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Effect of chronic hypoxia on antioxidative capacity of rat myocardium.
Závišková, Kristýna ; Nováková, Olga (advisor) ; Žurmanová, Jitka (referee)
Adaptation to chronic hypoxia activates endogenous signaling cascades, which lead to cardiac protection against acute ischemia/reperfusion (I/R) injury. The molecular mechanism of this phenomenon has not been fully clarified yet. However, it was proved that reactive oxygen species (ROS) take part in cardioprotective signaling pathway inducted by chronic hypoxia. The high level of ROS must be precisely regulated by antioxidative system of a cell. The aim of diploma thesis was to examine the effect of intermittent hypobaric hypoxia (IHH, 7 000 m) on relative amount of antioxidative enzymes (peroxiredoxin 6 - PRX6, thioredoxin 1 and 2 - TRX1 and TRX2, thioredoxin reductase 1 - TRXR1) and also enzymes of iron metabolism (heme oxygenase 1 and 2 - HO1 and HO2, aconitase 1 and 2 - ACO1 and ACO2), which participate in regulation of cell redox state. Moreover, we studied the effect of adaptation to IHH and an antioxidant tempol on relative amount of calcium-independent phospholipase A2 (iPLA2). iPLA2 can remove peroxidized fatty acids from membrane phospholipids. On the other hand, iPLA2 can damage cell in I/R conditions. All enzymes were studied in homogenates from normoxic and IHH adapted rat left ventricular myocardium by Western blot. Adaptation to IHH caused a decrease of PRX6 and on the opposite an increase of...
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Functional morphology of myocardium
Vebr, Pavel ; Žurmanová, Jitka (advisor) ; Míčová, Petra (referee)
The thesis is a literary review summarizing current knowledge about the ultrastructure of myocardium in the overall context of the development and anatomy of the heart. The first part of the study is a summary of heart anatomy and its embryonic development, with emphasis on the morphology of cardiomyocytes. The state of inner cytoarchitecture of myocardial cells and the quality of inter-cellular connection reflects the functionality of the heart. Location and condition of cell compartments reflect the overall condition of the cell. The following part is devoted to the basic microscopic analysis methods suitable for research ultrastructure of cardiac cells. The outcome of this work is a comprehensive overview of the organization of remarkable morphological formations in cardiomyocyte, possible changes in ultrastructure in context of physiological conditions and comparison of microscopic methods with regard to their use in research of cardiomyocytes ultrastructure. Powered by TCPDF (www.tcpdf.org)
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Effect of erythropoietin on myocardial ischemic tolerance
Jindrová, Helena ; Kolář, František (advisor) ; Žurmanová, Jitka (referee)
Adaptation to chronic hypoxia increases myocardial resistance to acute ischemia/reperfusion (I/R) injury, similarly to application of exogenous erythropoietin (EPO). Nevertheless, it is not known if EPO induced by chronic hypoxia plays a role in its cardioprotective mechanism. The aim of this study was to find out if protective effect of exogenous EPO adds up to protection offered by chronic hypoxia. Adult male mice (ICR) were adapted to intermittent hypobaric hypoxia 8 hours per day, 5 days per week for 5 weeks. The degree of hypoxia corresponded to 7000 metres. Control animals were housed for the same time in normoxic environment. Resistance to I/R injury was assessed according to size of myocardial infarction induced by 45-min global ischemia and 1-h reperfusion of the heart in vitro. Animals were treated 24 h before the experiment with 200 or 5000 U/kg EPO. Treatment with 200 U/kg EPO was sufficient to significantly limit infarct size in normoxic animals (33,56 ± 2,93 % vs. 25,71 ± 2,29 %). Hypoxic adaptation decreased infarct area to 23,49 ± 2,30%, but additive effect of EPO in hypoxic group was not detected. The results indicate that exogenous EPO employs the same cardioprotective mechanisms as adaptation to chronic intermittent hypoxia. Preliminary results indicate that repeated application of EPO...
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The effect of morphine on expression and distribution of the alpha and beta subunits of trimeric G-proteins in the rat myocardium
Bartoňová, Iveta ; Novotný, Jiří (advisor) ; Roubalová, Lenka (referee)
Morphine is a clinically very important drug from the opioid group that is used for treatment of severe pain because of its strong analgetic effect. Opioid receptors mediating the morphine effect interact with the Gi/o class of trimeric G-proteins. Opioid receptors also occur in heart tissue and morphine can thus potentially exercise its effect on the function of this organ. The major aim of this project was to pursue consequences of long-term treatment with morphine on expression and distribution of selected heterotrimeric G-protein subunits in the rat heart. Potential cardioprotective effects of this drug have also been studied. Laboratory rats of the Wistar strain were treated with morphine (1 mg/kg/day or 10 mg/kg/day) for 10 or 28 days. The control group was treated with saline solution. Prolonged treatment with morphine did not cause any effects on Gs, Gi, Gz, Gq/11, G subunits, but the expression of Go rather decreased. The results of subsequent experiments showed that prolonged administration of high doses of morphine may reduce the area affected by infarction and reduced the frequency of ventricle arrhythmias depending on dose and duration of morphine administration. Key words: morphine, myocardium, opioid receptor, G-protein subunits, infarction.
