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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...
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Tissue factor in acute coronary syndromes
Malý, Martin ; Hampl, Václav (advisor) ; Wilhelm, Jiří (referee) ; Vízek, Martin (referee) ; Málek, Ivan (referee)
In this review are summarized essentials of the physiology and the pathophysiology of TF in terms of the literature sources. But still, until today, there are many questions to be answered: the source and the level of TF in healthy subjects, the method how to measure the "trombogenic" potential of TF because its role in many biological processes, the "normal" levels, the possible impact of risk factors and possibility of risk stratification of "healthy" subjects according to the levels of TF like marker of the blood with procoagulant potential. Answering these questions and impact of the blocking of TF as a therapeutical approach in acute coronary syndromes is a challenging field of investigation in blood coagulation. Powered by TCPDF (www.tcpdf.org)
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The role of microRNA in hypoxic pulmonary hypertension
Tichý, Václav ; Hampl, Václav (advisor) ; Kolář, David (referee)
Pulmonary Arterial hypertension (PAH) is a devastating progressive disease that significantly decreases quality of life and has the average survival rate of only few years. One of the significant initiators of PAH is chronic hypoxia. After more than six decades of research that was initiated in 1946 by von Euler and Liljestrand, a new group of potential regulators of this pathology was discovered, that became heavily studied in the last five years. They are highly conserved molecules belonging to non-coding RNA. These 19-23 nucleotides long microRNA (miRNA) act as negative regulators of expression on various proteins. Many of them regulate traditional signalling pathways of hypoxic PAH (HIF-1, BMPR2) and miRNA is in turn regulated by other signalizations. Together, that creates an interconnected network of direct and indirect interactions and feedback loops, that we need to study in order to understand hypoxic PAH. This thesis summarizes findings about important miRNA molecules from the last few years and elucidates part of these regulatory mechanisms on several miRNA molecules (miR-17-92, miR-21, miR-210, miR-204 a miR143/145).
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Ventilation-respiratory changes and diffusion of gases in the simulated snow avalanche
Sýkora, Karel ; Bartůňková, Staša (advisor) ; Hampl, Václav (referee)
Title: Ventilation - respiratory changes and diffusion of gases in the simulated snow avalanche. Goals: The aim of this study was to investigate different ventilation-respiratory parameters with breathing into the simulated snow avalanche with and without any air pockets. Method: An intervention randomized double blind crossover study was conducted on 12 male students of Military Department at the Faculty of Physical Education and Sports of Charles University. The study was realized in the Krkonoše Mountains in the period January 14 - 18th, 2013 at an altitude of 762 m above sea level. Each volunteer underwent two phases of the experiment in a random order: 1st phase "AP"- breathing into the snow with a 1 L air pocket, and 2nd phase "NP"- breathing into the snow with no air pocket. Physiological parameters, especially fractions of O2 and CO2 in the airways and work of breathing (WoB) expressed as Pressure- Time Product (PTP) were recorded continuously. Results: The presence of the air pockets and size has an important role in the survival of buried avalanche victims. The finding of this study is that it is possible to breath in the avalanche snow even with no air pocket (0 L), but breathing under this condition is associated with significantly increased work of breathing. The limiting factor in no...
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Ventilation-respiratory changes and diffusion of gases in the simulated snow avalanche
Sýkora, Karel ; Bartůňková, Staša (advisor) ; Hampl, Václav (referee) ; Rožánek, Martin (referee)
Title: Ventilation - respiratory changes and diffusion of gases in the simulated snow avalanche. Goals: The aim of this study was to investigate different ventilation-respiratory parameters with breathing into the simulated snow avalanche with and without any air pockets. Method: An intervention randomized double blind crossover study was conducted on 12 male students of Military Department at the Faculty of Physical Education and Sports of Charles University. The study was realized in the Krkonoše Mountains in the period January 14 - 18th, 2013 at an altitude of 762 m above sea level. Each volunteer underwent two phases of the experiment in a random order: 1st phase "AP"- breathing into the snow with a 1 L air pocket, and 2nd phase "NP"- breathing into the snow with no air pocket. Physiological parameters, especially fractions of O2 and CO2 in the airways and work of breathing (WoB) expressed as Pressure- Time Product (PTP) were recorded continuously. Results: The presence of the air pockets and size has an important role in the survival of buried avalanche victims. The finding of this study is that it is possible to breath in the avalanche snow even with no air pocket (0 L), but breathing under this condition is associated with significantly increased work of breathing. The limiting factor in no...
