Preparing Starch Nanospheres And Resuscitation On Hemorrhagic Shock

Background The hemorrhagic shock is the most common type of shock. It isa state of inadequate organ perfusion for normal aerobic metabolism due to lossof circulating blood. Lack of organ perfusion disrupts normal cellular metabolismand, if not reversed, will ultimately lead to the multiple organ dysfunctionsyndrome, and even multiple organ failure. At present, treatment methods forhemorrhagic shock mainly include the rectification of acidosis, expansion ofplasma volume, and use of vasoactive drugs. In the rescue of shocks, we foundthat the transfusion therapy is the most effective treatment method. All the time,for treatment of hemorrhagic traumatic shock, most people contend that it isrequired to transfuse a lot of fluid rapidly before completely controlling massivehaemorrhage, to bring the blood pressure to return to normal level, so as to ensureblood perfusion of major visceral organs. However, this neglects input of muchcrystalloid solution, which does not contain hemoglobin and cannot be directlyand effectively increase blood and oxygen supply for major visceral organs, buton the contrary will accelerate deterioration of the body environment, seriously disrupt the protective mechanism of the body. For the early fluid resuscitation, itis reported that, if the fluid is transfused at low level and slow speed and theblood pressure is controlled at a stable level, it may less disrupt bodyenvironment, reduce occurrence of various complications of shock, so as toeffectively reduce the death rate at a later period. As a type of drug carrier, thecrosslinked starch nanospheres with N, N’-methylene bisacrylamide arebiologically compatible and biodegradable. Besides, they are nonpoisonous, freeof immunogenic, stable in storage, and low in price, and can be degraded byenzymes within the body. The crosslinked nanospheres are changeable, waterswellable and can keep a relatively long time during delivery. Therefore, on thebasis of swelling property of dry nanospheres in liquid medicine, we design anew type of resuscitation solution, i.e. the starch nanospheres Ringer’s solution.Similar to electrolytes of extracellular fluid, this solution can reach the requiredblood pressure at low volume, to help keeping blood circulation and protectingvital organs. In addition, without much disturbance to the body environment, it isable to create favorable conditions and win precious time for subsequent rescueand treatment. This experiment compares the starch nanospheres Ringer’ssolution and common crystalloid solution–Ringer’s solution to observe whetherthe starch nanospheres Ringer’s solution has a better effect on resisting thehemorrhagic shock.Objective: This study was to explore resuscitation effects of starchnanospheres solution on hemodynamics in rats with hemorrhagic shock.Materials and MethodsAnimalsSprague-Dawley rats (specific pathogen-free grade,10-12weeks old,230-250g) were obtained from the Experimental Animal Centre of Fourth Military MedicalUniversity, Xi’an, China. Animals were housed with free access to food andwater at a constant temperature of22±2℃at55±5%humidity with a12-hlight/12-h dark cycle. The study protocol was reviewed and approved by theEthics Committee of the Xijing Hospital of Fourth Military Medical University,Xi’an, China. Animal handling accords with the guidelines for the capture,handling and care of mammals, approved by the American Society ofMammalogists.Experimental Groups and MethodsThe starch nanospheres Ringer’s solution adopts anti-phase suspension polymericnanometer technology, takes soluble starch as material, and K2S2O8-Na2S03asinitiating agent. At last, it compounds starch nanospheres crosslinked with N,N’-methylene bisacrylamide, which is then turned into the starch nanospheresanti-shock fluid (0.1%,0.5%,1～6%concentration) through being dissolved inRinger’s solution. Rats were randomly divided into10groups: Ringer’s solution,Voluven solution and0.1%,0.5%,1～6%starch nanospheres Ringer’s solution,each with10animals. Before the experiment, rats were fasted, but water wastaken freely. All rats were anaesthetized with10%chloral hydrate (0.3ml/100g)by intraperitoneal injection. And insert tubes into femoral artery and femoral veinin right side and insert tube into right arteria carotis. The