Isihloko
I-methylene blue nempilo yenhliziyo: izifundo zezicubu, amamodeli ezilwane, nomongo wokusetshenziswa ezigulini
Umfundi uthola izitatimende ezimbili ngesonto elilodwa. Esinye sithi i-methylene blue ithuthukisa ukuphefumula kwama-mitochondria ezinhliziyweni zamagundane anesifo sikashukela. Esinye sithi isetshenziswa ezibhedlela ngesikhathi sokuhlinzwa kwenhliziyo. Isiphetho esingafika kalula engqondweni ukuthi i-methylene blue inezinzuzo enhliziyweni ezisiza ekwehlulekeni kwenhliziyo noma ekuvikeleni inhliziyo ngokujwayelekile.
Leso siphetho sixuba imiqondo emithathu ehlukene. Owokuqala umphumela wamakhemikhali ezinto eziphilayo ngaphakathi kwama-mitochondria ahlukanisiwe. Owesibili ushintsho kumakhemikhali ezicubu ezingaphandle komzimba. Owesithathu umphumela esigulini, njengokuncipha kwezimpawu, ukuvakashela esibhedlela izikhathi ezimbalwa, noma ukuphila isikhathi eside. Ngamunye unendlela yawo yokusebenza. Umphumela ezingeni elilodwa awudluleli ngokuzenzakalela kwelinye.
Lesi sihloko sigcina lawo mazinga ehlukene. Sibuyekeza ucwaningo lwama-mitochondria enhliziyo, ucwaningo lwezicubu zenhliziyo nemithambo yegazi yabantu, ucwaningo lwezilwane eziphilayo, kanye nesimo esihlukile sasesibhedlela lapho i-methylene blue ithinta khona ukujikeleza kwegazi.
Ithebula lobufakazi obuphathelene nenhliziyo
Leli thebula liyimephu eyinhloko yalesi sihloko. Lihlukanisa izicubu ezilungiselelwe ukuhlolwa ngaphandle komzimba, izilwane eziphilayo, nezimo zokwelashwa kweziguli ngoba kuphendula imibuzo ehlukene.
| Izinga lobufakazi | Okwahlolwa | Okwashintsha | Okungakufakazeli |
|---|---|---|---|
| Ama-mitochondria enhliziyo ahlukanisiwe, emagundaneni anesifo sikashukela naphilile | I-methylene blue engu-0.1 micromolar yengezwa ngesikhathi esifushane kuma-mitochondria anikezwe izinto ezisetshenziswa yi-complex I noma yi-complex II | Ukusetshenziswa kwe-oxygen kwakhuphuka kuzo zombili izinhlobo zezinto ezisetshenziswayo. Ukukhishwa kwe-hydrogen peroxide kwakhuphuka ngezinto ezisetshenziswa yi-complex I futhi kwehla nge-succinate, esetshenziswa yi-complex II. Ukugcinwa kwe-calcium akuzange kushintshe. | Akubonisi ukuthuthuka kokumpompa kwenhliziyo, kwezimpawu, noma kokusinda esigulini esiphilayo. Lawa ma-mitochondria alungiselelwe ukuhlolwa awanakho ukugeleza kwegazi emithanjeni yenhliziyo, ukulawulwa komfutho wegazi, izinso, izinzwa, noma ukusebenzisana kwemithi. |
| Inhliziyo yegundane eliphilayo elinesifo sikashukela, ukunikezwa komthamo isikhathi eside | I-methylene blue engu-10 mg per kg ngosuku, kuhlolwa nge-echocardiography, ngocwaningo lokugeleza kwegazi, nge-respirometry, nangokuhlaziywa kwamaprotheni | I-oxidation ye-NADH yanda, i-NAD yakhuphuka, ukusebenza kwe-sirtuin 3 kwakhuphuka, futhi i-acetylation ye-lysine yehla ezindaweni ezingu-83 kumaprotheni ama-mitochondria angu-34. I-oxidation yama-fatty acid yashintsha futhi ukusebenza kwenhliziyo kwathuthuka ezilwaneni ezinesifo sikashukela. Ukuphazamiseka kwe-complex I okuhlobene nesifo sikashukela ngokwako akuzange kulungiswe. | Akufakazeli ukwelashwa kokwehluleka kwenhliziyo nge-methylene blue kubantu. Uhlobo lwesilwane, imodeli yesifo sikashukela, umthamo, nezilinganiso ezimelela imiphumela yangempela kuvimbela ukudlulisela le miphumela ngokuqondile ekwehlulekeni kwenhliziyo kubantu. |
