional storage was detected in hepatocytes, bile duct epithelia, endothelial cells, and fibroblasts in the portal tracts. Biochemically HES was found in liver tissue at a concentration of 4% (w/w). Although in renal impairment plasma clearance of HES is not significantly different from normal individuals, long-term administration of HES must be regarded inadvisable because of tissue storage which apparently is especially significant in this condition.

     

Protein and starch digestibility and iron availability in developed weaning foods as affected by roasting

Locally available cereals and pulses such as rice ( Oryza sativa ), kangini ( Setaria italica ), sanwak ( Echinochloa frumentacea ), green gram [Vigna radiata) and jaggery (unrefined brown sugar) were used to formulate three weaning foods. Cereal, pulse and jaggery were mixed in the ratio of 70:30:25. Roasting was the main processing technique used in the formulation of these weaning foods. The developed weaning foods were found to be economical and acceptable. The chemical composition of developed weaning foods was within the range prescribed by Indian Standard Institute (ISI). On roasting, in vitro protein and starch digestibility of weaning foods increased by 15–21% and 16–19%, respectively. Roasting also improved in vitro iron availability by 12–19%. These observations indicated that the weaning foods prepared from locally available food ingredients resulted in significant improvement in protein and starch digestibility and iron availability and could be used as supplements for meeting the nutritional requirements of infants.     

Characterization and evaluation of dialdehyde starch as an erodible medical polymer and a drug carrier

The characteristics of dialdehyde starch as a polymer, particularly molecular weight distribution, dissolution and degradation behavior were investigated. The effects of salts, pH and temperature on dissolution and degradation were studied. Moreover, the usefulness of dialdehyde starch as a drug carrier was evaluated in vitro using its conjugate with isoniazid.     

A study of haemostasis following the use of high doses of hydroxyethyl starch 120 and dextran in major laparotomies

The safety of plasma expanders, hydroxyethyl starch 120 and dextran 70, administered in the highest recommended doses (20 ml/kg) as adjuncts of component therapy of surgical blood loss was studied in patients undergoing major abdominal surgery and compared with a group receiving 4% albumin solution for initial haemodilution and whole blood for further blood loss replacement. Each group consisted of five patients in a relatively severe surgical, but good general condition including a normal haemostatic function and serum albumin level. The dilutional effect of the expanders on serum albumin and prothrombin-proconvertin level was observed during the day of operation. On the first postoperative day these values were equally low in all groups. Platelet count and bleeding time remained on a safe level throughout the study in all groups. Partial thromboplastic time values were unchanged. The factor VIII procoagulant (C), related antigen (R:Ag, vWF:Ag) and ristocetin cofactor levels, which were high preoperatively due to the underlying disease, remained at a safe level throughout the study. The increase in factor VIII related antigen associated with the hypercoagulable state induced by the surgical trauma was prevented by the plasma expanders. We conclude that dextran and hydroxyethyl starch can be used safely in a dose of 20 ml/kg in component therapy of surgical blood loss, provided that haematocrit is kept at an acceptable level, attention is paid to the postoperative hypoproteinaemia, and the patient has a normal haemostatic function preoperatively.     

Diet of women with severe premenstrual syndrome and the effect of changing to a three-hourly starch diet

Following a large meal there is a transient and large increase in the metabolic clearance rate of progesterone.¹ Progesterone receptors do not bind to molecules of progesterone in the presence of adrenalin,² which is released when the blood glucose level is low. While awaiting their first appointment, 84 women with severe premenstrual syndrome (PMS) completed a questionnaire detailing all food and drink consumed on seven consecutive days. The average daytime interval between starch-containing foods was 7 hours, with an overnight interval averaging 13 ½ hours. This suggested that women with PMS might benefit from shorter food intervals between starch-containing foods and avoidance of large meals. On receipt of their questionnaires women were advised to follow a three-hourly starch diet, which was beneficial in 54 per cent with improvement in a further 20 per cent. The diet alone proved effective in 19 per cent, who needed no additional medication for full relief of premenstrual symptoms.     

