No description available.

Indiana University-Purdue University Indianapolis (IUPUI) / 17-β estradiol (E2) exerts protective effects in hypoxia-induced pulmonary hypertension (HPH) via endothelial cell estrogen receptor (ER)-dependent mechanisms. However, the effects of hypoxia on ER expression in the pulmonary-right ventricle (RV) axis remain unknown. Based on previous data suggesting a role of ER-β in mediating E2 protection, we hypothesized that hypoxia selectively up-regulates ER-β in the lung and pulmonary endothelial cells. In our Male Sprague-Dawley rat model, chronic hypoxia exposure (10% FiO2) resulted in a robust HPH phenotype associated with significant increases in ER- β but not ER-α protein in the lung via western blotting. More importantly, this hypoxia-induced ER-β increase was not replicated in the RV, left ventricle (LV) or in the liver. Hence, hypoxia-induced ER-β up-regulation appears to be lung-specific. Ex vivo, hypoxia exposure time-dependently up-regulated ER-β but not ER-α in cultured primary rat pulmonary artery endothelial cells (RPAECs) exposed to hypoxia (1% O2) for 4, 24 or 72h. Furthermore, the hypoxia induced ER-β protein abundance, while not accompanied by increases in its own transcript, was associated with ER-β nuclear translocation, suggesting increase in activity as well as post-transcriptional up-regulation of ER-β. Indeed, the requirement for ER-β activation was indicated in hypoxic ER-βKO mice where administration of E2 failed to inhibit hypoxia-induced pro-proliferative ERK1/2 signaling. Interestingly, HIF-1α accumulation was noted in lung tissue of hypoxic ER-βKO mice; consistent with previously reported negative feedback of ER-β on HIF-1α protein and transcriptional activation. In RAPECs, HIF-1 stabilization and overexpression did not replicate the effects of ER- β up-regulation seen in gas hypoxia; suggestive that HIF-1α is not sufficient for ER-β up- regulation. Similarly, HIF-1 inhibition with chetomin did not result in ER-β down-regulation. HIF-1α knockdown in RPAECs in hypoxic conditions is currently being investigated. Hypoxia increases ER- β, but not ER-α in the lung and lung vascular cells. Interpreted in context of beneficial effects of E2 on hypoxic PA and RV remodeling, our data suggest a protective role for ER-β in HPH. The mechanisms by which hypoxia increases ER-β appears to be post-transcriptional and HIF-1α independent. Elucidating hypoxia-related ER-β signaling pathways in PAECs may reveal novel therapeutic targets in HPH.

Thesis (M. Tech.) -- Central University of Technology, Free State, 2010 / This main aim of this study was to assess patients in a general cardiology practice in order to determine the systolic and diastolic profiles of these patients. The aim was also to determine what effect life style and risk factors may have on the echocardiographic variables measured during such an examination. The specific aim of this study was the importance of not only examining the systolic function but the necessity to also examine the diastolic profile of patients. Life-style plays an important role, with the main culprit being obesity. Obesity was the single most important factor that affected the diastolic profile of patients seen in this study. With obesity a combination of other risk factors related to obesity was observed. Most abnormalities found due to these risk factors were associated with diastolic changes in the left ventricle. Echocardiography is routinely used in daily practice, but the diagnostic value of this tool can be enhanced if proper analyses of the systolic as well as the diastolic profiles are determined. Many cardiologists only measure the systolic function of the heart as an indication of the well- being of the left ventricle, although in this study it was proven that systolic function did not alter with ageing or with changes in the risk profile. Hundred-and-twelve patients, divided into three age groups, were evaluated in this study. Both systolic and diastolic variables were measured and analysed for abnormalities. None of these patients had systolic function abnormalities, although they had detectable anatomic changes due to ageing, obesity and hypertension. Several abnormalities were found on the diastolic profile of these patients. Muscle thickness increased due to obesity and hypertension and even with ageing, but with no significant abnormalities in the systolic function of the heart. There was a slight increase in the circumferential shortening of the left ventricle and that both the septal and longitudinal functions decreased with ageing. It is noteworthy that even where the systolic function remained normal in ageing subjects, their diastolic profiles changed significantly. Assessment of left ventricular function required a meticulous and systematic approach. In this study forty- one percent of patients visiting this general practice had abnormalities of their diastolic function although their systolic function was normal. It was found that with ageing, especially in the older age group, important abnormalities occur in their