tube in femoral artery isused for observing blood pressure and bleeding blood. Through the tube infemoral artery, inject physiological saline with heparin (500U/kg) foranticoagulation. The tube in femoral vein is for drug administration. The tube inright arteria carotis through left ventricle is to measure hemodynamics indexes,including the systolic blood pressure (SBP), diastolic blood pressure (DPB),mean arterial pressure (MAP) and respiratory rate (RR). Make the shock model at 50%bloodletting for each group, stabilize15minutes. Within5minutes, reducethe MAP to5.33kPa (40mmHg), whose fluctuation should be within40±5mmHg.Then, the shock model is successfully copied. Later, transfuse resuscitationsolution. The whole solution is transfused within30minutes. We made a recordof changes of hemodynamics for all experimental rats every half an hour and pH,PCO2, PO2, SaO2, BE and Lac.Statistical AnalysesThe mean±SD of the data were calculated and statistical analyses wereperformed using SAS version9.0(SAS Institute, Cary, NC, USA). Data wereanalyzed by one-way analysis of variance with post hoc comparisons andBonferroni correction. To assess the effect of starch nanospheres solution versusRinger’s solution, the paired-sample t-test was used to compare normallydistributed data. Results were plotted using SPSS version15.0(SPSS Inc.,Chicago, IL, USA) for Windows. A P-value <0.05was considered statisticallysignificant.Results1. By the nano-particle size analyzer measurement of nano-starch microspheresparticle size of263.8±1.32nm. Starch polymer microspheres can be seen fromthe TEM map is more uniform in size and round.2. Below2%starch nanospheres solution, rats7days survival was100%.After groups of rats are made into a model of hemorrhagic shock, the SBP, DBPand MAP are obviously lower than base values, and HR is clearly faster than thebase value (P<0.05). Using Equal blood loss of2%starch nanospheres anti-shockfluid, HR, SBP and DBP and MAP are closer to base value level at different timepoints after recovery (P <0.05).For the2%starch nanospheres solution, Ringer’s solution and Voluven solution, changes in hemodynamics before and after resuscitation: SBP, DBP and MAPsignificantly drop and RR clearly becomes faster at shock than base values(P<0.05). After resuscitation in2%starch nanospheres solution and Voluvensolution HR, SBP, DBP and MAP at each time point get close to base values(P>0.05). However, for the Ringer’s solution, MAP after resuscitation at eachtime point are all evidently lower than the2%starch nanospheres solution andVoluven solution (P<0.05). PH, PaCO2, PaO2and SaO2change: before and endof the shock each index is no statistical difference in every groups (P>0.05).After resuscitation60min,90min, pH and PaCO2are no statistical difference (P>0.05). After resuscitation PaO2, SaO2in2%starch nanospheres solution andVoluven groups are no statistical difference (P>0.05).2%starch nanospheressolution and Voluven groups are increased significantly than LR liquid group(P <0.05). BE in the LR group was significantly lower than the2%starchnanospheres solution and Voluven group (P <0.05); Lac in LR group issignificantly higher than the2%starch nanospheres solution and Voluven groups(P <0.05). After resuscitation2%starch nanospheres solution and Voluvengroups, BE and Lac are no statistical difference (P>0.05).Conclusion1. Experimental synthesis of starch microspheres（263.8±10.05nm） with narrowsize distribution, concentrated. No part of the large particle size, no damage to thecoagulation of renal function, is more easily degradable, increased security, thediameter of the blood rheology requirements.2. After resuscitation,2%starch nanospheres anti-shock fluid could recover HR,SBP, DBP, MAP, pH, PCO2, PO2, SaO2, BE and Lac to baseline levels better. Ithas a better expansion effect, can radically improve hemodynamics, increaseeffective circulatory blood volume, improve systematic capillary leak syndrome and improve shocks resulted from a shortage of effective circulatory bloodvolume. It can reach the required blood pressure at low volume, to help keepingblood circulation and protecting vital organs.3. Starch nanospheres solution has better expansion. It less disturbs the bodyenvironment, so it is able to create favorable conditions and win precious time forsubsequent rescue and treatment.