| Amafutha aseduze kwenhliziyo nemithambo yegazi yabantu, ngaphandle komzimba | Amafutha angaphezulu kwenhliziyo naseduze kwemithambo yegazi athathwa ezigulini ezingu-25 ezinokwehluleka kwenhliziyo ezazihlinzwa inhliziyo, agcinwa ngaphansi kwezimo ezilawulwayo ne-methylene blue engu-0.1 micromolar amahora angu-24 | Zombili izinhlobo ze-monoamine oxidase zazikhona, ikakhulukazi i-MAO-A. I-methylene blue yehlisa ukukhiqizwa kwe-MAO nezinhlobo ze-oxygen ezisebenza kakhulu ngamakhemikhali. I-serotonin eyengeziwe yandisa i-hydrogen peroxide nge-MAO-A, futhi i-methylene blue yabuyisela emuva ingxenye yalokho kukhuphuka. | Izicubu ezingaphandle komzimba azilona ucwaningo lokuhlola ukwelashwa. Akubonisi ukuthi ukuthatha i-methylene blue kuthuthukisa ukusebenza kwamakamelo aphansi enhliziyo noma imiphumela ezigulini. |
| Izinja eziphilayo, eziqaphile ngesikhathi sokuzivocavoca | Umthamo wokuqala olandelwa ukufakwa okuqhubekayo kwe-methylene blue entsha ngesikhathi sokugijima emshinini wokuzivocavoca, kuqhathaniswa nesixazululo sikasawoti | Isilinganiso se-lactate ne-pyruvate egazini lemithambo ephuma enhliziyweni sehla, sibonisa ushintsho lwe-redox, kanti umthamo wegazi ompontshwa yinhliziyo ngomzuzu, izinga lokushaya kwenhliziyo, amandla okufinyela, umfutho wegazi emithanjeni ephuma enhliziyweni, nokusabela kwama-catecholamine ngesikhathi sokuzivocavoca akuzange kushintshe. | Akusekeli ukuthi ushintsho lwe-redox luthuthukisa ikhono lokuzivocavoca noma ukusebenza kwenhliziyo. Izinja zazingenakho ukwehluleka kwenhliziyo okuxilongiwe. |
| Izimo zasesibhedlela zokulawulwa kokugeleza kwegazi | I-methylene blue efakwa emthanjeni (IV) ye-vasoplegia ngemva kokuhlinzwa kwenhliziyo, ukunakekelwa okwengeziwe kokushaqeka okubangelwa ukutheleleka, nokwelashwa okugunyaziwe kwe-methemoglobinemia etholakala kamuva | Isilinganiso somfutho wegazi emithanjeni ephuma enhliziyweni nokumelana kwemithambo nokugeleza kwegazi kungakhuphuka, futhi isidingo semithi enyusa umfutho wegazi singehla ezimweni ezithile zokushaqeka okubangelwa ukunwebeka kwemithambo. I-methemoglobin iyehla ku-methemoglobinemia, kubuyiselwe ukuthuthwa kwe-oxygen. | Ukusekela umfutho wegazi noma ukuthuthwa kwe-oxygen nge-IV ngesikhathi esifushane akubona ubufakazi bokwelapha ngomlomo isikhathi eside isifo semithambo yenhliziyo, i-atherosclerosis, noma ukwehluleka kwenhliziyo. Indlela yokunikeza umuthi, umthamo, ubude besikhathi, nesifo kwehlukile. |
Qala ngokufunda ikholomu yokugcina. Leyo kholomu iqukethe ukulungiswa kwendlela yokucabanga okushiywa ngaphandle yizincazelo eziningi zezimangalo ze-methylene blue mayelana nenhliziyo.
