简介：Previousstudieshavedemonstratedthatendogenousnorepinephrine(NE)playsanimportantroleinthemediationofischemicpreconditioning.ThepresentstudyisdesignedtodeterminewhetherNEisalsoinvolvedinmediationoftheprotectiveeffectsofpostconditioning.MethodsTheratheartswererapidlyexcisedunderanesthesiaandattachedtoaLangendorffapparatusviatheaortaforretrogradeperfusionwithKrebs-Henseleitbuffersolution.Allheartsweresubjectedto30minofleftcoronaryarteryocclusionfollowedby60minofreperfusion,exceptthecontrolgroup.Animalswererandomlydividedinto5groupsasfollows:①controlgroup,theheartswereunderwentsameprocedureswithoutischemicinsult;②ischemiareperfusiongroup,theleftcoronaryarterywasoccludedfor30minandfollowedby60minofreperfusion;③ischemicpostconditioning(IPost)group,immediatelyattheonsetofreperfusion,theheartwasinitiatedwith1minoffullcoronaryflow,followedby1minofre-occlusion,repeatedforatotalofthreecycles;④IPostplusprazosingroup,theheartwasperfusedwithprazosinfor10minbeforeischemia;⑤IPostplusreserpinegroup,asingledoseofreserpinewasadministeredbyi.m.injection,24hoursbeforetheexperiment.Coronaryflowwasmeasuredbytimedcollectionofcoronaryeffluentandsampleofcoronaryeffluentat5minofreperfusionwerecollectedforthemeasurementofcreatinekinase(CK).Infarctsizeandriskareaweredeterminedattheendofexperiments.Results30minofischemiaandfollowedby60minofreperfusioncausedasignificantdecreaseincardiacfunctionandasignificantincreaseinCKreleaseandinfarctsize.Postconditioningwiththreecyclesof1-minischemiaand1-minreperfusionmarkedlyimprovedcardiacfunctionandreducedCKreleaseandinfarctsize.However,thecardioprotectionaffordedbypostconditioningwasabolishedbyprazosin(10-6M),aselectiveα1adrenergicreceptorantagonist,orbypretreatmentwithreserpine(0.45mg·

简介：Thesympatheticnervoussystemplaysacardinalroleinregulatingcardiacfunctionthroughreleasingtheneurotransmitternorepinephrine(NE).Incomparisonwithcentralnervoussystem,themolecularmechanismofNEuptakeinmyocardiumisnotclear.Inpresentstudy,weprovedthatinrattheCNStypeofNEtransporter(NET)wasalsoexpressedinmiddlecervical-stellateganglioncomplex(MC-SGcomplex)whichisconsideredtocontroltheactivityofheart,butnotexpressedinmyocardium.TheresultsalsoshowedthatNETexpressionlevelinrightganglionwassignificantlyhigherthanintheleft,renderingthegreatercapacityofNEuptakeinrightventricle,afactwhichmaycontributetothemaintenanceofrightventricularfunctionunderpathologicstate.

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简介：Objective:Toinvestigatetheunderlyingneurobiologicalmechanismoftheprotectiveeffectofelectroacupuncture(EA)duringcerebralischemia-reperfusion(CI-R).Methods:Inthefirstpartofthestudy,15SDratswereevenlyrandomizedintocontrolgroup,CI-R-48hmodelgroupandCI-R-48h+EAgroup.ThecorticalapoptosisandexpressionofBcl-2andBaxproteinsineachgroupweredetectedbyflowcytometer(FCM).Inthesecondpartofthestudy,75SDratswereevenlyrandomizedintocontrol,CI-R-3min,CI-R-3min+EA,CI-R-48handCI-R-48h+EAgroups.Corticalnorepinephrine(NE)concentrationwasdetectedbyfluorescencespectrometer.CI-Rmodelwasestablishedbyocclusionofthebilateralcommoncarotidarteriesandreperfusion.EA(4～16Hz,1～3V)wasappliedafterreperfusionrespectively.Results:Inthefirstpartofthisstudy,resultsindicatedthatthenumberoftheapoptoticneuronsandtheapoptosisrateofCI-R-48hgroupweresignificantlyhigherthanthoseofcontrolgroup;whilecomparisonbetweenCI-R-48h+EAandCI-R-48hgroupsshowedthatthenumberoftheapoptoticneuronsandtheapoptosisrateoftheformergroupweresignificantlylowerthanthoseofthelatergroup(P<0.05).Incomparisonwithcontrolgroup,afterCI-48h,Baxexpressionwasup-regulatedsignificantlyandBcl-2down-regulatedmarkedly(P<0.05).ComparisonbetweenCI-R-48handCI-R-48h+EAgroupindicatedthatBaxexpressionofthelatergroupwassignificantlylowerthanthatoftheformergroup,whileBcl-2expressionofCI-R-48h+EAgroupwassignificantlyhigherthanthatofCI-R-48hgroup(P<0.05),suggestingthatEAcouldreverseCIinducedreactionsofthesetwoindexes.Inthesecondpartofthestudy,incomparisonwithcontrolgroup,NEconcentrationincerebralcortexofCI-R-3mingroupincreasedsignificantly(P<0.05);whileNEcontentofCI-R-3min+EAgroupwassignificantlylowerthanthatofCI-R-3mingroup(P<0.05).NosignificantdifferencewasfoundbetweenCI-R-3mingroupandcontrolgroupincorticalNEl

