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Les comportements motivés tels que les comportements alimentaires ou sexuels sont émis de façon irrégulière sous l’impulsion du système nerveux central. Ils sont régulés par des informations sensorielles et des apprentissages. Dans un apprentissage associatif, le conditionnement opérant appétitif, l’animal apprend les conséquences de son action parl’association d’une action à l’obtention d’une récompense (un stimulus à forte valeur appétitive). Il est établi que cet apprentissage induit la transition d’une motricité initialement peu fréquente et irrégulière en une motricité rythmique, fréquente et régulière. Cependant, les mécanismes cellulaires du système nerveux central qui sont responsables de cettetransition, restent largement méconnus. Notre étude chez le mollusque aplysie nous a permis d’identifier ces mécanismes dans un réseau neuronal identifié et générateur des patterns moteurs du comportement alimentaire. Sur des préparations du système nerveux isolé, nous avons sélectivement contrôlé l’expression fréquente d’une part et régulièred’autre part de la motricité apprise grâce à la manipulation expérimentale de la plasticité fonctionnelle de neurones pacemakers identifiés. Ainsi, nous avons nouvellement établi un lien de causalité entre (1) des modifications membranaires et l’accélération motrice et (2) le renforcement de synapses électriques et la régularité motrice. Nous avons mis en évidence le rôle du transmetteur dopamine dans l’induction de ces plasticités fonctionnelles et l’expression de la motricité fréquente et régulière. Enfin, nous avons analysé les propriétés intrinsèques du neurone responsable de l’impulsion spontanée et irrégulière de la motricité des animaux naïfs. Pour conclure, l’ensemble de ces travaux de thèse offre une vue étendue des mécanismes cellulaires qui déterminent la variabilité d’un comportement motivé et sarégulation par apprentissage. / Motivated behaviors such as feeding or sexual behavior are irregularly expressed by impulsive drives from the central nervous system. However, such goal-directed acts are regulated by sensory inputs and learning. In a form of associative learning, appetitive operant conditioning, an animal learns the consequences of its own actions by making the contingentassociation between an emitted act and delivery of a rewarding (highly appetitive) stimulus. It is now established that this learning procedure induces the transition from an initially infrequent and irregular motor activity to a frequent and regular behavior. However the cellular and central network mechanisms that mediate this behavioral plasticity remain poorlyunderstood. Our study on the marine sea slug Aplysia has allowed us to analyze these mechanisms in an identified neuronal network that is responsible for generating the motor patterns of the animal's feeding behavior. Using in vitro neuronal preparations, we selectively controlled the frequency and regularity of the motor activity induced by operant learning with experimental manipulations of the functional plasticity in identified pacemaker neurons. We found for the first time a causal relationship between the learning-induced plasticity and (1) changes in pacemaker neuron membrane properties and the increased frequency of feeding motor activity, and (2), in the strength of their interconnecting electrical synapses and the regularized phenotype of this motor activity. We then addressed the role of the transmitterdopamine in the induction of this functional plasticity and specifically the expression of a frequent and stereotyped rhythmic feeding motor pattern. Finally, we analyzed the intrinsic membrane properties of the essential pacemaker neuron for generating the irregular motor drive in naïve animals. In conclusion, the data from this thesis work have provided novelinsights into the cellular and synaptic mechanisms underlying the intrinsic variability of a motivated behavior and its regulation by learning.

