Patients with terminal heart failure that cannot be treated with conventional therapies are indicated for heart transplantation. In acute deterioration, patients can be brought to transplant using a mechanical cardiac support that is able to partially or completely take over the role of the heart and allow the restoration of sufficient cardiac output (Fila et al., 2014). The period before and after transplantation represents a very challenging period for patients, when they feel not only physical, but especially mental and social needs, which change during their phases of life and at the same time affect their entire subsequent experience. The main goal of this diploma thesis was to monitor how the previous implantation of long-term mechanical cardiac support and the subsequent heart transplantation affect the needs and feelings of patients. Respondents were selected from patients who had been implanted with mechanical cardiac support prior to heart transplantation. The diploma thesis contained another five sub- objectives, which dealt with mapping the needs of patients before and after implantation of long- term mechanical cardiac support and after heart transplantation, as well as during compliance with regimen measures, information retrieval and education. For qualitative research, the method of...

Dita Kašparová Chronická hypoxie a exprese genů 4 Abstract Adaptation to chronic hypoxia (CH) is characterized by a variety of functional changes in order to maintain metabolic and energy homeostasis. It has been known for many years that both humans and animals indigenous or adapted to high-altitude hypoxia are more tolerant to an acute ischemic injury of the heart. Cardioprotective mechanisms activated by adaptive responses to chronic hypoxia can be the result of altered transcriptional regulations in left ventricles. Here we report results from the gene expression profiling of adaptive responses in three models of chronically hypoxic heart. Adult male Wistar rats were exposed for 21 days to either continuous normobaric hypoxia (CCH; 10% O2) or CCH interrupted daily by 1-hour reoxygenation (RCH) or CCH interrupted daily by 16-hour (CIH). Cardiprotective effect of CCH adaptation is abolished by brief daily reoxygenation, RCH adaptation. In the present study, we aimed to determine myocardial mRNA expression of 19 candidate genes divided into three important groups: i) Hypoxia inducible factor (HIF1α) and its prolyl and asparaginyl hyroxylases (PHDs and FIH respectively, ii) Creatine kinase (CK) isoenzymes which play important role in energy homeostases of heart and iii) the group of main enzymatic...

Cardiovascular diseases, particularly acute myocardial infarction, are the leading causes of death in developed countries including the Czech Republic. One of the ways to increase cardiac resistance against acute ischemia/reperfusion (I/R) injury is adaptation to chronic hypoxia. However, changes at the molecular level associated with this adaptation have still not been fully explored. It is obvious that the myocardial function depends on maintaining membrane integrity and cellular homeostasis of cardiomyocytes. From this perspective, phospholipases A2 (PLA2) are the key enzymes that take part in the remodeling and repairing of the cell membranes. Moreover, PLA2 are also involved in generation of lipid signaling molecules - free long chain fatty acids (FA) and 2-lysophopholipids. In myocardium, members of three major PLA2 classes are present: cytosolic PLA2 (cPLA2), calcium-independent PLA2 (iPLA2) and secretoric PLA2 (sPLA2). This thesis aimed to determine the following in the left ventricular myocardium of adult male Wistar rats: 1) The effect of intermittent hypobaric hypoxia (IHH; 8 hours/day, 5 days/week, 5 weeks, ~ 7000 m) on the expression of total cPLA2α and its phosphorylated form (p-cPLA2α, Ser505 ), and further iPLA2 and sPLA2IIA, as well as signaling proteins activating cPLA2α enzyme...

