Ntu 1: Cov Tswv Yim Txog Kev Tiv Thaiv Neuroprotection Thaum Ntxov Kev Kho Mob: Lub Xeev Ntawm Kev Tshawb Fawb

ali.ma@wecistanche.com

Palesa Motshabi-Chakane 1, Palesa Mogane 1, Jacob Moutlana 1, Gontse Leballo-Mothibi 1, Sithandiwe Dingezweni 1, Dineo Mpanya 2 and Nqoba Tsab Ntawv 2,*

Department of Anaesthesiology, Kws qhia ntawv ntawm Health Sciences, Tsev Kawm Ntawv Kho Mob,

University of the Witwatersrand, Johannesburg 2193, South Africa; Palesa.Motshabi@wits.ac.za (PM-C.); moganep@gmail.com (PM); drhlamatsi@gmail.com (JM); gleballomothibi@gmail.com (GL-M.); sdingezweni@ymail.com (SD)

Department of Internal Medicine, Division of Cardiology, Kws qhia ntawv ntawm Health Sciences,

Tsev Kawm Ntawv Kho Mob, University of the Witwatersrand, Johannesburg 2193, South Africa;

Dineo.Mpanya@wits.ac.za

Cov ntaub ntawv: Nqoba.Tsabedze@wits.ac.za

Citation: Motshabi-Chakane, P.; Mogane, P.; Moutlana, J.;

Leballo-Mothibi, G.; Dingezweni, S.; Mpanya, D.; Tsabedze, N. ContemporaryNeuroprotectionCov tswv yim thaum lub sij hawm phais plawv: Lub Xeev ntawm Kev Tshawb Fawb. Int. J. Environ. Res. Public Health 2021, 18, 12747. https://doi.org/10.3390/ ijerph182312747

Academic Editor: Paul B. Tchounwou

Cistanche tubulosa hmoov muaj cov nyhuv neuroprotective zoo heev

Abstract: Kev phais qhib lub plawv yog qhov ua rau muaj kev raug mob neuronal nyob rau hauv lub xeev perioperative, nrog rau qee cov neeg mob ua rau muaj teeb meem ntawm lub paj hlwb thiab delirium. Neurological fallout muab lub nra hnyav rau kev noj qab haus huv ntawm tus neeg mob, lawv tsev neeg, thiab kev noj qab haus huv. Ntau qhov kev sim randomized tswj (RCTs) tau sim txheeb xyuas cov tswv yim kho mob thiab kev cuam tshuam uas txo qis kev mob nkeeg thiab kev tuag nyob rau hauv cov neeg mob uas muaj teeb meem perioperative neurological teeb meem. Txawm li cas los xij, tseem tsis tau muaj kev pom zoo rau lub tswv yim zoo tshaj plaws uas ua rau cov neeg mob tau txais txiaj ntsig zoo dua qub, xws li cov qauv tsim.neurotiv thaivCov txheej txheem tsis muaj nyob rau hauv ib qho tseem ceeb ntawm cov chaw tshuaj loog. Qhov kev tshuaj xyuas no yog los tham txog cov pov thawj tam sim no rau kev tiv thaiv thiab tswj cov xwm txheej txaus ntshai rau kev raug mob neuronal, cov txheej txheem ntawm kev raug mob, thiabneurotiv thaivkev cuam tshuam uas ua rau cov neeg mob tau txais txiaj ntsig zoo dua. Tsis tas li ntawd, cov ntsiab lus ntawm RCTs uas twb muaj lawm thiab cov kev tshawb fawb soj ntsuam loj raug tshuaj xyuas los txiav txim siab seb cov tswv yim twg tau txais kev txhawb nqa los ntawm kev tshawb fawb thiab uas tsis muaj pov thawj tseeb. Peb tau tsim tias tag nrho cov pov thawj rau pharmacologicalneurotiv thaivtsis muaj zog. Feem ntau cov tswv yim tiv thaiv neuroprotective yog raws li kev tshawb fawb tsiaj, uas tsis tuaj yeem ua tiav tag nrho rau tib neeg cov pej xeem, thiab tseem tsis muaj kev pom zoo rau qhov zoo.neuroprotectivecov tswv yim rau cov neeg mob kho mob plawv. Cov kev tshawb fawb loj multicenter siv universal standardized neurological fallout txhais lus tseem yuav tsum tau soj ntsuam cov txiaj ntsig zoo ntawm cov uas twb muaj lawm.neuroprotectivecov txheej txheem.