Plasma exchange versus an affinity column for cholesterol reduction

The recent introduction of low-density lipoprotein (LDL)/very low-density lipoprotein (VLDL) selective-removal systems offers an alternative to plasma exchange (PE). For the last 10 years, we have treated a inale homozygous hypercholesterolemia type IIA patient with PE using 5% normal serum albumin (NSA) replacement. PE using 6% hydroxyethyl starch (HES) replacement, single dextran sulfate cellulose bead affinity column (DSAC) (Kaneka LA-40), and double DSAC. This report compares the performance of these systems in cholesterol reduction (total, LDL + VLDL), and high-density lipoprotein [HDL] and their effect on the total protein, albumin, and hematocrit levels. The number of procedures and average volume of plasma treated using PE-NSA, PE-HES, I-DSAC, and 2-DSAC were 113, 64, 15, 90 and 3,939, 3,270, 3,519. and 3,588 ml, respectively. The average pretreatment total cholesterol levels were baseline 864 mg/dL, PE-NSA 606 mg/dL, PE-HES 610 mg/dL, I-DSAC 467 mg/dL, and 2-DSAC 395 mg/dL with plasma reductions of 59%, S7%, 47%, and SS%, respectively. Average LDL + VLDL plasma reductions were PE-NSA 58%, PE-HES 59% (N = I), I-DSAC 4670, and 2-DSAC 56%. Average HDL plasma reductions were PE-NSA 58%, PE-HES 69% (N = I ), I-DSAC 58, and 2-DSAC 17%. The average total cholesterol and LDL + VLDL reductions were comparable for both types of PE and the 2-DSAC system. The average HDL loss was 53% lower for the DSAC systems than for PE systems. Of the four systems compared in this study, the 2-DSAC system offers equivalent efficiency in LDL + VLDL reductions as PE while retaining more of the beneficial HDL than PE without the use of replacement solutions. © 1992 Wiley-Liss, Inc.     

Influence of dietary carbohydrates upon the metabolism of lipids and minerals in rabbits

Rabbits were fed purified diets containing either corn starch, sucrose, glucose or fructose as 39.5% of the caloric content, or were fed a commercial diet. At the end of the 12-week trial period, glucose tolerance tests did not reveal a difference by treatment, and males had a lower tolerance than females. The serum cholesterol concentrations of the various density lipoproteins varied by treatment as determined weekly; often the HDL cholesterol was higher in the rabbits fed corn starch, and the VLDL cholesterol was higher in the rabbits fed corn fructose. Cholelithiasis at the end of the trial was prevalent in rabbits fed sucrose, glucose or fructose, was infrequent in the rabbits fed corn starch, and was absent in the rabbits fed the commercial diet. Lipid and cholesterol concentrations in the liver were greater in the rabbits fed the purified diets than in those fed the commercial diet. Cholesterol concentration in the thoracic aorta was greater in the rabbits fed the commercial diet than in those fed the purified diet. Analyses of liver and kidneys for Cr, Mn, Cu and Zn revealed treatment differences only in the case of the kidneys where Cr concentration was greater in the kidneys when the commercial diet was fed.     

Randomized study comparing the effects of hydroxyethyl starch solution with Gelofusine on pulmonary function in patients undergoing abdominal aortic aneurysm surgery

Background. Restoring blood flow to ischaemic tissue can causelung damage with pulmonary oedema. Hydroxyethyl starch (HES)solution, when used for volume replacement, may modify and reducethe degree of ischaemia–reperfusion injury. We comparedthe effects of HES solution with those of Gelofusine solutionon pulmonary function, microvascular permeability and neutrophilactivation in patients undergoing elective infrarenal abdominalaortic aneurysm surgery. Methods. Forty patients were randomized into two groups. Theanaesthetic technique was standardized. Lung function was assessedwith the PO₂/FI_O2 ratio, respiratory compliance, chest x-rayand a score for lung injury. Microvascular permeability wasdetermined by measuring microalbuminuria. Neutrophil activationwas determined by measurement of plasma elastase. Results. Four hours after surgery, the median (quartile values)PO₂/FI_O2 ratio was 40.3 (37.8, 53.1) kPa for the HES-treatedpatients compared with 33.9 (31.2, 40.9) kPa for the Gelofusine-treatedpatients (P<0.01, Mann–Whitney test). The respiratorycompliance was 80 (73.5, 80) ml cm^–1 H₂O inthe HES-treated patients compared with 60.1 (50.8, 73.3) mlcm^–1 H₂O in the Gelofusine-treated patients (P<0.01,Mann–Whitney test). The lung injury score 4 h after surgerywas less for the patients treated with HES compared with thepatients treated with Gelofusine (0.33 vs 0.71, P=0.01, Wilcoxonrank sum test). Mean (SD) plasma elastase was less in the HES-treatedpatients on the first postoperative day (1.96 (0.17) vs 2.08(0.24), P<0.05). The log mean microalbuminuria was less inthe HES-treated patients (0.41 vs 0.91 mg mmol^–1,P<0.05). This difference in microvascular permeability wasassociated with different volumes of colloid required to maintainstable cardiovascular measurements in the two groups of patientsstudied (3000 vs 3500 ml, P<0.01, Mann–Whitney test). Conclusion. Compared with Gelofusine, the perioperative pulmonaryfunction of patients treated with HES after abdominal aorticaneurysm surgery was better. Br J Anaesth 2004; 92: 61–6