Chinyorwa
Methylene blue neutano hwemwoyo: zvidzidzo zvematishu, mhuka dzekutsvakurudza, uye mamiriro ekushandiswa kuchipatara
Muverengi anosangana nemashoko maviri muvhiki rimwe chete. Mamwe anoti methylene blue inovandudza kufema kwemitochondria mumwoyo yemakonzo ane chirwere cheshuga. Mamwe anoti inoshandiswa muzvipatara panguva inoenderana nekuvhiyiwa kwemwoyo. Mhedziso iri nyore kusvikwa ndeyekuti methylene blue inobatsira mwoyo pakutadza kwawo kushanda kana kuti pakuudzivirira zvachose.
Mhedziso iyoyo inosanganisa pfungwa nhatu dzakasiyana. Yekutanga ishanduko yemaitiro emakemikari mukati memitochondria yakaparadzaniswa. Yechipiri ishanduko yemakemikari ematishu ari kunze kwemuviri. Yechitatu imhedzisiro yekurapwa mumurwere, yakadai sezviratidzo zvishoma, kushanya kuchipatara kushoma, kana kurarama kwenguva yakareba. Imwe neimwe ine musimboti wayo wekushanda. Mhedzisiro pane rimwe danho haiendi yega kune rinotevera.
Chinyorwa ichi chinoparadzanisa matanho iwayo. Chinoongorora kutsvakurudza mitochondria yemwoyo, matishu emwoyo netsinga dzeropa zvevanhu, mhuka dzine muviri wakazara, uye mamiriro akasiyana emuchipatara umo methylene blue inokanganisa kutenderera kweropa.
Tafura yeuchapupu pamusoro pemwoyo
Tafura iyi ndiyo gwara guru remusoro uyu. Inoparadzanisa matishu akabviswa mumuviri, mhuka dzine muviri wakazara, uye mamiriro ekurapwa nekuti zvinopindura mibvunzo yakasiyana.
| Danho reuchapupu | Zvakaedzwa | Zvakachinja | Zvaisingasimbisi |
|---|---|---|---|
| Mitochondria yemwoyo yakaparadzaniswa, kubva kumakonzo ane chirwere cheshuga neasina | Methylene blue ye0.1 micromolar yakawedzerwa kamwe chete kumitochondria yakapiwa zvinhu zvinodyiwa necomplex I kana complex II | Kushandiswa kweoxygen kwakakwira nemhando mbiri idzi dzezvinhu. Kubudiswa kwehydrogen peroxide kwakakwira nezvinhu zvinodyiwa necomplex I uye kwakadzikira nesuccinate, chinhu chinodyiwa necomplex II. Kuchengetwa kwecalcium hakuna kuchinja. | Hazviratidzi kuvandudzwa kwekupomba kwemwoyo, zviratidzo, kana kurarama mumurwere mupenyu. Matishu aya haana kuyerera kweropa mutsinga dzemwoyo, kudzora BP, itsvo, tsinga dzemanzwiro, kana kudyidzana kwemishonga. |
| Mwoyo usina kubviswa mumuviri wegonzo rine chirwere cheshuga, kupiwa mushonga kwenguva refu | Methylene blue pa10 mg per kg per day, ichiongororwa neechocardiography, kuongorora kutenderera kweropa, respirometry, uye proteomics | Oxidation yeNADH yakawedzera, NAD yakakwira, kushanda kwesirtuin 3 kwakakwira, uye acetylation yelysine yakaderera panzvimbo 83 mumapuroteni 34 emitochondria. Oxidation yefatty acid yakachinja uye kushanda kwemwoyo kwakavandudzika mumhuka dzine chirwere cheshuga. Kukanganisika kwecomplex I kwakabatana nechirwere cheshuga hakuna kugadziriswa. | Hazvisimbisi kuti methylene blue inorapa kutadza kushanda kwemwoyo muvanhu. Rudzi rwemhuka, muenzaniso wechirwere cheshuga, huwandu hwemushonga, uye zviyero zvinotsiva mhedzisiro chaiyo zvinodzivisa kushandisa zvakawanikwa izvi zvakananga pakutadza kushanda kwemwoyo kwevanhu. |
