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Disturbances of the hypothalamic-pituitary-adrenal axis and plasma electrolytes during experimental sepsis.doc

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Disturbances of the hypothalamic-pituitary-adrenal axis and plasma electrolytes during experimental sepsis

Flierletal.AnnalsofIntensiveCare2011,1:53 /content/1/1/53 RESEARCH OpenAccess Disturbancesofthehypothalamic-pituitary- adrenalaxisandplasmaelectrolytesduring experimentalsepsis MichaelAFlierl1,DanielRittirsch2,4,SebastianWeckbach1,MarkusHuber-Lang3,KyrosIpaktchi1,PeterAWard4and PhilipFStahel1,5* Abstract Background:Sepsiscontinuestobeapoorlyunderstoodsyndromewithahighmortalityrate.Whileweare beginningtodeciphertheintricateinterplayoftheinflammatoryresponseduringsepsis,thepreciseregulationof thehypothalamic-pituitary-adrenal(HPA)axisanditsimpactonelectrolytehomeostasisduringsepsisremains incompletelyunderstood. Methods:SepsiswasinducedinadultmaleSprague-Dawleyratsbycecalligationandpuncture(CLP).Plasma sampleswereobtainedasafunctionoftime(6-48hrs)afterCLPandcomparedwithhealthyanimals(negctrl). Sampleswereanalyzedforadrenocorticotropin(ACTH),corticosterone,andaldosteronelevels,aswellas concentrationsofsodium(Na+),potassium(K+),chloride(Cl-),andmagnesium(Mg2+). Results:ACTHlevelswerefoundtobesignificantlyreduced6-24hrsafterCLPincomparisontobaselinelevelsand displayedgradualrecoveryduringthelatercourse(24-48hrs)ofsepsis.Plasmacorticosteroneconcentrationsexhibited abell-shapedresponse,peakingbetween6and12hrsfollowedbyrapiddeclineandconcentrationsbelownegative controllevels48hrsafterinjury.Aldosteronelevelsinsepticanimalswerecontinuouslyelevatedbetween6and48hrs. WhereasplasmaNa+levelswerefoundtobepersistentlyelevatedfollowingCLP,levelsofK+,Cl-andMg2+were significantlyreducedasafunctionoftimeandgraduallyrecoveredduringthelatercourseofsepsis. Conclusions:CLP-inducedsepsisresultedindynamicchangesofACTH,corticosterone,andaldosteronelevels.In addition,electrolytelevelsshowedsignificantdisturbancesafterCLP.Theseelectrolyteperturbationsmightbe evokedbyadownstreameffectoradysfunctionalHPA-axisresponseduringsepsisandcontributetosevere complicationsduringsepsis. Introduction improvement [11]. Todate, the only clearly beneficial Sepsisremainsanenigmatic,poorlyunderstooddisease[1].