5 Abstract: Aims: The main objective of this work was to analyze in detail the effects of acute temperature changes on the function of isolated chick embryonic heart in vitro in comparison with natural conditions in ovo. Methods: The effects of temperature change (34 řC, 37 řC and 40 řC - hypo-, normo- and hyperthermia, respectively) on calcium dynamics in four days old isolated chick hearts in vitro were investigated by high-speed calcium optical imaging. For comparison and validation of in vitro measurements, experiments were also performed in ovo using videomicroscopy. Artificial electrical stimulation experiments were performed in vitro and in ovo to uncover conduction limits of different heart segments. Results: We observed almost linear dependence of sinus frequency on temperature in our temperature range. Sinus frequency during hypothermia and hyperthermia in vitro and in ovo changed about 20% in comparison with normothermia. We observed no significant changes in amplitude of calcium transients during temperature change to hypothermia but hyperthermia caused a significant decrease in amplitude of calcium transients (atria 35%, ventricles 38%). We observed a wide spectrum of arrhythmias, which occurred spontaneously even during normothermia in vitro. Occurrence of arrhythmias in vitro significantly...

Acute and chronic morphine administration can significantly reduce ischemia- reperfusion injury of the rat heart. However, the molecular mechanisms mediating the protective effect of morphine are not yet fully elucidated. Concurrently, there is a lack of information about the effects of the long-term action of morphine on heart tissue. Therefore, in the first part of the project, we studied the effect of long-term administration of high doses of morphine (10 mg/kg/day, 10 days) on rat heart tissue. In the second part of the project, we investigated the effect of 1 mM morphine on viability and redox state of rat cardiomyoblast cell line H9c2 that was influenced by oxidative stress elicited by exposure to 300 μM tert-butyl hydroperoxide (t-BHP). Our experiments have shown that long-term morphine administration affected neither the amount nor the affinity of myocardial β-adrenergic receptors (β-AR), but almost doubled the number of the dominant isoforms of myocardial adenylyl cyclase (AC) V/VI and led to supersensitization of AC. At the same time, proteomic analyses revealed that long-term morphine administration was associated with significant changes in the left ventricular proteome. In particular, there was an increase in the expression of heat shock proteins (HSP). Increased expression of HSP27...

Diploma project_ Belgrade_ Danube_ Sava As the theme of my thesis I chose the city of Belgrade in the magic we see everyday. An interesting feature is its strategic location at the confluence of the rivers Danube and Sava. The project first deals with research in a broader context. It focuses not only on Belgrade,but also the whole Serbia and its ethnic and religious diversity, the Balkan temper of the population. Survey maps on one side of the city, its beauty and challenges, on the other hand, thesociological context, which examines the main problems of the population of the former Yugoslavia, their mutual coexistence and conflict.. Stigma of the City The work sets in five most problematic points that directly affect the river basins. These problems selecting a continuous strip length of 10 kilometers. Urban areas have a water factor and the city, which is reflected in the grid of streets. Cross streets are straight line to the city, continuing today boulevards that leads to the Danube. Longitudinal its streets and roads follow the river undulation. Based on the original idea of creating islands of the other two islands which make their way onto the side of the Danube three cities waterfront. We get water in the city, which is not only artificial reservoirs, but water in its nature and dynamics. Most exposed parts of the scarred area, the left bank of the Marina Luka which leads to the Francouzská boulevard linking the main square to the Danube. In this area has focused more specifically in connection with the sociological survey. Stigma of the Nation Due to the fact that Belgrade was the capital of Yugoslavia, I focused on interpersonal and economic problems of the population of the former Yugoslavia and its dissolution. On the outside Yugoslavia was united in its time in terms of a strong state economy. After the disintegration of countries to stop cooperating and their economy has significantly dropped. Interpersonal ethnic hatred grew in mutual exploitation of minorities, whether ethnic, and religious. The hatred and conflict in humans are deep and mutual grievances will be difficult to erase. Stigma of the City + Stigma of the Nation = Peace Center Thus we come to the junction of scar and the scars of a nation and a way to deal with both. In a significant proportion of exposed and Belgrade should be the function that has a deeper meaning, overlap, and the importance for the nation, the whole Balkan peninsula. Shaping a platform for peaceful dialogue and mutual cooperation of the former states of Yugoslavia at all levels. Building project will be a peace organization, which will fill this space understanding, cooperation and reconciliation, heal the stigma of a nation and city. The Centre is engaged in projects in the economic, social, medical, religious and cultural. A strong element is the continued ramp-boulevard of the Danube, which shows that the path to the goal may have obstacles and the goal is far off, but worth it to continue. Torn heart_ Peace Center building_ Culture_ media_ Arts As Yugoslavia disintegrated in the Yugonostalgi a back to each other, and the design of the building is torn heart of Yugoslavia, which on itself can not completely back, so at least communicate through the atrium, but are otherwise separate entities.