| Mafuta emwoyo netsinga dzeropa zvevanhu, kunze kwemuviri | Mafuta ari pamusoro pemwoyo neakapoteredza tsinga dzeropa kubva kuvarwere 25 vane kutadza kushanda kwemwoyo vaivhiyiwa mwoyo, akachengetwa ne0.1 micromolar yemethylene blue kwemaawa 24 | Mhando mbiri dzemonoamine oxidase dzaivapo, zvikuru MAO-A. Methylene blue yakaderedza kugadzirwa kweMAO nemakemikari eoxygen anokurumidza kuita nemamwe. Serotonin yakawedzerwa yakawedzera hydrogen peroxide kuburikidza neMAO-A, uye methylene blue yakadzorera shure chikamu chekukwira ikoko. | Matishu ari kunze kwemuviri haasi muedzo wekurapa. Hazviratidzi kuti kutora methylene blue kunovandudza kushanda kwemakamuri epasi emwoyo kana mhedzisiro yekurapwa. |
| Imbwa dzine muviri wakazara uye dzakasvinura padzaiita maekisesaizi | Huwandu hwekutanga pamwe nekupinzwa kunoramba kuchienderera kwechinhu chinonzi new methylene blue panguva yemaekisesaizi patreadmill, zvichienzaniswa nemvura ine munyu | Reshiyo yelactate nepyruvate muropa reartery yakadzikira, ichiratidza shanduko yeredox, asi huwandu hweropa rinopombwa nemwoyo, kurova kwemwoyo, simba rekubatana kwemhasuru yemwoyo, BP yema artery, uye mhinduro dzecatecholamine panguva yemaekisesaizi hazvina kuchinja. | Hazvitsigiri kuvandudzwa kwekugona kuita maekisesaizi kana kushanda kwemwoyo kunobva pashanduko yeredox. Imbwa idzi dzakanga dzisina kutadza kushanda kwemwoyo kwakawanikwa pakurapwa. |
| Mamiriro ekutenderera kweropa muchipatara | Methylene blue inopinzwa mutsinga yeropa (IV) yevasoplegia mushure mekuvhiyiwa kwemwoyo, rubatsiro runowedzerwa pakurapa septic shock, uye kurapwa kwakabvumirwa kwem methemoglobinemia yakawanikwa | Avhareji yeBP yema artery nesimba rinodzivisa kuyerera kweropa mutsinga zvinogona kukwira, uye kudiwa kwemishonga inosimudza BP kunogona kudzikira mune mamwe mamiriro eshock inokonzerwa nekuwedzera kwetsinga. Methemoglobin inoderera mumethemoglobinemia, zvichidzorera kutakurwa kweoxygen. | Rubatsiro rweIV rwenguva pfupi rweBP kana kutakurwa kweoxygen harusi uchapupu hwekurapa nemushonga unotorwa nemuromo kwenguva refu kwechirwere chetsinga dzemwoyo, kuungana kwemafuta mumadziro etsinga, kana kutadza kushanda kwemwoyo. Nzira yekupiwa, huwandu, nguva, uye chirwere zvakasiyana. |
Tanga nekuverenga chikamu chekupedzisira kubva pamusoro kusvika pasi. Chikamu ichocho chinogadzirisa manzwisisiro anosiyiwa neruzhinji rwenyaya dzinoti methylene blue inobatsira mwoyo.
Zvinoratidzwa nemitochondria yakaparadzaniswa kubva mumwoyo
Chidzidzo chemwoyo une chirwere cheshuga chakaedza mitochondria yakabviswa kumakonzo ane utano uye kumakonzo akaitwa kuti ave nechirwere cheshuga nestreptozotocin. Respirometry ine kunyatsoyera kwakakwirira yakayera kushandiswa kweoxygen. Miedzo inoshandisa chiedza chefluorescence yakayera hydrogen peroxide nemabatirwo ecalcium.
Chinhu chinoshamisa uye chinobatsira ndechekuti mhedzisiro inoenderana nezvinhu zvinopiwa mitochondria. Neglutamate pamwe nemalate, zvinopa complex I, methylene blue yakawedzera kufema asi yakawedzerawo kubudiswa kwehydrogen peroxide. Nesuccinate, inopa complex II, yakawedzera kufema uye yakaderedza hydrogen peroxide. Saka kuidaidza kuti antioxidant hakutsananguri zvose zvainoita. Kuti makemikari eoxygen anokurumidza kuita nemamwe anokwira kana kudzikira zvinoenderana nenzira yekufema iri kushanda uye mamiriro eredox ecoenzyme Q.
