National Repository of Grey Literature 59 records found  1 - 10nextend  jump to record: Search took 0.01 seconds. 
Combined pharmacotherapy of different types of pulmonary hypertension
Krása, Kryštof ; Hampl, Václav (advisor) ; Neckář, Jan (referee) ; Al-Hiti, Hikmet (referee)
Pulmonary hypertension is a group of diseases characterized by increased mean pulmonary artery pressure. Especially in group 2, which is associated with heart disease and is the most prevalent of all types, and in group 3, associated with lung disease, no sufficiently effective treatment has yet been developed beyond the treatment of the underlying disease, which is problematic in many cases. Dehydroepiandrosterone sulfate (DHEA S) and statins have different mechanisms of action on pulmonary hypertension in some respects, so the question of the effectiveness of combining them on pulmonary hypertension versus either agent alone has been offered. To test this hypothesis, we induced pulmonary hypertension in adult male rats by three weeks of exposure to hypoxia (10% O2) and treated them with simvastatin (60 mg/L) and DHEA S (100 mg/L) in drinking water, either alone or in combination. Both simvastatin and DHEA S reduced mean pulmonary artery pressure (from a mean ± s.d. value of 34.4 ± 4.4 to 27.6 ± 5.9 and 26.7 ± 4.8 mmHg, respectively), but their combination was not more effective (26.7 ± 7.9 mmHg). Differences in the degree of oxidative stress (as indicated by malondialdehydedehydplasma concentration), the degree of superoxide production (electron paramagnetic resonance) or blood nitric oxide...
Heart failure with preseved ejection fraction
Charvátová, Běla ; Neckář, Jan (advisor) ; Galatík, František (referee)
Heart failure (HF) has been considered to be one of the biggest challenges in modern medicine. As a leading cause of mortality in industrialised countries, it is vital to understand the disease properly. Heart failure with preserved ejection fraction (HFpEF) represents approximately half of all HF cases. Even though it has been studied a lot recently, little we know about the pathophysiology and the treatment of this complex syndrome. Not only does it affect heart function, but also damage can be caused in other organs such as lungs, kidneys, skeletal muscle etc. It used to be called a diastolic heart failure, because in this syndrome the heart is unable to stretch, relax and fill properly during diastole causing a diastolic dysfunction. In addition, HFpEF is often associated with other diseases that can worsen the patients' outcomes, such as hypertension, diabetes mellitus type 2. obesity, chronic kidney disease, pulmonary hypertension etc. This link to other diseases (comorbidities) can complicate the treatment because of a great heterogeneity between patients with HFpEF. The need for specific treatment pathways for each patient's phenotype is the main drive for searching for adequate suiting animal models in research. In the first half, this work provides a comprehensive overview of HFpEF,...
Cardioprotective action of remote ischemic perconditioning in rats
Chalupová, Miloslava ; Neckář, Jan (advisor) ; Žaloudíková, Marie (referee)
Remote ischemic perconditioning (RIPerC) stimulated by brief nonlethal periods of ischemia and reperfusion of a remote organ or a tissue applied during myocardial infarction, is a powerful cardioprotective maneuver. Because of its easy realization, for example, through inflation and deflation of blood pressure cuff, this method has a big potential for translation to clinical settings. The main purpose of this thesis was to investigate the cardioprotective effect of RIPerC as a reduction of infarct size and the incidence and severity of ischemic and reperfusion arrhythmias and to examine, whether this protective effect will be confirmed also in rats with partial deletion of a transcriptional factor of hypoxia-inducible factor-1α (HIF-1α). HIF-1α is a main regulator of hypoxic intracellular signalization and its role was previously indicated in cardioprotection by local ischemic preconditioning. Anesthetized rats were subjected to 20 minutes of the left anterior descending coronary artery occlusion followed by 3 hours of reperfusion. RIPerC was performed by 3 cycles of 4 minutes of ischemia and 2 minutes of reperfusion with a pressure cuff placed on both hind-limbs. This study shows that RIPerC failed to induce protection in any observed factors of ischemia-reperfusion heart injury. Key words: heart,...
Lipidomic analysis of adipose tissue in patients with ischemic heart disease
Tomášová, Petra ; Vecka, Marek (advisor) ; Poledne, Rudolf (referee) ; Neckář, Jan (referee)
The ever-increasing incidence of coronary artery disease (CAD) in Czech Republic and worldwide is one of the most important health problem today. Obesity and type 2 diabetes mellitus (DM2T) are risk factors for the development of CAD. Lipid metabolism is greatly affected by these diseases and adipose tissue, previously considered a mere energy store, also plays an important role in these changes. Today adipose tissue is discussed also as an endocrine organ, which effect whole body metabolism significantly. Lipidomic analysis is an effective tool for monitoring lipid metabolism. Lipidomics combines the advantages of determining a large number of analytes and a small amount of sample and its rapid preparation. In the first part of study, I optimized the HPLC-MS method of untargeted lipidomic analysis in adipose tissue. Then, this method was used to compare subcutaneous and epicardial adipose tissue. Finally, I evaluated the effect of CAD and DM2T on the lipid profiles of subcutaneous and epicardial adipose tissues. Optimization of the pre-analytical phase enabled the analysis of 206 lipid molecules (in total) in both types of adipose tissue. Compared to subcutaneous adipose tissue, epicardial adipose tissue contained a higher proportion of phosphatidylcholines (e.g. PC(32:0), PC(32:1), PC(36:4)) and...