diastolic profile. The most common changes were that the E- peak velocity decreased and that the Apeak velocity of the trans-mitral flow increased. It seemed that passive filling decreased with ageing but that active filling increased simultaneously, causing the cardiac output to remain constant in older subjects. This is important to know because diseases affecting the atrium may have a profound effect on the cardiac output of older patients, even if they have normal systolic function, (due to the decreased passive filling they need their active filling or atrial contraction to support a normal cardiac output). An important marker will be to look at the ratio of the E/A- velocities in older patients to determine the ratio of active against passive filling. Other than that, a relatively new tool in echocardiography called tissue Doppler was used to determine what happened to the muscle with ageing. Here it was demonstrated that the different layers of the left ventricle acted differently with ageing. Results showed that the longitudinal fibres weakened with ageing although the circumferential fibres remained unchanged or even strengthened with ageing. It was apparent in this study that the traditional use of only systolic function may not be adequate when evaluating relative asymptomatic patients presenting at a general cardiology practice. It is important to also evaluate the diastolic profiles of these patients in order to scientifically quantify their heart health, even in asymptomatic patients. It is important to routinely evaluate the diastolic profile of patients so that early detection of these diastolic variables can be detected and timely consideration for its treatment can be given by their cardiologist. It is also important to take note of the significance of the obesity problem and the effect it has on the heart’s health. In conclusion, this study emphasizes the importance of the echocardiographic evaluation of diastolic cardiac function in addition to routine systolic evaluation in asymptomatic patients. This will enable the clinician to detect abnormalities early and tailor therapy accordingly. Lifestyle related risk factors, especially obesity, also have significant effects on diastolic cardiac function.

Bedömningen av höger kammares systoliska funktion kan med fördel göras med ekokardiografi, bl.a. med tekniker som tvådimensionell ekokardiografi, motion-mode (M-mode) och Tissue Doppler Imaging (TDI). Mätvärden som kan fås ut av dessa tekniker är Tricuspid Annular Plane Systolic Excursion (TAPSE) och s`. TAPSE beskriver annulus tricuspidalis longitudinella rörlighet. s´ beskriver den maximala systoliska hastigheten i annulus tricuspidalis. Syftet med examensarbetet var att undersöka sambandet mellan TAPSE och s´ vid högerkammarfunktionsbestämning. Studien är en retrospektiv tvärsnittsstudie och består av 99 deltagare i åldrarna 18–90 år. Både friska och hjärt-och kärlsjuka deltagare inkluderades, men inte patienter med förmaksflimmer eller individer som var yngre än 18 år. Deltagarna undersöktes med transthorakal ekokardiografi (TTE) vid Länssjukhuset Ryhov i Jönköping, vid undersökningen mättes TAPSE och s´. Det var samma biomedicinska analytiker (BMA) som utförde undersökningarna. McNemars test utfördes och ett Kappa-värde räknades ut. Resultatet visade signifikant skillnad och Kappa-värdet var lågt vilket talar för dåligt samband mellan de båda variablerna. Utfallet i studien visar att fler deltagare klassas med normal högerkammarfunktion mätt med TAPSE, medan samma individer klassas med högerkammardysfunktion mätt med s´. Orsaken till det dåliga sambandet mellan parametrarna är okänt och bör studeras vidare i kommande studier. / The assessment of right ventricular systolic function is done by echocardiography, with techniques as twodimensional echocardiography, motion-mode (M-mode) and Tissue Doppler Imaging (TDI). Measurements ​​obtained from these techniques are Tricuspid Annular Plane Systolic Excursion (TAPSE) and s`. TAPSE describes the longitudinal movement of annulus tricuspidalis. s´ describes annulus tricuspidalis maximal systolic velocity. The purpose of this essay was to explore the relationship between TAPSE and s´. The study consists of 99 participants between the ages of 18 and 90. The population was consisted of individuals with or without cardiovascular disease, but not individuals with atrial fibrillation. Participants were investigated with transthorakal echocardiography (TTE) at Länssjukhuset Ryhov in Jönköping. At the examination both TAPSE and s´ was measured. McNemar's test was performed and a Kappa value was calculated. The result showed a significant difference and the Kappa value was low which indicates a low relationship between the variables. The outcome of the study shows that several participants are classified with normal right ventricular function measured with TAPSE, but the same individuals are classified with right ventricular dysfunction measured by s'. The reason for the poor relationship between the parameters is unknown and should be studied further in future studies.