Chimwe chidzidzo chine chekuita nemakonzo ane chirwere cheshuga chinotsanangura mashandiro acho zvakadzama. Methylene blue inoshanda seimwe nzira yekutakura maelectron. Inobatsira kushandura NADH kuita NAD kuburikidza neoxidation, izvo zvinowedzera kushanda kwesirtuin 3, enzyme yemitochondria inobvisa mapoka eacetyl. Enzyme iyoyo inobvisa mapoka eacetyl pazvikamu zelysine zvemapuroteni emitochondria. Kuongorora mapuroteni kwakawana kuderera kweacetylation mumapuroteni ekutakura neoxidation yefatty acid, kutenderera kwetricarboxylic acid, kutakurwa kwemaelectron, kushandurwa kwemaamino acid, uye kutakura zvinhu. Kushanda kwemwoyo kwakavandudzika mumakonzo ane chirwere cheshuga akapiwa mushonga kunyange zvazvo kukanganisika kwecomplex I kwaivapo kwakaramba kuripo.
Funga izvi sekuchinjira maelectron kune imwe nzira pane kungobvisa maradical. Gwaro rekutakurwa kwemaelectron mumitochondria rinoisa pfungwa iyi yekuchinja nzira mucheni yakakura. Inoramba iri tsananguro padanho rematishu, kwete kurairwa kutora mushonga.
Zvinowedzerwa nematishu emwoyo wevanhu, uye zvaasingagoni kuwedzera
Chidzidzo chevanhu chinoswedera pedyo nevarwere nedanho rimwe chete asi hachivi muedzo wekurapa. Vanovhiya vakaunganidza mafuta eepicardial, ari pamusoro pemwoyo chaipo, nemafuta eperivascular, anopoteredza tsinga dzeropa, kubva kuvarwere vane kutadza kushanda kwemwoyo. Murabhoritari, masampuli akachengetwa aine methylene blue ine kusanganiswa kushoma kwezuva rimwe chete.
Matishu ose ari maviri aigadzira maenzyme emonoamine oxidase, zvikuru mhando yeMAO-A. Maenzyme aya anogona kugadzira makemikari eoxygen anokurumidza kuita nemamwe munzvimbo iyoyo. Methylene blue yakaderedza kugadzirwa kweMAO nezviratidzo zvekushushikana kunokonzerwa neoxidation. Vatsvakurudzi pavakawedzera serotonin, chinhu chinodyiwa neMAO-A, hydrogen peroxide yakakwira. Methylene blue yakadzorera shure chikamu chekukwira ikoko.
Izvi zvinokosha nekuti mafuta akapoteredza mwoyo netsinga zvino ava kuonekwa senzvimbo inobudisa mashoko anokurudzira kuzvimba neoxidation muzvirwere zvine chekuita nemwoyo nekushandurwa kwezvinhu mumuviri, kwete kungova zvinhu zvinozadza nzvimbo zvisina basa. Chidzidzo ichi chinoratidza nzvimbo inogona kuitirwa shanduko nemethylene blue mumatishu chaiwo evanhu.
Muganhu wacho unoramba uripo. Masampuli makumi maviri nemashanu ekuvhiya, akapiwa mushonga kunze kwemuviri kwemaawa 24, haagoni kuratidza kuti methylene blue yakamedzwa inosvika munzvimbo iyoyo pahuwandu hunoshanda, inoramba imomo zvakachengeteka, inoshandura kushanda kwemwoyo, kana kuchinja mhedzisiro. Kuti unzwisise mitemo yakajairika iri shure kwemuganhu iwoyo, ona maverengero ekutsvakurudza pamusoro pemethylene blue.
Zvinoratidzwa nechidzidzo chemhuka dzine muviri wakazara dzichiita maekisesaizi
Chidzidzo chembwa chinonyanya kukosha semhedzisiro isina kuratidza kuvandudzwa kwaitarisirwa. Imbwa dzakasvinura dzakamhanya patreadmill pamatanho maviri emutoro webasa. Rimwe boka rakapiwa mvura ine munyu. Rimwe rakapiwa huwandu hwekutanga hwemethylene blue pamwe nekupinzwa kunoramba kuchienderera. Rechitatu rakapiwa methylene blue risingaiti maekisesaizi.
