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TopicalTranexamicAcidDoesNotAffectElectrophysiologicorNeurovascularSciaticNerveMarkersinanAnimalModel 局部使用氨甲环酸不会影响动物模型坐骨神经的电生理或神经血管标记物的表达 RanSchwarzkopfMD,MSc,PhucDangMD,MicheleLuu,TahseenMozaffarMD,RanjanGuptaMD Abstract BackgroundTranexamicacidisasafeandeffectiveantifibrinolyticagentusedsystemicallyandtopicallytoreducebloodlossandtransfusionrateinpatientshavingTKAorTHA.Asthehipdoesnothaveadefinedcapsule,topicalapplicationoftranexamicacidmayentirelyenvelopthesciaticnerveduringTHA.Accidentalapplicationoftranexamicacidontothespinalcordinspinalanesthesiahasbeenshowntoproduceseizures;therefore,wesoughttoinvestigateiftopicalapplicationoftranexamicacidonthesciaticnervehasadeleteriouseffect. 摘要 背景氨甲环酸是一种安全有效的抗纤维蛋白溶解剂，全身和局部使用可减少TKA或THA患者的失血和输血率。由于髋关节没有明确的关节囊，全髋关节置换术中局部使用的氨甲环酸可能会完全包裹坐骨神经。腰麻中意外将氨甲环酸用于脊髓，已被证明会导致惊厥发作；因此，我们试图研究局部应用氨甲环酸是否会对坐骨神经造成伤害。 Questions/purposesWeexploredwhethertherewereanyshort-orlong-termalterationsin(1)electrophysiologicmeasures,(2)macrophagerecruitment,or(3)blood-nervebarrierpermeability.Ourhypothesiswasthatlocalapplicationoftranexamicacidwouldhaveatransienteffectornoeffectonhistologicfeaturesandfunctionofthesciaticnerve. 问题/目的：我们探讨（1）电生理监测，（2）巨噬细胞募集，或（3）血-神经屏障通透性是否存在短期或长期改变。我们假设局部应用氨甲环酸会对坐骨神经的组织学特征和功能产生短暂影响或没有影响。 MethodsWeusedaratprotocoltomodelsciaticnerveexposureinTHAtodeterminetheeffectsoftranexamicacidonneuralhistologicfeaturesandfunction.Weevaluated35ratsbythedorsalglutealsplittingapproachtoexposethesciaticnervefortopicaluseofcontrolandtranexamicacid.WeevaluatedEMGchanges(distallatency,amplitude,nerveconductionvelocity),histologicsignsofnerveinjuryviamacrophagerecruitment,andchangesinblood-nervebarrierpermeabilityatearly(4days)andlate(1month)timesaftersurgery,afterapplicationofsubtherapeutic(1mg/kgbodyweight[1.6mg]),therapeutic(10mg/kg[16mg]),andsupratherapeutic(mg/kg[mg])concentrationsoftranexamicacid.Differencesinblood-nervebarrierpermeability,macrophagerecruitment,andEMGbetweennormalandtranexamicacid-treatednerveswerecalculatedusingone-wayANOVA,withNewman-Keulsposthocanalyses,ateachtime.Aposthocpowercalculationshowedthatwiththenumbersavailable,wehad16%powertodetecta50%differenceinEMGchangesbetweenthecontrol,1mg/kggroup,10mg/kggroup,andmg/kggroup. 方法采用大鼠全髋关节置换术坐骨神经暴露模型，观察氨甲环酸对坐骨神经组织学特征和功能的影响。35只大鼠，背侧臀裂入路，解剖显露坐骨神经，设局部使用氨甲环酸组和空白对照组。术后早期（4天）和晚期（1个月）进行肌电图（检测远端潜伏期、振幅、神经传导速度）、巨噬细胞募集引起的神经损伤的组织学特征以及血神经屏障通透性检查。氨甲环酸组再分三个亚组：亚治疗剂量组（1mg/kg体重[1.6mg]）、治疗剂量组（10mg/kg[16mg]）和超治疗剂量组（mg/kg[mg]）。每次使用单因素方差分析和Newman-Keuls事后检验计算正常对照组神经和氨甲环酸处理组神经之间血神经屏障通透性、巨噬细胞募集和肌电图的差异。事后检验效能计算表明，根据现有数据，能够检验对照组、1mg/kg组、10mg/kg组和mg/kg组之间肌电图变化有50%差异的效能为16%。 ResultsAttheearlyandlatetimes,withthenumbersavailable,therewerenodifferencesinEMGexceptfordistallatencyat4days,macrophagerecruitment,orchangesinblood-nervebarrierbetweencontrolratsandthosewithtranexamicacid-treatednerves.Thedistallatencyinthe1mgtranexamicacid-treatedanimalsat4dayswas1.06±0.15ms(p=0.versusallothergroups,95%CI,0.89–1.25),whereasthedistallatenciesinthecontrol,the10mg/kg,andmg/kgtranexamicacidtreatedanimalswere0.83±0.11,0.89±0.05,and0.87±0.13,respectively.Distallatencieswerenotincreasedinanyofthegroupsat1monthwiththenumbersavailable(0.81±0.10,0.89±0.03,0.81±0.06,and0.83±0.08ms,respectively,forcontrols;1mg/kg,10mg/kg,andmg/kgforthetranexamicacid-treatedgroups). 结果对照组与经氨甲环酸处理组在早期和晚期，除第4天的远端潜伏期、巨噬细胞募集或血神经屏障改变外，肌电图无明显差异。1mg氨甲环酸处理组在第4天的远端潜伏期为1.06±0.15ms（与所有其他组相比，p=0.，95%可信区间为0.89–1.25），而对照组、10mg/kg和mg/kg氨甲环酸处理组的远端潜伏期分别为0.83±0.11、0.89±0.05和0.87±0.13。1个月时，任何一组的远端潜伏期均未增加（对照组分别为0.81±0.10、0.89±0.03、0.81±0.06和0.83±0.08ms；氨甲环酸处理组分别为1mg/kg、10mg/kg和mg/kg）。 ConclusionInourinvivoratmodelstudy,tranexamicaciddidnotappeartohaveanyclinicallyrelevanteffectonthesciaticnerveresultingfromtopicaladministrationupto1month.However,becauseourstatisticalpowerwaslow,thesedatashouldbeconsideredhypothesis-generatingpilotdataforlarger,more-definitivestudies. 结论在我们活体大鼠模型研究中，局部给药1个月后，氨甲环酸对坐骨神经似乎没有任何临床相关影响。然而，由于我们的统计效能较低，这些数据应被视为产生假设的预实验数据，以便于未来进行更大规模、更明确的研究。 ClinicalRelevanceTopicaltranexamicacidiseffectiveindecreasingpatientbloodlossduringTHA,andresultsfromourinvivoratmodelstudysuggesttheremaybenoelectrophysiologicandhistologiceffectsonthesciaticnerve,withthenumbersavailable,upto1month. 临床相关性局部使用氨甲环酸可有效减少全髋关节置换术中患者的失血量，我们的活体大鼠模型研究结果表明，在1个月内，可能不会对坐骨神经的电生理和组织学产生影响。 Introduction StudieshaveshownthattranexamicacidisaneffectiveantifibrinolyticagentthatmaybeusedsystemicallyinpatientsundergoingTKAorTHA[1,2,4,9,14,19,26,33,37,39].Tranexamicacid(Cyklokapron1,PfizerInc,NewYork,NY,USA),asyntheticinhibitoroffibrinolysis,blocksthelysine-bindingsiteofplasminogenandtherebyservesto |