Bakgrund: Pacemakerimplantation är en globalt förekommande behandling av symtomatisk bradykardi. I Sverige finns drygt 48 000 personer med pacemaker. Pacemakerbehandling medför livslång uppföljning samt eventuellt upprepade operationer för att byta pacemakerdosa eller elektroder. Enligt europeiska riktlinjer bör uppföljning ske med multidisciplinära team, och där har pacemakersjuksköterskan en viktig funktion. Vikten av personcentrad vård, eller omväxlande patientcentrerad vård, betonas. Utbildning och information är viktiga beståndsdelar. Syftet med denna litteraturöversikt var att belysa upplevelser hos personer som har en pacemaker. Metod: En litteraturöversikt med systematisk sökstrategi genomfördes. Arton vetenskapliga artiklar från databaserna PubMed och CINAHL inkluderades. Två av dessa var av kvalitativ metod och resterande 16 av kvantitativ metod. Samtliga artiklar kvalitetsgranskades med hjälp av ett bedömningsformulär. Artiklarnas resultat analyserades med tematisk analys för att identifiera regelbundenheter och inkonsekvenser, vilka organiserades i teman och underteman. Resultaten visade att pacemakerbärarnas upplevelser var mångfacetterade, med både positiva och negativa aspekter. Trots en initial förbättring av livskvaliteten efter implantation kunde en inte obetydlig andel av patienterna uppleva försämring framför allt på sikt. Distansmonitorering av pacemaker visade sig vara en lovande metod för uppföljning, med fördelar såsom ökad tillfredsställelse med behandlingen och minskat behov av fysiska mottagningsbesök, samtidigt kunde ingen skillnad ses gällande livskvalitet. I vissa fallnoterades brister i information och kunskap hos pacemakerbärarna, vilket ledde till oro och osäkerhet kring hantering av pacemakern, som i sin tur ledde till begränsningar i det vardagliga livet. Slutsatsen är att strukturerad och personcentrerad vård anpassad till den tekniska utvecklingen är viktigt. Det inkluderar förbättrad information och utbildning, som är avgörande för att öka pacemakerbärarnas kunskap. Därigenom kan oro minska samt livskvaliteten förbättras. Framtida forskning och utveckling inom området behövs för att möta de ökade behoven hos denna patientgrupp och förbättra vården på individnivå. / Background: Pacemaker implantation is a globally prevalent treatment for symptomatic bradycardia. In Sweden, there are more than 48,000 pacemaker recipients. Pacemaker treatment involves lifelong follow-up and possibly repeated surgeries to replace the pacemaker device or electrodes. According to European guidelines, follow-up should be conducted by multidisciplinary teams, in which the pacemaker nurse has an important function. The importance of person-centered care, alternatively patient-centered care, is emphasized and education and information are important components. The aim of this literature review was to illuminate experiences among individuals with pacemakers. Method: A literature review was conducted, using systematic search strategy. Eighteen scientific articles from the databases PubMed and CINAHL were included. Two of these were of qualitative method and the remaining 16 of quantitative method. All articles were quality reviewed using an assessment form. Data analysis was conducted with thematic analysis to identify regularities and inconsistencies, which were organized into themes and subthemes. The results revealed multifaceted experiences among pacemaker recipients, encompassing both positive and negative aspects. Despite an initial improvement in quality of life postimplantation, a non-neglible proportion of patients experienced long-term deterioration.Remote monitoring of pacemakers emerged as a promising method for follow-up, offering benefits such as increased satisfaction and reduced need for in-clinic visits, with no distinctimpact on quality of life. However, deficiencies in information and knowledge among pacemaker recipients were sometimes noted, leading to anxiety and uncertainty regarding device management, consequently restricting daily life. The conclusion is that structured and person-centered care adapted to technological advancements is important. This includes enhanced information and education, which are essential for improving pacemaker recipients’ knowledge and, consequently, reducing anxiety while improving their quality of life. Future research and development in the field are necessary to address the growing needs of this patient population and enhance care at an individual level.

Master of Science / Department of Computing and Information Sciences / John Hatcliff / The Heart is a specialized muscle that contracts regularly and continuously, pumping blood to the body and the lungs. Heart’s natural Pacemaker, the SA node is responsible for this pumping action by causing a flow of electricity through the heart. These electrical impulses cause the atria and ventricles to contract and thereby pump the blood to different parts of the body. Malfunction of the SA node leads to a disturbance in the heart’s rhythm in which heart beats lower than 60 times a minute ending up with Bradycardia. It also leads to ventricular arrhythmia which disrupts the ability of the ventricles to pump blood effectively to the body. This can cause a loss of all blood pressure leading to cardiac arrest and eventually death. In order to restore the heart’s natural healthy rhythm, an artificial pacemaker is necessary. A Pacemaker adapts to the present condition of the heart and responds to the heart by either pacing or just sensing it. It paces whenever there is some problem in the heart’s electrical activity and inhibits the pace when there is a proper intrinsic beat. There are various modes in which Pacemaker can operate based on the condition of the heart. Ventricles and atria are individually paced in few modes such as VOO, VVT, VVI, AOO, AAT, and AAI and paced together in some modes such as DVI, DI, DDD, DDDR as per the requirement of the heart. The main goal of this report is to understand the various modes, their nomenclature, working strategy, developing the pseudo code and implementing different modes namely VOO, AOO, VVI, AAI, VVT and AAT modes using an academic, dual chamber pacemaker.