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Succinate dehydrogenase as a hypoxia sensor in pulmonary circulation
Tichý, Václav ; Hampl, Václav (advisor) ; Žurmanová, Jitka (referee)
Hypoxic pulmonary vasoconstriction (HPV) is a local physiological mechanism in lungs that optimalises blood oxygenation during alveolar hypoxia. Arterioles in the affected region increase flow resistance which redirects blood to better ventilated parts of the lung. During global hypoxia - e.g. in high altitude or in chronic pulmonary illnessess - this mechanism doesn't work, as the blood cannot be redirected elsewhere. The pressure in pulmonary artery rises which leads to right heart hypertrophy and ultimately to cor pulmonale. This mechanism has been studied for decades, but specific signalling pathways still lack full description and therapeutical solutions are not available. This thesis offers description of selected properties of pulmonary circulation and patophysiological context of pulmonary hypertension, introduces the reader to HPV localization and signalization, and discusses its most important steps from decreased oxygen availability to vessel constriction. The practical part of this work explores Succinate dehydrogenase (SDH) - complex coupling Kreb's cycle to electron transport chain - as a primary detection site of hypoxia in pulmonary artery smooth muscle cells. We decided to test this hypothesis in isolated rat lungs by measuring if malonate (SDH inhibitor) causes vasoconstriction as...
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The role of microRNA in hypoxic pulmonary hypertension
Tichý, Václav ; Hampl, Václav (advisor) ; Kolář, David (referee)
Pulmonary Arterial hypertension (PAH) is a devastating progressive disease that significantly decreases quality of life and has the average survival rate of only few years. One of the significant initiators of PAH is chronic hypoxia. After more than six decades of research that was initiated in 1946 by von Euler and Liljestrand, a new group of potential regulators of this pathology was discovered, that became heavily studied in the last five years. They are highly conserved molecules belonging to non-coding RNA. These 19-23 nucleotides long microRNA (miRNA) act as negative regulators of expression on various proteins. Many of them regulate traditional signalling pathways of hypoxic PAH (HIF-1, BMPR2) and miRNA is in turn regulated by other signalizations. Together, that creates an interconnected network of direct and indirect interactions and feedback loops, that we need to study in order to understand hypoxic PAH. This thesis summarizes findings about important miRNA molecules from the last few years and elucidates part of these regulatory mechanisms on several miRNA molecules (miR-17-92, miR-21, miR-210, miR-204 a miR143/145).
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Ventilation-respiratory changes and diffusion of gases in the simulated snow avalanche
Sýkora, Karel ; Bartůňková, Staša (advisor) ; Hampl, Václav (referee) ; Rožánek, Martin (referee)
Title: Ventilation - respiratory changes and diffusion of gases in the simulated snow avalanche. Goals: The aim of this study was to investigate different ventilation-respiratory parameters with breathing into the simulated snow avalanche with and without any air pockets. Method: An intervention randomized double blind crossover study was conducted on 12 male students of Military Department at the Faculty of Physical Education and Sports of Charles University. The study was realized in the Krkonoše Mountains in the period January 14 - 18th, 2013 at an altitude of 762 m above sea level. Each volunteer underwent two phases of the experiment in a random order: 1st phase "AP"- breathing into the snow with a 1 L air pocket, and 2nd phase "NP"- breathing into the snow with no air pocket. Physiological parameters, especially fractions of O2 and CO2 in the airways and work of breathing (WoB) expressed as Pressure- Time Product (PTP) were recorded continuously. Results: The presence of the air pockets and size has an important role in the survival of buried avalanche victims. The finding of this study is that it is possible to breath in the avalanche snow even with no air pocket (0 L), but breathing under this condition is associated with significantly increased work of breathing. The limiting factor in no...
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Regulation of calcium influx via voltage-dependent calcium channels (L-VDCC) into the vascular smooth muscle of genetically hypertensive rats
Surovcová, Mária ; Kuneš, Jaroslav (advisor) ; Hampl, Václav (referee) ; Pácha, Jiří (referee)
The present in vivo study was focused on better understanding of the pathophysiological mechanisms contributing to high blood pressure maintenance in spontaneously hypertensive rats (SHR). Genetic hypertension is characterised by abnormally elevated activity of sympathetic nervous system (SNS) and increased sensitivity to catecholamine-induced vasoconstriction comprising both enhanced calcium influx to vascular smooth muscle cells via L-type of voltage-dependent calcium channels (L-VDCC) and altered vascular sensitivity to intracellular calcium mediated by RhoA/Rho-kinase pathway. Thus, our aims were to study the regulation of L-VDCC channels, to determine the role of "calcium sensitization" in hypertension and finally to evaluate which of these pathways is important in the maintenance of high blood pressure. Using conscious SHR rats and their normotensive controls, WKY, we have confirmed that high sympathetic tone is responsible for increased calcium influx via L-VDCC in hypertension. The experiments based on the pertussis toxin-induced inactivation of inhibitory G proteins (Gi) have revealed that the control of L-VDCC by SNS is mediated by Gi protein- coupled pathway, the elimination of which leads to the attenuation of sympathetic vasoconstriction and to the decrease of blood pressure response to...
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