Introduction: Des résultats récents indiquent que l’acétylcholine joue un rôle protecteur contre les insuffisances cardiaques et les fibrillations atriales ou ventriculaires. Les cholinestérases (ChE) contrôlent le niveau d’acétylcholine et jouent donc un rôle important pour le système cholinergique du cœur. Cependant, ces enzymes dans le cœur sont peu connues. L'objectif de cette thèse est d’étudier l'acétylcholinestérase (AChE) et la butyrylcholinestérase (BChE) dans le cœur, de quantifier ces enzymes et leurs formes moléculaires et localiser au niveau cellulaire. Méthodes : Nous avons utilisé des souris sans AChE ou BChE et sans ColQ et PRiMA leur protéines d’ancrage. Les activités de l’AChE et de la BChE ont été déterminées par la méthode d’Ellman, que nous avons adaptée pour la faible quantité de ChE dans un extrait brut. Les formes moléculaires des ChE ont été séparées en gradient de saccharose 5-20% et localisées dans des cœurs gonflés par la gélatine et sur coupe à froid. La morphologie globale du cœur a été étudiée en coupes transversales colorées avec l’hématoxyline et l’éosine. Résultats et conclusions : La plus forte activité en AChE a été mesurée dans les oreillettes, la plus faible activité dans le ventricule gauche et le septum. Dans tous les compartiments, PRiMA AChE et ColQ AChE ont été observés. Chacune des formes ancrées est distribuée sur l’épicarde à la base du cœur, et sont co-localisées avec des neurones intracardiaques. PRiMA AChE forme des branches fines à proximité des neurones intracardiaques. L’absence d’ancrage de l’AChE aboutit à une diminution significative du diamètre des cardiomyocytes. L’activité de la BChE est plus élevée que celle de l’AChE. La plus haute activité en BChE a été détectée dans le ventricule gauche et le septum. Le monomère amphiphilic constitue la forme prédominante dans le cœur. Dans le myocarde, le marquage de l’activité BChE est diffus, alors que dans l’épicarde il colocalise avec un seul neurone intracardiaque. Dans ce travail, nous avons réalisé une étude complète des ChE dans le cœur. Nos résultats peuvent aider à définir de nouvelles thérapies pharmacologiques plus efficaces. / Introduction: The results of current research suggest that acetylcholine has a protective role during heart failure and atrial or ventricular fibrillation. Cholinesterases (ChE) control the level of acetylcholine and thus play an important role in the cholinergic system of the heart. However, detail information about these enzymes in the heart is still missing. The aim of this thesis was to provide a complex study of acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) in the heart, specifically of their activities, molecular forms and precise localization. Methods: Mutant mice with lack of ChE or their anchoring proteins, ColQ and PRiMA, were used. AChE and BChE activities in heart compartments were determined by 2-step Ellman’s method, developed by us. Molecular forms of ChE were determined in 5-20 % sucrose gradients and localized in the hearts filled with gelatin and in the cryosections by activity staining method and by immunohistochemistry. Nerve and endothelial cells were identified using