Correction de la bradycardie et des troubles de conduction dans des modèles de dysfonction congénitale de l’automatisme cardiaque par l’inhibition pharmacologique du courant IKAChLa dysfonction du nœud sinusal (DNS) est l’une des principales pathologies de l’automatisme cardiaque. La DNS désigne une multitude de troubles caractérisées par l’incapacité du nœud sinusal (SAN) à générer ou à conduire l’impulsion cardiaque. La seule thérapie actuellement disponible pour la DNS est l’implantation d’un pacemaker électronique. Des études épidémiologiques prévoient un besoin croissant d’implantation de pacemaker électroniques au cours des 50 prochaines années à cause du vieillissement de la population. Le développement des thérapies innovantes pour la DNS est donc un enjeu médical et sociétal important. L’inhibition pharmacologique du courant potassique activé par l’acétylcholine (IKACh) pourrait constituer une nouvelle option thérapeutique pour traiter la DNS.Nous avons donc testé l’inhibition du courant IKACh par un peptide de venin d’abeille, la Tertiapine-Q, pour corriger le DNS et le dysfonctionnement de la conduction chez des souris modèle de pathologies cardiaque humaine en particulier les souris portant l’inactivation des canaux L Cav1.3 (Cav1.3-/-), les souris portant simultanément l’ablation de Cav1.3 et des canaux de type-T Cav3.1 (Cav1.3-/-/Cav3.1-/-), les souris porteuses de la perte de fonction des canaux f- (HCN4-CNBD) et les souris haplo-suffisantes Nav1.5 (Scn5a+/-).Nous avons enregistré par télémétrie, l’ECG, chez ces modèles murins avant et après l’administration de différentes doses de Tertiapine-Q.L’inhibition du courant IKACh par la Tertiapine-Q prévient des dysfonctions sinusales et améliore la conduction dans ces modèles de bradycardie congénitale suggérant la possibilité d’un développement d’un ciblage pharmacologique d’IKACh afin de parvenir à corriger la DNS et les troubles de la conduction. / Inhibition of KACh channels by the bee venom peptide tertiapin-Q rescues inherited cardiac conduction defects, sino-atrial bradycardia, and atrioventricular block in models of congenital dysfunctionSinus node dysfunction (SND) is a widespread disease of heart automaticity. SND refers to a multitude of sinus node (SAN) disorders characterized by failure to generate or conduct the cardiac impulse. The only currently available therapy for chronic SND is the implantation of an electronic pacemaker. Epidemiological studies forecast an increasing need for pacemaker implantation during the next 50 years, with the ageing of the population. It is thus an important medical and societal issue, to develop innovative therapies for SND. Pharmacologic inhibition of the G-protein activated K+ current (IKACh) could be a new therapeutic option to treat bradycardia and SND associated with other cardiac pathologies.We tested whether inhibition of IKAch by the peptide Tertiapin-Q could rescue SND and conduction dysfunction in Cav1.3-/- mice carrying concurrent ablation of L-type Cav1.3 and T-type Cav3.1 channels (Cav1.3-/-/Cav3.1-/-), mice carrying loss-of-function of f-channels (HCN4-CNBD) and Nav1.5 haploinsufficient (Scn5a+/-) mice.We employed telemetric ECG recordings of heart rate (HR), SAN pacemaking and AV dysfunction in mice before and after administration of different doses of Tertiapin-Q.Tertiapin-Q significantly improves the HR of Cav1.3-/-, Cav1.3-/-/Cav3.1-/-, and HCN4-CNBD from doses of 0.1 to 5 mg/kg. HRs of Tertiapin-Q-treated mice were similar to those recorded in untreated wild-type mice. Tertiapin-Q also improved cardiac conduction of Scn5a+/- mice by 24%.Pharmacological inhibition of IKAch by Tertiapin-Q prevents SAN dysfunction and improves conduction in three models of congenital bradycardia suggesting the possibility of pharmacologic development of IKACh targeting to manage SND and conduction disease, to delay or replace the implantation of an electronic pacemaker.

