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McDonald, Cameron. "Investigations in Cardiac Development and Cardiac Regeneration." Thesis, Griffith University, 2009. http://hdl.handle.net/10072/366063.
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Cardiovascular disease and congenital heart disease impose a massive burden on society around the world. From the cost in terms of lost human lives and diminished quality of life, to the financial expense of ongoing medical treatment, the heart’s inability to effectively repair and regenerate itself presents a major challenge for medical research. The research conducted within this thesis hoped to contribute to our knowledge of the molecular pathways of myocardial development, and to explore the potential of olfactory derived stem cells to repopulate insulted myocardium. A combination of molecular biology and classical embryology techniques were first used to characterise two novel cDNAs identified in an earlier study as being upregulated in the regions of cardiac development within the chick embryo. cDNA and genomic library screening along with RACE (rapid amplification of cDNA ends) produced products which were sequenced to identify both the transcript and genomic sequence for both of the genes. Protein expression constructs were then used to identify the localisation of the encoded proteins, and whole mount in situ hybridisation utilised to identify the temporal and spatial expression patterns of the genes. The first cDNA was identified as the vertebrate homologue of the Drosophila e(y)2 gene, and produces a transcript of approximately 600 bp in the chick with a genomic structure consisting of 5 exons covering approximately 6 Kb. The encoded protein localises to the nucleus. Its expression is ubiquitous both temporally and spatially, which is at odds with its initial method of identification. The second cDNA remains novel at the time of submission, and shows no homology to any characterised genes. This cDNA, named C1-3C, produces two alternative transcripts, one of approximately 700 bp, and a second of 9.9 Kb, with a genomic structure showing no introns within the 2 Kb of analysed sequence. The encoded protein again localises to the nucleus. Expression of the C1-3C gene demonstrated a discrete pattern, though this pattern is again contrary to an up-regulation within the cardiogenic regions. Whilst unfortunately neither of the investigated genes appear to play a direct role in cardiac development, the aim of characterisation of these novel cDNAs was achieved.Thesis (PhD Doctorate)
Doctor of Philosophy (PhD)
School of Biomolecular and Physical Sciences
Science, Environment, Engineering and Technology
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Paul, Ashok Abraham. "Investigation of cardiac and non-cardiac drugs that modulate cardiac Herg K⺠channels." Thesis, University of Bristol, 2002. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.274632.
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Baily, James Edward. "Role of cardiac perivascular cells in cardiac repair." Thesis, University of Edinburgh, 2015. http://hdl.handle.net/1842/15846.
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Ischaemic heart disease accounts for approximately 7 million deaths worldwide on a yearly basis and this figure is only set to rise as life expectancy in developing countries increases. Although no longer considered a post mitotic organ, the adult heart demonstrates only a very limited capacity for regeneration. Consequently ischaemic injury results in massive loss of contractile cardiomyocytes with damaged myocardium replaced by a non-contractile and poorly conductive collagen scar. This in turn often leads to the development of heart failure. Enhancing or supplementing the myocardial regenerative capacity of the heart is thus a key goal in the development of effective therapies for the treatment of cardiac infarction. Several stem cell populations of non-cardiac origin have been investigated for their capacity to contribute to myocardial repair when therapeutically transplanted into injured hearts. Recent efforts have focused on the “next generation” of donor cells, endogenous cardiac progenitor cells, as these are thought to be better adapted to survival in the cardiac environment and to possess enhanced cardiomyocyte differentiation potential. Pericytes, proposed as the source of the elusive mesenchymal stem cells (MSC) within multiple tissues, are a potential new cell type for use in regenerative medicine. This study tests the hypothesis that pericytes and another perivascular progenitor population, the adventitial cell, from foetal cardiac tissue will positively contribute to the repair of the myocardium post injury. Staining of human foetal ventricular myocardium confirmed the presence of large numbers of both cell types with pericytes tightly associated with capillaries and adventitial cells primarily located in the outer, adventitial layer of muscular arteries. CD146+ CD34- pericytes and CD146- CD34+ adventitial cells were isolated by FACS and expanded in culture. On examination of gene and protein expression both populations stably expressed a similar panel of pericyte markers, MSC markers and cardiac transcription factors as well as c-kit, a cardiac progenitor cell candidate marker. Co-culture with neo-natal rat cardiomyocytes induced expression of an additional cardiac progenitor marker Isl-1 and a mature cardiomyocyte marker ANP in adventitial cells but not pericytes. Labelled, co-cultured, perivascular progenitors readily adhered to rat cells but did not appear to contract independently. De-methylation of perivascular progenitors prior to co-culture resulted in expression of sarcomeric proteins and spontaneous cytoplasmic calcium fluctuations in both populations but more commonly in pericytes. This suggests that cardiac perivascular cells contain a minor sub-population capable of cardiomyocyte differentiation. When these populations were injected into the infarcted hearts of NOD/SCID mice, the animals treated with adventitial cells had significantly reduced cardiac function at 21 days post-surgery on ultrasound examination. An increased scar area and a non-significant trend towards increased scar length and a decreased wall thickness were also observed. Transplanted cells of both groups were detected in low numbers 21 days after injection. Adventitial cells were retained much more readily and in both populations retained cells exhibited three key morphologies: fibroblast type; macrophage type; and cardiomyocyte type. The majority of cells adopted a fibroblast type morphology, lesser numbers a macrophage like morphology and only rare cells a cardiomyocyte like morphology. Both fibroblast and cardiomyocyte type cells had single, human nuclear antigen positive nuclei suggesting true differentiation rather than cell fusion and pericytes exhibited an enhanced ability to differentiate into cardiomyocytes. This supports the in-vitro findings of a minor pro-cardiomyogenic subset within the perivascular cell population. As a result of these findings the starting hypothesis was modified to propose that perivascular cells play a significant role in cardiac fibrosis, largely mediated through expression of surface integrin receptors. This was tested using mice expressing fluorescent proteins under the control of the PDGFR-β promoter and mice in which the αv integrin subunit, common to 5 integrin receptors, had been deleted on the surface of PDGFR-β+ cells. Immunostaining and flow cytometry revealed the PDGFR-β expression to be tightly restricted to perivascular cells and co-expressed with the fibroblast markers, vimentin, PDGFR-α, CD90.2 and CD34 in a subset of cells. Cardiac fibroblasts isolated from reporter mouse hearts revealed strong expression of PDGFR-α and CD34 but PDGFR-β expression in only approximately 20% of the population on flow cytometry. Following angiotensin II induced cardiac hypertrophy and fibrosis approximately 50% of fibroblasts expanding the interstitium were PDGFR-β+. Genetic deletion of the αv integrin subunit on PDGFR-β+ cells resulted in a reduction in cardiac interstitial collagen content of about 50% compared to wild type controls. These findings suggest that the cardiac perivascular PDGFR-β+ population is heterogeneous with a sub-population likely to be fibroblasts or fibroblast progenitors and that the development of cardiac interstitial fibrosis is in part modulated by integrin receptor expression on these cells. In summary this study provides evidence of the existence of a pro-fibrotic progenitor population, which co-express pericyte and MSC markers, within the cardiac perivascular niche. These cells contribute to cardiac fibrosis both on transplantation and endogenously following cardiac injury with the latter mediated via αv integrin expression. Within the perivascular progenitor population however there also appears to be a minor subset of pro-cardiomyogenic cells which are able to adopt a cardiomyocyte phenotype both in-vitro and in-vivo.
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Gràcia, Sánchez Laura Maria. "Tomografía por emisión de positrones con 18F-FDG en patología cardíaca y vascular." Doctoral thesis, Universitat Autònoma de Barcelona, 2016. http://hdl.handle.net/10803/399846.
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En la última década la técnica PET-CT con 18F-FDG, ha demostrado ser de gran utilidad en el diagnóstico, extensión y control de diversas patologías inflamatorias e infecciosas. El territorio miocárdico, no obstante, sigue presentando un reto a la hora de valorar dichas patologías, dada su variabilidad a la hora de presentar o no, captación fisiológica de 18F-FDG.
Las metodologías prínceps para intentar frenar el metabolismo cardiaco fisiológico, son el ayuno prolongado, la dieta pobre en hidratos de carbono y rica en ácidos grasos, y la administración endovenosa de heparina minutos antes de la inyección de 18F-FDG, siempre y cuando no existan contraindicaciones.
Existen muchos pacientes que por sus antecedentes patológicos y por sus características individuales o sociales no pueden realizar ayunos prolongados o cumplir estrictamente dietas preestablecidas previas a la exploración tomográfica. Como último recurso muchos de estos pacientes únicamente disponen de la metodología heparinizante para intentar optimizar la captación miocárdica y a pesar de este hecho, la heparina endovenosa no acaba siendo efectiva en todos los pacientes.
La línea de investigación desarrollada en esta tesis doctoral responde a la necesidad de poder prever la efectividad del fármaco heparinizante, y poder determinar a priori, en que sujetos, dicho tratamiento podría ser óptimo dados sus antecedentes patológicos, uso de fármacos o características personales. Por consiguiente, se podría evitar la administración de un fármaco en aquellos sujetos que previsiblemente no va a ser efectivo, o indicarla claramente al grupo efectivo.
Se evaluaron 479 sujetos, (230 mujeres) con una media de edad de 65 años (22-86) con indicación de realizarse un PET-CT secundario a su enfermedad de base (proceso oncológico o sospecha de proceso infeccioso o inflamatorio en territorio cardiaco o vascular). Se estudiaron 5 grupos de sujetos: sujetos con diabetes mellitus, sujetos con dislipemia en tratamiento crónico hipolipemiante, sujetos con dislipemia sin tratamiento crónico para dicha patología y sujetos con síndrome metabólico (coexistencia de diabetes y dislipemia) y sujetos normales (presentan ausencia de las enfermedades anteriormente citadas). Se compararon dos protocolos: uno caracterizado por un ayuno mínimo de 6 horas y un protocolo heparinizante, caracterizado por un ayuno mínimo de 6 horas más la administración de heparina endovenosa minutos antes de la inyección de 18F-FDG, en relación al peso de cada sujeto.