Ntsiab lus: neuroprotection; cerebrovascular; delirium; kev phais mob plawv; mob tshuaj loog

1. Taw qhia

Neuroprotectionencompasses cov tswv yim uas khaws cov qauv neuronal thiab kev ua haujlwm. Neurological fallout yuav tsum tau tiv thaiv nyob rau hauv tag nrho cov neeg mob nyob rau hauv ib qho kev phais, tshwj xeeb tshaj yog cov xa mus rau kev phais plawv. Piv txwv li, hauv kev tshawb fawb uas muaj 10,250 tus neeg mob uas tau phais plawv, 221 (2 feem pua) tau ntsib kev mob stroke tom qab, thiab lub sijhawm mus pw hauv tsev kho mob tau ntev dua rau cov neeg mob no piv rau cov tsis muaj mob stroke tom qab (10 vs. 16 hnub, p <0.001) [1].="" ntau="" qhov="" kev="" sim="" ntsuas="" randomized="" (rcts)="" tau="" tshawb="" xyuas="" qhov="" ua="" tau="" zoo="" ntawm="" cov="" tshuaj="" tshuaj="" thiab="" cov="" tshuaj="" tsis="" yog="" tshuaj="" uas="" txo="" cov="" kev="" raug="" mob="" ntawm="" lub="" paj="" hlwb="" thaum="" lub="" sijhawm="" thiab="" tom="" qab="" phais="" plawv="" [2–4].="" txawm="" li="" cas="" los="" xij,="" tseem="" muaj="" kev="" tsis="" sib="" haum="" xeeb="" ntawm="" qhov="" pom="">neurotiv thaivlub tswv yim uas ua rau cov neeg mob tau txais txiaj ntsig zoo dua.

Qhov kev tshuaj xyuas no yog los tham txog cov pov thawj tam sim no rau kev tiv thaiv thiab tswj cov xwm txheej txaus ntshai rau kev raug mob neuronal, cov txheej txheem ntawm kev raug mob, thiabneurotiv thaivkev cuam tshuam uas ua rau cov neeg mob tau txais txiaj ntsig zoo dua.

2. Cov ntaub ntawv thiab cov txheej txheem

Cov ntaub ntawv ntawm RCTs siv ntau yamneuroprotectiveCov neeg sawv cev tau txais tom qab ua cov ntaub ntawv tshawb fawb hauv PUBMED, Scopus thiab Google tus kws tshawb fawb. Cov kab tshawb nrhiav hauv qab no tau siv: (neurotiv thaivtswv yim ORneurotiv thaivLOSSIS pharmacological therapy OR non-pharmacological therapy) THIAB (kev phais plawv LOSSIS cardiopulmonary bypass phais) THIAB (kev txawj ntse tom qab phais lossis mob stroke lossis delirium lossis qaug dab peg) THIAB cov neeg laus. Peb suav nrog randomized tswj kev sim, kev tshuaj xyuas thiab kev tshuaj ntsuam xyuas meta tau luam tawm hauv 15 xyoo dhau los. Lub hom phiaj ntawm kev tshawb fawb cov ntaub ntawv yog nyob rau hauv pharmacological thiab non-pharmacologicalneuroprotectivecov tswv yim (Table 1). Qhov twg muaj kev tshuaj xyuas los yog kev tshuaj ntsuam meta-kev soj ntsuam ntawm RCTs ntawm kev cuam tshuam muaj, cov no tau nyiam tshaj tawm rau ntau dua li tus neeg RCTs.

Table 1. Cov ntsiab lus ntawm randomized tswj kev sim sib piv cov kev cuam tshuam rau kev kho tus qauv rauneurotiv thaivhauv kev phais mob plawv.

