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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.
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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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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.
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Cardioprotective effects of exercise training
Zajíčková, Pavlína ; Neckář, Jan (advisor) ; Míčová, Petra (referee)
Ischemia-reperfusion myocardial injury is one of the main causes of death as a result of cardiovascular disease. Creation of a programme aimed at prevention attracts attention because number of patients suffering from this disease is increasing. One possibility is a regular physical activity whose positive effect on ischemic myocardium has been confirmed by empirical evidence. On the other hand we still do not know what activities are the most suitable and which intensity is the best for our health. Mechanisms which are created by regular exercise and contribute to heart protection have not been fully identified yet. The objective of this paper is to discover potential mechanisms and describe their role in protecting our heart. Moreover, it deals with possible ways of training which could activate such mechanisms and thus reduce significantly the risk of myocardial injury.
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Effects of Mechanical Loading on Early Conduction System Differentiation
Machálek, Jakub ; Sedmera, David (advisor) ; Neckář, Jan (referee)
6 ABSTRAKT Kardiovaskulární onemocnění představují celosvětově nejčastější příčinu úmrtí. Arytmie neboli poruchy srdečního rytmu k této mortalitě přispívají nemalou měrou. Výzkum v oblasti morfologie převodního systému srdečního má více jak stoletou historii, ale oblast ontogeneze není ani v dnešní době dostatečně prozkoumána. Přitom pochopení mechanismů indukce pracovního myokardu ve specializovanou tkáň by mohl být jeden z klíčů k otevření dveří nových možností diagnostiky a terapie onemocnění v této oblasti. Cílem této práce je pochopení vlivu mechanické zátěže na vznik a vývoj převodního systému srdečního. Chci prokázat, že mechanické zatížení srdce krevním oběhem hraje v embryonálním vývoji nezastupitelnou roli v diferenciaci převodního systému srdečního (PSS). Jako model pozorování jsem si vybral kuřecí srdce. Při porovnání dat získaných na srdci ptáků a savců můžeme najít drobné odlišnosti v detailech, nicméně hlavní principy a mechanismy se zdají být stejné. Kuřecí embryo se vyvíjí 21 dní, přičemž toto časové údobí lze podle Hamburgera a Hamiltona rozdělit do 46 stádií. Zpočátku představuje srdce pouze primitivní trubici, která se stáčí v srdeční kličku. Posléze je přeměněna na zralý čtyřoddílový orgán charakteristický pro vyšší obratlovce. Tyto morfologické změny korelují i se změnami šíření...
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The role of oxygen radicals in the early phase of exposure to hypoxia in the development of hypoxic pulmonary hypertension
Lachmanová, Věra ; Herget, Jan (advisor) ; Geršl, Vladimír (referee) ; Neckář, Jan (referee)
A pulmonary vascular bed is low-pressure system at adult subjects. Pulmonary vessels react to hypoxia by two different processes. These are hypoxic pulmonary vasoconstriction (HPV) and hypoxic pulmonary hypertension (HPH). They differ in mechanism of origin, but there seems to be important role of reactive oxygen species and nitric oxide. It was assumed in the past that HPV is isolated reaction of small pulmonary arteries to acute hypoxia and HPH to chronic hypoxia. Recently we believe that HPH is developed on the basis HPV (Crossno, Garat et al. 2007) and remodelation of peripheral pulmonary vessels (Reid 1986). Our main task was to learn, whether antioxidants given in the early phase of exposure to hypoxia influence pulmonary hypertension more than its late administration, in the period of already developed damage of pulmonary vessels. We have used N-acetyl-L-cysteine (NAC) as an antioxidant substance. We measured changes in resistance of pulmonary vascular bed, changes of reactivity of pulmonary vessels in dependence on concentration of oxygen in the inhalated air. Measurements were performed on the model of rat isolated perfused lungs. In addition we have observed influence of the early and late treatment of NAC on the pulmonary artery pressure at rats kept in hypoxic conditions. Our results show that...
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The effect of dietary n-3 polyunsaturated fatty acids in the regulation of insulin secretion and glucose homeostasis in mice
Doleželová, Šárka ; Rossmeisl, Martin (advisor) ; Neckář, Jan (referee)
Dietary intake of long-chain polyunsaturated fatty acids of n-3 series (n-3 LC-PUFA), especially eicosapentaenoic (EPA) and docosahexaenoic acid (DHA), exert hypolipidemic effect and prevent cardiovascular disease. One of the main targets of n-3 LC-PUFA is adipose tissue, where they activate so called "metabolic switch", resulting in an improvement of lipid and glucose metabolism. In this report, n-3 LC-PUFA suplementation decreased plasma levels of free fatty acids, accumulation of triacylglyceroles in the liver and improved systemic insulin sensitivity in mice fed a high fat diet. There was also a slight decrease in the -cell mass and lower dysfunction of -cells in response to n-3 LC-PUFA feeding. Incretin hormones are secreted from an intestinal cells in response to the ingestion of food, while they also enhance glucose-stimulated insulin secretion. This thesis also analyzed the effect of dietary n-3 LC-PUFA on insulin secretion induced either by the intraperitoneal or oral administration of glucose. The results demonstrated that n-3 LC-PUFA facilitate glucose clearance in response to its oral administration, an effect that is attributable to increased insulin secretion as compared to the effect of intraperitoneal glucose administration. These results suggest that elevated incretin secretion in response...
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The effects of dexrazoxane on ischemia-reperfusion injury in rat heart
Boudíková, Adéla ; Neckář, Jan (advisor) ; Hloušková, Patricie (referee)
Dexrazoxane (DEX) is clinically used to reduce cardiotoxic efects of anthracycline cytostatics. Its cardioprotective efect is caused by chelatation of free iron and defends myocard against dangerous hydroxyl radicals. This research finds out how dexrazoxane works in ischemic-reperfusion damages of rat's heart. Each rat was infused by DEX (50, 150, 450 mg/kg) or by control solution. Isolated perfused rat's hearts were exposed to local ischemia for 30 minutes than 10 minutes of reperfusion for studing ischemic arrhythmias followed by 15 minutes of local ischemia and 10 minutes of reperfusion to examine reperfusion arrhythmias. For evaluation of EKG (ventricular arrhythmias) was used software CAR and Lambeth convention. Global ischemias (15 min.) were induced in rat's hearts (DEX 150 mg/kg) and left ventricules were used for HPLC to determinate concentration of glutathion. In vivo experiments rats were infused by DEX 50, 150 mg/kg or control solution and were exposed for 20 minutes to local ischemia and for 3 hours to reperfusion. Infarct size was evaluated based on the cross section of heart (GIMP, Ellipse). Maximum total number of ischemic arrhytmias decreased by DEX 150 mg/kg (64% comparing to controls). Reperfusion score was reduced by DEX 150 to 48% and percents of ventricular fibrilation was...
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