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NITRIC OXIDE AND REACTIVE OXYGEN SPECIES IN ACUTE CORONARY SYNDROME
Šnorek, Michal ; Herget, Jan (advisor) ; Ošťádal, Petr (referee) ; Al-Hiti, Hikmet (referee)
In cardiology, there are different conditions associated with the release of free radicals in some forms of hypoxia, such as ventilatory hypoxia or reduced perfusion. The role of free radicals during hypoxia in cardiology is the key point of our interest. In presented thesis, we have focused on hypoxia-induced pulmonary vasoconstriction and acute myocardial ischemia. Hypoxic pulmonary vasoconstriction (HPV), an important physiological mechanism, is regulated by changes in the production of and interactions among reactive oxygen species (ROS). There is controversy, however, over whether HPV is mediated by an increase or a decrease in ROS production. Also, the role of nitric oxide (NO) in HPV remains unclear. Our results indicate that inhibition of HPV by the superoxide dismutase mimetic tempol does not depend on either NO production or a decrease in basal vascular tone. The effect of three-day fasting on cardiac ischemic tolerance was investigated in another experimental model. Short-term fasting conclusively decreases ROS production. Three-day fasting effectively protected rat hearts against major endpoints of acute ischemia-reperfusion injury. It prevented severe ventricular arrhythmias and reduced the extent of myocardial infarction. These beneficial effects can be linked to altered mitochondrial redox...
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Advanced heart failure in the 21st century: new physiological insights and new therapeutic avenues
Boilson, Barry Anthony ; Aschermann, Michael (advisor) ; Vítovec, Jiří (referee) ; Ošťádal, Petr (referee)
Countries with developed economies are currently facing an epidemic of heart failure (HF) and the prognosis of patients with advanced HF remains extremely poor. One of the therapeutic options for patients with advanced HF is heart transplant. The number of cardiac transplants performed in USA and other states each year has stagnated despite an increasing number of cases of end-stage heart failure each year, primarily due to limited donor supply. Therefore, novel therapies for cardiac replacement (such as left ventricular assist devices, LVADs), other cardiac assistance devices including arrhythmia treatment (cardiac resynchronization therapy, CRT or implantable cardiac defibrillators (ICDs) have been tested and are being used in clinical practice. Moreover, stem cell therapy has been tested as well as a role of endogenous progenitor cells has been explored. However, effects of the novel therapeutic approaches or their combination on pathophysiology of HF as well the involvement of endogenous progenitor cells are incompletely understood, which requires further research. The main aims of the thesis with corresponding main hypotheses were three as follows. First, to study the physiological effects of LVADs on pulmonary vascular resistance and the incidence and clinical tolerance of ventricular...
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Radial approach to coronary catheterizations and interventions
Bernat, Ivo ; Rokyta, Richard (advisor) ; Vojáček, Jan (referee) ; Ošťádal, Petr (referee)
Radial approach in coronary catheterizations and interventions has been only an alternative of the femoral approach. But due to some important advantages radial approach has a chance to become the first choice in majority of catheterized patients. The most important advantage is the reduction of vascular access site bleeding complications. Additonal benefits are patient satisfaction, cost reduction, shorter hospital stay and possibility of the same-day discharge catheterizations and interventions. The aim of our work was to try to answer three open questions: 1. is it possible to catheterize majority of our patients from the left radial artery when 90% of them are right-handed ? 2. what is the optimal care for the radial artery after the procedure in prevention and treatment of radial artery occlusion? 3. is it effective to implement radial approach in primary PCI as a first approach for STEMI patients? The first part relates the left radial approach. After construction of our special variable support for the left arm and forearm we succesfully used this approach in our studies in almost 90% of patients. The second part of this work contains our randomized trial comparing two different doses of unfractionated heparin in prevention of radial artery occlusion after diagnostic cardiac catheterizations....