specific markers. Basic heart morphology was studied in the transversal sections stained with hematoxyline and eosine. Results and conclusion: The highest AChE activity was determined in the atria, the lowest activity in the left ventricle and septum. In all compartments, PRiMA AChE and ColQ AChE were observed. Both anchored forms were distributed epicardially on the heart base, co-localized with intracardiac neurons. PRiMA AChE formed a subtle branching in the proximity of intracardiac neurons. The lack of AChE anchored forms led to significantly lower cardiomyocyte diameter. The BChE activity was higher than that of AChE. The highest BChE activity was detected in the left ventricle and septum. Amphiphilic monomers were the predominant form of BChE in the heart. In myocardium, the staining of BChE activity was diffused, while in epicardium it co-localized with a single intracardiac neuron. In this work, we have provided a complex study of ChE in heart. Our results could help in the design of new, more effective pharmacotherapy, which may reduce morbidity and mortality of the patients with various heart diseases. / Úvod: Výsledky súčasného výskumu nasvedčujú protektívnemu vplyvu acetylcholínu pri srdcovom zlyhávaní, či pri predsieňovej a komorovej fibrilácií. Cholínesterázy (ChE) regulujú hladinu acetylcholínu a tak zohrávajú dôležitú úlohu v cholinergickom systéme srdca. Avšak, hlbšie informácie o týchto enzýmoch v srdci chýbajú. Cieľom tejto práce bolo komplexné štúdium acetylcholínesterázy (AChE) a butyrylcholínesterázy (BChE) v srdci, konkrétne ich aktivít, molekulových foriem a presnej lokalizácie. Metódy: V projekte sme používali mutantné myši s chýbaním ChE alebo ich kotviacich proteínov, ColQ a PRiMA. Aktivity AChE a BChE sme v jednotlivých častiach srdca stanovili nami vyvinutou modifikovanou dvoj-krokovou Ellmanovou metódou. Molekulové formy ChE sme študovali v 5-20 % sacharózových gradientoch. ChE sme lokalizovali v srdciach vyplnených želatínou a v kryostatických rezoch, a to pomocou aktivitného farbenia a imunohistochémiou. Nervové a endotelové bunky sme identifikovali na základe špecifických markerov. Základnú morfológiu tkaniva sme študovali v priečnych rezoch srdca nafarbených hematoxylínom a eozínom. Výsledky a záver: V predsieňach sme pozorovali najvyššiu a v ľavej komore a septe najnižšiu aktivitu AChE, kotvenú pomocou PRiMA aj ColQ proteínov. PRiMA AChE aj ColQ AChE boli v epikarde distribuované na báze srdca a ko-lokalizované s intrakardiálnymi neurónmi. PRiMA AChE vytvárala jemnú spleť v blízkosti intrakardiálnych neurónov. Chýbanie kotvených foriem AChE viedlo ku signifikantne menším priemerom kardiomyocytov. Aktivita BChE v srdci bola vyššia ako aktivita AChE, s najvyššou aktivitou v ľavej komore a septe. Predominatnou formou BChE v srdci boli amfifilné monoméry. BChE aktivita bola v myokarde lokalizovaná difúzne a v epikarde ko-lokalizovala s jedným intrakardiálnym neurónom. V predloženej práci sme poskytli komplexný obraz o ChE v srdci. Naše výsledky môžu vo významnej miere napomôcť v dizajne novej, efektívnejšej farmakoterapie, ktorá by mohla znížiť morbiditu a mortalitu pacientov s vybranými chorobami srdca.