In order to address the long-term complications that arise from poor venous return, a hallmark of the Fontan physiology, we assessed the feasibility of a non-invasive, home therapy that will improve the health of the patient during the heart transplant waiting period and ameliorate the quality of life. In order to achieve this goal we tested a device that applies pressure to the lower extremities of the body (legs and abdomen) in a pulsating fashion with the goal of augmenting systemic blood flow to the pulmonary arteries. This treatment will enhance flow from the great veins and through the lungs and serve as adjunctive clinical treatment of single ventricle physiology. The specific aim of this study was to show improvements in cardiorespiratory measurements after applying external pressure as a proxy for improved health in the Fontan patient. Various studies have shown the impaired exercise capacity of post-operative Fontan patients, but very little data exists focusing on a period much later after the surgery. Our results among the two subjects completed so far have shown a moderately beneficial improvement in exercise capacity after the compression therapy. Subjects performed a treadmill exercise stress test at VCU that was followed by six days of applied external pressure treatment and finished with a final post-treatment stress test. Cardiorespiratory data was collected and analyzed for improvements from base level. Overall an improvement in exercise duration time, VO2 peak, ventilatory threshold, and OUES was observed, with only VE / VCO2 slope having mixed results. Both subjects seem to be relatively healthy Fontan patients, as indicated by their VO2 peak, VE/VCO2 slope and OUES. As a result, benefits of treatment may vary among a cohort of Fontan patients with poor health condition; a failing Fontan physiology for instance. The improvement in exercise capacity suggests that this therapy could be very beneficial to Fontan patients. These results warrants follow up studies to explore the extent of the clinical benefits of compression treatment among the Fontan population.

Background: The transposition of the great arteries (TGA) is a common congenital heart disease. In the 1980s the Senning procedure was the major approach in correction of TGA in the Czech Republic. Although the most recent operation technique called arterial switch is the method of first choice nowadays, patients after Senning procedure are still visiting the cardiology centre. The aim of this thesis was to evaluate the relationship between the selected parameters from the exercise test and quantified level of physical activity (PA) in these individuals. Methods: 71 patients after the Senning procedure underwent a cardiopulmonary exercise test and they completed an international physical activity questionnaire (IPAQ). Selected data from the questionnaire and the exercise test were evaluated by Pearson correlation coefficient (p < 0,05). Results: 56 patients meet criteria of IPAQ (71 % male, n = 40) and were included in the study. Total PA averaged 6576 ± 5204 MET-minutes/week (median 5271 MET-minutes/week) and 70 % individuals meet criteria for high level of PA according to IPAQ data. Peak VO2 averaged 31,9 ± 6,6 ml/min/kg, maximum heart rate was 177 ± 18,6 beats per minute, the highest work load was 2,7 ± 0,8 W/kg and systolic blood pressure was 185 ± 24,0 mmHg. We found statistically significant...

