心肌缺血治疗

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EffectsofOPonMyocardialInfarctSizeandNoReflowinaRatMyocardialIschemia/ReperfusionModelCardiovasc?Drugs?TherOriginalArticleEarlyRecent,Feb08,./s---7本文由“天纳”临床学术信息人工智能系统自动翻译点击文末“阅读原文”下载本文PDFPurposeThepresentstudywastodeterminewhetherOPcouldlimitmyocardialinfarctionsizeandtheno-reflowphenomenoninaratmyocardialischemia/reperfusionmodel.本研究旨在探讨OP对大鼠心肌缺血再灌注模型心肌梗死面积及无再流现象的影响。MethodsRatheart–isolatedmitochondria(RHM)wereusedtoinvestigatemitochondrialrespirationandmitochondrialreactiveoxygenspecies(mtROS)generationbothinnormalconditionsandinischemia/reperfusion-mimickingconditions(usinghighconcentrationsofsuccinate).Humanskeletalmusclemyoblasts(HSMM)inculturewereusedtoinvestigatethecellularintermittentdeprivationinenergysubstratesandoxygenasreportedinischemia/reperfusionconditions.Invivo,ratswereanesthetizedandsubjectedto30?minofleftcoronaryarteryocclusionfollowedby3?hofreperfusion.RatswererandomizedtoreceiveOPasanintravenousinfusionstartingeither5?minpriortocoronaryarteryocclusion(preventive),or5?minpriortoreperfusion(curative),ortoreceivevehiclestarting5?minpriortocoronaryarteryocclusion.Infusionscontinueduntiltheendofthestudy(3?hofreperfusion).用大鼠心脏离体线粒体(RHM)研究正常和模拟缺血/再灌注条件下(使用高浓度琥珀酸)线粒体呼吸和线粒体活性氧(mtROS)的产生。以体外培养的人骨骼肌成肌细胞(HSMM)为研究对象,研究了缺血/再灌注条件下细胞能量底物和氧的间歇性剥夺。在体内,大鼠被麻醉,左冠状动脉闭塞30min,再灌注3h。将大鼠随机分为两组,一组在冠状动脉闭塞前5分钟(预防性)或再灌注前5分钟(治疗性)开始静脉输注OP,另一组在冠状动脉闭塞前5分钟开始静脉输注载体。持续输注直至研究结束(再灌注3小时)。ResultsRHMtreatedwithOPshowedaconcentration-dependentreductionofsuccinate-inducedmtROSgeneration.InHSMMcells,OPtreatment(5–10?μM)during48Hpreventedthereductioninthesteady-statelevelofATPmeasuredjustafterreperfusioninjuriesanddecreasedthemitochondrialaffinitytooxygen.Invivo,myocardialinfarctsize,expressedasthepercentageoftheischemicriskzone,wassignificantlylowerintheOP-treatedpreventivegroup(44.5?±?2.9%)versusthatinthevehiclegroup(57.0?±?3.6%;p??0.05),withanon-significanttrendtowardasmallerinfarctsizeinthecurativegroup(50.8?±?3.9%).TheareaofnoreflowasapercentageoftheriskzonewassignificantlysmallerinboththeOP-treatedpreventive(28.8?±?2.4%;p?=?0.vsvehicle)andcurativegroups(30.1?±?2.3%;p?=?0.04vsvehicle)
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