Introduction: Des résultats récents indiquent que l’acétylcholine joue un rôle protecteur contre les insuffisances cardiaques et les fibrillations atriales ou ventriculaires. Les cholinestérases (ChE) contrôlent le niveau d’acétylcholine et jouent donc un rôle important pour le système cholinergique du cœur. Cependant, ces enzymes dans le cœur sont peu connues. L'objectif de cette thèse est d’étudier l'acétylcholinestérase (AChE) et la butyrylcholinestérase (BChE) dans le cœur, de quantifier ces enzymes et leurs formes moléculaires et localiser au niveau cellulaire. Méthodes : Nous avons utilisé des souris sans AChE ou BChE et sans ColQ et PRiMA leur protéines d’ancrage. Les activités de l’AChE et de la BChE ont été déterminées par la méthode d’Ellman, que nous avons adaptée pour la faible quantité de ChE dans un extrait brut. Les formes moléculaires des ChE ont été séparées en gradient de saccharose 5-20% et localisées dans des cœurs gonflés par la gélatine et sur coupe à froid. La morphologie globale du cœur a été étudiée en coupes transversales colorées avec l’hématoxyline et l’éosine. Résultats et conclusions : La plus forte activité en AChE a été mesurée dans les oreillettes, la plus faible activité dans le ventricule gauche et le septum. Dans tous les compartiments, PRiMA AChE et ColQ AChE ont été observés. Chacune des formes ancrées est distribuée sur l’épicarde à la base du cœur, et sont co-localisées avec des neurones intracardiaques. PRiMA AChE forme des branches fines à proximité des neurones intracardiaques. L’absence d’ancrage de l’AChE aboutit à une diminution significative du diamètre des cardiomyocytes. L’activité de la BChE est plus élevée que celle de l’AChE. La plus haute activité en BChE a été détectée dans le ventricule gauche et le septum. Le monomère amphiphilic constitue la forme prédominante dans le cœur. Dans le myocarde, le marquage de l’activité BChE est diffus, alors que dans l’épicarde il colocalise avec un seul neurone intracardiaque. Dans ce travail, nous avons réalisé une étude complète des ChE dans le cœur. Nos résultats peuvent aider à définir de nouvelles thérapies pharmacologiques plus efficaces. / Introduction: The results of current research suggest that acetylcholine has a protective role during heart failure and atrial or ventricular fibrillation. Cholinesterases (ChE) control the level of acetylcholine and thus play an important role in the cholinergic system of the heart. However, detail information about these enzymes in the heart is still missing. The aim of this thesis was to provide a complex study of acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) in the heart, specifically of their activities, molecular forms and precise localization. Methods: Mutant mice with lack of ChE or their anchoring proteins, ColQ and PRiMA, were used. AChE and BChE activities in heart compartments were determined by 2-step Ellman’s method, developed by us. Molecular forms of ChE were determined in 5-20 % sucrose gradients and localized in the hearts filled with gelatin and in the cryosections by activity staining method and by immunohistochemistry. Nerve and endothelial cells were identified using specific markers. Basic heart morphology was studied in the transversal sections stained with hematoxyline and eosine. Results and conclusion: The highest AChE activity was determined in the atria, the lowest activity in the left ventricle and septum. In all compartments, PRiMA AChE and ColQ AChE were observed. Both anchored forms were distributed epicardially on the heart base, co-localized with intracardiac neurons. PRiMA AChE formed a subtle branching in the proximity of intracardiac neurons. The lack of AChE anchored forms led to significantly lower cardiomyocyte diameter. The BChE activity was higher than that of AChE. The highest BChE activity was detected in the left ventricle and septum. Amphiphilic monomers were the predominant form of BChE in the heart. In myocardium, the staining of BChE activity was diffused, while in epicardium it co-localized with a single intracardiac neuron. In this work, we have provided a complex study of ChE in heart. Our results could help in the design of new, more effective pharmacotherapy, which may reduce morbidity and mortality of the patients