Introdução: O tratamento alternativo de Redução septal percutânea (RSP) em pacientes com cardiomiopatia hipertrófica obstrutiva é relativamente novo e há poucos trabalhos publicados sobre a evolução tardia. Objetivos: Avaliar nos pacientes com cardiomiopatia hipertrófica obstrutiva sintomáticos e refratários ao tratamento clínico, tratados com RSP, a sobrevida cardíaca e global, qualidade de vida, eventos maiores e as alterações encontradas no eletrocardiograma (ECG), ecocardiograma(ECO) e Holter 24h antes e na evolução tardia de até 15 anos. Método: Foram incluídos pacientes consecutivos que realizaram RSP no Instituto Dante Pazzanese de Cardiologia e no Hospital do Coração de Outubro de 1998 até junho de 2013. Todos os pacientes realizaram exame clínico, ECG e ECO, e a maioria Holter 24h e responderam o questionário DASI antes e pós-RSP. Os dados qualitativos foram descritos em frequências absolutas e relativas e os quantitativos resumidos em médias ± desvios padrão. Para as variáveis quantitativas foram utilizados modelos ANOVA com medidas repetidas, seguidos pelo método de comparações múltiplas de Bonferroni. O nível de significância de 0,05 foi aceito. Resultados: Dos 56 pacientes incluidos, 28 (50%) eram homens, a idade média foi 53,2 ±15,5 anos sendo 2 crianças e 11 (19,6%) tinham coronariopatia. A maioria estava em classe funcional III-IV, o gradiente médio basal por ECO foi 92,8 ± 3,3 mmHg, a espessura do septo 23,9 ± 0,6 e 62,5% tinha insuficiência mitral (IM) moderada. Durante a internação 1 (1,7%)paciente implantou marcapasso. Durante o seguimento de 7,4 ± 4 anos ocorreram 3 implantes de CDI, 2 por prevenção secundaria e 1 marcapasso, 1 nova RSP, 3 cirurgias de miectomias e houve 7 (12,5%) óbitos, apenas 2 de causa cardíaca. O tempo médio de sobrevida, estimado pelo método de Kaplan Meier foi de 13,3 anos (IC95% 12,2 a 14,5 anos), com expectativa de sobrevida de 96,4% em 1 ano, 87,7% em 5 anos e 81,0% a os 12 anos pós-RSP. Houve melhora significativa na qualidade de vida pelo questionário DASI e na classe funcional da NYHA que passou de 3,6 ± 0,5 para 1,2 ± 0,5 no pós-RSP. Na última avaliação do ECO o gradiente 9,37 ± 6,7 mmHg, o septo 12,87 ± 0,98 mm e a IM foi discreta em 90% todos com p < 0,001. Das variáveis analisadas somente o gradiente no estresse, p=0,039 e a massa p=0,024 foram associados a pior prognóstico. Conclusões: A redução septal percutânea mostrou, na evolução tardia com 100% de seguimento, ser uma técnica segura, eficaz em manter os benefícios tardiamente com baixa mortalidade, oferecendo melhora significativa da classe funcional e da qualidade de vida para os pacientes. / Introduction: Percutaneous septal Reduction (PSR) is a relatively new alternative treatment in patients with obstructive hypertrophic cardiomyopathy and there are few published studies on late evolution. Objectives: Evaluate in symptomatic patients with hypertrophic obstructive cardiomyopathy refractory to medical treatment and who underwent PSR, cardiac and overall survival, quality of life, major events and changes found on the electrocardiogram (ECG), echocardiography (ECHO) and Holter 24h before and after PSR during an evolution up to 15 years. Method: Consecutive patients who were submitted to RSP in Dante Pazzanese Institute of Cardiology and Heart Hospital from October 1998 were included. All patients went through clinical, ECG and ECHO examination, and nearly all answered DASI questionnaire, 24-hour Holter monitoring before and after PSR. Qualitative data were described as absolute and relative frequencies and quantitative summarized as means ± standard deviations. ANOVA models were used for quantitative variables with repeated measures, followed by Bonferroni method for multiple comparison. Significance level of 0.05 was accepted. Results: From 56 patients included, 28 (50%) were men , the mean age was 53.2 ± 15.5 years with 2 children and 11 (19.6%) had coronary artery disease . Most were in functional class III - IV from NYHA, the mean baseline ECO gradient was 92.8 ± 3.3 mmHg, the septal thickness 23.9 ± 0.6mm and 62.5 % had moderate mitral regurgitation (MR). During hospitalization 1 (1.7%) patient required permanent pacemaker. During follow-up of 7.4 ± 4 years, 3 patient required ICD implantation, 2 (for secondary prevention), 1 permanent pacemaker, 1 new RSP, 3 myectomy surgery. There were 7 (12.5%) deaths but only 2 of cardiac causes. The median survival time estimated by the Kaplan Meier was 13.3 years (95% CI 12.2 to 14.5 years), with expected survival of 96.4% at 1 year, 87.7% at 5 years and 81.0% at 12 years post-PSR. Significant improvement was seen in quality of life inferred by DASI questionnaire answers and NYHA functional class from 3.6 ± 0.5 to 1.2 ± 0.5. In last evaluation we found statistical significant reduction in ECO gradient 9.37 ± 6.7 mmHg, septum thikness 12.87 ± 0.98 mm and MR was mild in 90 % of patients. Of the variables analyzed only stress gradient (p = 0.039) and mass (p = 0.024) were associated with worse prognosis. Conclusions: The results of this study suggest that percutaneous septal reduction in late evolution with no loses in follow-up, is a safe technique, effective in reducing ventricular gradient and preserving the benefits in long-term evolution with low mortality, offering significant improvement in functional class and quality of life for patients.

