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Nuclear receptor PPARα and its role during development of heart failure
Goffová, Gabriela ; Fišerová, Ivana (advisor) ; Hrdlička, Jaroslav (referee)
Heart failure is a condition in which the mechanical pumping function of the blood is impaired and the oxygen and nutrients delivery to the tissue is not adequate to meet the needs of the body. PPAR receptors function as nuclear transcription factors of energy metabolism- related genes in cardiomyocytes. The PPARα isoform is a central regulator of myocardial fatty acid metabolism involved in the pathogenesis of heart failure. Activation of PPARα by specific ligands promotes fatty acid uptake, utilization, and catabolism by increasing the expression of genes involved in fatty acid transport, binding, activation, and β-oxidation. Studies to date have highlighted changes in PPARα expression, the influence of a non-functional gene studied in animal models with gene deletion, reduced expression of the coactivator PGC-1α, the influence of PPARα agonists, and the impact of these factors in the development of heart failure. The current results suggest that the level of PPARα expression may become a metabolic marker of cardiomyocytes. This bachelor thesis aims to summarize the current knowledge on PPAR receptors, with a focus on the PPARα isoform, especially with regard to its role in myocardial metabolism during heart failure. Keywords: nuclear receptor PPARα, metabolism, heart failure
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Physiotherapy in patients with long-term heart assist devices
Vaňková, Kateřina ; Chvojková, Lenka (advisor) ; Heřmanová, Ivona (referee)
BACHELOR THESIS ABSTRACT Name, surname: Kateřina Vaňková Supervisor: Mgr. Lenka Chvojková Title of bachelor thesis: Physiotherapy in patients with long-term heart assist devices Abstract: This thesis deals with the issue of physiotherapy in patients after the implantation of long-term heart assist devices (in this case of the type HeartMate 3). The goal of this thesis is to find the possibilities of physiotherapy within cardiovascular rehabilitation after surgical implantation of heart assist device and subsequent application of this knowledge in practice. The thesis is divided into theoretical and practical parts. The theoretical part consists of basic information about the heart muscle and heart failure as the most common cause of implantation of the long-term heart assist device. Next, both heart assist devices in general and concretely HeartMate 3 are presented. Finally, there is a chapter devoted to cardiovascular rehabilitation. The practical part was created based on professional practice in the IKEM hospital in Prague at the turn of July and August 2020. There is an elaboration of case studies of two probands using functional testing such as the 2 Minute Walk Test and Barthel Index. The results of comparing the input and output examinations are summarized in the discussion and conclusion. Key words:...
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Novel Approaches To Protect The Heart Against Postischemic Failure
Hrdlička, Jaroslav ; Papoušek, František (advisor) ; Zicha, Josef (referee) ; Vízek, Martin (referee)
Ischemic heart disease and resulting heart failure (HF) belong to the leading causes of death in developed countries. In order to prevent HF and improve clinical outcome in patients with myocardial infarction, novel therapies are required to protect the heart against the detrimental effect of ischemic injury. Due to the failure to translate numerous available experimental cardioprotective strategies into clinical practice, the need for novel protective treatments persists. We have, therefore, tried to apply a novel approach to cardiac protection against the postischemic HF induced in rats by ligation of the coronary artery. For this purpose, we have studied (i) the preventive and therapeutic effects of adaptation to continuous normobaric hypoxia (CNH; 12% O2) and exercise training (ExT; treadmill running), and (ii) the possible cardioprotective potential of epoxyeicosatrienoic acid (EET)-based therapy in order to attenuate the postischemic HF in rats. Adaptation to CNH and ExT is known for their cardioprotection in acute ischemia/reperfusion (I/R) injury manifested as reduction of infarct size. EETs exert antihypertensive effects and thus seem to be perspective for the research in clinically relevant models of cardioprotection in hypertensive animals. Our results have revealed that: - CNH prior to...
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Quality of patients life with heart failure in the working age
Škaroupková, Petra ; Tomová, Šárka (advisor) ; Bratová, Andrea (referee)
Heart failure (HF) constitutes a serious health and social problem. The number of patients with HF continues to increase and it concerns not only the elderly, but increasingly also young people in the working age. In the Czech Republic, the incidence of HF is reported in the range of 0.4 to even 4 % of the whole population. Every year, there are 0.4 % new patients diagnosed with the disease. In order to effectively meet the bio-psycho-social needs of HF patients, we should know the impact of the disease on these needs. To determine the negative effect of HF on patients' lives we used the standardized Minnesota Living with Heart Failure Questionnaire. The aim of this thesis was to identify the relationship between certain areas of patient quality of life and the degree of heart failure, and then to transfer our findings into the nursing practice. Obtained results showed that the degree of HF according to NYHA (the New York Heart Association functional classification) affects all aspects of the life's quality. The analysis of obtained data revealed that there is no difference in perception of the negative effects of HF between men and women. Moreover, we demonstrated that even the age does not have any significant impact on the perception of negative sensations caused by heart failure. The average...
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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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Proteomics as a tool for understanding molecular mechanisms of human diseases
Pospíšilová, Jana
Proteomics is a set of analytical methods which enable qualitative and quantitative characterization of the proteome. Expression proteomics quantitatively compares proteomes of cells, tissues, body fluids or other biological materials to find differencies in protein expression and, based on these differencies, to describe the biological processes occuring in investigated organisms. An initial material for expression proteomic studies are complex mixtures containing thousands of proteins, which are analyzed using separation (electrophoretic and chromatographic) methods, and identified, possibly quantified using mass spectrometry. The aim of this Thesis is to demonstrate the application of the tools of expression proteomics in solving diverse challenges in biomedicine. We employed various proteomic approaches and tools for studying molecular mechanisms of human diseases using pacient biological samples, or a model organism and a cell culture. We were conducting three different research projects, namely: A quest for potencial molecular targets for selective elimination of TRAIL-resistant mantle cell lymphoma cells; Investigation of molecular mechanisms of heart failure using a rat model of the disease induced by volume overload; and Searching for diagnostically usable serum biomarkers of ovarian...