with various heart diseases. / Úvod: Výsledky súčasného výskumu nasvedčujú protektívnemu vplyvu acetylcholínu pri srdcovom zlyhávaní, či pri predsieňovej a komorovej fibrilácií. Cholínesterázy (ChE) regulujú hladinu acetylcholínu a tak zohrávajú dôležitú úlohu v cholinergickom systéme srdca. Avšak, hlbšie informácie o týchto enzýmoch v srdci chýbajú. Cieľom tejto práce bolo komplexné štúdium acetylcholínesterázy (AChE) a butyrylcholínesterázy (BChE) v srdci, konkrétne ich aktivít, molekulových foriem a presnej lokalizácie. Metódy: V projekte sme používali mutantné myši s chýbaním ChE alebo ich kotviacich proteínov, ColQ a PRiMA. Aktivity AChE a BChE sme v jednotlivých častiach srdca stanovili nami vyvinutou modifikovanou dvoj-krokovou Ellmanovou metódou. Molekulové formy ChE sme študovali v 5-20 % sacharózových gradientoch. ChE sme lokalizovali v srdciach vyplnených želatínou a v kryostatických rezoch, a to pomocou aktivitného farbenia a imunohistochémiou. Nervové a endotelové bunky sme identifikovali na základe špecifických markerov. Základnú morfológiu tkaniva sme študovali v priečnych rezoch srdca nafarbených hematoxylínom a eozínom. Výsledky a záver: V predsieňach sme pozorovali najvyššiu a v ľavej komore a septe najnižšiu aktivitu AChE, kotvenú pomocou PRiMA aj ColQ proteínov. PRiMA AChE aj ColQ AChE boli v epikarde distribuované na báze srdca a ko-lokalizované s intrakardiálnymi neurónmi. PRiMA AChE vytvárala jemnú spleť v blízkosti intrakardiálnych neurónov. Chýbanie kotvených foriem AChE viedlo ku signifikantne menším priemerom kardiomyocytov. Aktivita BChE v srdci bola vyššia ako aktivita AChE, s najvyššou aktivitou v ľavej komore a septe. Predominatnou formou BChE v srdci boli amfifilné monoméry. BChE aktivita bola v myokarde lokalizovaná difúzne a v epikarde ko-lokalizovala s jedným intrakardiálnym neurónom. V predloženej práci sme poskytli komplexný obraz o ChE v srdci. Naše výsledky môžu vo významnej miere napomôcť v dizajne novej, efektívnejšej farmakoterapie, ktorá by mohla znížiť morbiditu a mortalitu pacientov s vybranými chorobami srdca.

(anglicky) The aspiration of this thesis is on behalf of (more authentic) Eros problematic "to shake" literary science, not to say its method of interpretation, and so open another, more sensitive approach to art. As a tangle of starting points, I used the dubious theories of authors such as late R. Barthes, G. Didi-Huberman, H. Bloom, G. Bataille or S. Sontag. But especially, I delve into the studies of European literature in order to expose my own "wounds", no less violently classified into thematic chapters (Cosmogony, God of Love, Desire, Philosophy, Heart, Arrow, Wing, Game, Topos, Instinct, Orpheus and others). Therefore I introduce Eros as multifaceted phenomenon, in contrast to monological tendencies of dominant (platonic or Christian) erotic interpretations. Moreover - in polemics with Bataille's eroticism - I try to make Eros "the work".

Role of Nkx2.5 on development and electrophysiology of the mouse heart Prague 2015 Bc. Peter Hámor ABSTRACT The objective of this thesis is to investigate the role of Nkx2.5 gene dosage on electrophysiology of the mouse heart in prenatal stage of its development, in which the physiological functions of the heart fail to function properly. The main goal of this work is to search for differences in conduction of electric impulses through the embryonic mouse heart according to their genotype. Special method of capturing the conduction of electric impulse through myocardium was used for this purpose, called optical mapping. Thanks to this method I was able to construct images and videos capturing transition of the impulse with marked beginning of the activation and its direction in the heart. These outputs, or optical maps, help to define anomalies and defects compared with a normal functioning heart. The thesis focuses on the expression of the transcription factor Nkx2.5 and regulatory components related with the correct formation and physiology of the heart until 9.5 days post coitum. Individuals in this developmental stage were optically mapped and compared according to their genotypes - homozygous non-mutant, heterozygote and homozygous mutant mouse embryos exhibited some degree of similarity, while other...