A exposição de animais a situações ameaçadoras de natureza inata ou aprendida resulta em exibição de um repertório de comportamentos defensivos espécie-específicos, alterações autonômicas e em inibição da dor, sendo esse conjunto de reações de alta relevância para a sobrevivência de uma espécie. Considerando este contexto, um importante componente da resposta do organismo a situações de emergência é a redução da capacidade de perceber a dor. O processamento de estímulos nociceptivos pode ser modulado no prosencéfalo, na medula espinal, no tronco encefálico e no diencéfalo, por mecanismos envolvendo diferentes neurotransmissores e neuromoduladores. Nos últimos anos, evidências têm demonstrado que o monóxido de carbono (CO), produzido a partir da enzima heme-oxigenase estimula a formação de guanosina 3, 5- monofosfato cíclico (GMPc), participando como neuromodulador de vários processos fisiológicos. Dentro deste contexto, mostrou-se que a via HO-CO-GMPc está envolvida na modulação periférica e espinal da dor inflamatória, bem como na modulação do estresse, porém não há conhecimento da participação desta via na modulação de estímulo doloroso agudo, bem como da antinocicepção induzida pelo estresse. Assim, este trabalho teve como objetivo avaliar o envolvimento da via HO-CO-GMPc na nocicepção e na antinocicepção induzida pelo estresse agudo em ratos, avaliada pelo índice de analgesia no teste de retirada da cauda (IARC). Nossos resultados demonstraram que a ativação da via HO-CO-GMPc por meio da administração ICV de heme-lisinato (substrato) tem efeito antinociceptivo, sendo este efeito dependente da atividade GMPc, desde que o pré-tratamento com inibidor da guanilase ciclase solúvel (GCs), ODQ, bloqueou o aumento do IARC. Ainda, esta modulação ocorre de maneira fásica e não tônica, pois o tratamento isolado ICV com o inibidor da HO, ZnDBPG ou com o inibidor da GCs, ODQ, não alterou o IARC. A antinocicepção induzida pelo estresse agudo (restrição física por 120 min) não é dependente da via HO-CO-GMPc, desde que o tratamento com o ZnDBPG, nem com o heme-lisinato alteraram o IARC. No entanto, esta antinocicepção é dependente da atividade do GMPc, pois o pré-tratamento com ODQ bloqueou o aumento do IARC. / The exposure of animals to threatening situations of innate or learned nature results in exhibition of a repertoire of species-specific defensive behaviors, autonomic alterations and pain inhibition. This group of reactions has high relevance for the survival of species. In this context, an important component of the response of the organism in the emergency situations is the reduction of the capacity to perceive pain. The processing of nociceptive stimulus can be modulated in forebrain, in spinal, and in midbrain, for mechanisms involving different neurotransmitters and neuromodulators. Recently, evidence has demonstrated that carbon monoxide gas (CO), produced from the enzyme heme oxygenase (HO), stimulate the formation of 3\', 5\' - cyclic guanosine monophosphate (cGMP), and this molecule has participated as neuromodulator in some physiological processes. In this way, it has shown that the HO-CO-cGMP pathway is involved in the peripheral and spinal modulation of inflammatory pain, as well as in the modulation of the stress. However, the involvement of this pathway in the modulation of acute painful stimulus, as well as in the antinociception induced by stress isn´t clarified. Thus, this study evaluated the involvement of the HO-CO-cGMP pathway in nociception and in antinociception induced by acute stress in rats, by means the of analgesia index in the tail flick test (AITF). Our results demonstrated that the activation of the HO-CO-cGMP pathway by means of heme-lysinate ICV administration has antinociceptive effect. Again, the increase of the AITF was dependent of the cGMP activity, since that the pretreatment with inhibitor of soluble guanylase cyclase (sGC), ODQ, blocked the antinociceptive effect. This modulation occurs in fasic and not tonic manner, because per se ICV treatment with inhibitor of the HO, ZnDBPG or with inhibitor of the sGC, ODQ did not modify the AITF. The antinociception induced by acute stress (physical restriction during 120 min) is not dependent of the HO-CO-cGMP pathway, since that neither the treatment with the ZnDBPG, nor with the heme-lysinate had modified the AITF. However, this antinociception is dependent of the activity of the cGMP, because the pretreatment with ODQ blocked the increase of the AITF induced by acute stress.