Okuboniswa ama-mitochondria enhliziyo ahlukanisiwe
Ucwaningo lwezinhliziyo ezinesifo sikashukela lwahlola ama-mitochondria akhishwa emagundaneni aphilile nasemagundaneni anesifo sikashukela esibangelwe yi-streptozotocin. I-respirometry enokunemba okuphezulu yalinganisa ukusetshenziswa kwe-oxygen. Ukuhlolwa okusebenzisa ukukhanya kwe-fluorescence kwalinganisa i-hydrogen peroxide nokuphathwa kwe-calcium.
Okumangazayo nokuwusizo ukuthi umphumela uncike entweni esetshenziswayo. Nge-glutamate kanye ne-malate, okunikeza i-complex I izinto ezisebenzisayo, i-methylene blue yakhuphula ukuphefumula kodwa yakhuphula nokukhishwa kwe-hydrogen peroxide. Nge-succinate, esetshenziswa yi-complex II, yakhuphula ukuphefumula futhi yehlisa i-hydrogen peroxide. Ngakho ukuyibiza ngokuthi ivikela ukulimala nge-oxidation akuchazi konke ukuziphatha kwayo. Ukuthi izinhlobo ze-oxygen ezisebenza kakhulu ngamakhemikhali ziyakhuphuka noma ziyehla kuncike ekutheni iyiphi indlela yokuphefumula esebenzayo nasesimweni se-redox se-coenzyme Q.
Ucwaningo oluhlobene nalolu emagundaneni anesifo sikashukela luyicacisa kabanzi le ndlela yokusebenza. I-methylene blue isebenza njengomunye umthwali wama-electron. Isiza ukushintsha i-NADH ibe yi-NAD nge-oxidation, okwandisa ukusebenza kwe-sirtuin 3, i-enzyme yama-mitochondria esusa amaqembu e-acetyl. Le enzyme isusa amaqembu e-acetyl ezinsaleleni ze-lysine ezikumaprotheni ama-mitochondria. Ukuhlaziywa kwamaprotheni kwathola ukwehla kwe-acetylation kumaprotheni ahilelekile ekuthuthweni nase-oxidation yama-fatty acid, emjikelezweni we-tricarboxylic acid, ekuthuthweni kwama-electron, ekuguqulweni kwama-amino acid, nasekuthuthweni kwezinto. Ukusebenza kwenhliziyo kwathuthuka emagundaneni anesifo sikashukela ayenikezwe umuthi nakuba ukuphazamiseka okuyisisekelo kwe-complex I kwasala.
Cabanga ngalokhu njengokushintsha indlela ama-electron ahamba ngayo kunokumane kubanjwe ama-radical. Umhlahlandlela wokuthuthwa kwama-electron kuma-mitochondria ubeka lo mqondo wokushintsha indlela ngaphakathi kochungechunge olubanzi. Lokhu kusalokhu kuyincazelo ezingeni lezicubu, hhayi umyalelo wokwelashwa.
Okunezelwa izicubu zenhliziyo yomuntu, nalokho ezingakwazi ukukunezela
Ucwaningo lwabantu lusondela ngesinyathelo esisodwa ezigulini ngaphandle kokuba ucwaningo lokuhlola ukwelashwa. Odokotela abahlinzayo baqoqa amafutha e-epicardial, ahlala ngokuqondile phezu kwenhliziyo, namafutha e-perivascular, azungeza imithambo, ezigulini ezinokwehluleka kwenhliziyo. Elabhorethri, amasampula agcinwa ngaphansi kwezimo ezilawulwayo ne-methylene blue enokugxila okuphansi usuku olulodwa.