Los resultados obtenidos objetivaron que el protocolo heparinizante obtiene mayor frenación del metabolismo glicídico miocárdico con resultados estadísticamente significativos en toda la población a estudio, y en la subpoblación de dislipémicos sin tratamiento hipolipemiante. También se observó un mayor número de sujetos con mayor frenación miocárdica aunque con un resultado estadísticamente no significativo, en la subpoblación normal y en la subpoblación con síndrome metabólico. Por lo tanto, en estos grupos de estudio, citados anteriormente serían tributarios de realizar un protocolo heparinizante para intentar optimizar de manera generalizada la frenación el metabolismo glicídico miocárdico.
Por el contrario, se observó que el protocolo heparinizante no es de utilidad con unos resultados casi significativos, en la subpoblación diabética, y en la subpoblación con dislipemia con tratamiento farmacológico hipolipemiante crónico. En estas dos subpoblaciones, sería más efectivo realizar un protocolo únicamente caracterizado por ayuno, mínimo de 6 horas.
Tras los resultados obtenidos en este trabajo se ha confirmado la aplicabilidad de la técnica heparinizante en nuestra comunidad y válida dicha metodología para implementarse en la rutina asistencial, únicamente en aquellos sujetos que realmente requieran de la misma, de manera individualizada en relación a unos antecedentes clínicos determinados.18F-FDG PET/CT is a valuable diagnostic tool in the evaluation of inflammatory and infection diseases. Appropriate patient preparation is important because the diagnostic accuracy of this procedure depends on an adequate suppression of physiologic glucose uptake in the myocardium. There are different methods to reduce myocardial 18F-FDG uptake, such as long fasting period, high fat and low-carbohydrate diet and the administration of heparin some minutes before the 18F-FDG dose injection only if there is no counter-indication Due to their pathological background or their individual characteristics, many patients are unable to do fast for many hours or to follow high fat and low-carbohydrate diet before the scan. The administration of heparin some minutes before the 18F-FDG dose injection is the only method to try to do an adequate suppression of physiologic glucose uptake in the myocardium. However, not always the heparin’s method works properly doing a suppression of physiologic glucose uptake in the myocardium. The aim of this project is to try to know when the heparin is going to be effective, depending on the pathological background of patients, chronic treatment and individual characteristics. Therefore, if it is known in which subjects is not going to be effective we could avoid treating them. 479 subjects were evaluated (230 women), mean age 65 years old (22-86) with indication of 18F-FDG PET/CT due to an oncological illness, or infection or inflammatory suspect of a cardiac or vascular process. Five groups of subjects were studied: Subjects with diabetes mellitus, subjects with dyslipidemia under chronic lipid lowering therapy, subjects with dyslipidemia but without chronic treatment for dyslipidemia, subjects with metabolic syndrome (diabetes and dyslipidemia coexistence) and the last group of normal subjects, without diabetes nor dyslipidemia. We compare two methods. One is based on at least 6 hours of fasting and the second one is based on at least 6 hours of fasting plus the administration of heparin some minutes before the 18F-FDG dose injection. We compare the suppression of physiologic glucose uptake in the myocardium in the different groups of study with both methodologies. The heparin method obtains more suppression of physiologic glucose uptake in the myocardium, with statistically significant results in all the global population and in the group with dyslipidemia but without chronic treatment for dyslipidemia. The heparin method obtains a bigger number of subjects but with no statistically significant results in the normal group and in the metabolic syndrome group. In these groups we should perform regularly the heparin methodology searching for an adequate suppression of physiologic glucose uptake in the myocardium. In contrast to those results, we observe that the heparin method is not useful with almost statistically significant results in the diabetes mellitus group, and in the group with dyslipidemia under chronic lipid lowering therapy. In these groups we should only perform long fasting period methodology. After the results obtained in this project we have confirmed the utility of heparin administration in our community, and the best way to use it with the appropriate subjects, depending on their pathological background, chronic treatment and individual characteristics.
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Burford, Evans J. "Myocyte Derived Cardiac Spheroids for Post Infarct Cardiac Regeneration." Digital WPI, 2014. https://digitalcommons.wpi.edu/etd-theses/145.
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Research has shown that autologous progenitor-like cardiac spheroids, when delivered to an infarcted heart, are able to restore mechanical function. These spheroids are made by isolating and expanding autologous cardiac progenitor cells. Though these results are promising, the process for creating cardiac spheroids is inefficient and time consuming, requiring a large amount of cardiac tissue. For every 10,000 cardiac myocytes in the heart there is only one cardiac progenitor cell; requiring a large amount of initial tissue. This clinical limitation could be overcome if cardiac myocytes, which are more abundant than cardiac progenitor cells, could be used to make cardiac spheroids. Research has shown that mesenchymal stem cells when co-cultured with adult cardiac myocytes cause the cardiac myocytes to behave like a progenitor cell. We found that, when co-cultured with mesenchymal stem cells, cardiac mycoytes could be made to form cardiac spheroid bodies. This was done by isolating adult myocytes from rat hearts and co-culturing them with human mesenchymal stem cells. After two weeks, cultures were observed to form spheroid bodies and the number of spheroids formed were compared to a pure myocyte control. Cardiac specific staining confirmed that the spheroids were made from the myocytes. It was also found that the mesenchymal stem cells, when co-cultured in the same well with the myocytes, form significantly more spheroids than myocytes treated with stem cell conditioned media. Further, no other cell type present in the co-cultures are able to create spheroid bodies when co-cultured with mycoytes or stem cells. The ability to create cardiac spheroid like bodies from adult myocytes offers a way to overcome the limitations of the time needed and the large quantity of autologous cardiac tissue required to currently make these types of bodies.
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Stirparo, G. G. "DEFINITION OF TRANSCRIPTIONAL LANDSCAPE IN CARDIAC MATURATION AND CARDIAC HYPERTROPHY." Doctoral thesis, Università degli Studi di Milano, 2014. http://hdl.handle.net/2434/247064.
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Heart failure (HF) is a syndrome resulting from a complex genetic predisposition and multiple environmental factors: it is a leading cause of morbidity and mortality. Specific gene expression patterns are activated in the hypertrophic and failing heart and are thought to contribute to the development of HF. Many regulatory molecules are involved in the control of gene expression: among these, long non-coding RNA (lncRNA) is gaining importance for several cellular process and diseases. However, little is still known about its involvement in HF. Many functions have been attributed to lncRNAs, such as cell proliferation, apoptosis and cell invasion, indicating that they may represent a major regulatory component of the eukaryotic genome. Not surprisingly, lncRNAs have been found implicated in several aspects of cancer, and in many neuronal diseases. Despite this, and the known role of other ncRNAs, such as miRNA, in HF, the function of lncRNAs in this pathologic state has been not studied. Thus, the general hypothesis behind this project is that lncRNAs have an important role in defining gene expression re-programming in HF. Consequently, the overall scientific objective of this proposal is to study the role of lncRNAs in gene transcription regulation accompanying heart failure. To this end, we propose to use high-throughput RNA sequencing (RNA-seq) to identify lncRNAs that are modulated in cardiomyocytes during HF. In order do to this, we performed RNA-seq on cardiomyocytes isolated from mice after 1, 2, 4 and 7 days of transverse aortic constriction (TAC) and from sham-operated mice. The importance of this study lies not only in the furthering of our understanding of the pathological mechanisms leading HF, but aims to generate – in the light of recent progress in RNA-based therapeutic strategies – data that may be instrumental to the development of improved therapeutic strategies for this increasingly frequent pathology.
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Veiga, Viviane Cordeiro 1976. "Avaliação ecocardiografica da terapia de ressincronização cardiaca : dois anos de seguimento." [s.n.], 2008. http://repositorio.unicamp.br/jspui/handle/REPOSIP/311904.