Cov ntawv luv: RCT, randomized tswj sim; CPB, cardiopulmonary bypass; POCD, postoperative kev txawj ntse tsis ua hauj lwm; MM-RR, Mantel-Haenszel txaus ntshai piv; CI, kev ntseeg siab; LOSSIS, odds ratio; TIVA, tag nrho intravenous anesthesia; WMD, hnyav txhais tau tias sib txawv; POD, postoperative delirium; CABG, coronary artery bypass grafting; MAP, txhais tau tias arterial siab; SD, tus qauv sib txawv. Lidocaine * bolus ntawm 1-1.5 mg / kg. Infusion ntawm 2-4 mg / kg / teev: nyob ntawm qhov chaw 'protocol. Lidocaine plasma concentration nyob ntawm 7 thiab 30 μmol / L. Magnesium * koob tshuaj tsawg kawg yog 2 g hauv 24 teev ntawm lub plawv nres lossis phais plawv. Rivastigmine *, 1.5 mg koob tshuaj 8 teev, txij thaum yav tsaus ntuj ua ntej ua haujlwm; tag nrho ntawm 22 koob tshuaj (txog hnub 6 tom qab phais). Sib sib zog nqus circulatory ntes (DHCA) nrog retrograde cerebral perfusion (RCP) *, txias rau nasopharyngeal kub ntawm 14.1 o C rau 20 o C. Tej thaj chaw deb ischemic preconditioning (RIPC)* los ntawm kev siv BP cuff nyob rau hauv lub sab sauv ceg nrog peb alternating voj voog. kev nce ntxiv (200 mmHg rau 5 min) thiab deflation rau 5 min (reperfusion). Cerebral oxygenation xyuas *: Cerebral deoxygenation ntu <60 feem="" pua="" ​​rau=""> 60s.

3. Qhov tshwm sim thiab qhov tshwm sim ntawm Neurological Deficit tom qab Kev phais plawv

Lub International Code of Nomenclature pom zoo rau lo lus "perioperative neurocognitive disorders" los piav txog ob qho tib si postoperative delirium (POD) thiab postoperative paub tsis meej / poob qis (POCD), nrog rau tom kawg tsis muaj Diagnostic and Statistical Manual of Mental Disorders 5 (DSM5) Cov txheej txheem rau kev kuaj mob [14,15]. Lwm cov lus siv dav dav siv yog "kev raug mob neurological tom qab phais plawv." Perioperative stroke, delirium, thiab encephalopathy yog qee yam ntawm cov paj hlwb ntawm kev phais plawv [16]. Qhov kev pheej hmoo ntawm mob stroke txawv nyob ntawm seb hom kev phais tau ua [17]. Piv txwv li, kev phais ob lossis triple valve yog txuam nrog 10 feem pua ​​​​ntawm kev pheej hmoo ntawm mob stroke, thaum qhov kev pheej hmoo qis dua rau cov neeg mob hu ua "taws-lub plawv", tseem hu ua "off-pump", coronary artery bypass graft (CABG) phais. [17].

Hauv kev txheeb xyuas meta-kev cuam tshuam nrog 174,969 tus neeg mob raug xa mus rau kev phais plawv, qhov sib koom ua ke ntawm kev mob stroke ntxov thiab qeeb yog txhua qhov tsawg dua 1 feem pua ​​[18]. Tsis tas li ntawd, delirium feem ntau tshwm sim hauv cov neeg laus, nrog qhov tshwm sim ntau dua ntawm 12 feem pua ​​[19]. Muaj qhov tsis txaus ntseeg ntawm cov kev tshawb fawb qhia txog cov teeb meem neurological tom qab kev phais mob plawv hauv cov neeg mob nyob hauv cov teb chaws tau nyiaj tsawg thiab nruab nrab (LMIC). Hauv daim duab qhia rov qab ntawm 1218 tus neeg mob sib law liag xa mus rau CABG phais hauv Johannesburg, tus nqi mob stroke perioperative yog 1.2 feem pua ​​[20]. Ntxiv mus, ib xyoos tom qab pib mob stroke, tus nqi txhua xyoo hauv cov phaus British ib tus neeg kwv yees li ntawm GBP 18,081, nce mus rau GBP 22,961 hauv cov neeg mob laus dua 84 xyoo [21]. Cov nqi kho mob siab no tsim nyog yuav tsum tau ceev nrooj rau cov tswv yim uas txo lub nra ntawm kev mob stroke tom qab phais plawv.