A major problem in healthcare today is the manual handling of administrative work. Few processes are automated and healthcare professionals are forced to spend a lot of time on paperwork, which means that their time with patients suffers. This has a major negative impact on patient safety. In addition, these manual processes mean that it is often not possible to trace implants in the care process. The purpose of this thesis is to investigate the effect that the implementation of traceability of implantable pacemakers can have on patient safety, on the working environment of healthcare professionals as well as on the financial incentives of hospitals. To answer the questions, a qualitative research strategy was used where first a scientific literature review was conducted; thereafter, interviews were conducted with healthcare professionals from clinics for implantation of active implants, as well as with professionals in the regulation of medical devices and the manufacture of pacemakers; later a regulatory document review was conducted. Lastly, based on the findings obtained, a proposal was formulated for a solution of a digital traceability process. The key results that could be found were that the methods and opportunities for conducting traceability in hospitals in Sweden differ. In addition, the results showed that in many places in the European and Swedish regulations, requirements were made for traceability to be conducted in hospitals, however, information and guidance are lacking on how traceability can be conducted in an efficient manner. Many interviewees also experienced this void of guidance documents and had a unanimous view that an effective digital traceability system would have an entirely positive impact on patient safety, on the healthcare environment's working environment and on hospitals' financial incentives. In summary, a guidance regulatory document is required to standardize traceability processes. In addition, an essential aspect of the possibilities for creating effective digital traceability systems is that there is collaboration at several levels to reach consensus and interoperability between healthcare systems. / Ett stort problem inom sjukvården idag är den manuella hanteringen av administrativt arbete. Få processer är automatiserade och sjukvårdspersonalen tvingas lägga mycket tid på pappersarbete, vilket gör att deras tid med patienter blir lidande. Detta har stor negativ påverkan på patientsäkerheten. Dessutom medför dessa manuella processer att det ofta inte går att spåra implantat i vårdprocessen. Syftet med detta examensarbete är att undersöka vilken effekt införandet av spårbarhet av implanterbara pacemakers kan ha på patientsäkerheten, på sjukvårdspersonalens arbetsmiljö samt på sjukhusens ekonomiska incitament. För att besvara frågeställningarna användes en kvalitativ forskningsstrategi där först en litteraturöversikt utfördes. Därefter genomfördes intervjuer med vårdpersonal inom mottagningar för implantering av aktiva implantat, samt med yrkesverksamma inom regleringen av medicintekniska produkter samt tillverkning av pacemakers. Efter detta utfördes en literaturstudie. Slutligen, baserat på de resultat som erhölls, formulerades ett förslag på en lösning av en digital spårbarhetsprocess. De nyckelresultat som kunde återfinnas var att metoderna och möjlig-heterna för att bedriva spårbarhet på sjukhus i Sverige skiljer sig åt. Dessutom visade resultaten att det på många ställen i de Europeiska och Svenska regelverken ställdes krav på att spårbarhet ska bedrivas på inom sjukvården, däremot så fattas information och vägledning om hur spårbarhet kan bedrivas på ett effektivt sätt. Många intervjudeltagare upplevde också detta tomrum av vägledande dokument och hade en enad uppfattning om att ett effektivt digitalt spårbarhetssystem enbart skulle ha positiv inverkan på patientsäkerheten, på vårdpersonalens arbetsmiljö samt på sjukhusens ekonomiska incitament. Sammanfattningsvis krävs det vägledande regulatoriska dokument för att standardisera processerna för spårbarhet. Dessutom är en väsentlig aspekt av möjligheterna för att skapa effektiva digitala spårbarhetssystem att det sker ett samarbete på ett flertal nivåer för att nå konsensus och interoperabilitet mellan sjukvårdens system.