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Treatment of pulmonary hypertension affect the metabolism of cyclic guanosine monophosphate
Al-Hiti, Hikmet ; Kettner, Jiří (advisor) ; Ošťádal, Petr (referee) ; Goncalvesová, Eva (referee)
Chronic damage to pulmonary vessels leads to pulmonary hypertension (PH). Different forms of PH are quite frequent and are associated with significant morbidity and mortality. The treatment of PH is most successful, if its cause can be identified and removed before irreversible damage to the pulmonary vascular bed occurs. For patients, in whom the elimination of the underlying cause is not possible or where the cause is unknown, the treatment is aimed at reduction of pulmonary vascular resistance and improvement of cardiac and circulatory response to pressure overload of the right ventricle. One option for the PH treatment is modification of metabolism of cyclic guanosine monophosphate (GMP), which is the second messenger of nitric oxide and induces vascular vasodilation. Cyclic GMP is degraded by phosphodiesterases (PDE 5). In the clinical part, we tested the hypothesis that acute inhibition of PDE5 by sildenafil provides more selective pulmonary vasodilation than high doses of prostaglandin E1 (PGE1). The study showed that the vasodilator effects of sildenafil on pulmonary circulation is more pronounced than in the systemic circulation and that sildenafil had a greater ability to detect reversible component precapillary PH due to advanced chronic heart failure than PGE1. The aim of our...
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The Primary Prevention of Atherosclerosis
Suchecká, Barbora ; Ošťádal, Petr (advisor)
The topic of atherosclerosis and its complications is currently the subject of much attention because it is a very common disease and the complications caused by her dying a large number of people. Cardiovascular disease (CVD) is the cause of 30% of all deaths worldwide. In the Czech Republic are the main cause of CVD death (in 2004 contributed to the overall CVD mortality of 51, 4%). 8 The topic I chose it because I care about, and in his medical practice with him will meet. I consider the prevention of atherosclerosis for a better solution than to treat complications or consequences that disease caused.
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Selected differences in pathophysiology of cardiovascular system in women
Yang, Shiann-Guey ; Kittnar, Otomar (advisor) ; Ošťádal, Petr (referee) ; Danzig, Vilém (referee)
(summary of doctoral dissertation) It has become increasingly apparent in recent years that there are important differences of many cardiovascular disorders including ventricular tachycardias in men and women. Gender differences have been observed in the epidemiology, pathogenesis and clinical presentation of various ventricular arrhythmias. Physiological menopause occurs as a part of a woman's normal aging process being based on the natural cessation of estradiol and progesterone production by the ovaries. The dramatic fall in circulating estrogens levels at menopause impacts many tissues including cardiovascular system. Because the incidence of coronary heart disease (CHD) rises significantly after menopause, it has been hypothesized that women's CHD advantage before menopause (in comparison to men of the same age) could be due to the protective effects of estrogens. However, controversial results have been reported since early nineties until today. While some studies found reduction in the incidence of CHD and in mortality from cardiovascular diseases some other studies failed to provide any evidence for an independent role of estradiol levels in determining CHD in postmenopausal women and some studies even found positive association of endogenous estradiol with the risk of CHD among women above...
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Risk factors of atherosclerosis
Kratochvíl, Filip ; Ošťádal, Petr (advisor)
The topic of my thesis I chose based on their interest in this issues. Atherosclerosis is a multifactorial disease occurring in the vessel wall due to the interaction of metabolic and structural properties of the vessel wall , the blood components and hemodynamic forces. It's a long ongoing inflammatory process, which affects the inner wall of the damaged artery chemical, physical or biochemical effects and leads to structural changes in the vascular wall Consequently fibroproliferative inflammation. The term arteriosclerosis was first used in 1829 to describe calcifications in the wall of the artery . The term atherosclerosis was then used in 1904 to describe lipid deposits in atherosclerotic arteries. The discovery of the relationship between clinical symptoms of myocardial infarction , atherosclerosis and coronary artery thrombosis made in 1912 by James Herrick . Atherosclerosis is the process involved in pathophysiological mechanisms of organ changes , which are manifested serious complications , such as coronary heart disease, peripheral vascular disease or ischemic cerebrovascular event . Taking a number of risk factors may condition the not only atherosclerosis , but also its rapid progress and spread to other areas.