4. Kev pheej hmoo cuam tshuam nrog kev poob qis

Ntxiv nrog rau hom kev phais, qhov kev pheej hmoo mob stroke yog nce ntxiv rau cov neeg mob uas muaj kab mob cerebrovascular, kab mob peripheral vascular, ntshav qab zib, kub siab, keeb kwm ntawm kev phais plawv yav dhau los, kab mob ua ntej, kev phais mob ceev, cardio-pulmonary bypass (CPB) lub sijhawm. ntau tshaj 2 h, qhov xav tau rau intraoperative hemophiltration, thiab siab transfusion yuav tsum [18]. Kev pheej hmoo rau kev paub txog kev poob qis tom qab kev phais mob plawv yog multifactorial (Daim duab 1). Cov txiaj ntsig ntawm paj hlwb muaj ntau haiv neeg thiab yav dhau los tau muab faib ua Hom I (xws li mob stroke lossis tsis tuag, stupor, lossis coma thaum tso tawm) thiab Hom II, uas suav nrog kev paub txog kev ua haujlwm tsis zoo, nco tsis txaus, lossis qaug dab peg [22].

Daim duab 1. Kev pheej hmoo rau kev raug mob neuronal ua ntej, thaum, thiab tom qab phais plawv.

Kev ntsuam xyuas rau kev paub txog kev ua haujlwm yuav tsum ua ua ntej thiab tom qab kev ua haujlwm uas siv cov cuab yeej ntsuas kev paub txog kev txawj ntse. Tsis tas li ntawd, lub sij hawm ntawm kev ntsuam xyuas cuam tshuam tus nqi ntawm kev kuaj mob neurological raug mob tom qab phais plawv [23]. Kev kuaj mob ua tiav hauv 30 hnub tom qab kev phais muaj kev tsis sib haum xeeb xws li mob tom qab phais, thiab kev siv tshuaj yuav cuam tshuam rau cov qhab nia ntsuas [15]. Emergency delirium tshwm sim ua ntej, thaum lub sij hawm, los yog tom qab sawv los ntawm kev siv tshuaj loog, thaum lub sij hawm postoperative delirium tshwm sim 24-72 teev tom qab, thiab postoperative kev txawj ntse poob yuav tshwm sim lub lis piam mus rau lub hlis tom qab [15,24]. Feem ntau ntawm cov teeb meem kev pheej hmoo rau POCD muaj feem cuam tshuam rau lawv lub peev xwm cuam tshuam nrog cov hauv paus ntsiab lus ntawm kev tiv thaiv lub cev, xws li kev xa cov pa oxygen, cov khoom siv hauv nruab nrog cev, cov khoom noj khoom haus, cov khoom noj uas twb muaj lawm, thiab muaj cov tshuaj lom thaum lub sij hawm phais [25]. Kev tiv thaiv ntawm POCD tom qab phais plawv yog qhia txog kev nkag siab thiab tswj cov kev pheej hmoo no.

5. Mechanism ntawm mob hlwb

Lub mechanism ntawm kev phais mob ntsig txog lub hlwb raug mob yog complex thiab multifactorial. Cov txheej txheem feem ntau tshwm sim los ntawm ischemic ua rau cerebral hypoperfusion thiab embolism [26,27]. Ntxiv nrog rau qhov ua rau ischemic, cov lus teb ua paug, cerebral hyperthermia, hyperglycemia, perioperative anemia, thiab atrial fibrillation kuj tau cuam tshuam (Daim duab 2) [27].

Daim duab 2. Mechanisms ntawm lub hlwb raug mob.

