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Effect of erythropoietin on level of circulating endothelial progenitor cells and outcome in patients after acute ischemic stroke.doc

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Effect of erythropoietin on level of circulating endothelial progenitor cells and outcome in patients after acute ischemic stroke

Yipetal.CriticalCare2011,15:R40 /content/15/1/R40 RESEARCH OpenAccess Effectoferythropoietinonlevelofcirculating endothelialprogenitorcellsandoutcomein patientsafteracuteischemicstroke Hon-KanYip1,2*?,Tzu-HsienTsai1,Hung-ShengLin3,Shu-FangChen3,Cheuk-KwanSun2,4,SteveLeu1,2, Chun-ManYuen5,Teng-YeowTan3,Min-YuLan3,Chia-WeiLiou3,Cheng-HsienLu3,Wen-NengChang3? Abstract Introduction:Erythropoietin(EPO)enhancesthecirculatinglevelofendothelialprogenitorcells(EPCs),whichhas beenreportedtobeassociatedwithprognosticoutcomeinischemicstroke(IS)patients.Theaimofthisstudywas toevaluatethetimecourseofcirculatingEPClevelandtheimpactofEPOtherapyonEPClevelandclinical outcomeinpatientsafteracuteIS. Methods:Intotal,167patientswereprospectivelyrandomizedtoreceiveeitherEPOtherapy(group1)(5,000IU eachtime,subcutaneously)at48hand72hafteracuteIS,orserveasplacebo(group2).Thecirculatinglevelof EPCs(double-stainedmarkers:CD31/CD34(E1),CD62E/CD34(E2)andKDR/CD34(E3))wasdeterminedusingflow cytometryat48handondays7and21afterIS.EPClevelwasalsoevaluatedoncein60healthyvolunteers. Results:CirculatingEPC(E1toE3)levelat48hafterISwasremarkablyhigherinpatientsthanincontrolsubjects (P0.02).At48handonDay7afterIS,EPC(E1toE3)leveldidnotdifferbetweengroups1and2(allP0.1). However,byDay21,EPC(E1toE3)levelwassignificantlyhigheringroup1thaningroup2(allP0.03). Additionally,90-dayrecurrentstrokeratewasnotablyloweringroup1comparedwithgroup2(P=0.022). MultivariateanalysisdemonstratedthatEPOtherapy(95%confidenceinterval(CI),0.153to0.730;P=0.006)and EPC(E3)(95%CI,0.341to0.997;P=0.049)levelsweresignificantlyandindependentlypredictiveofareduced90- daymajoradverseneurologicalevent(MANE)(definedasrecurrentstroke,NationalInstitutesofHealthStrokescale ≥8,ordeath). Conclusions:EPOtherapysignificantlyimprovedcirculatingEPCleveland90-dayMANE. Trialregistrationnumber:ISRCTN:ISRCTIntroduction Recently, thrombolysis usingtissue plasminogenacti- Stroke, agrowing epidemic, remains aleading causeof vator(tPA),amoreaggress