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Aortic stenosis
Šmíd, Michal ; Rokyta, Richard (advisor) ; Rosolová, Hana (referee) ; Ošťádal, Petr (referee) ; Sovová, Eliška (referee)
Aortic annulus and ascending aorta: comparison of preoperative and periooperative measurement in patients with aortic stenosis Introduction Precise determination of the aortic annulus size constitutes an integral part of the preoperative evaluation prior to aortic valve replacement. It enables the estimation of the size of prosthesis to be implanted. Knowledge of the size of the ascending aorta is required in the preoperative analysis and monitoring of its dilation enables the precise timing of the operation. Our goal was to compare the precision of measurement of the aortic annulus and ascending aorta using magnetic resonance (MR), multidetector-row computed tomography (MDCT), transthoracic echocardiography (TTE), and transoesophageal echocardiography (TEE) in patients with degenerative aortic stenosis. Materials and Methods 15 patients (9 males and 6 females, mean age 68.8 + 7,1 years,) indicated for aortic valve replacement due to degenerative aortic stenosis were enrolled into this prospective study. The study followed the principles established in the Declaration of Helsinki. The protocol was accepted by the local ethical board and informed consent was obtained from each patient. The study was performed in a tertiary medical centre. Preoperatively, TTE was performed in all patients, while TEE was...
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Left ventricle remodeling in patients with primary aldosteronism and essential hypertension
Indra, Tomáš ; Holaj, Robert (advisor) ; Ošťádal, Petr (referee) ; Paleček, Tomáš (referee)
Myocardial damage is one of the most serious consequences of arterial hypertension. Changes in the heart structure and function develop not only due to pressure overload itself, but many other hemodynamic and neurohumoral factors contribute to their formation. Our work has compared echocardiohraphic strucutural anf functional changes of the left ventricle, caused by essential hypertension and hypertension associated with primary aldosteronism (PA) as the most common reason for secondary hypertension. The first part of our work focused on the differences in left ventricle geometry in men with PA and essential hypertension after separating it's low-renin form (where, similarly to PA, the plasma volume expansion was considered to have the dominant effect on left ventricle remodelation). In men with low-renin forms of hypertension including PA, we observed greater both endsystolic and enddiastolic diameter of the left ventricle, lower relative wall thickness and more frequent eccentric type of hypertrophy when compared to essential hypertensives with normal renin levels. Whereas left ventricle cavity diameters were positively correlated to aldosterone levels, wall thicknesses were associated mainly with hypertension severity expressed as an average 24hour blood pressure and number of antihypertensives....
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Allooimmunosensitization in left ventricular assist device recipients and impact on post-transplantation outcome
Urban, Marián ; Netuka, Ivan (advisor) ; Ošťádal, Petr (referee) ; Mrázek, František (referee)
Background: In recent years mechanical circulatory assist devices became an established option in bridging patients with refractory heart failure to heart transplantation. One of the alleged limitations of mechanical devices is a high degree of antibody production with possible deleterious effect on subsequent heart transplantation outcome. Aim: The main goal of this study is to assess the role of antibodies on the outcome of surgical treatment of patients with end- stage heart failure. Method: Firstly, we present a literature review on the current state of knowledge of possible immunologic mechanisms involved in antibody production in left ventricular assist device (LVAD) recipients, new methods of antibody detection, desensitization strategies and overview of published evidence assessing the impact of sensitization on post-transplantation outcome. In the experimental part of our study we prospectively evaluated the presence of anti-Angiotensin II Type 1 Receptor (AT1R) antibodies in 83 Heart Mate II (HMII) recipients who were implanted at our institution between 2008 and 2012 and survived the first 60 days. On-device survival and device malfunction, major infection, major bleeding and neurologic dysfunction were compared between antibody positive and antibody negative recipients. Out of a total...
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