Effect of morphine on the resistance of the heart to ischemia
Mošovská, Linda ; Neckář, Jan (advisor) ; Žurmanová, Jitka (referee)
2. Abstract Opioids are considered as dangerous and addictive substances, mainly due to synthetic opioids such as heroin. It was discovered, that these substances can play an important role in myocardial ischemia because they can limit the damage of the heart tissue that occurs during a heart attack. Since that heart attack is the most common cardiovascular disease, the protective effect is significant. Cardioprotective effect is mainly mediated through δ opioid receptors, but the few studies have shown cardioprotective effect mediated through κ opioid receptors. The protective effect occurs by activation of opioid receptors by their agonists (eg. morphine or TAN-67), either before ischemia (opioid preconditioning) or before reperfusion (opioid postconditioning). The signaling pathway of cardioprotection include mitochondrial KATP channel, Gi/o proteins, protein kinase C, tyrosine kinases and reactive oxygen species.
The role of C-reactive protein in cardiac ischemic tolerance
Perglerová, Aneta ; Neckář, Jan (advisor) ; Vebr, Pavel (referee)
Ischemic heart disease (CHD) is a set of pathophysiological states, disorders of blood flow and oxygen supply of the myocardium due to vascular constriction or thrombus blockage. Inflammation plays an important role in CHD. The inflammatory response is associated with the synthesis of acute phase proteins in the liver such as C-reactive protein (CRP). CRP plays an important role in acute forms of CHD such as myocardial infarction (MI). The development of CHD may be supported by the occurrence of some of the risk factors (eg. atherosclerosis, hypertension, plasma CRP). Increased CRP levels may support the initiation of atherosclerotic plaque formation as well as in the case of hypertension the presence of CRP increases the risk of developing CHD. The healing proces after acute MI is accompanied by an inflammatory phase where CRP occurs naturally and CRP is important to accelerate inflammation. There may be a situation which inflammation goes into a chronic phase because it is not terminated in time, with constant CRP synthesis. High levels of CRP may decrease the prognosis after MI. The elevated plasma CRP has a negative effect on the expansion of MI and the associated ventricular dilatation, which may result in a rupture of the cardiac wall. Hypertrophy is the compensatory mechanism of the...
The effect of maternal diabetes on embryonic cardiovascular development and fetal programing
Čerychová, Radka ; Pavlínková, Gabriela (advisor) ; Nováková, Olga (referee) ; Neckář, Jan (referee)
Maternal diabetes mellitus negatively affects embryonic development and increases the risk for congenital malformations. Besides direct teratogenicity, diabetic intrauterine milieu can predispose an individual to chronic diseases later in life, including cardiovascular diseases, obesity, and diabetes mellitus, in a process termed fetal programing. Molecular mechanisms of embryonic and fetal responses to maternal diabetes are still not fully elucidated. Using mouse model, we show that maternal diabetes induces gene expression changes in the hearts of developing embryos. The most significant changes in the expression of 11 selected genes were detected at the developmental stage associated with completion of cardiac septation, myocardial mass expansion, and increased insulin production in the embryonic pancreas. These affected genes encode products involved in the epithelial-to-mesenchymal transition, a crucial process in heart development. Using immunohistochemistry, we detected increased hypoxia in the diabetes-exposed hearts at the critical stage of cardiac development. Correspondingly to increased hypoxia, the expression of hypoxia-inducible factor 1α (HIF1α) and vascular endothelial growth factor A was increased in the heart of diabetes-exposed embryos. Based on our results indicating the...
Opioid receptors and their signaling system in the myocardium
Ladislav, Marek ; Novotný, Jiří (advisor) ; Neckář, Jan (referee)
The main objective of this bachelor thesis is to systematically collect and sort information about opioid receptors and their signaling system in the myocardium. Heart activity is controlled mainly by adrenergic signaling, and this work therefore contains also some data concerning the characteristic and significance of other relevant receptors. For better understanding, general basic information about opioid system, especially about the receptors and their signaling, is also provided. Relatively little is known about opioid receptors in the myocardium even though these receptors may have an important role especially in various pathophysiological conditions. There can be several reasons for this. The possibility of further characterization of opioid receptors in the myocardium is rather difficult due to the relatively small number of these receptors in heart tissue. The situation is somewhat complicated also by some differences in the modulation of cardiac function among different species. The complete molecular mechanism by which opioid receptors act on the myocardium has not yet been fully uncovered. Especially in the case of humans this knowledge can be crucial, because these receptors and their ligands could be used for medical purposes.
The role of the endothelin system in development of hypertension and hypertensive end-organ damage in Ren-2 transgenic rats
Opočenský, Martin ; Červenka, Luděk (advisor) ; Neckář, Jan (referee) ; Widimský, Jiří (referee)
The role of the endothelin system in development of hypertension and hypertensive end- organ damage in Ren-2 transgenic rats Endothelin-I (ET-I) has been described as one ofthe most powerful vasoconstrictors, that also play a role in the regulation of renal hemodynamics. ET system plays an important role in the pathogenesis of salt-sensitive models of hl'pertension. The benefícial effects of ET receptor blockers in modulating target-organ damage arise rrom their antiproliferative action. There is, however, a large discrepancy in the effect of ET between various models of hypertension. The hypertensive rat strain transgenic for the mouse Ren-2 (TGR) renin gene is a valuable monogenetic model of renin-dependent and thus angiotensin lI(Ang ll) - dependent hypertension, which exhibits typical signs of fulminant hypertension,i.e. reduced glomerular fíltration rate and proteinuria associated with g1omerulosderosis. Moreover, it carries a salt- sensitive component. We have recently found that nonselective endothelin ETA/ETB receptor blockade markedly improves survival rate and ameliorates end'-organ damage in malcTGR without lowering blood pressure. Because activation ofthe ETA receptor may be responsible for the detrimental effects of ET in the development of hypertension, our study was performed to...

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