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Role of protein kinase C isoforms in cardioprotective mechanism of chronic hypoxia
Hlaváčková, Markéta ; Novák, František (advisor) ; Kopecký, Jan (referee) ; Novotný, Jiří (referee)
Cardiovascular diseases, particularly acute myocardial infarction, are one of the leading causes of death in developed countries. It is well known that adaptation to chronic intermittent hypobaric hypoxia (IHH) confers long-lasting cardiac protection against acute ischemia/reperfusion injury. Protein kinase C (PKC) appears to play a role in its cardioprotective mechanism since the administration of general PKC inhibitor completely abolished the improvement of ischemic tolerance in IHH hearts. However, the involvement of individual PKC isoforms remains unclear. Therefore, the primary aim of this study was to investigate the potential involvement of PKCδ and PKCε, the most prevalent PKC isoforms in rat heart, in the mechanism of IHH-induced cardioprotection. We showed that IHH up- regulated PKCδ protein in left ventricle, enhanced its phosphorylation on Ser643 and increased its co-localization with markers of mitochondrial and sarcolemmal membranes. PKCδ subcellular redistribution induced by IHH as well as the infarct size-limiting effect of IHH was reversed by acute treatment with PKCδ inhibitor rottlerin. These data support the view that PKCδ plays a significant role in IHH-induced cardioprotection. On the other hand, adaptation to IHH decreased the PKCε total protein level without affecting its...
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Myocardial phospholipases A2 and oxidative stress
Závišková, Kristýna ; Míčová, Petra (advisor) ; Chytilová, Anna (referee)
Heart and vascular diseases, in which oxidative stress plays an important role, are the most frequent cause of death in developed countries. Therefore today's researches focus on clarifying signaling pathway and their components that operates in these processes. One of the possible key factors can be phospholipases A2. These enzymes hydrolyze unsaturated fatty acids from C2 position on phospholipids, which easily subject to the oxidative modification due to their double bonds. There are five groups: the secreted, the cytosolic, the calcium independent, the platelet-activating factor acetylhydrolases and the lysosomal phospholipases A2. They differ in the requirement for calcium ions for its activity, molecular weight, position of disulfide bonds and amino acids sequences in the active site. Their main importance is to keep the stability and integrity of cell membranes and produce lipid signaling molecules (free fatty acids, lysophospholipids, eicosanoids). The phospholipases A2 play a dual role during oxidative stress in myocardium. First, they have a positive effect by protecting membranes against oxidative stress due to their higher affinity for removal of peroxidized fatty acids from membrane phospholipids. On the other hand, the phospholipases A2 can also cause destructive effects during...
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Effect of nitrogen free radicals in rats heart under hypoxic condition
Cardová, Michaela ; Žurmanová, Jitka (advisor) ; Neckář, Jan (referee)
Since 1987 when the ability of cells was discovered to produce endogenous NO and its role in vascular vasodilatation was found, NO became to be the subject of examination by many scientists. NO is the important signaling molecule for now occurring in all important organ systems. This work is focused on its functionality in cardiac tissue under hypoxic stimulus. Effect of nitric oxide has been recently considered as cardioprotective, in spite of its known and well documented harmful influence. Most of the cytotoxic effects can be explained by peroxynitrit, which originates in the spontaneous reaction of NO with superoxid. The aim of this work is to summarize the most important effects of nitric oxide in the heart.
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The role of TNF-alpha and IL-10 in cardioprotective effect of chronic hypoxia
Chytilová, Anna ; Bezouška, Karel (advisor) ; Hloušková, Patricie (referee)
The aim of the present study was to find out whether adaption to chronic hypoxia affects the expresion of TNF-α and IL-10 in rat myocardium. TNF-α is a proinflammatory cytokine, which amplifies inflammatory reaction, while IL-10 has opposite antiinflammatory effect. We also measured concentration of nitrotyrosine as a marker of nitrosative stress. We used male Wistar rats divided into four groups: 1) normoxic controls; 2) exposed to continous normobaric hypoxia (10% O2) for three days or 3) for three weeks and 4) exposed to intermittent normobaric hypoxia (10% O2) for three weeks with one hour daily reoxygenation. Cytosolic and membrane proteins (cytosolic and particulate fractions) were obtained from the left ventricle, right ventricle and interventricular septum. Concentrations of TNF-α and IL-10 in both fractions were measured by ELISA. Continous hypoxia increased TNF-α production in particulate fractions from all ventricular parts and decreased the ratio of IL-10/TNF-α in particulate and cytosolic fractions. Intermittent hypoxia redistributed TNF-α from cytosol into the particulate fraction and prevented the drop of IL-10/TNF-α ratio in the cytosolic fraction. The highest concentration of nitrotyrosine was found in the particulate fraction from the right ventricle after three days of hypoxia....
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Comparison of physiotherapy techniques after conventional and mini-invasive surgical myocardial revascularization
JÍRA, Pavel
This thesis is focused on surgical therapy of coronary artery disease and its following physiotherapy in acute state. The main task is to find the right form of physiotherapy and check its effectiveness during the early postoperative period. I compare two different surgical intervention the mini-invasive one and the conventional technique method of surgical myocardial revascularization. The thesis is divided into theoretical and practical part. In theoretical part is described the origin and the etiology of coronary artery disease, its therapy - particularly the surgical therapy and its following physiotherapy. This part is created by research of sources enumerated at the end of the thesis. In practical part are described the possibilities of physiotherapy and the progress of patients after the operations. It was created the special list of exercises. Exercises was aimed at breathing techniques and vascular gymnastics, improving of physical condition by light special exercises, practising of verticalizing and self-reliance. The exercises had to solve the muscles disbalances without interrupting the process of recovering the postoperative scar. Special exercises was the part of the healing process. For the first time patients were examined, then they were well educated about helping techniques and special precaution. Patients were examined again before leaving the cardiothoracic ward and the acquired values were compared in all observed aspects. Physical condition of all patient were improved, it has a huge influence on disbalances in shoulder girdle and muscles of thorax and scapula. The outcome of the research is the finding that the proper activity helps with process of recovering after the coronary revascularization.
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