The Effect Of Tow Medium Molecular Weight Hydroxyethyl Starch On Expressions Of Platelet Membrane Glycoprotein And Platelet [Ca～(2+)]_i

PrefaceHydroxyethyl starch (HES) preparations are used to expand intravascular volume and improve microcirculation. The third-generation products medium molecular weight and low substituted HES are currently wildly used to treat hypovolemia. The achievements of HES are seen about volume therapy, circulation stabilization and less use of blood. HES prepations are converted by native starches. The raw materials are drawed by maize or potato. The structure is similar to glycogen. HES is favorably received in clinic because of little anaphylaxis, no danger of hepatitis transmission and low treatment costs. But HES has some adverse effects such as tissue accumulation, influence on coagulation and kidney function et al. The adverse effects restrain its mass use. Especially, the reports of influence on coagulation are not the same and the mechanism is not explored completely. HES modulate the influence on blood coagulation by their mean molecular weight, their degree of substitution , and their C₂ to C₆ ratio. The greater the molecular weight, the higer the degree of substitution and the C₂ to C₆ ratio, the more a particular HESsolution will compromise coagulation. Warren reviewed the literatures about the influence of HES on coagulation and found the most considered HES compromise clotting factors and platelet function. The currently wildly used HES solution is 6% HES 200/0.5, the product name is HAES-steril. Recently, a novel HES solution 6% HES 130/0.4 (voluven) is used in clinic. It is reported that voluven has superior physicochemical characteristics such as low molar substitution, improved C2 to C6 ratio et al. Voluven is regarded as technological innovation of volume replacement. But the influence of voluven on blood coagulation should be explored futher.In this study, we use this two medium molecular weight and low substituted HSE: HAES-steril and voluven ,compared with lactated Ringer's solution, measure the expression of platelet membrane glycoprotein (GP) CD42b, CD61/41, CD62p and platelet[Ca2+]i before and after infusion by flow cytometry. Observe the effect of this two HES on expression of CD42b, CD61/41, CD62P and platelet [Ca2+]i- Thereby investigate the effect of HES on the coagulation of platelet and the clinical significance. Further explore the possible mechanism of the effect of HES on platelet function at the molecular level.ObjectiveTo observe the effect of expression of CD42b, CD61/41, CD62P and platelet[Ca2+]i on the two different degree of substitute medium molecular weight hydroxyethyl starch HAES-steril and voluven. Thereby investigate the effect of HES on the coagulation of platelet and the clinical significance. Further explore the possible mechanism of the effect of HES on platelet function at the molecular level.MethodsSixty ASA I II patients undergoing elective minor surgery were randomly allocated to receiving intravenous infusion of lactated Ringer's solution (L group), HAES-steril (H group) and voluven (V group) with the dose of 20ml/kg afterinduction of anesthesia respectively, with 20 cases in each group. The venous blood samples were taken before infusion, 15 minutes and 6 hours after infusion to measure expression of platelet membrane glycoprotein (GP) CD42b, CD61/41, CD62p and platelet[Ca2+]i by flow cytometry.Results1. The ADP -activated platelet expression of CD42b, CD61/41 and CD62P wasno statistically significant chang after infusion than that before infusion in L group (PX).Q5). The expression of CD42b, CD61/41 and CD62P was statistically significant lower 15 minutes after infusion than that before infusion in both H and V group(P<0.05 or i><0.01). The expression of CD42b, CD61/41, CD62P was statistically significant lower 6 hours after infusion in H group (p<0.01) while in V group the expression of GP returned to the level before infusion (p>0.05). The expression of CD42b, CD61/41 and CD62P was no statistically significant difference in three groups before infusion (i^O.05). The expression of CD42b, CD61/41 and CD62P was no statistically significant difference in H and V group at 15 minutes after infusion (PX).O5).While 6 hours after infusion, the expression of CD42b, CD61/41 and CD62P in V group was statistically significant higher than that in H group (p<0.01).2. The platelet [Ca2+]j was no statistically significant difference in three groups (P>0.05). There was no statistically significant change of the platelet [Ca2+]i after infusion in three groups (P>0.05).Conclusion1. Both HAES-steril and voluven can inhibit the coagulation of platelet.2. The novel medium molecular weight HES voluven inhibit the coagulation of platelet lower than HAES-steril. Voluven used to volume therapy and hemodilution are more advantageous in the clinic.3. HES inhibit platelet function by nonselect inhibiting the expression of platelet membrane glycoprotein CD42b, CD61/41 and CD62P. The coating phenomenon may be responsible for the antiplatelet effects of HES by blocking the access of endogenous ligands to the platelet membrane glycoprotein receptor.4. HES does not effect platelet [Ca2\ HES does not inhibit platelet by interfering with calcium-dependent intercellular signal transduction pathways.