Zombili izicubu zazikhiqiza ama-enzyme e-monoamine oxidase, ikakhulukazi uhlobo lwe-MAO-A. La ma-enzyme angakhiqiza izinhlobo ze-oxygen ezisebenza kakhulu ngamakhemikhali kuleyo ndawo. I-methylene blue yehlisa ukukhiqizwa kwe-MAO futhi yehlisa izimpawu zengcindezi yokulimala nge-oxidation. Lapho abacwaningi bengeza i-serotonin, esetshenziswa yi-MAO-A, i-hydrogen peroxide yakhuphuka. I-methylene blue yabuyisela emuva ingxenye yalokho kukhuphuka.
Lokhu kubalulekile ngoba amafutha azungeze inhliziyo nemithambo manje abhekwa njengomthombo osebenzayo wezimpawu zokuvuvukala nezokulimala nge-oxidation ezifweni zenhliziyo ezihlobene nokuphazamiseka kokuguqulwa kwezinto emzimbeni, hhayi njengento yokugcwalisa engasebenzi. Lolu cwaningo lubeka umphumela ongaba khona we-methylene blue kuleyo ngxenye yezicubu zomuntu zangempela.
Umngcele usalokhu ukhona. Amasampula angamashumi amabili nanhlanu athathwe ngesikhathi sokuhlinzwa, asetshenzwa ngaphandle komzimba amahora angu-24, awakwazi ukubonisa ukuthi i-methylene blue egwinyiwe ifinyelela kuleyo ngxenye ngokugxila okwanele ukuze ibe nomphumela, ihlala khona ngokuphepha, ishintsha ukusebenza kwenhliziyo, noma iguqula imiphumela ezigulini. Ukuze uthole imithetho ejwayelekile esekela lowo mngcele, bheka indlela yokufunda ucwaningo lwe-methylene blue.
Okuboniswa ucwaningo lokuzivocavoca ezilwaneni eziphilayo
Ucwaningo lwezinja luwusizo ikakhulukazi ngoba alutholanga umphumela owawulindelwe. Izinja eziqaphile zagijima emshinini wokuzivocavoca emazingeni amabili omthwalo wokuzivocavoca. Iqembu elilodwa lathola isixazululo sikasawoti. Elinye lathola umthamo wokuqala we-methylene blue olandelwa ukufakwa okuqhubekayo. Elesithathu lathola i-methylene blue ngaphandle kokuzivocavoca.
I-methylene blue yehlisa ngempela isilinganiso se-lactate ne-pyruvate egazini lemithambo ephuma enhliziyweni, okuyinkomba ehlobene nokulingana kwe-NADH ne-NAD. Umthamo wegazi ompontshwa yinhliziyo ngomzuzu lapho umzimba uphumule, izinga lokushaya kwenhliziyo, umfutho, nezilinganiso zamandla okufinyela kwenhliziyo kwashintsha kancane. Ngesikhathi sokuzivocavoca, umthamo wegazi ompontshwa yinhliziyo ngomzuzu waphindeka kabili futhi ukusetshenziswa kwe-oxygen emzimbeni wonke kwanda ngokuphindwe kathathu kuya kane emaqenjini womabili, elesixazululo sikasawoti nele-methylene blue. Ubudlelwano phakathi komthamo wegazi ompontshwa yinhliziyo ngomzuzu nokusetshenziswa kwe-oxygen abuzange bushintshwe yi-methylene blue.
Ngokwemibono, i-redox yashintsha kanti ukumpompa akuzange kushintshe. Ushintsho lwamakhemikhali ezinto eziphilayo aludingeki lushintshe ukusabela okuhlanganisa ukusebenza kwezingxenye eziningi, njengomthamo wegazi ompontshwa yinhliziyo ngesikhathi sokuzivocavoca. Lokho kwehlukana kuhlobene ngokuqondile nezimangalo zokuthi izilinganiso ezingcono zama-mitochondria kufanele zisho inhliziyo enamandla kakhulu ngesikhathi sokusebenza komzimba.