Methylene blue yakaderedza reshiyo yelactate nepyruvate muropa reartery, chinoratidzo chine chekuita nekuenzana kweNADH neNAD. Pakuzorora, zviyero zvehuwandu hweropa rinopombwa nemwoyo, kurova kwemwoyo, BP, uye simba rekubatana kwemhasuru yemwoyo zvakachinja zvishoma. Panguva yemaekisesaizi, huwandu hweropa rinopombwa nemwoyo hwakapetwa kaviri uye kushandiswa kweoxygen nemuviri wose kwakawedzera katatu kusvika kana mumapoka ose emvura ine munyu neemethylene blue. Hukama pakati pehuwandu hweropa rinopombwa nemwoyo nekushandiswa kweoxygen hahuna kuchinjwa nemethylene blue.
Kana tichitarisa pfungwa dzacho, redox yakachinja asi kupomba hakuna kuchinja. Shanduko yemakemikari mumuviri haifaniri kuchinja mhinduro inosanganisa mashandiro enhengo dzakasiyana, yakadai sehuwandu hweropa rinopombwa nemwoyo panguva yemaekisesaizi. Kuparadzana ikoko kunonyatsobata mashoko anoti zviyero zviri nani zvemitochondria zvinofanira kureva mwoyo une simba rakawanda panguva yekuita basa.
Kushandiswa muchipatara ipfungwa yakasiyana nekurapa kwenguva refu
Zvipatara zvinoshandisa methylene blue yeIV mumamiriro matatu anonzwika seane chekuita nemwoyo asi anoedza mibvunzo yakasiyana.
Chekutanga, vasoplegia mushure mekuvhiyiwa kwemwoyo zvinoreva kuderera kwakanyanya kwesimba rekuzvisunga kwetsinga dzeropa kunyange mwoyo uchipomba zvakakwana. Miedzo yaiwanzoshandisa anenge 1.5 kusvika 2 mg per kg IV achipinzwa kamwe chete. Chinowanzowanikwa iavhareji yeBP yakakwira nesimba rakawanda rinodzivisa kuyerera kweropa mutsinga, pamwe nekuderedzwa kwekudiwa kwemishonga inosimudza BP, pasina kukwira kunoramba kuchionekwa kwehuwandu hweropa rinopombwa nemwoyo. Ongororo yakadzama yemiedzo iri mupeji reuchapupu hwevasoplegia neseptic shock.
Chechipiri, rubatsiro runowedzerwa pakurapa septic shock runoshandisa zvirongwa zvakasiyana zveIV, kusanganisira chirongwa cha2023 che100 mg dzaipinzwa kwemaawa matanhatu zuva nezuva kusvikira dzapiwa katatu. Nguva yepakati kusvika pakumisa mishonga inosimudza BP yakaderera kubva pamaawa 94 kusvika pa69, uku kufa nenguva yekubatsirwa kufema zvakaramba zvakafanana. Ongororo dzakazobatanidza zvidzidzo dzinoratidza kuti panogona kuva nemhedzisiro pakufa munguva pfupi, asi dzinoti chokwadi cheuchapupu hwacho chakaderera uye chinochinja zvichienderana nemiedzo inosarudzwa. Chinonyanya kutsigirwa kuderedzwa kwekudiwa kwemishonga inosimudza BP, kwete kuvandudzwa kwekurarama kwakasimbiswa.
Chechitatu, methemoglobinemia yakawanikwa ndiyo mamiriro ayo kurapwa neIV kwakabvumirwa, kazhinji 1 mg per kg IV ine imwe dose inodzokororwa kana zvichidiwa. Pano methylene blue inodzoreredza kushanda kwehemoglobin nekuendeswa kweoxygen. Zviratidzo zvemuchipfuva zvinovandudzika nekuti kutakurwa kweoxygen kunovandudzika, kwete nekuti methylene blue inogadzirisa maumbirwo emwoyo.