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Orientador: Salomon Soriano Ordinola RojasDissertação (mestrado) - Universidade Estadual de Campinas, Faculdade de Ciencias Medicas
Made available in DSpace on 2018-08-12T15:05:14Z (GMT). No. of bitstreams: 1 Veiga_VivianeCordeiro_M.pdf: 4383215 bytes, checksum: 4ac235c87c9173ad91395fd7c6466208 (MD5) Previous issue date: 2008
Resumo: Introdução A terapia de ressincronização cardíaca é uma opção efetiva nos pacientes com insuficiência cardíaca avançada. No entanto, 20 a 30% dos pacientes não apresentam benefícios à esta terapêutica. Critérios clínicos, eletrocardiográficos e ecocardiográficos têm sido estudados na tentativa de selecionar os pacientes que serão beneficiados com a ressincronização cardíaca, sendo o ecocardiograma um método utilizado tanto na seleção, quanto na avaliação e otimização desta terapêutica. Objetivo: O objetivo deste trabalho é analisar a utilização do ecocardiograma na avaliação da terapia de ressincronização cardíaca em pacientes portadores de insuficiência cardíaca refratária, no seguimento a curto prazo (dez dias) e após dois anos de evolução. Casuística e Método: Foram avaliados 20 pacientes com indicação de implante de marcapasso biventricular para terapia de ressincronização cardíaca no período de dois anos, sendo 16 (80%) do sexo masculino, com idade variando de 27 a 80 anos (59,70 ± 12,59 anos). A etiologia da cardiomiopatia era isquêmica em 10 pacientes (50%), chagásica em seis (30%) e idiopática em 4 (20%). Quinze pacientes encontravam-se em classe funcional III (New York Heart Association) e cinco em classe funcional IV no momento do implante do marcapasso. Foi aplicado o Questionário de Qualidade de Vida de Minnesota e realizado o teste de caminhada de seis minutos para avaliação das condições clínicas dos pacientes. Realizado ecodopplercardiograma bidimensional para avaliação da função ventricular, diâmetros cavitários, índice de performance miocárdica, estudo da dissincronia interventricular (avaliação do atraso eletromecânico entre os ventrículos esquerdo e direito) e intraventricular (análise pelo modo unidimensional e Doppler tecidual), da função diastólica e do grau da regurgitação mitral. Dez dias após o implante do marcapasso biventricular, foi repetida toda a avaliação inicial e, novamente, após dois anos. Resultados: Em dois anos, cinco pacientes (25%) foram à óbito, sendo que destes, quatro apresentavam etiologia chagásica. A duração média do complexo QRS era de 154,5±18,48 x 129,0±22,91 x 134,0±24,14 ms, respectivamente nos períodos pré-operatório, dez dias e dois anos de pós-operatório. Não houve alteração estatisticamente significante da fração de ejeção entre os períodos pré-operatório e dez dias, mas houve alteração significante entre os períodos pré-operatório e dois anos e dez dias e dois anos. No seguimento de dez dias, houve piora da dissincronia intraventricular avaliada pelo Doppler tecidual, assim como a pontuação no escore de qualidade de vida foi maior, no grupo óbito. Conclusão: A ecocardiografia é uma tecnologia em evolução e dos parâmetros avaliados, somente a avaliação da dissincronia intraventricular pelo Doppler tecidual após o procedimento, foi capaz de predizer a eficácia da terapia de ressincronização cardíaca, em relação à mortalidade. Não houve correlação entre os parâmetros ecocardiográficos e a melhora clínica de alguns pacientes.
Abstract: Introduction In the cardiac resynchronization therapy is an effective option for patients with advanced heart failure. However, 20 to 30% of patients did not show benefits to this therapy. Clinical criteria, electrocardiography and the echocardiography have been studied in an attempt to select the patients who will benefit from the cardiac resynchronization, and the echocardiogram is a method used in both the selection, as in the evaluation and optimization of this therapy. Objective: The objective of this study is to evaluate the use of echocardiography in the evaluation of patients undergoing cardiac resynchronization therapy for a period of two years. Patients and Methods: We evaluated 20 patients with the implantation of biventricular pacemaker for cardiac resynchronization therapy for over two years, and 16 (80%) males, ranging in age from 27 to 80 years (59.70±12.59 years). The etiology of cardiomyopathy was ischemic in 10 patients (50%), Chagas disease in six (30%) and idiophatic in 4 (20%). Fifteen patients were in functional class III (New York Heart Association) and five in functional class IV at the time of implantation of the pacemaker. We applied the Quality of Life Questionnaire of Minnesota and conducted the test of a six-minute walk to evaluate the clinical conditions of patients. Directed two-dimensional Doppler echocardiography for evaluation of ventricular function, cavity diameters, myocardial performance index, study of interventricular dyssynchrony (eletromechanical delay left ventricle - the right ventricle) and intraventricular (by way dimensional analysis and tissue Doppler), the diastolic function and degree of mitral regurgitation. Ten days after implantation of biventricular pacemaker, was repeated throughout the initial assessment and again after two years. Results: In two years, five patients (25%) were to death, and that these, four had Chagas disease. The average duration of the QRS complex was 154.5±18.48 x 129.0±22.91 x 134.0±24.14 ms, respectively in preoperative, ten days and two years after surgery. There was no statistically significant change in the ejection fraction between preoperative and ten days but there was significant change between periods preoperative and 2 years and 10 days and 2 years. Following ten days, the evaluation of intraventricular dyssynchrony by tissue Doppler and quality of life scores were significantly higher in the group died. Conclusion: The echocardiography is an evolving technology and the parameters evaluated, only the assessment of intraventricular dyssynchrony by Doppler tissue after the procedure was able to predict the effectiveness of the cardiac resynchronization therapy, in relation to mortality. There was no correlation between echocardiographic parameters and clinical improvement in some patients.
Mestrado
Mestre em Cirurgia
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Dawson, Jennifer Elizabeth. "Cardiac Tissue Engineering." Thèse, Université d'Ottawa / University of Ottawa, 2011. http://hdl.handle.net/10393/20071.
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The limited treatment options available for heart disease patients has lead to increased interest in the development of embryonic stem cell (ESC) therapies to replace heart muscle. The challenges of developing usable ESC therapeutic strategies are associated with the limited ability to obtain a pure, defined population of differentiated cardiomyocytes, and the design of in vivo cell delivery platforms to minimize cardiomyocyte loss. These challenges were addressed in Chapter 2 by designing a cardiomyocyte selectable progenitor cell line that permitted evaluation of a collagen-based scaffold for its ability to sustain stem cell-derived cardiomyocyte function (“A P19 Cardiac Cell Line as a Model for Evaluating Cardiac Tissue Engineering Biomaterials”). P19 cells enriched for cardiomyocytes were viable on a transglutaminase cross-linked collagen scaffold, and maintained their cardiomyocyte contractile phenotype in vitro while growing on the scaffold. The potential for a novel cell-surface marker to purify cardiomyocytes within ESC cultures was evaluated in Chapter 3, “Dihydropyridine Receptor (DHP-R) Surface Marker Enrichment of ES-derived Cardiomyocytes”. DHP-R is demonstrated to be upregulated at the protein and RNA transcript level during cardiomyogenesis. DHP-R positive mouse ES cells were fluorescent activated cell sorted, and the DHP-R positive cultured cells were enriched for cardiomyocytes compared to the DHP-R negative population. Finally, in Chapter 4, mouse ESCs were characterized while growing on a clinically approved collagen I/III-based scaffold modified with the RGD integrin-binding motif, (“Collagen (+RGD and –RGD) scaffolds support cardiomyogenesis after aggregation of mouse embryonic stem cells”). The collagen I/III RGD+ and RGD- scaffolds sustained ESC-derived cardiomyocyte growth and function. Notably, no significant differences in cell survival, cardiac phenotype, and cardiomyocyte function were detected with the addition of the RGD domain to the collagen scaffold. Thus, in summary, these three studies have resulted in the identification of a potential cell surface marker for ESC-derived cardiomyocyte purification, and prove that collagen-based scaffolds can sustain ES-cardiomyocyte growth and function. This has set the framework for further studies that will move the field closer to obtaining a safe and effective delivery strategy for transplanting ESCs onto human hearts.
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Peace, Richard Aidan. "Quantitative cardiac SPECT." Thesis, University of Aberdeen, 2001. http://digitool.abdn.ac.uk/R?func=search-advanced-go&find_code1=WSN&request1=AAIU602292.
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Myocardial perfusion SPECT imaging is a sensitive and specific indicator of coronary artery disease (Fleischman et al. 1998). The clinical value of coronary scintigraphy is now established with a utilisation rate of eight procedures per 1000 population per year in the USA and two per 1000 in the EU (Pennell et al. 1998). While myocardial perfusion SPECT images are routinely interpreted by expert observers the classification is inevitably subject to inter-observer and intra-observer variability. An optimised and validated quantitative index of the presence or absence of coronary artery disease (CAD) could improve reproducibility, accuracy and diagnostic confidence. There are segmental techniques to automatically detect CAD from myocardial perfusion SPECT studies such as the CEqual quantitative analysis software (Van Train et al. 1994). However, they have not been shown to be significantly better than expert observers (Berman et al. 1998). The overall aim of this thesis was to develop, optimise and evaluate quantitative techniques for the detection of CAD in myocardial perfusion SPECT studies. This task was divided into three areas; quantification of transient ischaemic dilation (TID); quantitative detection and localisation of CAD; count normalisation of patient studies. Transient ischaemic dilation (TED) is the transient dilation of the left ventricle on immediate post stress images compared to resting technetium-99m imaging. Stolzenberg (1980) first noted TID as a specific marker for severe CAD. There are few published studies of fully quantitative evaluations of TID. The first aim of this thesis was to compare the performance of methods for quantifying TDD in myocardial perfusion SPECT. The second aim of this thesis was to investigate the use of image registration in myocardial perfusion SPECT for quantitative detection and localisation of CAD. This thesis describes two studies comparing six count normalisation techniques. These techniques were; normalise to the maximum value; to the mean voxel value; to the mean of the top 10% or 20% of counts; minimise the sum of squares between studies or the sum of absolute differences. Ten normal myocardial perfusion SPECT studies each with 300 different simulated perfusion defects were count normalised to the original studies. The fractional count normalisation error was consistently lower when the sum of absolute differences was minimised. However, a more clinically applicable measure of count normalisation performance is the effect on quantitative CAD detection. The Z-score method of automatic detection of CAD was repeated using each count normalisation technique. There was no statistically significant difference between the methods although the power of the ROC analysis was poor due to low patient numbers. The balance of evidence suggested that count normalisation by minimisation of the of absolute differences produced the best performance.
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Semenas, Egidijus. "Sex Differences in Cardiac and Cerebral Damage after Hypovolemic Cardiac Arrest." Doctoral thesis, Uppsala universitet, Anestesiologi och intensivvård, 2011. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-146314.
