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Perinatal hypoxia: mechanisms and etiology
Laštůvka, Zdeněk ; Riljak, Vladimír (advisor) ; Cendelín, Jan (referee) ; Vízek, Martin (referee)
Perinatal asphyxia is a condition resulting from hypoxic-ischemic injury in utero or during birth and causing perinatal morbidity and mortality. Up until now, numerous models of neonatal hypoxia-ischemia were created and presented simulating brain damage patterns and motor deficits. Rice-Vannucci model is a leading representative of animal rodent models of hypoxic injury. It uses unilateral ligation of the common carotid artery in combination with exposure to hypoxic environment. Seven-day-old mouse pups underwent unilateral ligation of the common carotid artery in combination with exposure to 8 % oxygen hypoxic air (Rice-Vannucci model modification). Experimental groups with isolated carotid artery ligation or only exposure to hypoxia were created, too. To assess the spontaneous behavior changes of mice we used an automated system for the continuous tracking of small rodent behavior (LABORAS ™). On postnatal day 60, the spontaneous behavior of mice was analyzed in various behavioral domains. The observed areas for histological analysis were the cerebral cortex, CA1 and CA3 regions of the hippocampus, hilus, and the dorsal and ventral blades of the dentate gyrus. Induced hypoxia and ischemia together generated substantial behavioral and morphological changes which led to significant differences in...
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Neuromodulation in heart failure
Naar, Jan ; Ošťádal, Petr (advisor) ; Rokyta, Richard (referee) ; Vízek, Martin (referee)
The prognosis of heart failure with reduced ejection fraction remains poor. Neurohumoral activation, including increased cardiac sympathetic nerve activity, plays an important role in the pathogenesis as well as disease progression. Recently, several neuromodulation strategies have been proposed that aim to directly affect the residual autonomic imbalance. Spinal cord stimulation is one of the proposed methods. In the clinical part of this project, we assessed the mid-term effect of spinal cord stimulation on cardiac sympathetic nerve activity and the acute effect on autonomic balance. In the total study population, we did not detect any changes in cardiac sympathetic nerve activity or heart rate variability. However, we observed that the patients with high baseline sympathetic nerve activity or low heart rate variability responded favourably to therapy, reflected in reduced cardiac sympathetic nerve activity and increased heart rate variability. Considering these results, we conducted an experimental study focused on the effect of acute severe heart failure on heart rate variability. In a porcine model of hypoxic myocardial dysfunction, we observed a significant reduction in heart rate variability in all parameters recorded. Our results indicate that spinal cord stimulation may improve autonomic...
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Resistance of immature heart muscle to insufficient oxygen
Charvátová, Zuzana ; Ošťádal, Bohuslav (advisor) ; Vízek, Martin (referee) ; Kuneš, Jaroslav (referee) ; Škovránek, Jan (referee)
Dle údajů Světové zdravotnické organizace jsou v zemích střední a východní Evropy nejčastější příčinou úmrtí choroby srdce a cév. Více než polovinu z tohoto množství zaujímá jediné onemocnění, jímž je akutní a chronická ischemická choroba srdeční (ICHS). Cílem klinických i experimentálních kardiologů, kteří se výzkumem prevence a terapie ICHS zabývají, je proto tuto nepříznivou situaci zlepšit. ICHS vzniká jako důsledek nerovnováhy mezi množstvím kyslíku (a substrátů) dodávaného srdeční buňce a množstvím kyslíku, které buňka aktuálně potřebuje ke splnění metabolických nároků. Při ischemii (na rozdíl od hypoxie) je navíc kromě dodávky živin narušen i odvod produktů a nežádoucích zplodin buněčného metabolizmu. Výsledkem je pak přechod srdečního svalu na anaerobní metabolizmus, hromadění metabolitů a porucha energetické a iontové homeostázy; to vede k poruchám kontraktility a konečným důsledkem omezení perfuze myokardu může být zánik srdeční buňky a vznik infarktu myokardu. V tom, zda poškození bude reverzibilní či ireverzibilní, hraje rozhodující roli délka trvání ischemie. Jedinou možností, jak zabránit či alespoň zmírnit nevratné poškození srdečního svalu, je včasné obnovení průtoku krve koronárním řečištěm v postižené oblasti. Rozsah ischemického poškození srdečního svalu nezávisí pouze na intenzitě a...
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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 protein kinase C and its targets in cardioprotection
Holzerová, Kristýna ; Hlaváčková, Markéta (advisor) ; Alán, Lukáš (referee) ; Vízek, Martin (referee)
The mortality of cardiovascular diseases remains high and it likely tends to increase in the future. Although many ways how to increase the resistance against myocardial ischemia- reperfusion damage have been described, few of them were transferred into clinical practice. Cardioprotective effect of chronic hypoxia has been described during 60s of the last century. Its detailed mechanism has not been elucidated, but a number of components has been identified. One of these components presents protein kinase C (PKC). The role of PKC was described in detail in the mechanism of ischemic preconditioning, but its involvement in the mechanism of cardioprotection induced by chronic hypoxia remains unclear. One reason is the amount of PKC isoforms, which have often contradictory effects, and the diversity of hypoxic models used. The most frequently mentioned isoforms in connection with cardioprotection are PKCδ and PKCε. The aim of my thesis was to analyze changes in these PKC isoforms at two different cardioprotective models of hypoxia - intermittent hypobaric (IHH) and continuous normobaric hypoxia (CNH). We also examined the target proteins of PKCδ and PKCε after the adaptation to IHH, which could be involved in the mechanism of cardioprotection. These included proteins associated with apoptosis and...