Ukusetshenziswa esibhedlela kwehlukile ekwelashweni kwesikhathi eside
Izibhedlela zisebenzisa i-methylene blue nge-IV ezimweni ezintathu ezizwakala zihlobene nenhliziyo kodwa ezihlola imibuzo ehlukene.
Okokuqala, i-vasoplegia ngemva kokuhlinzwa kwenhliziyo isho ukuncipha okukhulu kokuqina kwemithambo nakuba inhliziyo impompa ngokwanele. Izifundo zokuhlola ngokuvamile zasebenzisa cishe u-1.5 kuya ku-2 mg per kg nge-IV, kufakwa kanye. Umphumela otholakala ngokuphindaphindiwe ukukhuphuka kwesilinganiso somfutho wegazi nokumelana kwemithambo nokugeleza kwegazi, kanye nokuncipha kwesidingo semithi enyusa umfutho wegazi, ngaphandle kokukhuphuka okuhambisanayo komthamo wegazi ompontshwa yinhliziyo ngomzuzu. Ukubuyekezwa okuningiliziwe kwezifundo zokuhlola kutholakala ekhasini lobufakazi be-vasoplegia nokushaqeka okubangelwa ukutheleleka.
Okwesibili, ukunakekelwa okwengeziwe kokushaqeka okubangelwa ukutheleleka kusebenzisa izinhlelo ezihlukahlukene ze-IV, kuhlanganise nohlelo lwango-2023 lwe-100 mg efakwa phakathi namahora ayisithupha ngosuku, imithamo emithathu. Isikhathi esimaphakathi sokuyeka imithi enyusa umfutho wegazi sehla sisuka emahoreni angu-94 saya kwangu-69, kanti izinga lokufa nesikhathi sokusekelwa kokuphefumula kwakufana. Ukuhlaziywa okuhlanganisa izifundo okwenziwa kamuva kusikisela ukuthi kungase kube nokuncipha kokufa ngesikhathi esifushane, kodwa kubeka ukuqiniseka kwalobu bufakazi ezingeni eliphansi futhi kubonisa ukuthi kuyathinteka ngokuthi kukhethwe ziphi izifundo zokuhlola. Isimangalo esisekelwa kangcono ukuncipha kwesidingo semithi enyusa umfutho wegazi, hhayi ukwanda kokusinda okuqinisekisiwe.
Okwesithathu, i-methemoglobinemia etholakala kamuva iyisimo esigunyaziwe sokusetshenziswa kwe-IV, ngokuvamile u-1 mg per kg nge-IV, umthamo uphindwe kanye uma kudingeka. Lapha i-methylene blue ibuyisela ukusebenza kwe-hemoglobin nokulethwa kwe-oxygen. Izimpawu zesifuba ziyathuthuka ngoba ukuthuthwa kwe-oxygen kuyathuthuka, hhayi ngoba i-methylene blue ishintsha ukwakheka kwenhliziyo.
Asikho kulezi zimo esihlola ukuthathwa kwe-methylene blue ngomlomo nsuku zonke ukuze kwelashwe ukwehluleka kwenhliziyo okuhlala isikhathi eside, isifo semithambo yenhliziyo, noma ukuvimbela izifo. Izindlela zamanje zokwelapha ukwehluleka kwenhliziyo nesifo semithambo yenhliziyo aziyifaki njengokwelashwa okunconyiwe kwesikhathi eside. Ubufakazi obuphathelene nomfutho wegazi benza umehluko ofanayo wendlela yokunikeza umuthi nesimo sokusetshenziswa ngokuphathelene nokuqina kwemithambo: ukusabela komfutho wegazi ku-IV ngesikhathi sokushaqeka akubikezeli ukusabela okungalinganiswa ngebhande lomshini wasekhaya ngemva kokuthatha umkhiqizo ngomlomo.