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Resuscitation from haemorrhagic shock and the subsequent circulatory arrest remains a major clinical challenge in the care of trauma patients. Numerous experimental studies in sexually mature animals have shown a gender dimorphism in response to trauma and haemorrhagic shock. The first study was designed to evaluate sex differences in outcome after resuscitation from hypovolemic circulatory arrest. We intended to examine innate sex differences, and chose to study sexually immature animals. The study showed that cerebral cortical blood flow was greater, blood-brain-barrier was better preserved and neuronal injury was smaller in female as compared to male piglets. The second study demonstrated that female sex was associated with enhanced haemodynamic response, cardioprotection, and better survival. This cardioprotective effect was observed despite comparable estradiol and testosterone levels in male and female animals, indicating an innate gender-related cardioprotection. In both studies (I and II) female sex was associated with a smaller increase in the cerebral expression of inducible and neuronal nitric oxide synthase (iNOS and nNOS). Thus in the study III we tested the hypothesis that exogenously administered 17β-estradiol (E2) could improve neurological outcome by NOS modulation. The results showed that compared with the control group, animals in the E2 group exhibited a significantly smaller increase in nNOS and iNOS expression, a smaller blood-brain-barrier disruption and a mitigated neuronal injury. There was also a significant correlation between nNOS and iNOS levels and neuronal injury. A hypothesis if female-specific cardioprotection may be attributed to a smaller NOS activity was tested in study IV. The animals received methylene blue (MB) during CPR, but were otherwise treated according to the same protocol as studies I-II. The female-specific cardioprotection could be attributed to a smaller NOS activity, but NOS inhibition with MB did not improve survival or myocardial injury, although it abated the difference between the sexes.
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Ede, Mauricio. "An alternative agent to induce cardiac arrest for normothermic cardiac surgery." Thesis, National Library of Canada = Bibliothèque nationale du Canada, 1998. http://www.collectionscanada.ca/obj/s4/f2/dsk2/tape17/PQDD_0022/NQ32879.pdf.
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Thomas, Nia Lowri. "Molecular mechanisms underlying cardiac ryanodine receptor dysfunction in sudden cardiac death." Thesis, Cardiff University, 2005. http://orca.cf.ac.uk/54084/.
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Ca2+ release via the cardiac ryanodine receptor (RyR2) is a fundamental event in excitation-contraction coupling. Point mutations in the gene encoding RyR2 are associated with arrhythmogenic right ventricular dysplasia type 2 (ARVD2), a disease likely characterised by abnormal release of Ca2+ that may result in sudden death. GFP-tagged RyR2 mutants (R176Q/T2504M, L433P and N2386I) were generated and expressed in a human embryonic kidney (HEK) cell model, enabling profiling of the amplitude and temporal characteristics of caffeine-evoked Ca2+ release through homotetrameric channels using confocal microscopy. Mutants were functionally heterogeneous and demonstrated profound differences in Ca2+ release when compared with WT channels, including the novel observation that one of the mutants (L433P) exhibited reduced sensitivity to caffeine activation. The molecular basis of this heterogeneity was investigated by determining the sensitivity of the mutant channels to cytoplasmic Ca2+. This was achieved by evaluation of caffeine-induced Ca2+ release from WT or mutants channels in streptolysin-O permeabilised HEK cells, where the cytoplasmic Ca2+ concentration was clamped. Although resting ER Ca2+ store and cytoplasmic Ca2+ levels were comparable in all cells, RyR2 mutants were characterised by a profound loss of Ca2+-dependent inactivation. We also investigated whether these mutations disrupted the interaction between RyR2 and accessory proteins involved in normal channel function. cDNA encoding mutation susceptible regions were constructed and screened against a human cardiac cDNA library using a yeast two hybrid system. The N2386I mutation abolished association of the RyR2 domain with two cardiac proteins, which robustly occurred with the corresponding WT domain. These findings demonstrate that ARVD2-linked RyR2 mutations critically affect channel activation and suggest that differential sensitivity to cytoplasmic Ca2+ may be a causative mechanism in the pathogenesis of this disease.
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Drexler, Samona Smith. "Quality Improvement Project| Cardiac Risk Stratification Prior to Non-Cardiac Surgery." Thesis, University of Louisiana at Lafayette, 2016. http://pqdtopen.proquest.com/#viewpdf?dispub=10163292.
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The occurrence of major adverse cardiac events (MACE) is a common perioperative complication and contributing factor for the increase risk of morbidity and mortality in adult patients undergoing non-cardiac surgery. The most reasonable and evidence-based option to reduce the risk of MACE and perioperative morbidity and mortality is a consistent assessment of the functional capacity for non-cardiac patients prior to non-cardiac surgical procedures. According to Fleisher et al. (2014), individuals with a decreased or unmeasurable functional capacity should be referred to a cardiologist for evaluation and cardiac risk stratification prior to surgery. The Duke Activity Status Index (DASI) tool has demonstrated to be an effective tool in assessing functional capacity and identifying individuals without a known cardiac history who may be at risk for perioperative cardiac complications.
This quality improvement project focused on the implementation and use of the DASI tool into the preexisting formal preoperative procedure. Use of the DASI tool focused on accurate measurements of the surgical patient’s functional capacity and evaluation of potential risk factors for MACE. As a result of using the DASI tool in the preoperative process, several non-cardiac adult patients were recognized as being at risk for MACE and underwent cardiac interventional procedures following referral to a cardiologist for preoperative evaluation. Assessing functional capacity using the DASI tool prior to non-cardiac surgical procedures has proven to be both valuable and medically beneficial for the non-cardiac adult patients in evaluation of the risk for MACE.
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Johnson, Jonas. "The Cardiac State Diagram : A new method for assessing cardiac mechanics." Doctoral thesis, KTH, Medicinsk avbildning, 2015. http://urn.kb.se/resolve?urn=urn:nbn:se:kth:diva-202743.
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Jeffords, Megan E. "Tailoring Material Properties Of Cardiac Matrix Hydrogels For Cardiac Tissue Engineering." University of Akron / OhioLINK, 2015. http://rave.ohiolink.edu/etdc/view?acc_num=akron1430838968.
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Yamada, Tetsu. "Impact of the cardiac arrest mode on cardiac death donor lungs." Kyoto University, 2015. http://hdl.handle.net/2433/200492.
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Nicholson, Suzanne Maria. "Uncertainty in cardiac transplant recipients prior to and after cardiac catheterization." Thesis, The University of Arizona, 1987. http://hdl.handle.net/10150/276609.
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The purpose of this study was to describe the presence of uncertainty experienced by heart transplant recipients at one and two year diagnostic follow-up evaluations. Twelve one year and eleven two year transplant recipients completed the Mishel Uncertainty in Illness Scale (MUIS), prior to and after cardiac catheterization. There was a decrease in uncertainty levels from pre to post-catheterization, for both one and two year recipients, however, findings were not significant. Recipients prior experience with catheterization and the interaction effects of the complete evaluation process or future health status may have affected the subject's uncertainty response. Two year transplant recipients demonstrated significantly higher uncertaintly levels, before and after cardiac catheterization, when compared to one year recipients. These findings lend initial and tentative support to the proposal that uncertainty increases with time post-transplant. The yearly follow-up evaluation may represent an episodic focusing for the transplant recipient on health status.
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Gibbons, David D. "Stabilization of the Cardiac Nervous System During Cardiac Stress Induces Cardioprotection." Digital Commons @ East Tennessee State University, 2012. https://dc.etsu.edu/etd/1219.
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The cardiac nervous system consists of nested reflex feedback loops that interact to regulate regional heart function. Cardiac disease affects multiple components of the cardiac nervous system and the myocytes themselves. This study aims to determine: 1) how select components of the cardiac nervous system respond to acute cardiac stress, including myocardial ischemia (MI) and induced neural imbalance leading to cardiac electrical instability, and 2) how neuromodulation can affect neural-myocyte interactions to induce cardioprotection. Thoracic spinal cord stimulation (SCS) is recognized for its anti-anginal effects and ability to reduce apoptosis in response to acute MI, primarily via modulation of adrenergic efferent systems. The data presented here suggest that cervical SCS exerts similar cardioprotective effects in response to MI, but in contradistinction to thoracic SCS, uses both adrenergic and cholinergic efferent mechanisms to stabilize cardiomyocytes and the arrhythmogenic potential. SCS potentially can use efferent and/or anti-dromically activated cardiac afferents to mediate its cardioprotection. Thoracic SCS mitigates the MI-induced activation of both nodose and dorsal root ganglia cardiac-related afferents, doing so without antidromic activation of the primary cardiac afferents. Instead, thoracic SCS acts through altering the cardiac milieu thereby secondarily affecting the primary afferent sensory transduction. In response to cardiac stressors, reflex activation of efferent activity modifies mechanical and electrical functions of the heart. Excessive activation of neuronal input to the cardiac nervous system can induce arrhythmias. Stimulation of intrathoracic mediastinal nerves directly activates subpopulations of intrinsic cardiac neurons, thereby inducing atrial arrhythmias. Neuromodulation, either thoracic SCS or hexamethonium, suppressed mediastinal nerve stimulation (MSNS)-induced activation of intrinsic cardiac neurons and correspondingly reduced the arrhythmogenic potential. SCS exerted its stabilizing effects on neural processing and subsequent effects on atrial electrical function by selectively targeting local circuit neurons within the intrinsic cardiac nervous system. Together these data indicate that neuromodulation therapy, using SCS, can mitigate the imbalances in cardiac reflex control arising from acute cardiac stress and thereby has the potential to slow the progression of chronic heart disease.
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Belian, Elisa. "The instructive role of cardiac transcription factors in triggering transition of cardiac progenitor cells into the cardiac muscle fate." Thesis, Imperial College London, 2013. http://hdl.handle.net/10044/1/40196.