published_or_final_version / Medicine / Doctoral / Doctor of Philosophy

En pacemaker eller implantable cardioverter defibrillator (ICD) kan för många innebära en upplevelse av att de får en ny chans till livet. Sedan den första pacemakern sattes in på 50-talet har utvecklingen gått framåt och många livshotande rytmrubbningar kan behandlas. Att behandlas med pacemaker eller ICD kan innebära både fysiska och psykiska omställningar i det vardagliga livet. Dessa fysiska och psykiska omställningar kan påverka patientens livsvärld, levda kropp, hälsa och välbefinnande samtidigt som det kan inge ett hopp inför framtiden. För att vårdpersonal och närstående ska kunna ge ett bra stöd till personerna med pacemaker eller ICD är det av stor vikt att belysa upplevelsen av hur det är att leva med detta hjälpmedel. Syftet är att undersöka upplevelser av att leva med pacemaker eller ICD. För att svara på syftet genomfördes en litteraturstudie där Fribergs (2006, ss. 115-124) modell användes för analys av data. Resultatet bygger på analyser av åtta kvalitativa och två kvantitativa studier, dessa redovisas i form av fyra huvudteman; Att uppleva livsförändringar, att vara i behov av stöd och utbildning, att hitta sin egen väg till acceptans och att uppleva oro. Att behandlas med en pacemaker eller ICD kan för många innebära att livet förändras. Det kan innebära att individen får en mer positiv inställning till livet men det kan också innebära en del begränsningar som i sin tur kan leda till att personen drar sig undan. Det finns ett stort behov av mer stöd och utbildning från vårdpersonal för att individerna ska uppleva en trygghet i sin vardag. Den nya livssituationen kan innebära att individen måste försöka finna en egen väg mot att acceptera sin livsvärld. Det kan även finnas en oro inför framtiden och hur deras sjukdom kommer att påverka deras barn. För att patienten ska uppleva en trygghet i sin vardag behöver vårdpersonalen en större insikt och förståelse i patientens liv och på så sätt kunna ge en bättre information och utbildning. / Program: Sjuksköterskeutbildning

Introdução: Pretende-se com a estimulação cardíaca artificial promover melhor qualidade de vida a portadores de complicações cardíacas graves, porém, a falta de conhecimento dos pacientes e o despreparo dos profissionais de saúde podem influenciar nos hábitos de vida e no surgimento de possíveis complicações. Objetivo: Avaliar a qualidade de vida relacionada à saúde (QVRS) de pacientes portadores de marca-passo (MCP) e explorar as associações entre QVRS e variáveis sociodemográficas, clínicas e sintomas de ansiedade e depressão. Método: Estudo observacional analítico, de corte transversal, realizado em hospital universitário do interior paulista. Uma amostra consecutiva e não probabilística foi constituída de pacientes de ambos os sexos, maiores de 18 anos, portadores de MCP há pelo menos um mês. Para a avaliação da QVRS, foi utilizado um instrumento genérico (SF-36) e um específico (AQUAREL). Para investigarmos a associação da QVRS com o sexo e o estado civil, utilizamos o teste t de Student. Para QVRS com a idade, o tempo de implante de MCP e os sintomas de ansiedade e de depressão, utilizamos o teste de Correlação de Pearson. O nível de significância foi de 0,05. Resultados: Participaram 88 pacientes, maioria do sexo masculino e com companheiro. Sua média de idade foi 64,3 (DP=13,0). Utilizando o SF-36, o domínio que apresentou maior média foi \"Aspectos Sociais\", e a menor, \"Aspectos Físicos\". Utilizando o AQUAREL, o domínio de maior média foi \"Arritmia\", e o de menor, \"Dispneia\". Quanto às associações, as mulheres apresentaram menores médias nos domínios \"Capacidade Funcional\", \"Estado Geral de Saúde\", \"Vitalidade\", \"Saúde Mental\" e \"Componente Mental\" do SF-36, bem como nos domínios \"Arritmia\" e \"Dispneia\" do AQUAREL, com significância estatística. Os pacientes sem companheiro apresentaram menores médias nos domínios \"Capacidade Funcional\", \"Vitalidade\" e \"Aspectos Sociais\" do SF-36, e nos domínios \"Arritmia\" e \"Dispneia\" AQUAREL, com significância estatística. Quanto à idade, as correlações foram significativas com os domínios \"Capacidade Funcional\" e \"Aspectos Físicos\" do SF-36, com baixa força de correlação. Quanto ao tempo de implante de MCP, as correlações foram