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Pes equinovarus:New Treatment Strategies and Pathogenetic Mechanisms
Ošťádal, Martin ; Herget, Jan (advisor) ; Vízek, Martin (referee) ; Poul, Jan (referee)
Idiopathic pes equinovarus (also referred to as clubfoot) is a congenital deformity of the foot and lower leg; it has five components: equinus, varus, adductus, cavus and supination of the foot. At present two principle methods are mostly used for the treatment of clubfoot: physiotherapy and continuous motion without immobilization and the Ponseti method (serial manipulation, cast application, Achilles tenotomy and transposition of m. tibilalis ant.). This method has been reported to have short-term success rates approaching 100%, and the long-term results have been equally impressive. We believe, however, that the data on the success rate may be significantly influenced by the duration of the period after termination of the treatment. The purpose of the first part of our study was, therefore, to compare the short-term (up to three years) and long-term (three to seven years) results of treatment of idiopathic clubfeet with the Ponseti method and to determine the factors for recurrence. We have tested the hypothesis whether is it possible to cure all clubfeet with the Ponseti method only. We have found significant difference between the evaluation of the short- term and long-term results: the number of relapses during the first three years of treatment, indicated for surgical intervention, was...
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Regulation of parameters of biological activity of colorectal cancer
Svobodová, Šárka ; Svačina, Štěpán (advisor) ; Beneš, Zdeněk (referee) ; Vízek, Martin (referee)
Colorectal cancer (CRC) has been considered to be the most frequent cancer disease based on prevalence rate and mortality rate. The earlier diagnostics provides the better therapy outcomes. Many new laboratory tests and techniques for early detection of CRC have been developed recently. Not many of the can be used for daily routine clinical practice so far. The aim of this dissertation thesis was to measure a large spectrum of parameters in patients with early stage of CRC and to evaluate them for routine practice, as they may play a potential regulatory role in cancer development and control process. (...) Our finding of a very low sensitivity of tumor markers CEA and CA 19-9 for CRC in early stages I.-III. is fully corresponding with literature data. When monitoring some parameters during chemotherapy course we have found that only TK seems to be important for adjuvant therapy control, but TK and CEA and CA 19-9 can be used of palliative therapy monitoring. TK increases after every chemotherapy cycle but it decreases before the beginning of the following cycle if the therapy is successful. But it is continuously increasing if the therapy is unsuccessful. CEA and CA 19-9 are permanently within reference intervals in adjuvant therapy. Before palliative therapy beginning all the parameters are elevated and...
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název v anglickém jazyce není uveden
Klusáčková, Pavlína ; Pelclová, Daniela (advisor) ; Hajduková, Zdeňka (referee) ; Vízek, Martin (referee)
Early diagnosis of occupational asthma is important especially for the prognosis of this disease. The confirmation of the diagnosis of occupational asthma is sometimes difficult using diagnostic methods available nowadays. That is why searching new methods is very important. Analysis of exhaled breath condensate (EBC) by liquid chromatography combined with mass spectrometry enables the separate detection of cysteinyl leukotrienes (LT) - LTC4, LTD4, LTE4; LTB4 and 8-isoprostane. If patients with occupational asthma and controls were compared, only LTC4 was significantly higher among all EBC parameters studied in asthmatics (despite corticosteroid treatment). This marker could be used in the future diagnostics. Monitoring of 24-hours variability of EBC parameters in patients, in whom occupational asthma is suspected, showed relatively high intraindividual and interindividual variation. It is evident therefore, that if only one daily measurement in asthmatics would be possible (which is common in articles of several authors), it should be collected in the same period of day in all persons. In negative bronchoprovocation tests significant changes of EBC parameters were not found. The evaluation of positive bronchoprovocation tests was limited by small number of patients, however in five persons from six, the...
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Experimental pulmonary embolism - pathophysiological aspects
Mizera, Roman ; Herget, Jan (advisor) ; Lischke, Robert (referee) ; Vízek, Martin (referee)
- Experimental pulmonary embolism, pathophysiological aspects MUDr. Roman Mizera Theoretical part of the thesis deals with mechanisms of pulmonary hypertension after pulmonary embolism (PE) and summarizes the knowledge of literary sources in this issue. Peripherally deals with the mechanical obstruction of pulmonary vessels, particularly discusses vasoconstriction after the PE. In the experimental part are described three separate experiments. The first experiment tested effect of reactive oxygen species (ROS) and preventive administration their scavenger - superoxide dismutase inhibitor tempol on basal perfusion pressure, vasoconstriction, NO synthase activity and the production of NOx after acute PE. Results show that after PE grows NO synthase activity and the production of NOx, the administration of tempol reduces basal perfusion pressure and vasoconstriction after PE. In the second experiment, we measured basal perfusion pressure and vasoconstriction after PE in lungs exposed to 5 day chronic hypoxia. We tested influence of PDE-5 inhibitor sildenafil on the pulmonary vessels tone. Sildenafil decreased basal pressure after PE in chronic hypoxia, its administration does not affect the pulmonary vasoconstriction of pulmonary vessels, but increases their compliance. The last project tested effect...
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