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The mechanisms that maintain cardiac progenitor cells (CPCs) in a state of arrested development and prevent their spontaneous differentiation are unknown. This study is aimed at investigating potential mechanisms responsible for the striking paradox of cardiac transcription factors' expression without activation of their direct cardiomyocyte-specific target genes. Expression analysis of a range of CPC-derived clonal lines, characterised by Sca-1 expression and the SP phenotype, showed that all analysed cardiac transcription factors are expressed as nuclear-localised proteins. Hence, the absence of nucleartargeted protein expression is not the reason for lack of transcriptional activity. Interestingly, none of the clones expressed the complete triad of Gata4, Mef2c and Tbx5 (GMT) that reportedly reprograms cardiac fibroblasts into cardiomyocytes. However, forced expression of the respective missing factor(s) in CPCs induced few of the tested cardiac markers, indicating that lack of co-expression of these three factors is not the reason for the cells' failure to undergo differentiation. As a third potential barrier, the cardiac muscle-specific isoform of the transcriptional coactivator Myocardin (Myocd) was investigated and found to be absent in all analysed clones. Conversely, rescue with exogenous Myocd plus Tbx5 was found to robustly activate nearly all tested RNA and protein markers diagnostic of the cardiomyocyte lineage. In summary, this study demonstrates that rescuing the lack of Myocd in combination with other cardiac transcription factors is sufficient to induce expression of a range of cardiac genes and proteins characteristic of differentiated cardiomyocytes, suggesting that the lack or insufficient level of these factors is a limiting mechanism maintaining CPCs in the undifferentiated state. Evidence presented in this study indicates that Myocd is not only crucial in regulating cardiac muscle formation during embryogenesis but pivotal to induce the transition of adult cardiac progenitor cells toward the cardiac muscle fate.
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Ferrer, Cuadros Debora. "Programa de prevención y rehabilitación cardíaca integral: cardiomove." Master's thesis, Universidad Peruana de Ciencias Aplicadas (UPC), 2020. http://hdl.handle.net/10757/655111.
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El Programa de Prevención y Rehabilitación Cardiaca Integral: CARDIOMOVE ; es una empresa de salud con fines de lucro que busca rentabilidad económica y social, cuyo objetivo es mejorar clínicamente al paciente; tanto del punto de vista cardiológico, como psicológico a quienes han sufrido de una cardiopatía isquémica como ; infarto o ataque al corazón, sometidos a una intervención coronaria percutáneo , cirugía de revascularización, angina crónica estable, implantación de dispositivo, trasplante cardiaco, insuficiencia cardíaca, intervención sobre válvulas cardiacas, enfermedad arterial periférica, y pacientes sin ninguna cardiopatía pero con factor de riesgo cardiovascular (hipertensión, diabetes mellitus , obesidad y dislipidemias)
El Programa de Prevención y Rehabilitación cardíaca Integral: CARDIOMOVE; está compuesto por pilares fundamentales como el control de los factores de riesgo, la mejoría de la capacidad física, optimización del tratamiento médico, la educación de hábitos de vida saludable, y el soporte psicológico y nutricional. Nuestro servicio va dirigido para el público mayor de 18 años con cardiopatía o sin ella, pero con factor cardiovascular pertenecientes al nivel socioeconómico B y C de Lima Metropolitana con posibilidad de pago de bolsillo. El Programa de Prevención y Rehabilitación Cardíaca Integral: CARDIOMOVE: tiene su sede central localizada en el distrito de Jesús María, debido a que es un lugar de fácil acceso geográfico desde los distintos distritos de Lima.
La idea de negocio, nace ante la prevalencia de enfermedades cardiovasculares, el aumento de factores de riesgo y pobre fomentación de estilos de vida saludable, ausencia de programas de rehabilitación prevención cardiovascular, ausencia de programa de rehabilitación cardiaca como estrategia de prevención secundaria demostrada, la desinformación sobre los grandes beneficios de la rehabilitación cardiaca ; la escasa derivación de pacientes a dichos programas casi inexistentes y el crecimiento de las enfermedades no transmisibles.
Nuestra propuesta de valor es mejorar la calidad de vida; reincorporándolo laboral y socialmente; evitando el deterioro psicológico, fortaleciendo la capacidad física; brindando una experiencia única y segura; mediante una atención multidisciplinaria y personalizada a las personas que requieran un programa de prevención y rehabilitación cardiaca Integral.
Todo esto es posible con un equipo humano profesional de salud y administrativo, cuyos valores principales son: Hospitalidad, Respeto, Responsabilidad, Calidad y Espiritualidad.
Respecto a la evaluación económica financiera; se ha estimado una inversión de S/427,369 nuevos soles, el cual se financia 30% por capital y 70% por deuda. Con un precio promedio de venta por paquete completo del programa de prevención y rehabilitación cardíaca integral de S/. 1440 nuevos soles, un costo mensual de S/ 480 nuevos soles y un costo variable unitario promedio de S/. 40 nuevos soles. Con un tiempo de retorno de la inversión del segundo semestre del 1 año. Obteniendo un valor actual neto económico de la empresa de aproximadamente S/1,067.984nuevos soles. Respecto a la Tasa Interna de Retorno de la empresa corresponde de 30.83 %.
Después de lo expuesto según los datos de rentabilidad financiera y estudios de sensibilidad, se concluye que se trata de una inversión de moderado riesgo con una gran posibilidad de crecimiento en el tiempo aunado a un gran impacto de salud de las personas.The Comprehensive Cardiac Prevention and Rehabilitation Program: CARDIOMOVE; is a for-profit health company that seeks economic and social profitability, whose objective is to improve the patient clinically; both from a cardiological and psychological point of view to those who have suffered from ischemic heart disease such as; infarction or heart attack, undergoing percutaneous coronary intervention, bypass surgery, chronic stable angina, device implantation, heart transplantation, heart failure, intervention on heart valves, peripheral arterial disease, and patients without any heart disease but with a risk factor cardiovascular (hypertension, diabetes mellitus, obesity and dyslipidemias) The Comprehensive Cardiac Prevention and Rehabilitation Program: CARDIOMOVE; It is made up of fundamental pillars such as control of risk factors, improvement of physical capacity, optimization of medical treatment, education of healthy lifestyle habits, and psychological and nutritional support. Our service is aimed at the public over 18 years of age with or without heart disease, but with cardiovascular factors belonging to socioeconomic status B and C of Metropolitan Lima with the possibility of paying out of pocket. The Comprehensive Cardiac Prevention and Rehabilitation Program: CARDIOMOVE: has its headquarters located in the Jesús María district, due to the fact that it is a place with easy geographic access from the different districts of Lima. The business idea was born due to the prevalence of cardiovascular diseases, the increase in risk factors and poor promotion of healthy lifestyles, absence of cardiovascular prevention rehabilitation programs, absence of a cardiac rehabilitation program as a proven secondary prevention strategy, misinformation about the great benefits of cardiac rehabilitation; the scarce referral of patients to these programs almost non-existent and the growth of non-communicable diseases Our value proposition is to improve the quality of life; reincorporating him to work and socially; avoiding psychological deterioration, strengthening physical capacity; providing a unique and safe experience; through multidisciplinary and personalized care for people who require a comprehensive cardiac prevention and rehabilitation program. All this is possible with a professional health and administrative human team, whose main values are: Hospitality, Respect, Responsibility, Quality and Spirituality. Regarding the financial economic evaluation; An investment of S / 427,369 nuevos soles has been estimated, which is financed 30% by capital and 70% by debt. With an average sale price for a complete package of the comprehensive cardiac prevention and rehabilitation program of S /. 1,440 nuevos soles, a monthly cost of S / 480 nuevos soles and an average unit variable cost of S /. 40 new soles. With a return on investment of 1 years. Obtaining a net present economic value of the company of approximately S / 1,067.984 new soles. Regarding the Internal Rate of Return of the company it corresponds to 30.83%. After the above, according to the financial profitability data and sensitivity studies, it is concluded that it is a low risk investment with a great possibility of growth over time coupled with a great impact on people's health.
Trabajo de investigación
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Mayfield, Audrey. "Encapsulation of Cardiac Stem Cells to Enhance Cell Retention and Cardiac Repair." Thesis, Université d'Ottawa / University of Ottawa, 2014. http://hdl.handle.net/10393/31500.
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Despite advances in treatment, heart failure remains one of the top killers in Canada. This recognition motivates a new research focus to harness the fundamental repair properties of the human heart, with human cardiac stem cells (CSCs) emerging as a promising cell candidate to regenerate damaged myocardium. The rationale of this approach is simple with ex vivo amplification of CSCs from clinical grade biopsies, followed by delivery to areas of injury, where they engraft and regenerate the heart. Currently, outcomes are limited by modest engraftment and poor long-term survival of the injected CSCs due to on-going cell loss during transplantation. As such, we explored the effect of cell encapsulation to increase CSC engraftment and survival after myocardial injection. Transcript and protein profiling of human atrial appendage sourced CSCs revealed strong expression the pro-survival integrin dimers αVβ3 and α5β1- thus rationalizing the integration of fibronectin and fibrinogen into a supportive intra-capsular matrix. Encapsulation maintained CSC viability and expression of pro-survival transcripts when compared to standard suspended CSCs. Media conditioned by encapsulated CSCs demonstrated superior production of pro-angiogenic/ cardioprotective cytokines, angiogenesis and recruitment of circulating angiogenic cells. Intra-myocardial injection of encapsulated CSCs after experimental myocardial infarction favorably affected long-term retention of CSCs, reduced scar burden and improved overall cardiac function. Taken together, cell encapsulation of CSCs prevents detachment induced cell death while boosting the mechanical retention of CSCs to enhance repair of damaged myocardium.