5.1. Hloov Cerebral Perfusion

Cov teebmeem ntawm kev phais plawv thiab CPB ntawm cerebral perfusion tuaj yeem muab faib ua cerebral hypoperfusion thiab reperfusion. Cerebral hypoperfusion uas tshwm sim los ntawm kev txo qis hauv lub paj hlwb (CBF) thaum lub sij hawm CPB yog thawj qhov ua rau ischemic hlwb raug mob. Daim ntawv ntawm kev raug mob no tuaj yeem ua rau hnyav ntxiv los ntawm kev tsis pom zoo ntawm micro-emboli thaum lub sijhawm txo CBF. Hnub nyoog Advanced, kab mob cerebrovascular, thiab keeb kwm ntawm mob stroke ua rau muaj kev pheej hmoo ntawm cerebral hypoperfusion [26]. Lub sij hawm thaum ntxov ntawm CPB feem ntau yog txuam nrog lub sijhawm ntawm lub siab qis qis qis (MAP) thaum lub sij hawm cannula insertions thiab manipulation ntawm cov hlab ntsha loj ntawm lub plawv. Raws li qhov tshwm sim, cerebral hypoperfusion tuaj yeem tshwm sim, thiab cov ntshav ntws hauv thaj chaw dej hauv lub hlwb yuav ua rau txo qis. Txog rau thaum xaus ntawm CPB, cerebral reperfusion tshwm sim, ua rau lub cim ntawm cov pa dawb radicals [28]. Thaum lub sij hawm ischaemia / reperfusion raug mob, ntau yam txheej txheem thib ob tau pib thiab thaum kawg ua rau kev tuag ntawm cov neurons.

5.2. Hypoxia Related Cerebral Injury

Hypoxic tej yam kev mob tshwm sim thaum lub sij hawm ntawm cerebral hypoperfusion tshwm sim nyob rau hauv lub upregulation ntawm ntau yam molecules, xws li hypoxia-inducible factor (HIF) thiab sulfonylurea receptor 2A (SUR2A) protein, uas tom qab ntawd pib cov xwm txheej uas yuav ua rau muaj kev raug mob neuronal [28]. Ib qho kev poob qis hauv cov pa oxygen ua rau kev hloov pauv ntawm HIF mus rau hauv cov cell nucleus. HIF yog suav nrog ib qho thiab subunit. Lub subunit yog constitutively qhia. Txawm li cas los xij, nws sai sai degrades nyob rau hauv ib txwm oxygen concentrations. Tsis tas li ntawd, hypoxia yog cuam tshuam nrog kev poob qis hauv adenosine triphosphate (ATP) qib, uas ua rau tsis ua haujlwm ntawm ATP-dependent ion twj, nce hauv intracellular sodium thiab calcium ntau ntau, thiab thaum kawg cytoplasmic thiab mitochondrial o, uas tuaj yeem ua rau cell tuag. [28].

5.3. Reperfusion Related Cerebral Injury

Cov theem reperfusion yog txuam nrog reactive oxygen hom (ROS) ntau lawm, feem ntau nyob rau hauv mitochondria. ROS react nrog nitric oxide (NO) los tsim peroxynitrite. Cov molecule no yog heev reactive thiab nitrosylates proteins, ua rau neuronal kev ua haujlwm tsis zoo thiab raug mob hlwb [28].

5.4. Cerebral Macro- thiab Micro-Embolism

Kev phais mob plawv feem ntau ua rau muaj ntau yam khoom siv embolic. Raws li qhov loj me, emboli tuaj yeem sib txawv rau hauv macro-emboli, uas cuam tshuam cov hlab ntsha ntawm txoj kab uas hla ntawm 200 µm lossis ntau dua, thiab micro-emboli, uas ua rau cov hlab ntsha me me, cov hlab ntsha thiab cov hlab ntsha. Atherosclerotic plaques tshwm sim los ntawm lub aorta yog macro-emboli [26], whereas micro-emboli muaj gaseous emboli thiab biologic aggregates xws li thrombus, platelet aggregates thiab rog [26,28,29]. Emboli tshwm sim los ntawm cov khib nyiab tsis zoo xws li tawg ntawm polyvinyl chloride tubing thiab silicone antifoam tau tshaj tawm yav dhau los [29].