OBJETIVO: Desenvolver peças anatômicas que simulem uma condição real de ventriculomegalia para serem utilizadas como uma ferramenta no treinamento dos neurocirurgiões nas técnicas de neuroendoscopia e viabilizar estudo anatômico dos ventrículos. MÉTODO: Foram utilizadas vinte peças anatômicas de encéfalo de cadáveres de indigentes, com a aprovação do Comitê de Ética em pesquisa da FMUSP sob o número 046/10. As peças foram retiradas da base do crânio com a persistência da superfície óssea (parte da calvária) para serem submetidas aos seguintes procedimentos: canulação do IV ventrículo por meio da abertura mediana do IV ventrículo (forame de Magendie); tomografias pré-experimento e injeção de água destilada no sistema ventricular. A água injetada estava à temperatura ambiente e os cérebros foram resfriados até 4º C e, após 12 horas, foram congelados a uma temperatura de 0º C (no estado sólido) por 24 horas. Esses procedimentos foram realizados na frequência de três vezes. Após o experimento, foram realizadas tomografias pós-experimento e procedimentos neuroendoscópicos ventriculares. Foram excluídos encéfalos com lesões traumáticas ou antecedentes de enfermidades transmissíveis. Não foram critérios de exclusão o sexo e a idade. Foram avaliadas, nas imagens tomográficas, a variação pré e pós-experimento dos seguintes parâmetros: coeficiente corno frontal/diâmetro interno; índice de Evan; e tamanho do corno temporal. As análises estatísticas foram realizadas no programa SPSS (Statistical Package for the Social Sciences) versão 13, para ambos os grupos. RESULTADOS: A avaliação da relação Corno frontal/Diâmetro interno, antes e pós-experimento apresentou média de 11,98% e 19,46%, respectivamente. Estudo estatístico (t Student) mostrou diferença estatística (t= -5142, gl =19; p < 0,01). O Índice de Evan também apresentou diferença significativa (t = -5,172, gl = 9; p < 0,01) entre os resultados antes (média de 10,86%) e após experimento (média de 18,35%). A análise do tamanho do corno temporal mostrou diferença significativa entre os grupos antes e depois do experimento (t = -2,297, gl = 9; p< 0,01), indicando que o tamanho mediano do Corno Temporal é maior após o experimento (média de 2,65cm). CONCLUSÕES: A exploração das características físico-químicas anômalas da molécula da água pode nos fornecer um bom mecanismo expansor de cavidades ventriculares para a indução de ventriculomegalia em uma peça anatômica de encéfalo, em que o endoscópio poderá ser introduzido pelas vias habituais, podendo, assim, realizar observação anatômica e simular o procedimento cirúrgico com a mesma sensibilidade tátil que irá encontrar no procedimento real / PURPOSE: To develop anatomical models which simulate real conditions of ventriculomegaly and to use them as tools to train neuroendoscopic techniques and allow the study of the ventricles. METHODS: A total of twenty brains, with the approval of the Ethics in Research Committee from FMUSP (046/10) were used to perform this research. The brains were separated from the skull base, but keeping part of the calvaria, and then underwent the following procedures: cannulation of the fourth ventricle through the median open of the fourth ventricle (foramen of Magendie); CT scans performed before the experiment; and then injection of distilled water into the ventricular system. The water was injected at room temperature, and then the brains were cooled to 4ºC. After 12 hours, they were then frozen at 0ºC for 24 hours.These procedures were repeated three times. After the experiment,CT scans were performed after the injections and neuroendoscopic procedures. Brains, which had traumatic injuries or history of infectious diseases, were excluded. Gender and age were not exclusion criteria. The statistical analysis was performed with the SPSS program (Statistical Package for the Social Sciences) version 13, for both groups. To assess the variation of the frontal horn (FH)/internal diameter (ID) coefficient, such as Evan\'s index\'s variation, and to analyze the temporal horn (TH) size, thet-Student test was used. RESULTS: The results of the t-Student test showed that the FH/ID, with an average of 11.98% before the experiment, had significant difference (t = -5.142, gl = 