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Yılmaz, Ayten. "Studies on cardiac pacing emphasis on pacemaker sensors and cardiac resynchronization therapy /." [S.l. : Amsterdam : s.n.] ; Universiteit van Amsterdam [Host], 2005. http://dare.uva.nl/document/79548.
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Williams, Lynne Kirsty. "Mechanisms by which cardiac resynchronisation therapy improves cardiac performance in heart failure." Thesis, University of Birmingham, 2010. http://etheses.bham.ac.uk//id/eprint/1051/.
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This thesis assesses the mechanisms by which biventricular and left ventricular pacing improves cardiac performance in patients with heart failure. We demonstrated for the first time that CRT results in an improvement in acute haemodynamic variables in heart failure patients with a narrow QRS duration that is comparable to the effects seen in heart failure patients with a broad QRS duration. In addition, we have shown that both biventricular (BIVP) and left ventricular pacing (LVP) significantly reduce external constraint to left ventricular filling, resulting in an increase in effective filling pressure. In heart failure patients with evidence of external constraint at rest, the acute haemodynamic benefits of both BIVP and LVP were principally due to the relief of external constraint and preload recruitment. However, in those patients with evidence of electrical dyssynchrony and a broad QRS duration, a significant haemodynamic benefit was derived from an enhancement in left ventricular contractility, presumably as a result of a reduction in left ventricular dyssynchrony. Patients with external constraint appear to derive a greater haemodynamic benefit from pacing due to the significant increase in stroke work that is associated with relief of external constraint and preload recruitment, in addition to the increase in stroke work derived from enhanced contractility due to a reduction in dyssynchrony. These findings will inform better patient selection for this therapy and also optimisation of pacing strategy in individual patients.
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Mendoza, James Patrick. "The cardiac myocyte-specific role of PKG-1 alpha in cardiac remodeling." Thesis, Boston University, 2012. https://hdl.handle.net/2144/12517.
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Thesis (M.A.)--Boston University
PLEASE NOTE: Boston University Libraries did not receive an Authorization To Manage form for this thesis or dissertation. It is therefore not openly accessible, though it may be available by request. If you are the author or principal advisor of this work and would like to request open access for it, please contact us at open-help@bu.edu. Thank you.Current dogma holds that the cGMP dependent protein kinase (PKG) acts in the cardiovascular system (CVS) mainly through the vascular smooth muscle cell (VSMC) to regulate blood flow and vascular tone via nitric oxide (NO) induced vasodilation. Yet, the role of PKG in the CVS, outside the VSMC, remains largely unexplored. Recent studies have revealed that PKG also functions as an anti-hypertrophic molecule in the heart, attenuating cardiac remodeling and preventing the progression of congestive heart failure (CHF). However, those studies used pharmacological agents which increased whole-body cGMP to activate PKG. One more attractive therapeutic strategy would be to activate PKG in cell-types specific to the heart, but not to the peripheral vasculature, since this might provide a more direct treatment for CHF with fewer adverse side effects. Therefore, we tested the specific hypothesis that PKG-Iα attenuates cardiac hypertrophy and remodeling in vivo through a specific role inthe cardiac myocyte (CM). Genotypically, we compared aMHC-Cre+/-, PKG-Iαfl/fl (Cre+) mice to aMHC-Cre-/-, PKG-Iαfl/fl (Cre-) control mice. Here we have shown that Cre+ mice lose the ability to inhibit cardiac remodeling in an unstressed state. Cre+ mice have increased heart weights, CM size, fibrosis, and contractile dysfunction, compared to Cre- mice. Additionally, Cre+ mice show increased fetal gene expression indicative of remodeling. Lastly, these effects worsened in an age-dependent manner. These data suggest that inhibition of cardiac remodeling occurs principally through PKG-Iα in the CM, and reveal new roles for PKG in the CVS, and as a novel target for CHF therapy.
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Fan, Zhaobo. "Control of Cardiac Extracellular Matrix Degradation and Cardiac Fibrosis after Myocardial Infarction." The Ohio State University, 2016. http://rave.ohiolink.edu/etdc/view?acc_num=osu1480662216531284.
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Whelen, Elizabeth Anne. "Illness perceptions, cardiac rehabilitation and quality of life in cardiac surgery patients." Thesis, University of Manchester, 2011. https://www.research.manchester.ac.uk/portal/en/theses/illness-perceptions-cardiac-rehabilitation-and-quality-of-life-in-cardiac-surgery-patients(63ce3eb5-16c7-487a-8d51-c727a4399a19).html.
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Background: Previous research indicates that for some individuals, quality of life (QoL) post-cardiac surgery (CABG or PTCA ) declines from pre-surgery levels. Using the framework of Leventhal's Common-Sense Model, this longitudinal study examined the associations between patients' illness perceptions and coping strategies, their QoL, attendance at cardiac rehabilitation and lifestyle changes. It was hypothesised that a more negative profile of illness beliefs (weaker control beliefs, belief in more severe consequences, poorer understanding of the condition, and negative emotional representations) together with the use of more emotional coping strategies would be associated with poorer QoL. It was also hypothesised that attendance at cardiac rehabilitation would be associated with greater control beliefs, more severe consequences and a causal attribution of lifestyle. Sample and Methods: 113 patients (93 male, mean age 66 (8.93) who were about to undergo cardiac surgery were recruited from two hospitals. Questionnaire measures of illness perceptions (IPQ-R), coping (CHIP) and cardiac-specific QoL (MacNew) were administered at four time points: pre-surgery, post-surgery, post cardiac rehabilitation, and one-year follow up. Data on attendance at rehabilitation and health behaviours were collected via hospital records and patient report. Results: The best predictors of QoL were not cognitive representations of the cardiac problems, but negative emotional representations and associated emotion-focussed coping strategies, implying that an emotion-regulation intervention could be targeted to improve outcome. The predictive ability of initial QoL on QoL at later stages implies this might be best introduced pre-surgery. Having less severe consequence beliefs prior to surgery predicted greater attendance at cardiac rehabilitation. A better understanding of the cardiac condition predicted attendance at cardiac rehabilitation. There was no evidence of change in lifestyle post-rehabilitation.Discussion: The findings that emotional representations of cardiac problems and the use of emotion focussed coping strategies were predictors of quality of life suggest that interventions to foster adaptive emotion regulation may improve outcome in these patients. Findings with respect to attendance at rehabilitation varied somewhat from the previous literature, possibly because the present study sampled patients who were having elective surgery, rather than those who had recently had a heart attack. The importance of studying defined populations and also the issue of when measures are obtained in relation to cardiac events were also highlighted.
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Lionetti, Fred. "GPU accelerated cardiac electrophysiology." Diss., [La Jolla] : University of California, San Diego, 2010. http://wwwlib.umi.com/cr/ucsd/fullcit?p1474756.
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Thesis (M.S.)--University of California, San Diego, 2010.Title from first page of PDF file (viewed April 14, 2010). Available via ProQuest Digital Dissertations. Includes bibliographical references (p. 85-89).
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De, Vos Jacques Pinard. "Automated pediatric cardiac auscultation." Thesis, Link to the online version, 2005. http://hdl.handle.net/10019/1008.
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Lord, Stephen. "Reinnervation after cardiac transplantation." Thesis, University of Oxford, 2003. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.410568.
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Bach, Thuthuy. "Computerized cardiac mapping system." Thesis, University of Ottawa (Canada), 1990. http://hdl.handle.net/10393/5878.
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This thesis presents the results of the work on a computerized cardiac mapping system for recording simultaneously the signals from three electrodes placed at different sites on the heart in order to diagnose the sites causing arrhythmias. The signals are buffered, amplified, filtered and transferred to a personal computer via a multiplexing A/D converter. The computer controls the data acquisition process and stores the data in the memory. Activation times of the heart are estimated by a computer algorithm and displayed on a screen. The digitized waveforms and the vertical time marker of the activation time on each waveform are also displayed for verification. Corrections of computer-estimated activation times are possible using an interactive computer program. With this system, the region initiating an arrhythmia can be localized within a few minutes. The system has been used clinically and proved to be effective in detection of the sites of early activation causing cardiac arrhythmia.
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Lodgek, Erika. "History of Cardiac Anesthesia." The University of Arizona, 2018. http://hdl.handle.net/10150/626588.
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Lipšic, Erik. "Erythropoietin in cardiac ischemia." [S.l. : [Groningen : s.n.] ; University Library Groningen] [Host], 2006. http://irs.ub.rug.nl/ppn/293076030.
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Robinson, Monique Renee. "Cardiac pathophysiology of obesity." Thesis, University of Oxford, 2005. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.414224.
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Kluvitse, C. D. "Discrimination of cardiac activity." Thesis, University of Hull, 1987. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.233949.
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Al-raqad, Mohammed. "Cardiac involvement in dystrophinopathies." Thesis, University of Newcastle Upon Tyne, 2013. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.627742.
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Taylor, Kelly A. "Benefits of cardiac rehabilitation." Honors in the Major Thesis, University of Central Florida, 2001. http://digital.library.ucf.edu/cdm/ref/collection/ETH/id/251.
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This item is only available in print in the UCF Libraries. If this is your Honors Thesis, you can help us make it available online for use by researchers around the world by following the instructions on the distribution consent form at http://library.ucf.edu/Systems/DigitalInitiatives/DigitalCollections/InternetDistributionConsentAgreementForm.pdf You may also contact the project coordinator, Kerri Bottorff, at kerri.bottorff@ucf.edu for more information.Bachelors
Health and Public Affairs
Nursing
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Smetana, Peter. "Dynamics of cardiac repolarisation." Thesis, St George's, University of London, 2008. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.479379.