Txawm hais tias lub tshuab CPB muaj cov cuab yeej tiv thaiv, xws li cov ntxiab npuas [28], gaseous emboli tseem tuaj yeem nkag mus rau hauv CPB Circuit Court los ntawm venous cannulation, kev tswj hwm cov tshuaj thiab los ntawm qhov qhib lub plawv ntawm sab laug lub plawv [26]. Tsis tas li ntawd, kev tswj hwm ntawm lub aorta thaum lub sij hawm phais ua rau muaj kev pheej hmoo ntawm embolization txawm tias qhov tso tawm ntawm cov hlab ntsha hauv cov hlab ntsha [28,30]. Cerebral micro-embolism raws li lub tswv yim rau kev paub tsis meej yog kev txhawb nqa los ntawm kev muaj kev sib raug zoo ntawm cerebral macro/microemboli load thaum CPB thiab kev paub tsis meej hauv ntau yam kev tshawb fawb [26,31–34]. Tsis tas li ntawd, macro/micro-emboli tuaj yeem tshwm sim thaum lub sij hawm aortic decannulation, tshwj xeeb tshaj yog thaum tus neeg mob tsis tau txais kev kho mob anticoagulation txaus.

5.5. Inflammatory Teb

Cov txheej txheem inflammatory cuam tshuam nrog CPB ntxiv exacerbate neuronal injury [27]. Kev sib cuam tshuam ntawm cov neeg mob ntshav nrog CPB cov khoom xws li tubing, reservoirs, oxygenator thiab kev sib txuas ua rau muaj kev ua kom lub cev ua kom tiav, ua rau kev tso tawm ntawm pro-inflammatory cytokines xws li interleukin (IL)-6, IL. -8, IL-10, thiab qog necrosis factor-alpha (TNF ) [28,35]. Qhov no systemic inflammatory teb ua rau cov ntshav-hlwb barrier to, cerebral edema thiab thaum kawg cerebral derangement [28].

5.6. Cerebral Hyperthermia

Hyperthermia kuj tau tshaj tawm tias ua rau lub hlwb puas tsuaj nyob rau hauv ntau yam kev kho mob thiab tau pom tias yuav ua rau mob ntshav qab zib ntau dua tom qab ischemia. Cov teebmeem ntawm hyperthermia nyob rau hauv lub hlwb muaj feem xyuam rau hyperthermia-induced cell o thiab necrotic tuag nyob rau hauv cov ntaub ntawv ntawm kub heev [36]. Thaum lub sij hawm kev phais plawv ntawm CPB, cerebral hyperthermia yuav tshwm sim vim qhov sib thooj ntawm lub aortic cannula rau cov hlab ntsha hauv hlwb lossis qis dua lub hlwb los ntawm kev saib xyuas tus qauv [27].

5.7. Hyperglycemia

Qhov kev ntxhov siab cuam tshuam los ntawm CPB thiab hypothermia thaum lub sij hawm phais plawv ua rau cov ntshav qabzib nce siab txawm tias nyob hauv cov neeg mob uas tsis muaj ntshav qab zib [27]. Lub pathophysiology ntawm hyperglycemia tshwm sim los ntawm cerebral raug mob yog multifactorial. Hyperglycemia tsub kom reactive oxygen hom ntau lawm los ntawm cov protein kinase C-mediated txoj kev thiab nce zus tau tej cov nicotinamide adenine dinucleotide phosphate (NADPH) [37]. Cov hom pa oxygen reactive tuaj yeem ua rau kev tuag neuronal, raws li tau piav qhia ua ntej. Kuj tseem muaj kev piav qhia zoo ntawm kev sib koom ua ke ntawm hyperglycemia thiab nce kev qhia ntawm nuclear factor-kappa B [38]. Cov teebmeem metabolic ntawm hyperglycemia, xws li nce lactic acid ntau lawm nrog acidosis tom qab thiab mitochondrial dysfunction, yog lwm txoj kev pom zoo ntawm hyperglycemia cuam tshuam txog kev mob hlwb [39].