significativas com o domínio \"Capacidade Funcional\" do SF-36 e com o domínio \"Arritmia\" do AQUAREL, com baixa força da correlação. Quanto à correlação da QVRS com os sintomas de ansiedade, foi significativa com os oito domínios do SF-36 e com os dois componentes, negativa, de forte magnitude no domínio \"Saúde Mental\" e no Componente Mental, e moderada em outros seis domínios. A correlação da ansiedade com os três domínios do AQUAREL foi negativa, significativa e de moderada magnitude. Quanto à correlação da depressão com a QVRS, foi significativa com os oito domínios do SF-36 e com os dois componentes, negativa, de forte magnitude no domínio \"Saúde Mental\" e moderada magnitude em quatro domínios e no Componente Mental. A correlação da depressão com os três domínios do AQUAREL foi negativa, significativa e de moderada magnitude. Conclusão: Os pacientes apresentaram pior QVRS nos domínios que avaliaram o quanto as condições físicas interferem no dia-a-dia. As mulheres, os pacientes sem companheiro e com maior sintomatologia de ansiedade e depressão apresentaram pior avaliação. / Introduction: Artificial cardiac stimulation aims to offer a better quality of life to those with severe cardiac problems. However, the lack of knowledge of the patients and the lack of preparation of health professionals can influence the life habits and lead to the surfacing of potential complications. Objective: Evaluating the health-related quality of life (HRQOL) of patients who have pacemakers (PM) and explore the associations between HRQOL and sociodemographic and clinical variables and symptoms of anxiety and depression. Method: Observational, analytical and cross-sectional study, conducted in a teaching hospital in the countryside of the state of São Paulo. A consecutive non-probabilistic sample was created including male and female patients above 18 years old who had had an MP for at least a month. To evaluate their HRQOL, a generic (SF-36) and a specific (AQUAREL) instruments were used. To investigate the association of HRQOL with sex and marital status, Student\'s t-test was used, and to analyze its relationship to age, time since MP implantation, and depression and anxiety symptoms, Pearson\'s Correlation Coefficient was used. The significance level was 0.05. Results: 88 patients participated, most were male and had partners. Age average was 64.3 (SD=13.0). The SF-36 domain with the highest average was \"Social Aspects\", and the one with the lowest, \"Physical Aspects\". The greatest average among AQUAREL domains was \"Arrythmia\", and the lowest, \"Dyspnea\". As to associations, women presented lower averages in the domains \"Functional Capabilities\", \"General Health State\", \"Vitality\", \"Mental Health\" and \"Mental Component\" of the SF-36. The same was true for AQUAREL domains \"Arrythmia\" and \"Dyspnea\", all these correlations statistically significant. Patients with no partners had statistically significant lower averages in the SF-36 domains \"Functional Capabilities\", \"Vitality\" and \"Social Aspects\", and in the AQUAREL domains \"Arrythmia\" and \"Dyspnea\". As to their age, correlations were significant with the SF-36 domains \"Functional Capabilities\" and \"Physical Aspects\", with low-strength correlations. As to the time passed since the PM implantation, low-strength correlations were significant in the SF-36 domain \"Functional Capabilities\" and the AQUAREL domain \"Arrythmia\". As to the correlation of HRQOL to anxiety symptoms, it was significant for the eight SF-36 domains and its two components, being negative and strong in the \"Mental Health\" domain and in the Mental Component, and moderate in the other domains. Anxiety was negatively, significantly and moderately correlated to all three AQUAREL domains. The correlation of depression to HRQOL, was significant in the eight SF-36 domains and its two components, negative and strong in the \"Mental Health\" domain and moderately strong in four Mental Component domains. Depression was negatively, significantly and moderately correlated to all three AQUAREL domains. Conclusion: Patients had lower HRQOL in the domains which evaluated how do physical conditions interfere in their daily lives. Women, patients with no partners and more anxiety and depression symptoms had worse results in the evaluation.