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Bourke, L. T. "Cardiac injury in lupus." Thesis, University College London (University of London), 2014. http://discovery.ucl.ac.uk/1458423/.
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Systemic lupus erythematosus (SLE) carries a significantly enhanced risk of developing cardiovascular disease (CVD) and remains a leading cause of death in these patients, accounting for ~25% of all causes of mortality. Although there is clear evidence li nking accelerated atherosclerosis to SLE (and consequently an increase in cardiovascular events), another factor that may contribute to CVD related morbidity and mortality is reperfusion injury that occurs post - ischaemia. This is termed ischaemic / reperfu sion (I/R) injury and is a known important contributor to the size of the eventual infarct in the heart, which in animal studies has been shown to account for up to 40 - 50% of the final infarct size. Hydroxychloroquine (HCQ), originally an anti - malarial dr ug, is now used to treat autoimmune disorders, including SLE. HCQ has been shown to modulate inflammation in rheumatic diseases such as SLE and rheumatoid arthritis as well as have potential cardiovascular benefits in these patients. One of the keys aims o f this thesis was to explore the potential use of HCQ in reducing cardiac I/R injury. HCQ was found to be cardioprotective in an in vitro neonatal cardiomyocytes simulated I/R injury model as well as in an in vivo cardiac I/R injury model. This was found to be through an ERK - dependent mechanism which was blocked in the presence of the ERK inhibitor U0126 both in vitro and in vivo . Another relevant question addressed in this thesis was if I/R injury is enhanced in lupus. There is evidence from an autoimmune prone mouse model that lupus IgG are pathogenic in mesenteric I/R injury . However, no study as yet has investigated human lupus IgG in a heart model. IgG was purified from the serum of SLE patients (aPL +ve vs aP L – ve), antiphospholipid syndrome (APS) patients, juvenile onset SLE (JSLE) patients and healthy volunteers. The pre - treatment of neonatal rat cardiomyocytes with IgG from all 3 patient groups enhanced simulated I/R injury. However, the most pathogenic wer e those who were aPL positive. Interestingly, JSLE patients who were all aPL negative, enhanced I/R injury to similar levels as those who tested positive in the adult patient cohort. An enhanced p38 MAPK phosphorylation was observed in the presence of aPL positive IgG and this pathogenic effect was blocked in the presence of the p38 inhibitor SB23580. The results ob tained in this thesis have identified a potential role for HCQ in the cardiovascular field as a cardioprotective therapeutic in myocardial I/R injury. Additionally , IgG purified from patients with SLE , APS and JSLE have been shown to accelerate myocardial I/R injury.
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Couper, Keith. "Debriefing for cardiac arrest." Thesis, University of Warwick, 2015. http://wrap.warwick.ac.uk/67921/.
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Early data from North America supports the use of educational cardiac arrest debriefing as a strategy to improve the quality of cardiopulmonary resuscitation (CPR) in the hospital setting. As some debriefing approaches are challenging to deliver in the NHS setting, there was a need to develop debriefing approaches that are both effective and suited to NHS working practices. This thesis is modelled on the Medical Research Council framework for the development and evaluation of complex interventions. Undertaken between October 2011 and January 2015, it describes the development and feasibility assessment of three cardiac arrest debriefing approaches, which were specifically designed to be deliverable in NHS hospitals. Development work comprised three work packages (systematic review, process evaluation, qualitative study). These studies provided evidence to support the use of cardiac arrest debriefing, but showed that weekly group debriefing is undeliverable in many NHS hospitals. Through qualitative work, I identified six distinct mechanisms by which debriefing may affect clinical practice. Synthesis of these data led to the development of three cardiac arrest debriefing approaches (monthly group debriefing, individual oral debriefing, written feedback). We tested the feasibility of delivering these interventions by implementing them in three NHS hospitals (one intervention per hospital). In a before/after study, it was demonstrated that, despite practical challenges, interventions were deliverable in NHS hospitals. However, they were found to have no effect on either CPR quality or patient outcome. This finding was attributed to high performance in study hospitals at baseline. This thesis demonstrates that the developed cardiac arrest debriefing interventions are deliverable in NHS hospitals. It has also generated important new theory about the mechanisms by which debriefing may affect clinical practice. This thesis lays the foundation for future work to evaluate the clinical and cost-effectiveness of these cardiac arrest debriefing interventions.
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Cook, Stuart Alexander. "Regulation of cardiac apoptosis." Thesis, Imperial College London, 2000. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.393164.
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Akinjolire, O. J., and J. H. Mohanad. "Open-chest cardiac massage." Thesis, Сумський державний університет, 2013. http://essuir.sumdu.edu.ua/handle/123456789/32745.
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Open-chest cardiac massage is an emergency procedure for managing a heart that is not beating or beating ineffectively(cardiac arrest). It is done in conjunction with the administration of drugs directly into the heart or vein and the use of direct electrical defibrillation. It is applied in chest surgery, chest injuries or n chest rigidity that precludes adequate external massage.
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Stewart, Kelley Christine. "Hydrodynamics of Cardiac Diastole." Diss., Virginia Tech, 2011. http://hdl.handle.net/10919/26837.
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Left ventricular diastole (filling) is a complex process with many features and coupled compensatory mechanisms which coordinate to maintain optimal filling and ejection of the left ventricle. Diastolic filling is controlled by the left ventricular recoil, relaxation, and compliance as well as atrial and ventricular pressures making left ventricular diastolic dysfunction very difficult to understand and diagnose. An improved understanding of these unique flows is important to both the fundamental mechanics of the cardiac diastolic filling as well as the development of novel and accurate diagnostic techniques.
This work includes studies of in-vivo and in-vitro vortex rings. Vortex rings created in the left ventricle past the mitral valve during diastole are produced in a confined domain and are influenced by the left ventricular walls. Therefore, an in-vitro analysis of the formation and decay of vortex rings within confined cylindrical domains using particle image velocimetry was conducted. Varying mechanisms of vortex ring breakdown were observed over a wide range of Reynolds numbers, and an analytical model for vortex ring circulation decay of laminar vortex rings was developed. Also, in this work a novel method for analyzing color M-mode echocardiography data using a newly developed automated algorithm is introduced which examines the pressure gradients and velocities within the left ventricle. From this analysis, a new diagnostic filling parameter is introduced which displays a greater probability of detection of diastolic dysfunction over the conventionally used diagnostic parameter.Ph. D.
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Semple, Scott I. K. "Clinical cardiac functional MRI." Thesis, University of Aberdeen, 2000. http://digitool.abdn.ac.uk/R?func=search-advanced-go&find_code1=WSN&request1=AAIU602018.
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The purpose of this project was to assess techniques which could be implemented in clinical cardiac MRI using a moderate gradient performance imaging system in order to aid in the assessment of myocardial function. Possible improvements in image contrast were assessed using four different magnetisation preparation schemes applied prior to MR image acquisition in order to aid in the delineation of myocardial borders, and therefore improve cardiac image assessment quality. The usefulness of several novel T2*-weighted acquisition techniques were assessed in clinical cardiac applications in order to indirectly assess myocardial perfusion. Four magnetisation preparation schemes were applied in order to attempt to improve image contrast in short axis gradient-echo cardiac MRI; T2, T1, Magnetisation Transfer Contrast (MTC), and Double Inversion (DI). The T2, and preparation schemes proved to be the most effective, showing an initial improvement in image contrast by approximately 100% and proving effective in improving image contrast over the entire imaging duration {550 ms through the cardiac cycle). The MTC preparation scheme showed a 50% improvement in image contrast, again being effective over the entire imaging duration. The DI preparation scheme proved useful in creating a black blood gradient-echo image but showed no improvement in contrast throughout the imaging duration (since the DI preparation technique is essentially a 'snapshot' technique). Recent developments in cardiac MRI have moved towards assessment of myocardial perfusion, using first-pass contrast-enhancement imaging. This approach requires assessment of a large enough volume of the heart to allow assessment of perfusion as well as retaining a high temporal resolution of 7 or 2 seconds, and therefore a more modem high performance imaging system. For moderate performance gradient MR systems an alternative method of assessing myocardial perfusion is therefore required. Several novel techniques to assess myocardial T2* values in order to indirectly infer myocardial perfusion are introduced. The use of an original multi-echo gradient-echo imaging sequence to acquire T2* pixel-maps was investigated in phantoms and compared with commercially available sequences in order to validate its use.
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Anaya, Demetrio Donald. "Ultrasound-Compatible Cardiac Simulator." Thesis, Harvard University, 2015. http://nrs.harvard.edu/urn-3:HUL.InstRepos:17417571.
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Devices are being developed so that robots can perform cardiac surgery. These robots will steer catheters through a beating heart using image guidance from ultrasound imaging. An appropriate ultrasound-compatible cardiac simulator has been developed in order to test these systems. This simulator mimics the geometry and the complex motion of a beating human heart. The left ventricle phantom is comprised of a soft echogenic material that mimics heart tissue in an ultrasound image. The cardiac simulator will be a useful tool for research and industry applications where testing on an ultrasound compatible phantom is desirable.Mechanical Engineering
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Luczak, Elizabeth Diane. "Modifiers of cardiac adaptation." Connect to online resource, 2007. http://gateway.proquest.com/openurl?url_ver=Z39.88-2004&rft_val_fmt=info:ofi/fmt:kev:mtx:dissertation&res_dat=xri:pqdiss&rft_dat=xri:pqdiss:3305611.
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Guedes, Elaine Castilho. "Análise do microRNA-22 na hipertrofia cardíaca induzida pela dieta hiperlipídica." Universidade de São Paulo, 2016. http://www.teses.usp.br/teses/disponiveis/42/42131/tde-08082016-084757/.