Noma yikuphi ukuhlanganiswa kobufakazi kwesikhathi esizayo mayelana nezimangalo zezifo ezihlala isikhathi eside kuzodinga idatha evela ezifundweni ezabela abantu emaqenjini ngokungahleliwe, ezihlola izimpawu, ukusebenza, ukulaliswa esibhedlela, nokuphepha ngohlelo lwangempela lokuthatha umuthi ngomlomo, hhayi okunye ukuhlolwa kwama-mitochondria.
Imibuzo yokuphepha okufanele abafundi abanezinkinga zenhliziyo bayicacise kuqala
Iziguli zenhliziyo zivame ukuthatha imithi eminingana engase isebenzisane. Ukuhlola izinto ezintathu zokuphepha kufanele kwandulele noma yimaphi amathemba asuselwa endleleni yokusebenza.
Okokuqala, i-methylene blue ivimbela kakhulu ukusebenza kwe-monoamine oxidase. Ilebula ye-IV inesexwayiso esibekwe ebhokisini nge-serotonin syndrome lapho isetshenziswa nama-SSRI, ama-SNRI, imithi evimbela i-MAO, nama-opioid athile. Izimpawu zihlanganisa ukungahlaliseki, ukudideka, umkhuhlane, ukujuluka, izinga lokushaya kwenhliziyo noma umfutho wegazi ongazinzile, ukuthuthumela, ukuqina kwemisipha, ne-clonus. Iziguli zenhliziyo kufanele zilethe uhlu oluphelele lwemithi kudokotela noma kusokhemisi futhi akufanele ziyeke ngokwazo imithi yokudangala noma yezinhlungu.
Okwesibili, ukuntuleka kwe-glucose-6-phosphate dehydrogenase kuyisizathu sokungawusebenzisi lo muthi ngoba i-methylene blue ingabangela ukubhidlika okukhulu kwamangqamuzana abomvu egazi. Isilinganiso esivamile somshini okala i-oxygen egazini ngomunwe asikwazi ukukhipha le ngozi. I-methylene blue ingaphinde iphazamise izilinganiso zalo mshini nezeminye imishini yokuqapha ngesikhathi sokubulala izinzwa, okuyisinye sezizathu zokuthi ukusetshenziswa esibhedlela kuhlale kuqashwe.
Okwesithathu, ukucabanga ngokulandelana kwezindlela zokusebenza akuwona umhlahlandlela womthamo. Ama-nitrate asebenza nge-nitric oxide ne-cyclic GMP. I-methylene blue inganciphisa ukukhululeka kwemithambo okubangelwa yi-nitric oxide ekuhlolweni, kodwa lokho akubonisi ukuthi ingamelana ngokuphepha nomphumela we-nitrate noma ithathe indawo yomuthi wenhliziyo onqunyiwe. Imiphumela yomfutho wegazi ebikiwe nge-methylene blue ye-IV ihlanganisa kokubili umfutho wegazi ophezulu nophansi, kanye nokushaya kwenhliziyo ngokushesha nokungashayi kwayo ngesigqi esijwayelekile, ngakho ukuqapha kubalulekile.
Umthetho osebenzisekayo ulula. Okutholwe ezicutshini nasezilwaneni kuyizizathu zokwenza izifundo zokuhlola ngokucophelela, hhayi izizathu zokuzelapha isimo senhliziyo. Noma ubani onokwehluleka kwenhliziyo, isifo semithambo yenhliziyo, ukungashayi kwenhliziyo ngesigqi esijwayelekile, noma idivayisi yenhliziyo kufanele axoxe nethimba lakhe lezokwelapha inhliziyo nganoma yikuphi ukuthatha noma ukuthola i-methylene blue, kubhalwe phansi umkhiqizo, ukugxila kwawo, inani, indlela onikezwe ngayo, isikhathi, nezimpawu.