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Proteomics as a tool for understanding molecular mechanisms of human diseases
Pospíšilová, Jana ; Petrák, Jiří (advisor) ; Šulc, Miroslav (referee) ; Kovářová, Hana (referee)
Proteomics is a set of analytical methods which enable qualitative and quantitative characterization of the proteome. Expression proteomics quantitatively compares proteomes of cells, tissues, body fluids or other biological materials to find differencies in protein expression and, based on these differencies, to describe the biological processes occuring in investigated organisms. An initial material for expression proteomic studies are complex mixtures containing thousands of proteins, which are analyzed using separation (electrophoretic and chromatographic) methods, and identified, possibly quantified using mass spectrometry. The aim of this Thesis is to demonstrate the application of the tools of expression proteomics in solving diverse challenges in biomedicine. We employed various proteomic approaches and tools for studying molecular mechanisms of human diseases using pacient biological samples, or a model organism and a cell culture. We were conducting three different research projects, namely: A quest for potencial molecular targets for selective elimination of TRAIL-resistant mantle cell lymphoma cells; Investigation of molecular mechanisms of heart failure using a rat model of the disease induced by volume overload; and Searching for diagnostically usable serum biomarkers of ovarian...
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Pulmonary pathophysiology during circulatory support.
Popková, Michaela ; Mlček, Mikuláš (advisor) ; Rohn, Vilém (referee) ; Otáhal, Michal (referee)
Introduction: Left-ventricular (LV) distension and consequent pulmonary congestion are complications frequently discussed in patients with severe LV dysfunction treated with veno- arterial extracorporeal membrane oxygenation (VA ECMO). The goal of this study was to describe the influence of high VA ECMO flows to LV distension, lung hemodynamics, and lung fluid accumulation. Methods of LV decompression were studied to prevent lung edema. Methods: In all experiments porcine models under general anesthesia were used. The effects of high extracorporeal blood flow (EBF) on LV heart work were assessed in a chronic heart failure model. The effects of LV afterload on lung fluid accumulation were evaluated by electrical impedance tomography (EIT) on acute heart failure models. Phase and frequency filtration and mathematical analysis were applied to the raw EIT data. Subsequently, mini- invasive techniques of LV decompression were evaluated for LV work. Results: The stepwise increases of VA ECMO flow improved both hemodynamic and oxygenation parameters. Nevertheless, it also caused distension and increased work of LV. The rise in EBF led to increased pulmonary capillary wedge pressure and lung fluid accumulation assessed by EIT in heart failure. The methods for LV decompression (Impella pump, atrial...
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Life after a heart transplant
Kováčová, Anna ; Kordulová, Pavla (advisor) ; Dynáková, Šárka (referee)
Patients with terminal heart failure that cannot be treated with conventional therapies are indicated for heart transplantation. In acute deterioration, patients can be brought to transplant using a mechanical cardiac support that is able to partially or completely take over the role of the heart and allow the restoration of sufficient cardiac output (Fila et al., 2014). The period before and after transplantation represents a very challenging period for patients, when they feel not only physical, but especially mental and social needs, which change during their phases of life and at the same time affect their entire subsequent experience. The main goal of this diploma thesis was to monitor how the previous implantation of long-term mechanical cardiac support and the subsequent heart transplantation affect the needs and feelings of patients. Respondents were selected from patients who had been implanted with mechanical cardiac support prior to heart transplantation. The diploma thesis contained another five sub- objectives, which dealt with mapping the needs of patients before and after implantation of long- term mechanical cardiac support and after heart transplantation, as well as during compliance with regimen measures, information retrieval and education. For qualitative research, the method of...
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Hemodynamic adaptation mechanisms of heart failure to percutaneous venoarterial extracorporeal circulatory support
Hála, Pavel ; Kittnar, Otomar (advisor) ; Szárszoi, Ondrej (referee) ; Havránek, Štěpán (referee)
Introduction: Venoarterial extracorporeal membrane oxygenation (VA ECMO) is widely used in the treatment of circulatory failure, but repeatedly, its negative effects on the left ventricle (LV) have been observed. The purpose of this study is to assess the influence of ex- tracorporeal blood flow (EBF) on systemic hemodynamic changes and LV performance parameters during VA ECMO therapy of decompensated heart failure. Methods: Porcine models of low-output chronic and acute heart failure were developed by long-term fast cardiac pacing and coronary hypoxemia, respectively. Profound signs of circulatory decompensation were defined by reduced cardiac output and tissue hypoperfusion. Sub- sequently, under total anesthesia and artificial ventilation, VA ECMO was introduced. LV performance and organ specific parameters were recorded at different levels of EBF using an LV pressure-volume loop analysis, arterial flow probes on carotid and subclavian arteries, and transcutaneous probes positioned to measure cerebral and forelimb regional tissue oxygen saturations. Results: Conditions of severely decompensated heart failure led to systemic hypotension, low tissue and mixed venous oxygen saturations, and increase in LV end-diastolic pressure. By increasing the EBF from minimal flow to 5 L/min, we observed a...
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