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Recentes estudos têm revelado o envolvimento de microRNAs (miRNAs) no controle da hipertrofia cardíaca e na função do miocárdio. Ainda, várias pesquisas têm demonstrado que o consumo de dieta rica em gordura pode induzir hipertrofia e remodelamento cardíaco. No presente estudo, investigou-se o efeito de dietas contendo diferentes porcentagens de gordura na expressão do miRNA-22, um miRNA que está diretamente envolvido na regulação da morfologia e da função cardíaca e um importante mediador da hipertrofia e falência cardíaca deflagradas por diferentes estímulos. Para isso, camundongos C57BL/6 machos, com idade entre 4 e 5 semanas, foram alimentados com uma dieta controle (10% das calorias provenientes de lipídeos) ou dietas hiperlipídicas (HF) contendo 45% de kcal de gordura (HF45%) e 60% de kcal de gordura (HF60%) por 10 ou 20 semanas. A dieta HF60% promoveu um aumento do peso corpóreo, aumento dos níveis de glicose, insulina, leptina, colesterol total e triglicérides e induziu intolerância a glicose. As dietas HF promoveram remodelamento cardíaco, conforme evidenciado pelo aumento no diâmetro transverso dos cardiomiócitos e deposição de colágeno. A análise de sequenciamento de RNAs demonstrou que as dietas ricas em gordura induziram padrões distintos de expressão de miRNAs no coração, incluindo o miRNA-22. Análise de bioinformática identificou a caveolina-1 como potencial alvo do miRNA-22 e seus níveis encontraram-se aumentados no grupo HF60% tratado por 20 semanas. Considerando que o miRNA-22 está envolvido no desenvolvimento da hipertrofia cardíaca e falência do coração, é possível que algumas destas alterações estruturais e funcionais cardíacas induzidas pela dieta rica em gordura sejam, ao menos em parte, influenciadas pelo aumento da expressão deste miRNA. Entretanto estudos funcionais são necessários para determinar a contribuição do miRNA-22 para os efeitos promovidos pela dieta rica em gordura no coração.Recent studies have revealed the involvement of microRNAs (miRNAs) in the control of cardiac hypertrophy and myocardial function. In addition, several reports have demonstrated that high fat (HF) diet induces cardiac hypertrophy and remodeling. In the current study, we investigated the effect of diets containing different percentages of fat on the miRNA-22 expression, which is a miRNA involved in the control of the cardiac morphology and function and an important mediator of cardiac hypertrophy and heart failure triggered by different stimuli. To address this question, 4-week-old male C57Bl/6 mice were fed with a low fat diet (10 kcal% fat) or high fat diets (HF), containing 45 kcal% fat (HF45%) and 60 kcal% fat (HF60%) for 10 and 20 weeks. HF60% diet promoted an increase on body weight, fasting glycemia, insulin, leptin, total cholesterol, triglycerides and induced glucose intolerance. HF feeding promoted cardiac remodeling, as evidenced by increased cardiomyocyte transverse diameter and interstitial fibrosis. RNA sequencing analysis demonstrated that HF feeding induced distinct miRNA expression patterns in the heart, including miRNA-22. Bioinformatics analysis identified caveolin-1 as a potential target of miRNA-22 and its levels were increased in HF60% group treated for 20 weeks. Considering that miRNA-22 is involved in the development of cardiac hypertrophy and heart failure, it is possible that some of the cardiac structural and functional alterations induced by high fat diet are, at least in part, influenced by the increased expression of this miRNA. However functional studies are needed to determine the contribution of miRNA-22 in the effects promoted by high fat diet in the heart.
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Youssef, Asser M., Jahromi Alireza Hamidian, and Cuthbert O. Simpkins. "Arterial versus Venous Fluid Resuscitation; Restoring Cardiac Contractions in Cardiac Arrest Following Exsanguinations." BAQIYATALLAH UNIV MEDICAL SCIENCES, 2016. http://hdl.handle.net/10150/626110.
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Background: Arterial cannulation and intra-arterial (IA) fluid and blood resuscitation in the patients with severe shock is an easier approach compared with the intravenous (IV) access if concerns regarding the efficiency and safety of this approach are addressed. Objectives: We hypothesized that IA fluid resuscitation is more effective than IV resuscitation in restoring cardiac contractions (CC) of cardiac-arrested mice following severe hemorrhagic shock. Methods: Mice (N = 22) were anesthetized using ketamine/xylazine. Arterial and venous systems accessed through cannulation of the carotid artery and the Jugular vein, respectively. As much blood as possible was aspirated from the carotid artery access. Mice were observed until the complete cessation of chest wall motions. Following 30 seconds delay, IV (N = 5) and IA access (N = 6) were used for fluid resuscitation using Ringer Lactate (RL) in a similar volume to the aspirated blood. Mice were observed for restoration of chest wall motions. In phase-II of the study, after cessation of chest motions, mice (N = 11) underwent a thoracotomy and CCs were observed. In three mice, IV RL Infusion after cardiac arrest failed to restore CCs and was followed by IA RL infusion. In eight mice, following cardiac arrest intermittent IA RL infusion was performed. Results: While IV RL Infusion failed to restore chest motion in mice (N = 5), IA RL infusion restored chest motion in all mice examined (N = 6) (P = 0.0067). In three mice, IV RL infusion after cardiac arrest showed no effect on CC. After failure of venous infusion, IA RL infusion was performed which resulted in restoration of CC for 13.33 +/- 1.76 minutes. In eight mice, intermittent IA infusion of RL after cardiac arrest, sustained CC for 31.43 +/- 10.9 minutes (P = 0.017). Conclusions: IA fluid resuscitation is superior to IV resuscitation in hemorrhagic shock induced cardiac arrest.
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Artis, Nigel John. "Echocardiography in the assessment of cardiac dyssynchrony and its implications for cardiac resynchronisation." Thesis, University of Leeds, 2009. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.509821.
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Jackson, Katy Filer. "The experiences of partners of cardiac patients : sense of coherence and cardiac beliefs." Thesis, City University London, 2011. http://openaccess.city.ac.uk/7798/.
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The cardiac literature has shown that the stress of a patient’s illness may increase the partner’s vulnerability to develop psychological and physical illness. However, not all partners experience a crisis in response to the patients’ illness. The following study explored the experiences of being a partner of a person with cardiac problems. The aims of the study were a) to determine whether cardiac partners were distressed b) to investigate the reasons for the partners distress c) to explore the relationship between sense of coherence, cardiac beliefs and levels of partners distress d) to identify gaps in the care provided and opportunities for service development. A cross-sectional questionnaire study, followed by smaller scale interviews of partners of patients eligible for cardiac rehabilitation was conducted. 89 partners completed a questionnaire which included data on a) The “Sense of Coherence Scale” (SOC); b) cardiac beliefs; c) HADS; d) general questions on demographics problems, needs and experiences. Following analyses of the questionnaire, it was decided that the interviews would focus on the group of partners with the lowest HADS scores, as they would benefit the most from additional support. 8 partners were interviewed. In general, the sample of partners was in good health and coping well. The linear regression analysis showed that the partners’ sense of coherence and cardiac beliefs accounted for 62.5% of the variance in the partners psychological distress. Out of the two variables, SOC was a better predictor of HADS. The main reasons for partners’ dissatisfaction and distress included poor health, caregiver burden, conflict within the relationship, and inadequate support from health professionals. A framework of partners interventions was discussed, so that partner interventions would become both an integral and an intrinsic part of nursing care. The cardiac beliefs questionnaire has a valuable role in cardiac partner interventions, not only as a research tool, but also as a, cost effective, easy to deliver clinical intervention. The SOC would provide cardiac staff a framework to organise both the questions that they ask the partners and the information that they provide them. In addition to providing support for partners in distress, a salutogenic framework could help staff promote the resources to ensure that the non-distressed partners (and patients) remain healthy.
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Wake, Emily. "The role of the intrinsic cardiac nervous system in cardiac physiology and disease." Thesis, University of Leicester, 2017. http://hdl.handle.net/2381/40499.
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It is well recognised that the complex neuronal hierarchy of the autonomic nervous system is important in the pathology of heart disease. In addition to the peripheral autonomic nerves, there is a dense network of intrinsic cardiac ganglia located at the level of the heart and acting as the final stage in the autonomic regulation of cardiac function. Understanding the role of this network in cardiac function could prove vital in understanding heart disease. The aims of this study were to characterise the topography and neurochemical phenotype of the rabbit intrinsic cardiac nervous system (ICNS) as well as to investigate the functional effects of electrical stimulation of intrinsic cardiac ganglia on the sinus and AV nodes. A coronary artery ligation heart failure model was used to examine the effects of myocardial infarction (MI) and heart failure (HF) on both the topography of the ICNS and the functional role of the ICNS. Histochemical staining revealed an intricate network of nerves and ganglia located primarily on the heart hilum. Significant neuronal remodelling was evident following MI, with the enlargement of somata within ganglia that are known to preferentially innervate the ventricles. Heart rate changes occurred primarily as a result of stimulation of ganglia within the right atrial (RA) and right neuronal cluster (RNC) regions. MI resulted in exaggerated bradycardic responses during stimulation of the RA and RNC regions, accompanied by a significant increase in tachycardia responses during stimulation of ganglia within the RA and RNC. In conclusion, it is becoming increasingly evident that the ICNS is a key network in the cardiac neuronal hierarchy. The ability of the ICNS to function both in normal physiology and also to adapt following MI and HF suggests that the ICNS could be a significant potential therapeutic target for the prevention and treatment of cardiac disease.