简介：AbstractBackground:The peripheral perfusion index (PI), as a real-time bedside indicator of peripheral tissue perfusion, may be useful for determining mean arterial pressure (MAP) after early resuscitation of septic shock patients. The aim of this study was to explore the response of PI to norepinephrine (NE)-induced changes in MAP.Methods:Twenty septic shock patients with pulse-induced contour cardiac output catheter, who had usual MAP under NE infusion after early resuscitation, were enrolled in this prospective, open-label study. Three MAP levels (usual MAP -10 mmHg, usual MAP, and usual MAP +10 mmHg) were obtained by NE titration, and the corresponding global hemodynamic parameters and PI were recorded. The general linear model with repeated measures was used for analysis of variance of related parameters at three MAP levels.Results:With increasing NE infusion, significant changes were found in MAP (F = 502.46, P < 0.001) and central venous pressure (F = 27.45, P < 0.001) during NE titration. However, there was not a significant and consistent change in continuous cardiac output (CO) (F = 0.41, P = 0.720) and PI (F = 0.73, P = 0.482) at different MAP levels. Of the 20 patients enrolled, seven reached the maximum PI value at usual MAP -10 mmHg, three reached the maximum PI value at usual MAP, and ten reached the maximum PI value at usual MAP +10 mmHg. The change in PI was not significantly correlated with the change in CO (r = 0.260, P = 0.269) from usual MAP -10 mmHg to usual MAP. There was also no significant correlation between the change in PI and change in CO (r = 0.084, P = 0.726) from usual MAP to usual MAP +10 mmHg.Conclusions:Differing MAP levels by NE infusion induced diverse PI responses in septic shock patients, and these PI responses may be independent of the change in CO. PI may have potential applications for MAP optimization based on changes in peripheral tissue perfusion.

简介：Thenorepinephrinetransporter(NET)isamemberoftheNa^+/Cl^-dependentneurotransmittertransporterfamilyandconstitutesthetargetofseveralclinicallyimportantantidepressants.TodelineatethecriticalaminoacidresiduesandthefunctionofC-terminalinregulatingtransportactivityofNET,hereweconstructedtwositemutants(V70F,F72V;V70I,F72V)andoneC-terminaltruncatedmutant(Δ611-617).ThewildtypeandmutantsofNETwereexpressedinXenopusoocytesbyinjectionoftheircRNA.Wefoundthatallofthesemutantslosttheirtransportactivity.TheseresultsindicatethattheaminoacidresiduesofV70andF72,andthelastsevenaminoacidsofC-terminalareessentialtothetransportactivityofNET.

简介：AbstractBackground:In recent years, norepinephrine has attracted increasing attention for the management of maternal hypotension during elective cesarean section with spinal anesthesia. Intermittent bolus is a widely used administration paradigm for vasopressors in obstetric anesthesia in China. Thus, in this randomized, double-blinded study, we compared the efficacy and safety of equivalent bolus norepinephrine and phenylephrine for rescuing maternal post-spinal hypotension.Methods:In a tertiary women’s hospital in Nanjing, China, 102 women were allocated with computer derived randomized number to receive prophylactic 8 μg norepinephrine (group N; n = 52) or 100 μg phenylephrine (group P; n = 50) immediately post-spinal anesthesia, followed by an extra bolus of the same dosage until delivery whenever maternal systolic blood pressure became lower than 80% of the baseline. Our primary outcome was standardized maternal cardiac output (CO) reading from spinal anesthesia until delivery analyzed by a two-step method. Other hemodynamic parameters related to vasopressor efficacy and safety were considered as secondary outcomes. Maternal side effects and neonatal outcomes were collected as well.Results:Compared to group P, women in group N had a higher CO (standardized CO 5.8 ± 0.9 vs. 5.3 ± 1.0 L/min, t = 2.37, P = 0.02) and stroke volume (SV, standardized SV 73.6 ± 17.2 vs. 60.0 ± 13.3 mL, t = 4.52, P < 0.001), and a lower total peripheral resistance (875 ± 174 vs. 996 ± 182 dyne·s/cm5, t = 3.44, P < 0.001). Furthermore, the incidence of bradycardia was lower in group N than in group P (2% vs. 14%, P= 0.023), along with an overall higher standardized heart rate (78.8 ± 11.6 vs. 75.0 ± 7.3 beats/min, P = 0.049). Other hemodynamics, as well as maternal side effects and neonatal outcomes, were similar in two groups (P > 0.05).Conclusions:Compared to equivalent phenylephrine, intermittent bolus norepinephrine provides a greater CO for management of maternal hypotension during elective cesarean section with spinal anesthesia; however, no obvious maternal or neonatal clinical advantages were observed for norepinephrine.