Hapana pamamiriro aya panoedzwa methylene blue inotorwa nemuromo zuva nezuva pakutadza kushanda kwemwoyo kwenguva refu, chirwere chetsinga dzemwoyo, kana kudzivirira. Nzira dzazvino dzekurapa kutadza kushanda kwemwoyo nechirwere chetsinga dzemwoyo hadziinyori semushonga unokurudzirwa wenguva refu. Uchapupu pamusoro peBP hunoitawo musiyano iwoyo wenzira yekupiwa nemamiriro acho pamusoro pesimba rekuzvisunga kwetsinga: kukwira kweBP kunokonzerwa neIV panguva yeshock hakufanotauri zvinozoratidzwa nechiyereso cheBP chepamba kubva kuchigadzirwa chinotorwa nemuromo.
Chero kubatanidzwa kweuchapupu mune ramangwana pamusoro pezvinonzi zvinoitika muzvirwere zvenguva refu kunoda data remiedzo ine kupatsanurwa kwemapoka zvisina kurongwa maererano nezviratidzo, kushanda, kuradzikwa muchipatara, uye kuchengeteka pachirongwa chaicho chekutora nemuromo, kwete mumwe muedzo wemitochondria.
Mibvunzo yekuchengeteka inofanira kutanga yagadziriswa nevaverengi vane matambudziko emwoyo
Varwere vemwoyo vanowanzotora mishonga yakawanda inogona kudyidzana. Kuongorora zvinhu zvitatu zvekuchengeteka kunofanira kutanga kusati kwava netariro inobva patsananguro yemashandiro.
Chekutanga, methylene blue chinhu chine simba chinodzivisa monoamine oxidase. Chinyorwa cheIV chine yambiro iri mubhokisi pamusoro peserotonin syndrome kana ichishandiswa nemaSSRI, maSNRI, zvinodzivisa MAO, uye mimwe mishonga yeopioid. Zviratidzo zvinosanganisira kusagadzikana, kuvhiringidzika, fivha, kudikitira, kurova kwemwoyo kana BP zvisina kugadzikana, kudedera, kuoma kwemhasuru, uye clonus, uko mhasuru dzinobatana dzichidzokorora zvisingadzorwi. Varwere vemwoyo vanofanira kuendesa runyorwa rwakazara rwemishonga kunyanzvi yezveutano kana wemishonga uye havafaniri kuzvimisira mishonga yekuora mwoyo kana yekurwadziwa.
Chechipiri, kushomeka kweglucose-6-phosphate dehydrogenase mamiriro anoita kuti methylene blue isafanira kushandiswa nekuti inogona kukonzera kuparara kwakanyanya kwemasero matsvuku eropa. Kuverengwa kwakajairika nepulse oximeter hakugoni kubvisa mukana wenjodzi iyi. Methylene blue inogonawo kukanganisa kuverengwa kweoximeter nemimwe michina yekuongorora panguva yeanesthesia, chinova chimwe chezvikonzero nei kushandiswa kwayo muchipatara kuchiramba kuchitariswa.
Chechitatu, kufunga pamusoro penzira dzemakemikari hakusi gwara rehuwandu hwemushonga. Nitrate dzinoshanda kuburikidza nenitric oxide necyclic GMP. Methylene blue inogona kuderedza kuzorora kwetsinga kunokonzerwa nenitric oxide mumiedzo, asi izvozvo hazviratidzi kuti inogona kupikisa nitrate zvakachengeteka kana kutsiva mushonga wemwoyo wakarairwa. Mhedzisiro paBP yakashumwa nemethylene blue yeIV inosanganisira BP yakakwira neyakaderera pamwe nekurova kwemwoyo kunokurumidza nekusarongeka kwekurova kwawo, saka kuongororwa kunokosha.
Mutemo wekushandisa uri nyore. Zvakawanikwa mumatishu nemhuka zvikonzero zvekuita miedzo yakangwarira, kwete zvikonzero zvekuzvirapira chirwere chemwoyo. Chero munhu ane kutadza kushanda kwemwoyo, chirwere chetsinga dzemwoyo, kusarongeka kwekurova kwemwoyo, kana mudziyo wemwoyo anofanira kukurukura chero kushandiswa kwemethylene blue nechikwata chekurapa mwoyo, achinyora chigadzirwa, kusanganiswa kwacho, huwandu, nzira yekupiwa, nguva, uye zviratidzo.