19; p < 0.01) after the experiment, with an average of19.46%. The Evan\'s index also showed a significant difference (t = -5.172, gl = 9; p < 0,01) with an initial average of 10.86% and a final average of 18.35%. The analysis of the temporal horn size showed a significant difference between the size before and after the experiment (t = -2.297, gl = 9; p < 0.01), indicating the significant increase of the temporal horn (with an initial average of 0.02cm and a final average of 2.65cm). CONCLUSIONS: The use of the anomalous physical and chemical characteristics of water can provide us with a good expanding mechanism of the ventricular system, creating ventriculomegaly in anatomical models, allowing the endoscope to be introduced by the usual approaches, to perform anatomical observation, and to simulate a surgical procedure with the same sensitivity of a real procedure

La coordination des battements cardiaques est assurée par la propagation rapide de l’activité électrique dans le système de conduction ventriculaire (SCV). Etudier la formation du SCV est crucial pour comprendre l’origine des troubles de conduction de l’adulte. Au cours de l’embryogénèse le SCV est issu des trabécules, des projections myocardiques à la surface interne des ventricules. Les trabécules subissent une compaction avant la naissance qui est nécessaire à la maturation du myocarde. Des défauts au cours des étapes embryonnaires seraient en cause dans l’apparition d’une cardiomyopathie rare nommée Non-Compaction du Ventricule Gauche (LVNC). LVNC et troubles de conduction observés chez des patients et des souris mutantes sont associés au gène NKX2-5, qui code pour un facteur de transcription clé pour le développement du cœur.Mon premier objectif de thèse consiste à étudier le rôle de Nkx2-5 dans l’origine et l’évolution pathologique de la LVNC. Mon second objectif consiste à définir le rôle de Nkx2-5 au cours du développement trabéculaire et de la formation du SCV afin de comprendre l’origine de l’hypoplasie du SCV chez les souris Nkx2-5 hétérozygotes.Des systèmes génétiques complexes ont été utilisés pour induire la délétion de Nkx2-5 dans les trabécules à plusieurs étapes du développement et suivre le destin des trabécules afin d’établir la fenêtre de ségrégation du lignage conducteur. L’ensemble de mes résultats ont permis d’identifier les étapes clés du développement du SCV et un rôle majeur de Nkx2-5 afin de mieux appréhender les troubles de conduction. Enfin mes résultats ont mis en évidence une nouvelle cible potentielle pour des perspectives thérapeutiques. / The rapid propagation of electrical activity through the ventricular conduction system (VCS) controls the spatiotemporal contraction of the ventricles. A better understanding of VCS development is crucial to comprehend the etiology of conduction disturbances observed in adults. During embryogenesis, the VCS originates from ventricular trabeculae that are myocardial protrusions in the lumen of the ventricles. Before birth, trabeculae undergo a compaction step required for maturation of the myocardial wall. Impairment of these developmental steps can lead to the apparition of a rare cardiomyopathy referred as Left Ventricular Non-Compaction (LVNC). LVNC and conduction defects have been observed in patients and mutant mice carrying mutations in NKX2-5, encoding a key transcriptional regulator of heart development.The first objective of my thesis is to decipher the involvement of Nkx2-5 in the origin and pathological evolution of the LVNC. The second objective is to decipher the temporal requirement of Nkx2-5 during trabecular morphogenesis and VCS development and to understand the origin of the VCS hypoplasia observed in Nkx2-5 heterozygous mice. Complex genetic technics were used to induce the deletion of Nkx2-5 in ventricular trabeculae at different developmental time points and to trace the fate of trabeculae and establish the temporal window of the conductive lineage segregation during development.Altogether, my results identify key steps in the VCS development, demonstrate a crucial role of Nkx2-5 and contribute to improve understanding of conduction defects. Interestingly, my results potentially identify new target cells for therapeutic intervention.