To evaluate whether cervical spinal neurons can influence cardiac indices and myocyte viability in the acutely ischemic heart, the hearts of anesthetized rabbits subjected to 30. min of LAD coronary arterial occlusion (CAO) were studied 3. h after reperfusion. Control animals were compared to those exposed to pre-emptive high cervical cord stimulation (SCS; the dorsal aspect of the C1-C2 spinal cord was stimulated electrically at 50. Hz; 0.2. ms; 90% of motor threshold, starting 15. min prior to and continuing throughout CAO). Four groups of animals were so tested: 1) neuroaxis intact; 2) prior cervical vagotomy; 3) prior transection of the dorsal spinal columns at C6; and 4) following pharmacological treatment [muscarinic (atropine) or adrenergic (atenolol, prazosin or yohimbine) receptor blockade]. Infarct size (IS) was measured by tetrazolium, expressed as percentage of risk zone. C1-C2 SCS reduced acute ischemia induced IS by 43%, without changing the incidence of sudden cardiac death (SCD). While SCS-induced reduction in IS was unaffected by vagotomy, it was no longer evident following transection of C6 dorsal columns or atropinization. Beta-adrenoceptor blockade eliminated ischemia induced SCD, while alpha-receptor blockade doubled its incidence. During SCS, myocardial ischemia induced SCD was eliminated following vagotomy while remaining unaffected by atropinization. These data indicate that, in contrast to thoracic spinal neurons, i) cranial cervical spinal neurons affect both adrenergic and cholinergic motor outflows to the heart such that ii) their activation modifies ventricular infarct size and lethal arrhythmogenesis.

京都大学 / 0048 / 新制・課程博士 / 博士(医学) / 甲第19606号 / 医博第4113号 / 新制||医||1015(附属図書館) / 32642 / 京都大学大学院医学研究科医学専攻 / (主査)教授 小池 薫, 教授 YOUSSEFIAN Shohab, 教授 川村 孝 / 学位規則第4条第1項該当 / Doctor of Medical Science / Kyoto University / DFAM

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Bakgrund: Under 2019 överlevde ca 18% av de som drabbats av hjärtstopp. Dödligheten vid hjärtstopp är hög och konsekvenserna kan bli stora och konvalescensen lång. För att förstå vad patienter upplever efter överlevnad krävs kunskap om ämnet. Syfte: Att belysa patienters upplevelser efter att ha överlevt ett hjärtstopp. Metod: En litteraturöversikt med kvalitativ design genomfördes. Resultat: Analysen resulterade i temat ett främmande liv med nytt perspektiv innehållande tre subteman; att vakna i kaos, att leva i närvaron av sitt hjärtstopp och att se livet med andra ögon, samt temat ett begränsat liv i ett nytt sammanhang innehållande fyra subteman; att inte lita på sin kropp, att leva i skuggan av mental ohälsa, att vara i behov av stöd och att fortsätta leva livet. Slutsats: Överlevnad var förenat med upplevelser av lidande vilket medförde begränsningar i det dagliga livet men det gav också nya perspektiv. Det upplevdes svårt att komma hem efter utskrivning relaterat till osäkerhet och minskad tillit till kroppen. Sjukvården upplevdes inte tillmötesgå patienternas behov av information och rådgivning vilket förorsakade ytterligare lidande. Att i framtiden utforska behovet av stöd och uppföljning utifrån ett långsiktigt perspektiv är relevant då studieresultatet visar att det har upplevts saknats för patienterna. / Background: Mortality from cardiac arrest is high and the consequences can be big and the convalescence long. In terms of being able to understand what patients experience after survival, more knowledge is required. Aim: To illuminate patients' experiences after surviving a cardiac arrest. Method: A literature review with qualitative design was conducted. Results: The analysis resulted in the theme of a foreign life with a new perspective containing three subthemes; to wake up in chaos, to live in the presence of the cardiac arrest and to see life with different eyes. The other theme was a limited life in a new coherence containing four subthemes; not to trust their body, to live in the shadow of mental illness, to be in need of support and to continue living life. Conclusions: Survival was associated with experiences of suffering, which led to limitations in daily life, but also gave new perspectives on life. It was difficult to come home after discharge related to insecurity and decreased confidence in the body. Healthcare was perceived as not being able to meet patients' needs for information and advice, which caused further suffering. According to the result, it is relevant to further explore the need for.

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Voltage-gated sodium channels are composed of pore-forming α-subunits, and modulatory and multifunctional associated β subunits. While much of the field of cardiac electrophysiology and pathology has focused on treating and preventing cardiac arrhythmias by targeting the α subunit, there is also evidence that targeting the β subunits, particularly SCN1B, the gene that encodes β1 and an alternatively spliced variant β1B, has therapeutic potential. The first attempt at targeting the β1 subunit was with the generation of and treatment with an SCN1B Ig domain mimetic peptide βadp1. Here we describe further investigation into the function and mode-of-action of both βadp1 and novel peptides derived from the original βadp1 sequence. We find that in a heterologous expression system βadp1 initially disrupts β1-mediated trans-homophilic adhesion, but after approximately 30 hours eventually increases adhesion. Novel mimetic dimers increase β1 adhesion up to 48 hours post-treatment. Furthermore, it appears that βadp1 may increase β1 adhesion by upregulating the intramembrane proteolysis of β1, a process which has important downstream implications and effects on translation. Despite these exciting findings, we were unable to translate them into a primary culture of cardiac cells with endogenous expression of β1 because we found that both neonatal rat cardiomyocytes and isolated adult mouse cardiomyocytes do not express β1 at detectable levels, whereas they do appear to express β1B. In summary, we show exciting findings on the function and mode-of-action of SCN1B mimetic peptides and their therapeutic potential in targeting the β1 subunit, but further work is needed to determine the translatability of our findings to in vivo models and eventually to humans. / Doctor of Philosophy / Voltage-gated sodium channels have two main parts: the pore-forming α-subunits and the modulatory β subunits. Most research in heart function and issues has focused on fixing problems with the α subunit. However, there's evidence that working on the β subunits, specifically the SCN1B gene that makes β1 and another version called β1B, could be helpful. Previously, researchers used a peptide that is designed exactly like a part of β1, called βadp1, to target the β1 subunit. In our study, we explore more about how βadp1 works and test new peptides based on βadp1. We found that βadp1 initially disrupts trans-homophilic adhesion, where 2 β1 subunits interact with each other across the space between 2 cells, but after about 30 hours, it actually increases adhesion. New mimetic dimers also boost adhesion up to 48 hours later. It seems like βadp1 might enhance adhesion by triggering a process called intramembrane proteolysis of β1, which has important effects on translation. Despite these exciting findings, we couldn't confirm the presence of this protein in heart cells because we discovered that certain heart cells don't have enough β1, although they do have β1B. In conclusion, our study shows promising results about how SCN1B mimetic peptides work and their potential for treating arrhythmia. However, more research is needed to see if these findings apply to real-life situations and eventually to help people with cardiac conduction abnormalities.

京都大学 / 新制・課程博士 / 博士(医学) / 甲第23809号 / 医博第4855号 / 新制||医||1058(附属図書館) / 京都大学大学院医学研究科医学専攻 / (主査)教授 渡邊 直樹, 教授 浅野 雅秀, 教授 安達 泰治 / 学位規則第4条第1項該当 / Doctor of Medical Science / Kyoto University / DFAM

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